Fiesers' Reagents for Organic Synthesis (Volume 17)

i ha;rI, L .^-t' . t .. . . ' | ' r

Fieserand Fieser's

Reagentsfor OrganicSynthesis VOLUME SEVENTEEN

Mary Fieser Harvard University

PUBLICAIION A WILEY-INTERSCIENCE John Wiley & Sons, Inc. NEW YORK / CHICHESTER / BRISBANE / TORONTO / SINGAPORE

,i}-

\.

' ( ) I v li

I

ADVISORS JEFF ROHDE

MARK BIL,ODEAU

STRUCTURE COMPOSITION TIMOTHY GRINSTgweR

MIHer Azrrutoene MeRr Russerr MencaRsr Hsu

Ttu JeursoN Tee Bun SHIN Onr-euoo ScHRRBn SspBsRSaRsHe,n

PROOFREADERS MlcHRnL H. KRESS

RBssccaM. MensH RrcHenoM. GoonveN

ALEXANDER R. MucI DAVID H. RIPIN BRYAN E. R0BERTS

JAY F. LARRow

Dnsoneu EvReno

Susan L. VeNnsRvsr-op, DEBORAH T, HuNc

KARLENE A. CIMPRICH

PI ltl r{l d

F d

It

paper' This text is printed on acid-free & Sons' Inc' Copyright O 1994 by John Wiley s i m u l t a n c o u s l yi n C a n a d a A l l r i g h t s r e s e r v e t lP u b l i s h c d any part of this work beyond Reproductionor translationof r08 of the 1e76 United or r07 ;v Section ;;i';;i;;;. permissionofrhe. copyright Siut". Copyrigni Act without the or further permission for Requests owner is untu*ful to thc PermissionsDepartment' inforrnution should be addressed NY Third Avenue' New York' John Wiley & Sons, lnc', 605 I 0 15 8 - 0 0 1 2 . in Publication Data: Lihrary of Cong,ressCataloging ISBN 0-471-00074-4 ISSN 0271-616X of America Printcd in rhe United Stares 1

0

98

1

6

5

4

3

2

l

PREFACE This volume of Reagentsincludes material published in late 1990 to early 1993.As usual,this volume hasreceivedtremendoushelp from Harvardgraduate students.Mark Bilodeau and Jeff Rohde have read and correctedlarge portions of the manuscript.Other advisers have provided invaluable correction of the page proofs. Another group, for the first time, was responsiblefor composition of the chemical formulas in ChemDraw. MARY FIESER C ambridge, M assachusetts June 1994

CONTENTS

Reagents 1 Author Index 409 Subject Index 425

Acylsilanes. Review. Cirillo and Panekr have reviewed progress in the chemistry of these compounds during the last two to three years (48 references).A new synthesis involves (l)2 to form homologationof aldehydeswith methoxybis(trimethylsilyl)methyllithium enol ethersof an acylsilane(equationI). Acylsilanes can be preparedin high yield by

?rr'

(l) Liclsi(cH3)312 Tl|'n. H'

/ocHs

H.o,

?

'si1cH.;. 5t-e2'l" RCH2/ -si1cH.;.

1

o

(rr) *Asr, (ilr)

o

CuCN

+ Atlsi(cH3)313 T H F

83-98%

e, CH3CN/ H2O ---;*"-

*A.,("rr), O

*Ar,("r.).

1X3,,"r.,.

reactionof S-2-pyridyl esterswith aluminum tris(trimethylsilane)and CuCN (1 equiv.), equationII.3 A third general synthesis of acylsilanes involves anodic oxidation of 2-alkyl-2-trimethylsilyl-1,3-dithianes (equationIII)4. Acyldimethylphenylsilanesundergohighly selectivehydrogenation(Pd/C) to aldehydes without effect on benzyl or BOM ether groups, acetonides,or r-butyldimethylsilyl groups (equationIV).

(CHe)e 'l - -o Mo M

(tU CoHs-Si-'.\,CH3 i l l

o

H2,Pd lc c2HsoH

osi(cH3)3

75o/"

OMOM I H\.,r\,\..CH3

i l l o osi(cH3)3

Acylsilanesundergohighly diastereoselective reactionswith RLi and RMgX to afford s_r'n-adducts, particularly when the chiral center is substitutedby a phenyl group.5

Alanine

gt.

CHq

t -J.- -Si(CH3)3

coHs- lf o

bULI 92"/o

9t. . c"n,ft;Btrr.E',T.,4>;;

Cra" |1^'

> 100:1

asx j euor.r-r CHq

C.H.

t cuHrlY"

cl

OH

Acylsilanesarereducedtoa-alkoxysilanesbyavarietyofmetalhydrides.Reductionwith provides(R)-alcoholsin >80% ee and in 30-65Vo (-)-chlorodiisopinocamphenylborane yield.6

L-rl

su fbr ,

rrkl O

It -S|(CH3)3

(CH3)zCH-

C) - tpe2BOl

rnr,zo"60%

9H

rs

s:ndr!

"\si(cH3)3 (cH3)2cH H,98o/o ee

e rP. F. Cirillo and J. S. Panek,Or8' Prep' Proc' Intl'' 24' 553 (1992)' (1991)' 2J. Yoshida,S. Matsunaga,y. Iiicni, f' Makawa' and S' Isoe' J' org'' 56' 1307 4929 (1991'). 3 M. Nakada, S. Nakamura, s. rJuyu.r,i, and M. Ohno, TetrahedronLetters, 32, a K. Suda, J. Watanabe,and T. Takanami,ibid'' 33' 1355 (1992)' s P. F. Cirillo and J. S. Panek, ibid', 32' 45'7 (1'991)' 3l' 46'77 6J.A. Soderquist,c.L. Anderson,'E.I. Miranda, and I. Rivera, TetrahedronLetters' S' Modi' D' Williams' and Khasnis' D' Lamb' G'W' Strickland' B' (1990); J.D. Breynak, J H. Zhang,J. Org'' 56,7076 (1991)'

Alanine, CH3CH(NH2)COOH' a.Methyta-aminoacids.lTheseaminoacidsareofgenera|interestbecausesuch substituentsinpeptidescanrestricttherotationalfreedomofamidebonds'andhence A general synthesis is an extension of the secondary and tertiary structures of proteins' acids' but involves alkylation of the Seebach'smethod tbr a-methylation of a-amino the schiff baseformed from this o-amino a_methyl a_amino acid o_ or i-alanine. Thus acidandbenzaldehydeiscyclizedbybenzylchloroformatetothe(2S,4R)-oxazolidinone l.Theenolateof|'isalkylatedbyvariouselectrophilesfromthefaceoppositetothatof can be hydrolyzedby brief treatment the phenyl group. The products,such as (2S'4S)-2' derivativeof the a-methyl a-amino with LioH or NaoH in cH3oH/H2O to a protected

i \ h

t-rb Sl r-lr Ll j.rn

p-Alanine

1) C6H5CHO

.Bu ,OH

CH3, ,,H

;H2N-g-CooNa

2)ctcooBzl

305"/"

1) LDA 2) BTCH2CO2C(CH3)3

P-(o cuHu""

(*4.cHt n cbl

76"/."

(2S,4R)-1

P-
LioH,cHsoH H2O,25'

(cHg)s

(cH3)3cooccHr,.rrcH" CbzHN CoocH.

41"/"

tzs,+ni-r

lr, ::s ith acid, such as a-methylasparticacid (3). The enolateof (2S,aR)-1can also undergoMichael addition to r-butyl acrylate.The yield is low, but the adduct is obtained \n 987o ee. This reaction provides a route to a derivative of 2-methylglutamicacid (equationI). V:l

(r) (2s,4R)-1

1) LDA 2)CH2=Cx996616H.;.

P-
CoH5""1 )--Ctl"CtlrCOOC(CH3)3 ''cH^ ,N' Cbz 'zaoz. -'-

, -rI 1677 ll::-:.. rnd

:J-.i

t , ^Llun', , I

I

c H 3 o HH , 2O

(cH3)3cooccH2cH2,cH3 coznu^-coocH3

sUCh

a!:.1tcncc il(:l.l()n Of I t ,, : \ r f t h e

'8. Altmann,K. Nebel,andM. Mutter,Helv.,74,800(1991).

tr . .rmino 2,'ll,lrnone t :., thatof [::r.1tmcnt fl ir -JITllIlO

B-Alanine, H2NCH2CH2COOH. Stereoselectiveallqlation. As an extension of a method for diastereoselective alkylation of a-amino acids (14, 263-264), Seebachet al.l have convertedthis simple 2 via an imine with pivaldehyde. B-amino acid into the 2-t-butylperhydropyrimidinone

Alkylaluminum halides

(

CHs p

ll."#5$""" f-( .I".l"o!9* (cH3)3cl

e,, HoAcHzcH2NH2

44o/o

-llh"f

/

Ltt

rac-2

(CH3)3C-{

/

* l .1i

o

Hcl *;;

tl nol)(\r.rHz

NJ

Bi

R 4 (86-97%ds)

3

group has the axial of 2 show-s that the r-butyl Surprisingly, an X-ray analysis with high diastereoselectivity oii r"u"t with alkyl halides configuration. rn" .notut. (3) can be hydrolyzed to (C) (u"o axial)' These,products to give the trans-produ"t This overall processshould with 6N HCI at t60-180"' a-substitutedB-amino *td;i4; p-amino acids' oi emantiomericallypure be applicableto u tyntn"ti' (1991)' ' J' Org'' 56' 2553 andD' Seebach B' Lamatsch' 1E. Juaristi,D. Quintana, na!!1. with the Atkylaluminun " des.r Reaction of (CH3!AI with p'formylproViolalt RAIC| of Rrortion CHrAlClz with reaction but the no 'tt"ottl""tivity' ;-tffi; B-formylpropionamides cH3Ticl3 is erythro-selective' with reaction the """o"r, shows high threo-selectiiirv.'i"

o

O H ?

o

RM' .".'^+f'"t'

,.1+T-"" o I

l

cH3Alcl2

63"/"

CH3TiCl3

38"/o

o l

,,AA*'cHt r r l ' i -L -cHs CHe cH{

O H ?

. cH.tl:"t' cH3 cH3

cH3 dH3

CH3 CH3

97:3 2:8

o H O RM' cH., --.AN."tt

o H ? . cH.\'\T'"t' or'AcH?H'

"r.A"r,?tt

CH3AlCl2

62"/"

C2H5AlCl2

72"/"

(1{./ r(tl.

(xl ,i*-

CHr : / ,P / ,N1 ""*

.afftil

oq.1

99:1

Alkylaluminum halides

the cyclization of eporydienes. corey and Sodeoka2 have examined in detail acids, Lrwis several optimum conditions for cyclization of the epoxydiene 1. Of (cH3)2Alcl or cH3Alcl2 was found to increase the rate of cyclization more than is superior to chlolide (CH3)rAlOTf, but the yield was comparablein all cases.Methylene cyclization the conditions clcH2cH2cl, cH3No2, or toluene as solvent. under optimal are products -78" principal The for t hour followed by silylation. was carried out at under all formed 3, ketone the silyloxy ketone 2 and the monocyclic silyloxy methyl conditions as a minor Product

OSi(Bzl)3

1) (cH3)2Alcl, cH2clz, -78" 2) ClSiMe2-f-Bu

al t\

fY"t'ot"".

l()

rld

RsSiO -'\--l

RO

3 , 1 0- 1 5 " 6 2, f = SiR3(75 -79o/")

hc ll: ta

Deoxygenationofketones.Reductivedeoxygenationofketonescanbeeffected of diaryl with an aluminum source and a Irwis acidic aluminum reagent.In the case acidlrwis the well as as source hydride ketones i-BuAlCl2 can be used as the

2i-BuAlCl2

n

H3

CaHst

X-CuH,

h€Ptane>

(coHs)zcHz 79o/o

?ut' coHui cHsAcHs 8"/"

reduction Reductive deoxygenation of alkyl aryl ketones is best effected in two steps: addition by increased be yield can The AlBrr. with i-BuzAlH followed by treatmentwith of Cp2TiCl2 in the second steP.

)Hs 1) i- BuAIH 2) AlBr3,Cp2TiCl2

C6H5COCH3

75"/o

sequential Reductive deoxygenation of dialkyl ketones is best effected in three steps: catalyst. Ni(acac)2 a and iBu2AlH finally and AlBr3, with i-BuzAlH, treatment

AlkYlaluminum halides

1)i-Bu2AlH

O

I

nonenes

sri-au2,Lil:rN:i(acacr'n - nonane

-Bu

(32o/ol

(48y.\

CH3(CHjal

Thesereactionscanbeusedforreductionofthecorrespondingsecondarya|coholsto primary alcohols ol p:enols' alkanes, but do not reduce an alkynylmagnesium brocomplexes'a Reaction of Cyclization of oWnyiu{inium midewithdichlorobis(cyclopentadienyl)titanium'resultsinaTicomplexlinessentially and to water than is more stable to air oxidation quantitative yield' This ""rnpttl< these complexes with an alkylaluminum halide' the Grignard reagent' On i"utrntnt to a 4-' attached alkene to an exocyclic trisubstituted (n: l_3)undergo "y"rjut^i* (2)' 5-. or 6-memberedring

R

R

'l'

'l' 'l'

?'

*(cHr)i

o"l)#3iJB[."t'i'*(cHr);'t'"'"0' 5O - 79o/o

1 ,n = 1 - 3 n = 1 - 3 1) RAlCl2or R2AlCl -30' -'-78" 2) HOAo'H2O 72 '93"/o

sol+ ,*" L""r,.". 2,n=1-3

'syn-insertionto thus 3 undergoesintramolecular This cyclization is regioselective; product' give 4 as the exclusivecyclic

<;,^ CHe

-,aCH" ,r/V'/.TiClCp2

I

\,r

I CHs

1)c2H'Atct2 2) H3o- -

a31"

5:95

\,,ACHE

CHe

3 for Diels-Alder is the most effective catalyst Diels-Akler catalyst's C2HsAlCl2 reactionis a key step in a This i'*itt' silyloxy-1'3-dienes' reactionsof (S)-(+)-carvon" (S)-carvone' (5) in a0% overall yield from total synthesisot 1+1-a-cyperone

Alkyllithiums

("" (cHd3sioCHg

(+)-1

rl. t()

l ' r r tltrilr

1)CzH5AlCl2 2) H3O+

:t.ln lcri:

?

_

CHg

77"/"

CHz

2a

H CH 2b

9 1: 9

1) H3O. 2) ClSi(cH3)3,

several steos

CHg

CHz

DDO,C6H6

(cH3)3sio

CHs

87v"

CHs (+) - 5, ca +91"

'1 -.

' . - \i J c r flrna

rH. fulii, M. Taniguchi,K. Oshima, and K. Utimoto,TetrahedronLeuers,33,45'19 (l,992). 2E.J. Corey and M. Sodeoka,TetrahedronLeuers, 32,7005 (1991). 3 J . L . E i s c h ,Z . - R . L i u , a n d M . P . B o l e s l a w s k iJ, . O r g . , 5 7 ' 2 1 4 3 ( 1 9 9 2 ) . aA. E. Harms and J. R. Stille, Tetrahedron Letters, 33' 6565 (1992). 5A.A. Haaksma,B.J.M. Jansen,and A. de Groot, Tetrahedron,4S'3121 (1992)'

Alkyllithiums. with an alkyllithium(3 equiv.) 2,4-Diallqlphenols.tReactionof p-benzoquinone in 60-7074isolatedyield' followedby an acidichydrolysisprovides2,4-dialkylphenols

8

Alkyllithiums

TL r

o

I Bu. ,oH I

tl

3 BuLi

r-

)r

rHF,-78i

l . , \ l " . o ' l l t i l t - ; . |

\.,.-

It

Bu

T

|

,\

I

\"t

lr

a

I rr^ot I

o

I

" * | Ji3,lTiill:""i"Jl"1, ?u"'

,"^\

l l t --

OH

o ll

ra) v' tl

o

1) C2H5Li 2) NaH, CH3l

Lffi]

ocHs

Thealkylgloupscanalsobederivedfromdifferentalkyllithiums.2,4-Dialkyl-

."-};#,'ff

orrHF pentane, inether, co2(sorid) forms

?fi?^[:"]#]'i?:i'Jith

with lithium hydride -10' provides a product a that on treatment -40 * ketone after at RrLi or R2Li gives a (43-72% r*"ll-*""tttn alcohol' aldehyde :' .u :ith tertiary an work-up provides a tt"""O RLi to b before hydrolysis. Addition "' "

l\

[ ?'-'I ''\**.\6p,"i

|N ] + c. o z L - r r = " *

-I

,r"o | ,'^ I

o ll

z+H t\N- r l

l

l' = * -b

I

sa'2.H.oI o tl (-(-'" \N-

Allylbarium

rtagents

This protocol provides a ready accessto a fange of aldehydes or ketones with moderate to high yield. (Aminosilyl)lithiums.3 Silyl anions are unstable and are usually generatedin situ in the presenceof a quenching agent. Aminosilyl anions are more stable both to substitution with lithium and a-elimination. They can be preparedby reactionof aminochlorosilanes dispersedin THF or with lithium wire. Yields are generally in the range 80-1007o and the products are stable at 0" for 1-6 days. The reagents couple with chlorosilanes to form disilanes. They undergo conjugate addition to unsaturated esters.

(cH3)sicl

(c2H5)2N(C6H5)2SiLi

AcCl 78"k

(cH3)3sisi(c6Hs)2cl

(foHs)z

(C2H5)2NCH3C6H5SiLi TMEDA 470/o

6r.1rg'

-s'-sic6H5cH3N (czHs)z

{. 1) (C2H5)2N(C6Hs)25iLi 2) CHgl;CzHsOH

f ) r . : l k lr,': I HF f :,,rms n!

.ittcr

sl,,,hol.

(c6Hs)2sioc2H5

ar.&tooc2H5

CH3-\'-COOC2Hs

CHa HzOz KF, KHCO3 35"/o

OH I cHslAYcooc2H5 CHs

,-l t,Ul

) L l

l

3v

Bu

rF. Alonso and M. Yus, Tetrahedron, 48,2709 (1992). 1G. Zadel and E. Breitmaier,Angew. Chem. Int. Ed., 31, 1035 (1992). I K. Tamao, A. Kawachi, and Y. Ito, Am. Soc., ll4,3989 (1992).

Allylbarium reagents, CHz: Q11611rguat. These reagentscan be generatedin situ by reaction of allylic chlorides with barium(O) with retention of the double bond geometry. B,y-(Insaturated carboxylic acids.t Carboxylation of allylbarium reagents,generatedin situ,proceedswith high a-selectivity. Note that carboxylationof allylmagnesium proceedswith high y-selectivity.

4-Allylcyclobutenones

- F

-

ct

tr

Ba,THF

CsHIICHO

-82% -

n-czHrsMaacl

n-CrHtu"^\'/\Cl

llr

ll

n-crtt,u/*1cuH" OH ah =98'.2

cl M g ,T H F

-=, n-C7H15

n-C7H15

cooH

Vsct COr I

l ^ , ,

-

.,.-\.'/

99v" n-C7H.,u/'\y'wn2 1/c= 99: 1

113, 9955 rA. yanagisawa, S. Habaue,and H. yamamoto'Am. soc., (1992)' 593 Synlett' Yamamoto, H. K. Yasui and

(1991);A. yanagrsawa'

4-AllylcYclobutenones. reagents react with cyclobutenediones Bicyclo[3.2-0]heptenones't Allyl Grignard when heatedin refluxing toluene products yield' The to give 1,2-adducts(l) in moderate ring yield' The reaction evidently involves give bicyclo[3.2.0lheptenones(2) in high a and + 2]cycloaddition of a vinyl ketene opening followed by an intramolecular[2 methylene grouP. coHg \-4

CoHs ,p

ll t cH3d

CHz=CHCHzMOB'

V

------ ---58"/"

'O

t

cH3l

/o

e5"/"

l$cH,cH=cHz -

cH3o

I

oH 1a

"tnur7o

+1

flcarcH=cHz

CH3O

OCH3

1

T . o \"u"r--l"""("rr\ 0 ' c l l

l

l*r.o/focn. II L

a

""o;12o -

l

cHso_\__L_l

l

Allyl(diisopinocampheyl)borane

II

This methodologyhas been extendedto 4-alkynyl-4-(propargyloxy)cyclobutenones,' formed by additionof lithium acetylidesto dimethyl squarate(3) followed by treatmentof the 1,2-adductswith propargyl iodides.Theseproducts(4) when heatedat 135'rearrange (5), which isomerizein an acidic medium to benzofurans(6)' to methvlenebenzofurans

cHsoY4'o

CH3O. _O \__/ LiC=CBu

+ 897o

crrl{O )Hz

i l l f-f-c=cBu

CH3O

OH

3

cftoY-/'o i l l /TC=CBu cH3o d"rr"=ar,.

138.c

CH3O

75o/"

CHrO

4 5

h,,ncs r l u cn c s ring a:rJ a

I 95"/. I HrO* V -

OH

cH3o cH30 6

r s .L . Xu, H . X i a , a n d H . W . M o o r e ,J . O r g . , 5 6 , 6 0 9 4 ( 1 9 9 1 ) r s .L . Xu, M . T a i n g ,a n d H . W . M o o r e , i b i d . , 5 6 , 6 1 0 4 ( 1 9 9 1 ) .

Allyl(diisopinocampheyl)borane'

cH3YcH3 K;,1:BCH2cH=cH2

PrC=CCHzl Agzo

12

Allyltributyltin reagents

Enantioselective allylboration; (R)-y-amino'B-hydrorybutyric acid.l Reaction of with I in ether at -100'provides the (R)-bromohydrin 2 in 89% bromoacetaldehyde ee (-5OVo yield), which is converted to the (R)-epoxide 3 on treatmentwith KOH' This epoxide is a precursorto 4, (R)-(-) y-amino-B-hydroxybutyric acid (GABOB)' a

Crh{cl

neuromodulator.

BTCH2CHO

1

,r-#c

-5Oo/"

,

KoH> -70%

|

c>+-rlc

OH (R) - 2, 897oee 1) NalOa'RuClg 2) NH3

>/'\r'cH2

CXrCt{=

"^y'\cooH"N* " l OH

(R)-3

(R) - 4, 89o/oee

1Y. N. Bubnov,L. I. Lavrinovich,A. G. Zykov, andA. V. Ignatenko,Mendeleev Comn.' 86 (7992). Allyltributyltin reagents, CHr: 6g6g2SnBu3 (1). ' Allylation of dioxane acetalst (ct. 12, 375-378). Allylation of chiral dioxane acetals such as 2 has been shown to proceed with marked stereoselectivitywith allyltrimethylsilane promoted by TiCla/Ti(O-i-Pr)a. A more recent study, indicates that

cH3Y,-)....cH3

CHr:C116".t*.

Ll

rt.Gr.rd rrhrrtr

;Ldrlx r 'TT { r0

CH" CH.

i - l oYon I

fu!'r tlrr

tk-s

n-C6H134CH2CH=CH2

TiC14, Ti(O-,-Pr)4

o-t-o

CH"- CHq -

,

f 9-^--4ot

n-c6H13 H (x)-2 tL ' til

-^-

n-C5H13M=Si,R=CH3 M=Sn,R=Bu M=Sn,R=CoHs

lOOo/o 100o/o 1O0/"

ut-3

-CH2CH=CH2

58:1 27O:1 90:1

allyltributylstannane(1) is significantlymore selectivethan allyltrimethylsilaneand that phenyl groups on the metal decreasethe selectivity.The sameselectivityis shown in the case of dioxane acetalsbearing other alkyl, aryl, and alkynyl groups. B,y-Enones.2 Organic halides are known to undergo tin hydride mediated carbonylation.This reactioncan be extendedto a three-componentcoupling of RI, CO, and allyltins to form B,y-enones.

clj'

\i Lr - l.'l H . \ ra"r

Allyltributyltin reagents

Rcrctionof in 2 in 89Vo s rrh KOH. ((i.\BOB),a

* ""r=-f"' cH3(cH2)7r bH2snBu,

?r. +

o-

lcHl cH3(cH2)s

tc"=

13

".3:'i3yg -"r.(""r)r'/5cusn -ft' 74%

co CHs(CHrs "' \ Jt \-/ *CH, CH2=Ct1611rgntr. : 600/o I 0Hs

+ cHz{ cH3cH=cH(cH2)31 CH2SnBu3

r

R ?t'^"", ?t' .

O

.n (1992).

hu:l dioxane irr:r *ith alr n J r . . t t e tsh a t itl.

-oH

-i- ,.r. 6:s4 Lf '-q",

Asymmetric addition of allyltins to RCHO.3 Addition of 7-substituted allylstannanes to aldehydesto form homoallylic alcohols can proceed in high diastereo-and enantioselectivitywhen carried out in the presenceof I equiv. of the Yamamotochiral acyloxyborane| (16,314). If trifluoroaceticanhydride is used as promotor, then only catalytic amounts of I are required. Mrtually quantitativeyields are obtained if I and (TFA)2O are used in the ratio I eq:1.2 eq.

rk-3

r- 1- f-{ ^

cH.

I

OH

ul-3

H= C H z

cH3''-\,-cHo

*

cHa"'--f\snaua

(1 : 1.2), 1, (CFgCO)zO cH3cH2cN, -78" 85"/"

CHs

: rrl.'nc and that s.:r,,$n in the mrJidted caroi Rl. CO, and

CHz

cH"/ 95o/oee, syn/anti = 92 :8 r S . E . D e n m a r ka n d N . G . A l m s t e a d ,J . O r g . , 5 6 , 6 4 8 5 ( 1 9 9 1 ) . r I. Ryu, H. Yamazaki,K. Kusano, A. Ogawa, and N. Sonoda,Am. 9oc.,113, 8558 (1991). 'J.A. Marshall and Y. Tang, Synlett,653 (1992).

14

Allyltrifluorosilanes

1R--oa---.SiFe

rb

R2 Allyltrifluorosilanes, y-selective coupling with electrophilies.l In the presenceof a Pd(0) catalyst and BuaNF (1 equiv.), aryl, vinyl, or allylic halides, triflates, or acetatescouple with allyltrifluorosilanesat the 7-position, with migration of the double bond. Pd(oAc)2 and dppb in combination with TASF (tris(diethylamino)sulfoniumdifluorotrimethylsilicate)

':. 3|t

o

"rr/li

Pd(o),BU4NF T H F ,8 0 ' > 95"/.

*%' CH31-Z'.,..-.SiF3

CHs 1

=cH,

oT{

I

/^-\

to'olblltt

ff

|

|

il

I

|

\/\./

i

|

-

850/"

is particularly effective for coupling of enol triflates. Only one coupling of an allylic acetate in low yield was reported. This coupling provides a practical route to the antiinflammatoryagent ibuprofen (equationI).

CHs lld

+

1 950k | : a

Br

.x5 I

Naro4 ro%) I r; xtrlnoo, rFA (78%) z1xsi1c2nuy3, I

TL ( t

CHg

tD CHs

cooH

a r: 1l II

I Y. Hatanaka,Y. Ebina, and T. Hiyama, Am. Soc., f n'

7075 (1991).

-

(R)- and (S)-l-Amino-2-methoxymethylpymlidine

!'l .rnd I rrh al-

(1, Ramp, Samp)

Aluminum chloride. Acylation.t Acylation of 2-methylbutanewith the crotyl chloride I in CH2C|2 in the presenceof AlCl3 and CuSOa/CH3NO2provides a synthesisof cyclopentenones (equationI). A similar reactionof alkenyl chlorideswith methylcyclopentaneor methyl-

cr. and ; rI r c a t c)

o tl

cH3\

Cl.'\

cH.AcH. )H;

Arcr3 CHs

L-CHs; ;

CHs

t ?

zsz crl),1 I \ v i o \-^

r.rllvlic :,, rhe

cHs-< I ) YfvcHs cil.

cyclohexaneprovides a synthesisof tetrahydropentalenones or tetrahydroindenones. Fries rearrangement,review. Martin2hasreviewedthe rearrangement of aryl csters to o- and p-hydroxyaryl ketones,usually effected with AlCh. Thc rearrangementcan occur at room temperaturesin polar solvents(nitroalkanes).Photo-inducedrearrangement usually provides the same products as obtained by Lewis acid induced rearrangemcnt. The review lists 281 referencesto literaturemainly from 1964 to 1990. r-8".1

rC. Morel-Fourrier, J.-P.Dulcdre, andM. Santelli, Am.Soc.,ll3, u062(1991). : R. Martin, Org. Prep.Proc. Int., 24, 373 (1992).

(R)- and (S)-1-Amino-2-methoxymethylpyrrolidine (1, Ramp, Samp). Asymmetric Michael cyclization; trans-disubstituted cyclopentanecarboxylates.r The lithium enolatesof SAMP hydrazones(2) of methyl ketones react with methyl (E)6-bromohex-2-enoate(3) to form the Michael adducts (4), which are cleaved by ()zoneto give /rans-disubstitutedcyclopentanecarboxylates 5 with high diastereo-and cntantioselectivity.

Aniline and Nitmbenzene

.\ri

Thrs

er-,u

Br. )

LDA,THF -78"

I

tsd

/-coocH3

(-Jl

cH3o--'HrA"r.

(E)-3

(s)-2

I

54"/" I overall I

/ \

. *

03, CH2C|2 -78"

(:),.'coocH3 l l (F1) I

cn.

o (1S,2R) - 5

> 9 9 o / od e 97o/oAE

t s-

I D. Enders,H. J. Scherer,and G. Raabe,Angew' Chem' Int' Ed' 3O' 1664 (1991)' Aniline

r h

and Nitrobenzene.

Addition and 4-nilrodiphenylamine't . of animixture to a 2Hzos (cH3)4NoH to tetramethylammonium hydroxide dihydrate, Direct coupling

to 4-nitrosodiphenylamine

lineandnitrobenzeneresu|tsinaa-complexl,whichisthenconvertedtoamixture (3)' The ratio of 2 and 3 of 4-nitrosodiphenylamine (2) and 4-nitrodiphenylamine

oH

C6H5NH.

-. o-

C6H5NH2 + C6H5NO2

Cur,r,U"-$*O 2

I I

c6H5NO2

tol

cuHuxH$uo, 3

ratio of nitrobenzeneis increased' dependson the ratio of aniline and nitrobenzene.As the act as an intermolecularoxidizing the yield of 3 is increased.Evidently nitrobenzenecan agent of I to give 3. I M. K. Stern,F. D. Hileman,and J. K. Bashkin,Am' Soc'' ll4' 923'1(1992)'

:-t

Lr ;.r / Lr! i c

{

2-Arenesulfonyl-3-aryloxazirdin€s

)cH3

Antimony(V) chloride- Silver hexafluoroantimonate. This combinationgeneratesSbCU . SbF; (l). Beckmann rearrangemenL The antimony(V) salt I is an effective catalyst for Beckmannrearrangementof ketoxime trimethylsilyl ethersto amidesor lactams.l

lilosi(cH3)3 1 , C H 3 C NA,

\

C6H5NHCOCH3

cH,

c.Hu

/n3

t7

/

V

-----------> 77"/o

NOSi(CH3)3

l3 S-

rlc

t": ee

Pinacol rearrangement.2 This reaction is generally effected with at least one equiv. of conc.HzSOr. It can alsobe effectedwith the salt (l), preparedfrom SbCls and AgSbFr, in high yield under mild conditions.In addition only 20 molVaof I is required.

o i l n

1,CH2C|2 15-20"

rdJrnon (' l a n l -

av

ml\turc .rnd 3

OH

Hzo

{.\o2

-_Noz

Nrc.lscd,

)\rJizing

o

| 9sHs

c6H5-l\-c6H5 CnH" - - oI H

99

lcuHuy.cAcuHu

lT. Mukaiyama and T. Harada,Chem. Letters, 1653 (1991). 2lbid, idem, sl (1992).

2-Arenesulfonyl-3-aryloxaziridines,ll, 108; 12, 392-393; 13, 23-24; 14,22. Oxidative desulfunylation; d-diketones.t The potassium enolate of an d-sulfonyl ketoneon oxidationwith a typical oxaziridineof this type, 2-[(p-chlorophenyl)sulfonyl]3-(p-chlorophenyl)oxaziridine(1), is converted into an a-diketone in 78-85Vo yield. Use of lithium or sodium basesresultsin poor yields. Addition of HMPA or l8-crown6 can be beneficial.The procedureis applicableto cyclic and acyclic systemsand is compatiblewith olefins, even allenic groups.

Arene(tricarbonyl)chromium

complexes

t

o Ar-tLtX

H'

'sorAr

r il.1 :-l{r

1, Ar = 4-ClCoHa

I1r

o

TS T(

So2ror llfl#Fl|;

t-.4

81v"

i-Pr

'i-Pr

i-Pr

i_pr

I D.R. Williams, J. org.,57,3740(1992). G.S.Amato,andM.Y. Osterhout, L.A. Robinson, Arene(tricarbonyl)chromium complexes. Nucleophilic substitution.t carbon nucleophiles react with the cr(co)3 complex or of indane followed by oxidative decomplexation(iodine) to effect highly selective exclusive substitution a to the ring junction. Similar but less pronouncedselectivity Good but obtains in reactionsof the Cr(CO)3 complex of 1,2,3,4-tetrahydronaphthalene.

CN

(cH3)2c-cN 1) Lic(cH3)2cN 2) lz 90%

ra\1 \/<

(CH3)2C--.,..\,.-\ i l t

* \ N

\

9 1: 9 (' C -H a-) r Cl - C N

/,,\,,1

V')

Cr(CO)3

CN

-a) \/\..'

(CH3)2C-._..\".,\

.

l

\/\./

l

l

l

73:27

(cH3)2c-cN CHs CHs

,\ratr

l

l

V-cH.

l

cN (cH3)2c--,.1-cHs

*

l

l

\Z\cHs

l

20:80 opposite selectivity can be obtained even in substitutionof o-xylene. Evidently some steric effects are operativeas well as electronic effects. stereoselective benzylic substitution reactions.2 A novel synthesis of the phenolic reacditerpenedihydroxyserrulaticacid (6) dependson highly regio- and stereoselective tions of a tetralin(tricarbonyl)chromiumcomplex with nucleophiles.Thus the Cr(CO)3 2 on hydride reductionfollowed complex f. is convertedin high yield to the endo-acetate by acetylation.This product reacts with an (E)-crotylsilanecatalyzedby BF3 etherate to give the exo-isobutenylatedtetralin complex (3) with the desiredsyn-selectivityat

Arene(tricarbonyl)chromium

complexes

19

C11. The carbonyl group of 3 is converted to an endo-methyl group by addition of CH:Li followed by ionic hydrogenolysisto provide the complex 4. Reactionof 4 with 2Jithio-1,3-dithianeresultsin substitutionmetalo the methyoxy group to provide 5 after demetalation.This product has the desired trans-anangementof the groups at C1 and Ca as well as the precursorfor the carboxyl group at C6 for the complete synthesisof the diterpene6. The conversionof 5 into 6 was completedin four conventionalsteps.

Pr 1) LiArH4(95"6) 2) AczO,DMAP (98o/.)

.r.1 ,

c ,' n r p l c x

'o

cH3o o'

: e: l \ c 0 r :lci:ir ity r,. ,J hut

CHr

'$""t' 1) CH3L|(60%) 2) (C2H5)35iH, cF3cooH (7s7o)

(E) CH3CH=CHCH25i(CH3)3 BF3'O(C2H5)2 I 720/"

cH3o

o

exo-3

CH) i'\--.rt l 1) Lil

Fr ) SJ

2) tz

CH:

cH3o

CHs

4

un3

11.-CH3

n :I \ \ ( ) m c

severat steos

HOOC

: lhcnolic I)\ ! rcac: t :r('O)3 t f,'llrrwed , Jlhcrate e.:l\itv at

HO

CHs (t)-6

45% overall from 1

20

Arcne(tricarbonyl)chromiumcomplexes

Asymmetricreaction of the (R)4)-nluaktehyde(tricarbonyl)chromium complex' (TosMic).3 This complex reactswith TosMic in (R)-1, with tosylmethylisocyani.de at 0" to form only one(2) of thefour possibleproducts.Decomplexation K2CO3/CH3OH followed by LiAlHa reductionprovides(S)-3 in I$OVode'

cHo

K2C03 cH3oH,0' + P-CH3C6HaSOzCHzNC + 95%

Eru ;an ht

(R)-1

(CO)3Cr-

1)hv (Go7o)

/cH3

>5

t-r-*

NHCH3

z)unino

\_l^1<+e)-H H Tos

(S)-3, >99% ee

anti-Selective aldol reactions.a The racemic tricarbonyl[o-(trimethylsilyl)benz2 in the aldehyde]chromium(0) complex I reacts with the acyclic o-silyl ketene acetal -78' to form a with cAN decomplexation by followed at in cHzclz presenceof Ticl+ of is independent anti-selectivity 7l'29.The ratio in the syn-aldols mixture of anti- and itself o-trimethylsilylbenzaldehyde Surprisingly, acetal. ketene silyl the geometry of the also reacts with silyl ketene acetalswith comparableanti-selectivity.The complexed (-)-f' aldehydes,however, have the advantagethat they can be resolved to (+)- and highly also are ee and 92-98% in proceed can aldehydes complexed Reactionsof these

Po/lj< -i rTtictl i{ e cr cr. :e:=ellr r lxlrxl |]\:

anti-selective.

1i){r f\.l:rtl

r'\7cHo llr I 'si(cH3)3 (jo\"cY-z (+)-1

96"/"

: CHs si(cH3)3 (-)-2 96% ee, anti/svn = 96 : 4

t

f:'a.XriJ

?t5 rrr

Arene(tricarbonyl)chmmium

complexes

2l

omplex, 6\{lc

ln

si(cH3)3

ilc\atton

cHo

96"/o

(+l-2 94o/oee, anti/sYn= 95 : 5

(-)-1

Enantioselectiveadditionof(CzH)zZntoRCH0.5Chiralcomplexesofthetype can be effective catalysts for this reaction'

-N(cH3)2

-oH I R

CHO + (Et)zzn

hr Jc itself cr,ntplcxed rnJ (-)-1. el*, highlY

toluene,ooc

Et

I

r''\ri-oH i l l \/

S, 93% ee S, 87% ee

87o/" 98/"

+1a +lb srl\I )henzrl I in the : ( r t ( ) r ma pnJcnt of

1 a ,R = E t lb, R=CoFs

complexes are best Polycyclic arene(tricarbonyl)chromium complexes'6 These and BFr etherate'As in preparedby treatmentof polycyclic areneswith (NHr)rC(CO):7 is complexedselectively' complexationwith c(co)6, the terminal or most aromaticring However,thelowertemperaturesusedinthenewermethodareadvantageouswith for substitutionreactions thermally labile polycyclic arenes.These complexesare useful of the arenedirectly' one at positionsthat are not availableby electrophilicsubstitution suchreactionishydroxylationeffectedbysimultaneousreactionwithabase(BuLior workup' Regioselective LDA) and tributoxyborane(excess)followed by H2O2/HOAc and (cHr)rSicl with silvlation is effected by reaction of the complex with LiTMP

.ZY\ I ..\/\/

ll | YZ\/ Cr(CO)3

I t1urue,B(oBu)3

ll

2) Hzoz,HoAc ,

|

se'2.

Ho

22

5-Aza-semiconins, chiral

similaryield.Carboethoxylationiseffectedbyreactionwithethylchloroformateand abase.Sincethecarboethoxygroupissmallerinsizeandelectron-withdrawing,the mixture of 2-carboethoxypyrene'1'2reaction with the pyr"n" "o.pl"" 11; gi"t' a -ticarboethoxypyrene' dicarboxyethoxypyrene, and 1,2,3 complex of an 2-Arylcarboxylic acJds.8 a-Lithiation of a tricarbonylchromium

iffcr o Et :x-ulert ftw

Cl(

alkylarenefollowedbyreactionwithCo2providescomplexesofa-arylcarboxylicacids.

l+2 QHg | I

1)LiN(c2H5)2

Il

I ll \-Y - 'Cr(CO)3

cooH

57o/"

Tt llr lx

74,2009 (1991)' 1 E.p. Ktindig, c. Grivet, E. Wenger,G. Bernardinelli,and A.F. williams, Helv'' (1991)' 5402 113, Soc., Am. Hayashi, Y. and 2 M. Uemura, H. Nishimura, t. ilinami, A DeCian' Tetrahe3 A. Solladi6-Cavallo,S. Quazzotti' S. Colonna, A' Manfredi' J' Fischer' and dron: AsYmmetry' 3, 28'7 (1992)' a C. Mukai, M. Miyakawa, n. Minira, and M Hanaoka' J ' org'' s7 ' 2034 (1992)' s M. Uemura, R. Miyake, and Y' Hayashi,l' C' S' Chem' Comm" 1696 (1997)' 6J.A. Morley and N.F. Woolsey' J Org'' 57' 648'7(1992)' 7 G . A . R a z u v a e ve t a l . , O r g a n o m e tC ' hem',rlf' 131 (1976)' (1992)' sv.N. Kalinin, I.A. Cherepanov,and S.K. Moiseev, MendeleevComm'' 113

:rlt'

chiral' o- or t-- pyroglutamic acid' An attractive These ligands are generally prepared from and 5 aza-semicorrins such as I are known short synthesis is shown in .quuiion I. Several

5-Aza-semicorrins,

2

/Y" < l

r\

\-.'NH -a

cHs-T-oH CHs

HN[(S|(CH3)312 rsoHr

-nG

(

lr

f>..NS.-1 | ll

) \--N HN<

: \ (cH3)3sio-icH"- cHt-IoSi(cH3)3 L/n3

CHg

cH2cl2 60 - 7o'l.lcH3l,

?t' /---.-.-N

( l l \r-N -a

(CH3)35iOtCH3

osi(cH3)3

ur

{ -r *l =.I:t

r

l

Azidotrinethylsilane

nrl.

and

r rn!. the enc. I,2-

- Chromic anhydride

differ only in the nature of the substituent (R) at the stereogenic centers. Enantioselective clclopropanation and allylic allElatiot.r These semicorrins' particularly when treatedwith CuOTf, are comparableto bis(oxazoline)ligands(f6, 38-41) for cyclopropanation.

f\ ()t an 'lri rrcids.

CuOTf

'f::::

cuH,-A-H

? Nrx.AOer-;**

H-S S-COOEI 94o/o AA

r

H-A-H cuHu/Rs-cooEt

75:25

68% ee

They appearto be more useful than bis(oxazolines)as ligandsfor palladium-catalyzed allylic alkylation with dimethyl malonate/BSAIN,O-bis(trimethylsilyl)acetamide]. l^.r l()91). n

j, truhe'

OAc l coHsMcoHs

*

NaCH(COOCHs)z/

BSA

pd-2

CH3OOC--.COOCH3

ee% cuHuMcuH'

CH. t "

95oloee

al-\'1 NJ \--ru RoH2c-i L.t::rJCtlvg tn, 'rr n afld

\"rro*

R=Si(CHs)ztBu 2 I U. I-eutenegger, (1992). G. Umbricht,C. Fahrni,P. von Matt,andA. Pfaltz,Tetrahedron,48,2143

hl

Azidotrimethylsilane - Chromic anhydride. Acyl azides.t A mixture of NrSi(CH.). and CrO3 (1:1) in CHzClzeffectsconversion of aldehydesto acyl azidesin 7O-9OVoisolatedyields. In the caseof aryl aldehydes,the reactionis conductedat 25", but the conversionof aliphatic aldehydesis best conducted at -10" to prevent rearrangementof the acyl azide to the alkyl isocyanatc. N3Si(CH3)3,CrO3

coHscHo,#* {:r:

cH3(cH2)6cHo

c6HscoN3

""'-t'|:'-to'" cHs(cHz)ocoNs 74o/"

rJ. G. Lee and K. H. Kwak, TetrahedronLetters, 33' 3165 (1992).

Azidotrimethylsilane-Chmmic

anhydride

acid' Azidotrimethylsilane-TFifluoromethansulfonic acid is an efficient catalyst for Trifluoromethanesulfonic alkenes.l Azidation of also facilitated by silica gel or is reaction The alkenes. to acid addition of hydrazoic hydrolysis of alumina. A further advantageis that these adsorbentscan effect fu situ particularly useful azidotrimethylsilaneto hydrazoic acid, HNr. This new procedureis for preparationof tertiary, benzylic, and allylic azides'

Berium. r Conpl ,'f Bal: h)

A (-,,i

"t'Xt cFasogH'siozorAr2os + N3si(cH3)t ---ioo%(, No

Z-'>r'\ (-l-)

+ Nssi(cHg)s

45o/"


/ "

urlh rctcn hr a.o -cr t>l'i

r ic-ld

n-CJ 2

/

l 2 G . W . B r e t o n .K . A . D a u s ,a n d P . J Kropp. J. 0rg ' 57' 6646 ( 1992).

n-C7H.

.4llyk lrrhium trq e l l rI a l l rI r hr rJrorrlat i\ruPlct* r * rth prcsc

\ -\G cH?x

t x= 2.X=

t r s l rs t f o r [-: lcl or r L , l r : i so f rlr uscful

Barium, activated (Ba*). Coupling of altylic halides.l In the presenceof Ba+, prcpared in situby reduction of BaI2 by lithium biphenylide, cis- or trans-allylic halides undergo' a,a'-coupling with retention of the double bond geometry. Unsymmetrical dienes can be prepared by a,a/-cross coupling. Thus (E,E)-farnesyl chloride is converted into squalene in 64Va yield. Ba*,

,n-ctH*\Z\.-c,

n-c7H15

#a (cr,c'/u,y'= $$;51

?"

15-n

2

n-C7H15

v

,Br -

50/"

I n-C7H15 (o'c'/tr'1'= 77:23\

n-C7H15\r-z:._.BaCl

-"r*-

+ Br/"6C7H15-n

n - C 7 H 1 5'\/\r/V\c7H'5-n ' Allyl-allyl coupling.2 The reaction of (E)-prenyl chlorides with Bal2 2H2O and for an used been has lithium biphenylide (2 equiv.) to form allylbarium reagents allylic by preparcd I' allyl/allyl coupling to form diisoprenoids.Thus the allylic alcohol bromide This 2. bromide hydroxylationof geraniol,was convertedinto the corresponding coupleswith geranylbarium(3) to give 4 (61Voyield) with only primary/primarycoupling with preservationof the geometry of both allyl units.

CHs

OS|R3 +

1,X=OH 2,X=Br

Ba(L)

OY

THF -78" - 23" 61o/"

4, Y = SiR3 5,Y=H

26

Benzeneselenenyl chloride

Coupling of (E,E)-farnesylbromide with farnesylbariumprovides all (E)-squalene (79Vo yield). goc.,113,5893,8955(1991);A' Yanagisawa, 1A. Yanagisawa, andH. Yamamoto,AmS. Habaue, Org., 57,6386(1992)' Yamamoto,J. and H. Y. Hisada, Habane, H. Hibino,S. 2E. J. Corey and W.-C. Shieh,TetahedronLetters,33, 6435(1992).

8enz1'bhr Srillc r unsaluratcd,

coupline.: *ith an
as a l:l mr R

o )i:o

1,2-[(Benzenediolato)-O,O']oxotitanium,

Ho

o

I

(c

1 (16;19) stereoselective 1,2-cisglycosylation of tribenzJl-D-arabinofurunose (2).t The reaction of 2 with various trimethylsilyl etherswhen catalyzedby I and trimethylsilyl triflate (3). formation of 1,2-ci.s-arabinofuranosides. results in stereoselective

BzlO osi(cH3)3

Bu3SnH 8(qHJ3

1, (CH3)3siorf c*zct^--23"+ c6H5(cH2)3osi(cH3)3 92/o

BzlO O(CH2)3C6H5

+

(I - anomer

92:8

8u3snr"

I T. Mukaiyama, Chem.Letters,l4O1(1992). S. Suda,Y. Yokomizo,andS. Kobayashi, M. Yamada, Benzeneselenenylchloride. Cyclization of triethylsilyl ethers of cis-2,S-Disubstitutedtetrahydrofurans,t 3-hydroxyalkeneswith coHsSecl in thc presenceof K2cor providesci.s-2,5-disubstituted tetrahydrofuranswith high stereosclcctivity.Othcr protcctinggroups show generallylow stereoselectivity.

"utu\,

t\-"'\R

"?';i"^l'"t9,"'cuHsYo)'-t osi(c2H5)3

l

l

Y

c6H5se'

R = CHzOTBDMS

92"/o

cis / trans > 1 0 0 :1

R = CH(CHg)z

83o/"

> 1 0 0 :1

R = CHg

91To

1 5 :1

r S . H . K a n g , T . S . H w a n g , W . J . K i m , a n d J . K . L i m , T e t r a h e d r o n L e t t e r s , 3 24' 0 1 5 ( 1 9 9 1 ) '

* ith LiOH I >iX)n ricld

under 3 atm r*\ used to d or onll proi

J E. Baldru .\-(Beonld

N-(Benzyldimethylsilyl)methyl-2-(+)-methoxymethyl)pyrmlidine

le- .,ll (E)-squalene

-\ Yanagtsawa,

t-. . F:

27

Benzylchlorobis(triphenylphosphine) palladium(II). Stille macrocyclization. Several macrocylic antibiotics contain a y-oxo-a,Bunsaturatedestergroup. Macrolidesof this type can be obtainedby Stille intramolecular coupling.r The substratesare availablefrom Mitsunobu esterificationof propriolic acid with an crr-hydroxyester followed by hydrostannylationto give B-stannyl alkenoates1 as a L:1 mixture of (Z)- and (E)-isomers.Selectivesaponificationof the methyl ester R I

R o ll r{ -o- '\I

P(c6H5)3, -c_,. . , r _ o . . c rDEAD .

Hol\1cHr)ecH2coocH3

"H-COOH vvv'7/'

-1cHr)ecH2coocH3

H. lorr tll.l The reacrrr-r Jlh\ lsilyl triflate

t

Bu3SnH B(C2H5)3

o

I

Bu3Sny'v-O

lcf

s oTf t t -

(( - anOmef

F

lCHr;nCH2COOCH3 >eo"/o

R

Pd(il),co i l l /^o tcHz)ro100" i ll

Jr

cocl

Bu3Sn9 2 3

I

')(cog!fl:

'l(ZJE=1:1)

O

-

1)LioH

R

2

R=H

53"/"

R = CH.-

7Oo/"

O (E)-3

'. r\. l10l (1992).

r"' . ,.ilr I ethers of s. 1.5-disubstituted F . ,"\ rrcncrallylow

with LiOH provides the free acid which is convertedinto the acid chloride to give 2 in >9OVo yield. Intramolecularcoupling of 2 to form 3 is effected with a Pd(II) catalyst under 3 atms. of carbon monoxide at high dilution in toluenc. This cross coupling can be usedto obtain 12- to 20-memberedrings. Dimeric macrolidesare formed as the main or only products in the case of shorter precursors. I J.E. Baldwin,R.M. Adlington,andS.H. Ramcharitar, J. C.S. Chem.Comm.'94O(1991)-

,C

--R

N-(Benzyldimethylsilyl)methyl-2-(+ )-methoxymethyl)pyrrolidine.

l-

s :':.s

"rr).iT c6H5cH2 |

cH3o\,/() -r: : l5 (1991).

(S)-(+)-1

28

l,l/-Bi-2,2/'naphthol-Dichlorodiisopmpoxytitanium The anion (sec-Buli) of (S)-1 reacts with

Asymmetric synthesisof l,3-diols't

ethyleneoxidetogiveasingleproduct2.oxidativecleavageoftheC-Sibondgivesthe r,:-oiot(S>(_)-3in>ggToee.Similarreactionoftheanionoflwith/-butyloxirane which are separable by or L,2-epoxyhexane gives a mixture of two diastereomers' chromatographyandconvertedtosyn-andanti-|,3-diolsonoxidativecleavage.In the 1,3-diols have the (1S)these reactionsas in the reaction with aliphatic epoxides, configuration.

1) sec-BuLi

(S)-(+)-1

2 ) o ,/\ --r**

: CHs)Si._ CHs I

KF,H2O2 65"/"

,N.

cH3o__{_jr

C6H5--1.^---,OH : 6H (S)-t)-3 (>99o/.ee)

2

C6H5.-.-,.^-...-.Bu{ CHs-Si1)sec-BuLi ')A c1o,.1. cH;'-l (S)-(+)-1

,*

6ff

,N. rH3o__<_J

,

anti-4

+

.{t h-{s t2

1:1

lh'lr.tr

sYn-4

I 65% ltol V

C6H5-9,-..9.Bu-t : 0H 6H sYn-5

I 75./" tol I V

C6H5--9,----7.Bu{

:

l

cHzl

OH OH anti-5 .jfl

xthrl rT.H. Chan and K.T. Nwe, J. Org', 57,6107 (1992)

I (l)' 15' 26-27;16'24-25' L,lt-Bi-2,2t-naphthol-Dichlorodiisopropoxytitanium The titanium comaldehydes't unsaturated of Enantioselective ene cyclization plex(R)-lacaneffectenantioselectivecatalyticcyclizationof2and3.Substitutionof thechlorineatomsbyperchlorateimprovestheenantioselectivitysignificantly.

-naphthot- Dichlorodiisopmpoxytitanium 1,1/-Bi-2,2/

)ct\ with { t \ L ' st h e

i.r

\ li,\irane rr.rt'lc bY a\ .rqc. In

(R)-1a,X = Cl (R)-1b,x = clo4

rhc ( 1S)-

gH fi"

o \

+Atusr*"He*

a-H 5

6-)

(3R,4R)-trans

(3R'4S)-c,b

o. t

79o/oee 74o/o@e

.9H

\-H

a

47:53 80:20

70/o aa g4o/oeA

+1a +1b

ts. ee)

a1'u''\cH.

6-)

7c(cHs)z 2

gH 3"

t

rr "\----l

CHr

ru,+Aus

.lL-cH3

43"/"

l

t

l

o l \AcH, 91o/oa@

3

allylic alcoAsymmetric carbonyl-ene reaction with 1.2 The reaction of racemic asymmetric remote with hofs (2) with methyl glyoxalate catalyzedby (R)-1 can proceed components' ene two the induction,which suggeststhat (R)-1 can discriminatebetween

9H. ?H. , Bu-t

cH,/fcH' osiR3

n

CH3 CH2 OH I ll I

(R)-la' ?

QH2ct2,'^

iH'A^^^^ -COOCH3

cH'/tY'^"''-coocH3 osiR3 3, syn/anti = 99:1

2

(2) with Asymmetric glyoxytate ene reaction.3 The reaction of exocyclic alkenes ee' in 63-99% proceeds sieves molecular methyl glyoxylate in the presenceof (R)-1 and

/ f o - t

f <

3nlum comrl..lrtution of n ll r

W 2

CHr -

+Atts, 1n1-t,

* "A"oo.r,

cH2cl2 69o/"

coocH3 OH

30

Bis(acetonitrile)dichlompalladium(Il)

lK.Mikami,E.Sawa'M..l.erada,andT.Nakai,TetrahedronLetters,32,6571(1991);K.Mikami (1992) and M. Shimizu, Chem. Rev', 92, 1'021 (|992)' 2K' Mikami, S. Narisawa' M. Shimizu, and M. Terada,Am. Soc.,||4,6566 (1992). 6695 33, 3 F. T. van der Meer and ts. L. Feringa, TetrahedronLetters,

CHt'

Bis(acetonitrile)dichloropalladium (II)' orygenationofatlylicamides.|oxygenationofallylicamides(orlactams)inthe p r e s e n c e o f a P d ( I I ) - C u C l c a t a l y s t i n l , 2 . d i c h l o r o e t h a n e c o n t a i n i n g H M P A ( e s sae n t i a l ) water' the oxygenation results mainly in results in an aldehyde' In the presenceof methyl ketone.

o

o T ILB (1 il

^ ,, )'t*,'^"-r'cH2 l\

UAFIs

:T TL

cuHuAt..1"---t"cHo 02' Pd(ll)cucl' HMPA clcH2cH2cl' CHs

o

' cHs

90:10

52"/" + H2o

6:e4

GZo/o

Itir[t{ Po rrth )

O

+

tl

"uruAf-y""' cH3 o

nlrtun i,tr-tr6l : Ymrll

:trcnr I -" Plr Theal|ylacetatelisoxidizedundertheseanhydrousconditionstoanaldehyde(2) in reasonableYields'

O

o il

cHr

^,,

6/\y'"n2 1

02,Pd(r) CuCl 760/o

, CH3/

O

Jt-O- -^-._,.cHo* v L.l cH.AolcHt UHg+

2

O 65'3s

Amidationofelectron-deficientalkenes.2InthepresenceofCI2(CHTCN)zPdand COOR' COR' CHO' or CONR2 groups CuCl (1:1) amidesreact with l-alkenes bearing yield' Cyclic amides are more reactive than to form (E)-enamidesin generally good reactive' open-chainamides.Carbamatesare particularly

Bis[(allyl)trifl uomacetato]nickel(II)

o

r i. \l ikami

ot l

cat.,DMF

A -NHz+ CHt:616oocH3 CHs'

650/"

cH.AN&coocH3 H EIZ= 61:39

o

o

cat., HMPA, DME

tl A*',

+ CH2:CHCOCH3

tl

ArrycocH3

80v"

t-:a,r) in the d ' l.sential) m . 1 r n l \i n a

o tl

tl o

ttH

+ CH2:CHCOOCH3

oAru&coocH3

84o/"

rT. Hosokawa. J.C'5. Chem. Y. Yoshida,andS.-1.Murahashi, S. Aoki, M. Takano,T. Nakahira, Comm.,1559 (1'991). 2T. Hosokawa,M. Takano,Y. Kuroki, and S.-1.Murahashi,Tetrahedron Letters,33,6643 (1992).

.

_.,cH3

Fl:

O

,iJfhvdc (2)

Bis[(allyl)trifl uoroacetato]nickel(II)' 1. poly(p-phenylene),5.1 This catalyst has been used to polymerize 1,3-butadiene with >97Vo 1,4-regioselectivity.Attempts to polymerize phenylenesdirectly results in mixtures of para-, meta-, and ortho-linkedoligomers. In contrastpolymerizationof cls2 with I in CcHsCI results in exclusive 5,6-bis(trimethylsilyloxy)-1,3-cyclohexadiene 3. This polymer is convertedinto poly(pformation of the 1,4-poly-1,3-cyclohexadiene phenylene)(5) by conversionof the trimethylsilyloxy groups to acetyl groups followed by pyrolysis.

"o

1,

c6Hscl

.Jor-\J,t,,r. 3

(cH3)3sior-\ si(cH3)3

(cHs)

2

-..,.CHs

({})

93o/"

tI

1)F 2) CH3OH

{ ( \l:Pd and :( )\ R. group" r . . 1 . l i v ct h a n

(o)

+

1) Ac2O,Py 2) , -CHSCOOH

)J1;^ 4

I D. L. Gin. V. P. Conticello, and R. H. Grubbs,Am. Soc., 114,316'7 (1992).

32

Bis(1,5-cyclooctadiene)nickel-Tbiphenylphosphine

Bis(cyclooctadiene)nickel. Phenol synthesis. In the presenceof this Ni(O) catalystcyclobutenonescan couple with internal alkynesto form phenolsin 50-80% yield. Two phenolsare obtainedfrom unsymmetricalalkynes with only slight regioselectivitybased on the size of the alkyl substituents.Modest selectivity obtains with oxygen-substitutedalkynes.

R1

--/o

ill

I

.lll

CHz

f

I

CoHs

cH3ooc\ I (t)

R1

R2

0" Ni(coD)2,

products (endol diene substitue

R2

R1 C5H5

R2 75Yo

R1, R2 = CzHs R1 = CHg, R2 = (CH2)2OTHP

65:35

47o/o

cHgooc

This phenolsynthesisdiffers from the thermalreactionof cyclobutenoneswith alkynes (15, 160) in that activated alkynes are not required and the ultimate positions of the alkyne substituentsin the phenol are different.

(il) cHr:91

1M.A. HuffmanandL.S. Liebeskind, Am. Soc.,ll3' 21'71(1991)' Bis(1,5-cyclooctadiene)nickel(0)-Chlorotrialkylsilane,Ni(COD)2-ClSiR3' Conjugateadditionofalkenyltributylstannanestoa,B-enals.Thereactioncan Ni(COD)z be effected with a chlorotrialkylsilane(1 equiv.) and a catalytic amount of evidently reaction The yield.l in 48-79Vo (E)-silyl ether enol in an in DMF and results involves a 1-silyloxyallylnickel(Il) intermediate(a)'

CHr:611"tO

+

CHr:611tntr.

+

,liene with pha The preser orvnorbornadk rdduct (equalx

",|l(l),.

+ ClSiR3

(ilr)

4*.OSiR3

I CtNiT ' 2

a

-;**

z

f''\'OSiR3

("r,

EIZ=>SO:'|

rB.A. Grisso, Am.Soc',l14, 5160(1992)' andP.B. Mackenzie, J.R. Johnson,

These prclu on the regiosc tnho- and fru \t. l:utens ar

-Ttiphenylphosphine' Bis(1,5-cyclooctadiene)nickel In the presenceof [2 + 2 + 2] Homo-Diels-Alder reactions of norbornadiene,t alkenesat 80' with activated react can Ni(coD), and P(c6H5)3 (1:2) norbornadienes indicate that regioselectivity the of studies to give 12 + 2 + 2] adducts.Preliminary Thus molecules' of complex for synthesis this homo-Diels-Atder reactioncan be useful two in only results acrylonitrile with reaction of methyl norbornadiene-2--carboxylate

Bis(cyclopcrtr p-Kcto ct heramethl'ldis Jre convertd

Bis(cyclopentadienyl)chloro(hydrido)zirconium

C.1na()Uple :r:e,l from rt :hc alkYl

R1 t^

products (endof exo : 2.3:I), in which the electron-withdrawing groups are para to the diene substituent (equation I). Only two products are formed from reaction of the same

^

\

Ni(coD)2 cH3ooc. rl\

"Jgi'li,E u,"^"oo">> €

i

33

cnr:Lncrtr

6Hroocy\

Ua"*

'cN

exo-para

enoo-para Rz

2.3:1

:r."".&..r."".&

N cH3ooc\l\ r r:h .rlkvnes t r , . n .o f t h e

(tt)

SO2C6H5 C6H5S02

cHr:cHsircuHu

exo-para

exo-meta 2 : 1

t.r!li()n

can

,( \itCOD)z or: cr idently

diene with phenyl vinyl sulfone, the exo-para and exo-metaisomersin a ratio of 2:1. The presenceof a methoxy group on the diene lowers the reactivity, but 2-methoxynorbornadienecan react with methyl vinyl ketone to provide a single endo'ortho adduct (equationIII).

(ilr)

o$o"'"

+

CHr:\ po ci.

,.l\ ( YocHs 51v" *oo"r, endo-ottho

These preliminary resultsindicate that substituentgroups can exert a marked effect on the regioselectivityof this homo-Diels-Alder reactionwith a generalpreferencefor ortho- and para-isomers. I M. Lautensand L.G. Edwards, J. Org., 56,3761(1991). c lrc\cnce of l\cnc: at 80' r : r J r c a t et h a t rlriulcs. Thus , lr ()nly two

Bis(cyclopentadienyl)chloro(hydrido)zirconium,CpzZrHCl. B-Keto esters - enoales.l The enolates of B-keto esters, prepared with lithium in DME, on reactionwith the Schwartzreagent(1 equiv.) at0-2O' hexamethyldisilazane are converted into enoatesin 55-70% yield.

2,2i-Bis(diphenylphosphino)-1,1/binaphthyl

o.

.co2cH3

X

groups of the PhosPhin useful percursorto thc ,

DME 1) LiNlsi(cH3)312, 2\ Cp2Z(HQl

o

o

i l l l cH3l^focx, I -ruHcoq

o A -"or=,

CoHsNCo2Et

2

CoHs-

rA.G.GodfreyandBGanem'TetrahedronLefters'33"746'l(1992) 1'' Bis(2,6-diphenytphenoxide)tris(4-methylbenzyl)niobium(V)' aryloxide is an effiniobium This arenes'2 i)y'u't'a' All-cis Hydrogrr"tu,'tj cientcatalystforregioselectiu"t'yo,og.nutionofpolynucleararenes.Thusphenanthrene isreducedtotheg,l0-dihydrodcrivativeandanoctahydrophcnanthrenc'Anthraccneis H z ,1 C6H12,80oC

(78/o)

(22o/")

H

Z\,'\' I

l l

\-\2

|

' l

f^ff

l l \''-'/'\l

2-alkylidenecYcloPen

o

) H

(95.5%)

Asymmetric hYdroT tion can be effectc'd I regardlessof the gcom

(4.5o/o\

rH NMR spcctra indicates that Analysis of thc convertedto an octahydro derivativc' thchydrogcnatomsareallintroducedonthesamcfaceinthccascofnaphthalene' anthracene,and acenaPhthcnc' 10' 321 Rothwcll'Organometallics' f R.W. Chcsnut, G.G. Jacob,J'S' Yu' P'E' Fanwick'l'P Am Srtc''rr4'1s2'7(tssz)' an
ll o"\

o

) CH

2,2/-Bis(diphenylphosphino)-l,libinaphthyl

groups of the phosphine are replacedby 3,5-di+-butyl phenyl groups. (2S,3R)-3 is a useful percursorto the B-lactam 4.

)o:cH3

o

o

i l i l

CHs-

_\

Ru(il).1. cH2clz,cH3oH

-\ -OCH3 -a

l-NHcocuHu-

CO2EI

5

35

o H o l l l + (2R.3R)-3 cH.-^)focH. \ -NHCOC6H5

2

ee: 1

(2S,3R)-3(99%ee)

I n , : . 1 , , \ i d ci s a n e f f i F I :r. phenanthrene is rr:-- . .-\nthracene

1

OH

I

/t__\

(78/.) H

H .1.5ol")

l

?-*' 4

--\_/ _

,,

cH3-\Z: t

Asymmetric hydrogenation of 2- and 4-alkylidene-y-butyro-lactones.2 This rcaction can be effected by catalysis with Ru(ll)/(S)- or (R)-BIN Ap in 94-98o/o ee rcgardlessof thc geomctry of the olefinic group. This method is also applicable to 2-alky Iidenecyclopenta nes.

o

o

H2, CH2C|2, 500 Ru(ll)-(R)-1

o1:l.

,

Et

\__/

tl

o1n_

trI

\__/

(S), 92oloee

o

( '. . I rr

r.

\

/

CHs

ryttullics, 10, 321

(R), 94ol. ee

,l- ( 1992).

.:r \\ hich the phenyl

o1

Ru(ll)-(S)-1

/CHz

r:i .-:Jrl p-keto ester 2 h\.:' '\\ cstcr3 in 90% j1,- ,.rrrhhigh cnantio-

o tl

H2,

of

[ . : - . : r . r i n d i c a t e st h a t ! - -- rrf naphthalenc,

o tl 1t\z\ \__/

H2,

Ru(ll)-(R)-1

Bu

o tl o/\---'..^ Eu \-/

(S), 9a% ee

36

(R)-or(S)-2,2I-Bis(diphenvlphosphino)l,l/-binaphthvl

(BINAP) (R)- or (S)-2,21-Bis(diphenylphosphino)1,1/-binaphthyl triflate I with tetrabutylamvinyl of the Asymmetric Heck reaction3 Treatment and (S)-BINAP in Pd(OAc)2 of amount monium acetate(1.7 equiv') and a catalytic formed by a Heck ee, in 807o 2 pentanoid bicyclic DMSO at 20. results in the fused into 3, an convertcd be can product This process. reactionfollowed by an anion capture

Chiral sp iodoaniline(2 chiral ligand r

addedpromor of a basic tt'nt 1,2,2,6.6-pen

ffi; w

CHz Pd(OAc)2,(S)-BINAP Bu4NOAc,DMSO 89v"

CHs

2 ($O%ee) COOC2H5 I

QHg I H

s'eps(\t
several

o-

e

H

cHs 3

intermediatein the synthesisof several scsquiterpcnes' effected by a catalytic asymmetric arylation of alkenes.a This arylation can be Pd(oAc)z/(R)by catalyzed Hcck{ypc arylation of 2,3-dihydrofuranwith an aryl triflate (proton spongc)as basc. BINAP in rhc prcsenceof l.tl,-bis(dimcthylamine)naphthalcne activating factor. platelet This reactionwas used to preparean antagonist(4) of Pd(il)-(R)-BINAP base, C6H6, 40"

C6H5orf .

[)-o

tr-\

\o'2""'6u11u

(s)

(R) 46"/",>960/"a@

2-NaphthylOTf +

r-\

\o,

a

,,rNph

52o/o, >960/o ee

a

+ \o"\coH5 2 4 Y " . 1 7 Ye"e

'

Enantia pentenalssu ee by use of

\O"truPn 2 6 0 / " , 1 O o /E" €

"t.oy.\f,-Q.,,,(y) l) cat., 2-NaphthyloTl

CHsO--.1.OT{ 2)cat., ll I CH3O"-V

cHso/.v

\l^\/ p-Alll,ir,

hvdrogenatio

37 (R)-or(S)-2,2r-Bis(diphenylphosphino)l,l/-binaphthyl

ll:.:'tttVlam-

r-l.il\AP in | ^r a Heck :d lnl() 3. an

Chiral spirooxindoles.s An asymmetric Heck reaction of the acryloyl 2tand (R)-1 as the iodoaniline (2) effected with tris(dibenzylideneacetone)dipalladium upon an depending 3 spiroindole of the chiral ligand can provide either enantiomer addition whereas (S)-(+)-3, provides salt of a silver addedpromotor. Thus the presence aminc is effcctive Thc most (R)-(-)-3. of formation of a basic tertiary amine can favor (PMP). 1,2,2,6,6-pentamethylpiperidine

( B, ) - 1 ,8 0 " Pd2(dba)3 Ag3PO4,CH3CON(CH3)2

81"/o

o tl (^-ir^N"tt

( S ) - ( + ) - 3 ,7 1 o / oE a

f+--'A<' \.-o I ll \-,/

NCH3

(R Pd2(dba)3 , )-1,80'

:tl-itcd bY a 'g r I \c)1/(R)-

P M P ,C H 3 C O N ( C H 3 ) 2

)cir I lls base. .

t.

,.

(R)-(-)-3, 66% ee

. ^ \c5H5 U

S ,c-

.7oo

ee

-Noh :

'l'c

cyclization of 4Enantioselective cyclization of 4-disubstituted 4-pentenals.6 pentenalssuch as 2 to 3-substitutedcyclopentanones(3) can be effected in >997o ee by use of Rh[(S)- or (R)-BINAP]CIOa as catalyst'

9€

Rh[(s)-BTNAP]Cl04

cHo \

QH2CI2,20'

rcHz

\ 3 /

1"

R 2, R = t-Bu

o tl

87o/o

R = C(CHs)zCHzCHg 84% R=Bu

9Oo/o

3, S, >99% ee S, >99% ee S , 9 1 %e e

enantioselective B-Amino acids.T A useful route to chiral B-amino acids involves such as 1. Thus hydrogenationof (E)-1 hydrogenationof methyl B-(acylamino)acrylates

38

ll,4-Bis{diplc

(R)-or(S)-2,2r-Bis(diphenylphosphino)l,l/-binaphthvl

catafyzedby a complex of Ru(OCOCHT)zwith (R)-BINAP furnishes(S)-2 in 960/oee. Surprisingly (Z)-1 is convertedunder the same conditions to (R)-2 in 5Vo ee. Hydro-

CH3..\..NHCOCH3

H2 Ru(ll)-(R)-BINAP

cH..-fruHcoor.

o H &

(r)

I

tl cH3ooc'-

1,4-Bis(diphenylphosg Diastereoselectirc I diols.' This catalvstis alcohols (12, 426- 121 and vinylsilaneshavinc

cH3ooc'-

( E ) -1

I

c*t'',M

(S) - 2, 96% ee

oH cr flr) genation of either (E)- or (Z)-l catalyzedby Rh+(CH3OH)2CIO4 complexcd with (R)-BINAP resultsin (R)-2 but with modest enantioselectivity(45-6lqa cc). optically Asymmetric carbonylation of alkenyl hatides; a-methylene lactones.' active a-methylene lactoncscan bc preparcdby carbonylationof alkenyl halides such o/o)in the presenceof thallium acctate. as I catalyzedby PdCl2-(R)-BINAP (5 mol

CHz

cH3Fl r

P d c r 2 - ( R )- B I N A P TlOAc,CH3CN

+

Ho-
C

O 74"/"

Ho\&o

I M. Lautens, C.-H.Zhan

2,50/o ee

1

BINAP-Ru(II)

)'-,r'

CHz ,p cH" )-(

\__J

\JJ

CeHr

complexes.e

A

suitable BINAP-Ru(II)

catalyst for

asymmetric

hydrogenation of ketones (14, 40-41) can be prepared most readily by heating (R)- or (S)-BINAP with [Rucl2 (benzene)]2 in DMF at 100'to effect ligand exchange. A suitable catalyst can also be obtained by ligand exchange with RuCl2[Sb(CoHs):]., prepared from Ruclr and Sb(ccHs):, in o-dichlorobenzene at 160". Either of these catalysts gives satisfactory results in hydrogenations at 100 atm. at 25" or at 4 atm. at 100"' lK. Mashima, Y. Matsumura, K. Kusano, H. Kumobayashi, N. Sayo, Y' Hori, T' Ishizaki, S' Akutagawa, and H. Takaya,J.C.S. Chem. Conm.,609 (1991)2T. Ohta, T. Miyake, N. Siedo, H. Kumobayashi, S. Akutagawa, and H. Takaya' Tetrahedron Letters, 33, 635 (1992). 3 K. Kagechika and M. Shibasaki,J. Org., 56, 4093 (1991). a T. Hayashi, A. Kubo, and F. Ozawa, Pure Appl. Chem., 64, 421 (1992)' 5 A. Ashimori and L. E. Overman, J. Org., 57, 4571 (1992)6 X.-M. wu, K. Funakoshi, and K. Sakai, TetrahedronLetters, 33, 6331 (1992)' 7 W. D. Lubell, M. Kitamura, and R. Noyori, ktrahedron Asymmetry,2,543 (1991)' 8 T. Suzuki, Y. Uozumi, and M. Shibasaki,J. C. S. Chem. Comm., 1593 (1991)' eM. Kitamura, M. Tokunaga,T. Ohkuma, and R. Noyori, TetrahedronLetters,32,4l63 (1991).

[ 1,4-Bis(diphenylphoc nate, l(14, 44-45). Diastereoselectivc I tion of the vinyl sulfo Similar hydrogenation rate oxidation gives tlx

c6Hsso2

9H' cuHurs\cHs

o o H (R,R)- 4

R _

[1,4-Bis(diphenylphosphino)butane]norbornadienerhodium

! r:' 'l(r'i ec. Ilvdro-

i" .,

triffuorcmethanesulfonate

39

1,4-Bis(diphenylphosphine)butane(norbornadiene)rhodium(I)tetrafluoroborate, l.l Diastereoselectivehydrogenation of 7-hvdroxyvinylsilanes and -tins, Syn-l!hydrogenationof chiral allylic diols.r This catalystis known to effect diastereoselective hydrogenationof vinyltins alcohols (12,426-428). It can also effect diastereoselective and vinylsilaneshaving a 7-hydroxyl group (equationsI and II).

Bu

OH

ocH3 (l)

r

Hz,1

l

c5Hl1MSnBu3

snBu3

?t c5H11,MBu

75"/"

syn(>100:1) 2

flt) with

nrli\.d

CeHrr

?' ?'. ,/'-z'\sic6H5(cH3;

sic6H5(cH3)2 ?" c.Hrr'l\-AcH.

Hz,1

syn(>500:1) '

t )pticallY

I

I l.,li.lcs such

oo-"

ln' :!ctatc.

{-- / /. p t

I KBr, HOOAc

J

OH OH -\'z-,^ -CHs

CeHtt-

\

Honc r.raoRc,

syn - dlol

2^' to

I M. Lautens, Angew.Chem.Int. Ed., 31,232 (1992). C.-H. Zhang,andC. M. Crudden,

;=' ""

(\r .t\\'mmetfic hs.ttinq (R)- or nr:r

A suitable

1., 1,. prcpared i . . 1 l . r l v s t sg i v e s

II,4-Bis(diphenylphosphino)butanelnorbornadienerhodium trifluoromethanesulfonate, l(14, 44-45). Diastereoselectivehydrogenation of vinyl sulfones and sulfoxides.r Hydrogenation of the vinyl sulfone 2 with the Rh catalyst I proceeds in 99Vo de to give 3. Similar hydrogenationof the correspondingsulfoxide provides 5, which on perborate oxidation gives the threo-isomerof 3. Apparently the steric course of hydrogen-

9H,

lrrt' r

I

L:\.'

fdrahedron

0H anti -3,9910 de

2

.. Rhl'tt', Rh.1

pHr cuHu-s\cH.

o ) : - 1 h . r( 1 9 9 1 )

cuHusor&cH.

c6H5so2\cH3 OH

I s h i z a k i ,S .

t|,.

CH.

Rh.1H , 2,25"

(R,R)- 4

o

H

CHs oxidation cuHusor\cH.

CHr cunu-s\icH.

o

o

syn - 5,99o/ode

H

o svn - 3

H

40

Bis(dipivaloylmethanato)nickel(Il)

o

ation of sulfones is controlled by the hydroxy group, whereas the configuration at sulfuf controls the course of hydrogenation of sulfoxides.

)-''."'

I D. Ando,C. Bevan,J.M. Brown,andD.W. Price,J.C.S. Chem'Comm',592(1992)'

(,

""ol-

(TRAP)' 2,2//-Bis[1-(diphenylphosphino)ethyl]-1,1//-biferrocene

\Z^\

I rT. Yamada, K. Takah.

(s,s)-(R,R)-TRAP

( l ee1).

[N,M-Bis(4-methoxl

CHtt"'1"tt P(C6Hs)2 A catalyst prepared from RhH(co)[P(c6Hs)r]: Asymmetric Michael adilition.t ketones and TRAP can effect asymmetric addition of a-cyano carboxylatesto vinyl selectivity' or acrolein. Note that isopropyl estersshow the highest

O

NC.--.-COO-iPr

l l ^ , r + J CHs"'-\y'w'1z

CHs

3-5"

o ),,--,-,-coo-t-Pr CHs cf;\N R (B4oloee)

o ^)--,,o"^r*

Ncrcoo-i-Pr CHs

o 11A.--'-*Coo-i-Pr cH]'ctl R (84oloee)

Expoxidation ol t epoxidation with oxr'1 reductantis 2-meth1'l alkenes.

cr

cH.A

I M. Sawamura, andY. Ito, Am. Soc-,ll4' 8295('1992)' H. Hamashima, Bis(dipivaloylmethanato)nickel(ID, Ni(dpm)r. 1,3Baeyer-Villiger ox'dation.t Complexes of nickel coordinated with several aldehyde an and oxygen molecular with diketones are effective catalysts for oxidations involving or alcohol reductant(16,30-32). Such oxygenationsare much saferthan those oxygenation catalyzed a such peracid. a peroxide or the usual oxidantssuch as hydrogen can be used for Baeyer_ Yilliger oxidation of either cyclic or acyclic ketones.Highest yields are obtained with bis(dipivaloylmethanato)nickel(Il)as catalyst (l mol%) and isovaleraldehyde as reductant.

cl

' T . T a k a i ,E . H a t a , K. Y

1,2-Bis(methylene)c B,y-Enones. Rr siumprovidesa magn

1,2-Bis(methylene)cycloalkane-Magnesium

o

)ri .r: \ulfur

t

93%

l

\-.-

L)""

02, RCHO,Ni(dpm)2 ctcH2cH2ct,25"

/-'-a"'"

)

"r,o.]-

cH3oY\

-"Y

4l

CHs

o

\o\o4.,.

76%

o IT. Yamada, K. Takahashi,K. Kato, T. Takai, S. Inoki, and T. Mukaiyama, Chem. Letters, 647 (1991). I),

lN,M-Bis(4-methoxysalicylidene)-o-phenylenediaminelcobaltfl

cH3o

9CHs

; { t '(r, H s ) r ] r in\ I kctones (1)

a

COO-i-Pr

\ ^ . ,I\

Expoxidation of alkenes.t In the presence of this complex, alkenes undergo epoxidation with oxygen (oxidant) and cyclic ketones as reductant.The most useful Yields are -8OVo for trisubstitutedor exo-terminal reductantis 2-methylcyclohexanone.

\-

,r

alkenes.

COO-l-Pr

t *

1.' O,.- r-{/

CH. t cH./\--czHrs

n .lcral

1,3-

ri .'n aldehYde h,'.c involving rJ,,rrgenation 1,'xg. Highest 11 nrol%) and

"r.t).

1ao

/ \

g

\__J

/cH.\ n -v

CHa t -

cn^4-y'c'Htu -o-

#rs u*- sn.Alc,H,,

rT. Takai,E. Hata,K. Yorozu,andT. Mukaiyama, (7992). Chem.Letters,2O77 1,2-Bis(methylene)cycloalkane-Magnesium,16, 198. with activated magneB,y-Enones. Reaction of 1,2-bis(methylene)cyclohexane sium providesa magnesiumcomplex (1). This complex reactswith ethyl acetateat - 10'

42

Bis(oxazolines)

when heated to form a spiro enol containing a cyclopropane ring (a). This intermediate undergoes ring expansion and protonation to form 2'

cHz

+i..t;

r->--f I ll ,Ms

cH3cooEt

-78'-

Enantio*l t S)-phenr'lglr rs a highlv cn * ith -j-acn lor'

-10"

\-,ry

CHz

6Hs)1 ' CHs-

1

2)H3o' a>r-\ .."-ZcH" -oH I | -oMsoEt (-L-A"t' '''' ** Wcr, 2

(r) cHz

Ms/-<"" Cil"n HcH,

PTCOOC2H5

\_-^J

@K:l

overall

I H. Xiong and R.D. Rieke,Am. Soc.,ll4, 4415(1992)'

Bis(oxazolines)' 16, 38-41. r Bis(oxazolines) (1) are easily prepared by reaction Asymmetric hydrosilylation of(S).aminoalcoholswithdiethyloxalatefol|owedbycyclization.Whenpresentin cxcess,ligandsofthistypecaneffectenantiose|ectiveRh(I)-catalyzedhydrosilylation

(

Enantiml from t-leucino complex(2) *r *ith ethvl dia

P-------q l l l l) r NJ

\-N {

c6H

"

R CuHrA

The highest enanof acetophenoneto give (R)-1-phenylethanolas the major product' but using chiral results, Similar tioselectivity, 84%, obtains with l(R:CHzCoHs).1 enantioselectivity highest case, this In pyridyloxazolines,havebeenreportedby Brunner.2 obtains with the ligand bearing l-butyl as the alkyl group' in a Michael or a These chiral bis(oxazolines)effect only slight enantioselectivity ligand' this by inhibited is actually Reformatskyreaction.The latter reaction

G. Helmchen. : ll. Brunner ar 'E.J. Corel and ' D. A. Evans- X

Bis(oxazolines)

tr( ',\hcnheated

Enantioselective Diels-Alder catalyst.3 The chiral bis(oxazoline) 1, preparedfrom (2) serves (S)-phenylglycine,in combinationwith MgI2 or magnesiumtetraphenylborate of cyclopentadiene reaction for the Diels-Alder catalyst as a highly enantioselective with 3-acryloyloxazolidine-2-one(equationI). CH3 ,CH3

cH...r,ro#o\-cH. cH./Wiv ru-/-cs.

1 ' M g [ ( C 6 H 5 ) 4 8 ] 2( 2 )

'aunu

cuH{ 1

2'c*2ct2t

-oH

N

.,,=rLA.O#&":j, g

?

-Pr

\J endo/exo = 97:.3 90.4o/oee Enantioselective cyclopropanation (16, 38-39||.4 The bis(oxazoline) I, prepared chloride), forms a white, crystalline from r-leucinol and 2,2-dimethylpropane-1,3-dioyl complex (2) with CuOTf which is an effectivecatalystfor asymmetriccyclopropanation

T.1:JJhY reactron \\ hcn present in

with ethyl diazoacetate.

cH3rcH3

r.::rdrosilYlation

P--\o..

( i l i l ) NJ \.-N '-I (cH3)3c c(cH3)3 1

o\, fi

c6H5

cH, + N2cHcooc2H5

r, cHct3

-CHa i c .

c6Hs'*"\cooc2Hs I:.t highestenans. i.ut using chiral s: r nuntioselectivitY r rr .r Michael or a i. lrsand.

(1R,2R),96% ee

* "urAcooc2Hs 73 i 27

(1 R,2S), 94o/oEa

: G. Helmchen, A. Krotz, K.-T. Ganz, and D. Hansen, Synlett, 257 (1991). I H. Brunner and U. Obermann, Ber., 122, 499 (1989). 'E.J. Corey and K. Ishihara, TetrahedronLetters,33,68O'f 0,992). ' D. A. Evans, K. A. Woerpel, and M. J. Scott, Angew. Chem. Int. Ed., 31, 43O (1'992).

U

Bis(pentamethylcyclopentadi€nyl)methylyttrium

yttrium' Bis(pentamethylcyclopentadienyl) [bis(trimethylsilyl)methyl] (1)' (C5Me5)2YCH[S(CH3)31, is an effective catalyst for hydrosilylaHydrositylation of alkenes.r This lanthanide at 20' in C6H6or CeHsCH:' Hydrosilylation tion of mono- and l'l-disubstituted alkenes olefin is highly selective' of dienes with a terminal and an internal

=at, -]#At*

/YCH, (,\,^cH,

(cH2)3cH2siH2coH5 cH3cH=cH

oc(c6Hd3 cHrx,A(cH"lrr

.-Y",, ;;*

Hydrogenation ol dic' ' methane to form catall'st terminal doublebonds in tl

(\.4(cH2)3siH2c6H5

1G.A. Molanderand M' Julius,J' Org', 57' 6347(1992)' Cp;YCH3(THF)' 1' Preparation'r Bis(pentamethylcyclopentadienyl)methylyttrium' of 1 with hydrogen generates Cyclization of 1,5- and 1,6-dienes'2 Treatment ..cpjvH,,(2)withreleaseolCHa.Thishydrideisaneffectivecatalystforcyclization of1,5-and1,6-dienes,eventhosewithbulkysubstituents.Nocyclizationisobserved SO2C6H5groups' when the substratebears CN, COOCH3, or

327,3r (1e87).

F cn/\("'zcHz

' K. H. den Haan, J. L. de &r

*

(^)''cH'

R.^,y,"\'-CH3

\__/

: G.A. Molander andJ.O. H t ldem' J. Org., 57, 3266tl

R = OBzl = OC(CoHs)g

(5%)

(6: 1),84% ( 2 1: 1 ) , 9 9 %

oc(c6H5)3

CHz=rr.-rr^.-zcHz

*.

oc(c6H5)3

oc(c6Hs)3

Bis(pentamethylcyclopcr ( C s M e s ) 2 S m ' T H F( l ) . h Hydroboration v'ilh t tirr hydroborationof a u'i the order: monosubstitut rrisubstituted.

,rAr,. C5H11CH:Cl

100:1 (7O/o)

25o/o

P"' ,if"r, \),'zcHz

\r'-J 53o/"

%czHs 26o/o

W. J. Evans and T. A. Ulih K. N. Harrison and T.J. ll

Bis(pentanethylcyclopentadienyl)samarium

)r r,\ drosilylalr jr,'silylation

Hydrogenation of dienes.3 This organolanthanide when treated with H2 loses "Cp2YH," which can effect highly selective hydrogenation of methane to form catalyst terminal double bonds in the presenceof other double bonds, even those of allylic ethers.

H z ,1 , c6H6,-78"C

9H=CHz {2SrH2C6H5

tetrahydrofuran

.....'.."......................................,.-'.........................*

oc(c6Hs)3 cH2\..\(cH2)3cH=cH2

aC:Hs

. l'rcparation.i lr,,*cn generates \r 1',r cyclization alr,'n is observed

oc(c6Hs)3 ?c(coHs)s cHzxA(cH2)4cH3 , cHs\,.\(cHd4cH3 (e6%)

(1 o/o)

' K H' den Haan, J. L. de Boer, J. H. Teuben,w. J. J. smeets,and A. L. Spek,J. organo met. Chem.,

a"."-/YcH3 (5"/")

oc(c6H5)3

327,31 0981. I c.A. Molander andJ.O. Hoberg, Am.Soc.,ll4, 3123(1992). i ldem.,J. Org., 57,3266(1992).

Bis(pentamethylcyclopentadienyl)samarium tetrahydrofuran. (CsMes)zSm'THF (l). preparation.l Hydroboration with catecholborane (CB).2 This ranthanide is an efficient cataryst fbr hydroborationof a wide range of arkeneswith cB at 25". Highest rates obtain in thc order: monosubstitutedterminal ) disubstituted terminal > disubstitutedinternal ) trisubstituted.

p'Ap, 1) 1, C6H6,25o

C5H11CH:QH2 + CB

2) H2o2'NaoH

-

78o/o

CzHs

- .4^ C)-"r3 \__J 7s/"

L/--"t.

CeHs 26%

W.J. Evans and T.A. Ulibarri, Inorg. Synth., 25,2g7 (1990). K. N. Harrison and T.J. Marks, Arn. Soc., ll4, 9220 Ogg2\.

46

chiral BisPiPerazines,

CoHs Bis(phospholanes). of (3 and 4) can be preparedby reaction The C2-symmetricbis(phospholanes) L'4-diols' the cyclic sulfate (2) of chiral dilithium bis(phosphidol"tttunt1f; with

cHr--l--VcH. urP^eu,

|

1

+

o),tao

1

9

/RN

?

1tr^R\/ a*

0 0

1,n=2,a)R

\_J Rs _/ CoHs

(s,s)-3,R = CHg

R-a) ''* 1) BuLi 2\2

PHz

-=)tt

l l l

%.r-l* R,"( I

PHz

\-.,/

(s,s)-4,R = CHs

Enantioselectivehydrogenation.|Rhodiumcatalystsbearingtheseligandseffect RCH:C(COOCHT)NHAc' In general' asymmetrichydrogenationof acetamidoacrylates' enantioselectivitiesofaboutloovoareobtained,particularlywithligandsoftype(S'S)-4, R:CzHs. Highenantiomericexcesscanbeobtainedinhydrogenationofenolacetatescata|yzed b y a R h c a t a l y s t w i t h t h e s e c h i r a l l i g a n d s . l n t h i s r e a c t i o n , n o o n e l i g a n d iand s c othe n s i sR/ tent|y with R in the bis(phospholanes) superior, but the enantioselectivity;aries in the enol acetate.

CHr i l -

n'Aonc

Rh.(s,s)-4,R=czHs?"' -oAc R' '

R'= CzHsOzC

>997" ee

1M.J. Burk,Am. Soc.,113,8518(1991)' Bispiperazines, chiral. by of N,N/-dialkyl bispiperazineslinked AsYmmetric osmYlation' Chiral ligands transof dihydroxylation :2) can effect highly enantioselective two carbons (L, n disubstitutedalkenes.

Whenn:3or4.thcsc group, the enantioselectivit osmylation of mono- and < alkenes. 'K. Fuli,K. Tanaka, andH V

Bissteroidal pyrazines. A new group of steror cytotoxic, are comPosedof t

Smith and Heathcockr hav identical steroid groups arc {SchemesI and II). !

?

Bisstemidal pymzines

CoHs

CoHs ir!:l()n

Of a

il,'1.

RN, ,N-(CH2hN \-J \---J

CoHs

R II

NR CoHs CHg

1 , n = 2 , a ) R = C H 3 ,b ) C H 2 C ( C H 3o) 3 r c, p H 2 {

)--\ )-CH.

CHs 11

_

v

',CaHu

, J

OsO4,L*

CoHs

r-t

L* = la =lb =lc

",,,?t.zcaHs ""^{-[n^

84o/o 87o/o 84"/"

94o/oee 91%ee 89%ee

When n : 3 or 4, these ligands suppressthe reaction completely. If R is an acyl group, the enantioselectivityis depressed.These ligands (l) can also effect asymmetric osmylation of mono- and disubstitutedtcrminal alkenes, but not of ci.r-disubstituted alkenes. =CH3

Lrr.,n.ls cffect e In gcneral, rrpc (S,S)-4, r:;. catalyzed s ;,,nsistcntly s, .'nd the R'

I K. Fuli, K. Tanaka,and H. Miyamoto,Tetrahedron Letters,33,4021(1992). Bissteroidal pyrazines. A new group of steroidal alkaloids, known as cephalostatinsand shown to be cytotoxic, are composedof two identical steroidalgroups connectedby a pyrazine unit. Smith and Heathcockr have developed two routes to alkaloids of this type in which identical steroid groups are linked at C2 and C3 of thc A ring to the pyrazine ring (SchemesI and Il). 1) C6H5NH*Br3-HOAc

Nsr,.

2) NaN3 510/o

o

ir::. linked by ttr,'n rlf /ransSchemeI

ln contrast. I reacr l.-l-butadienc(equz

(S.S)-Bis'p-tolylsullinylmethane

HzNr,

1)cH3oNH3+cr H2o,THF 2) P(c6Hs)3,

c"H.crjaol-

a

87"h

(r)(s.s)

4 Schemell

or anunsYmmefi:iJ:t#i"i:T","u"il"ilT; a svnthesis alsoincludes rhereport at 5r are heated first ^"td-1t..'Oation

of 4' and

1) 4, c6H5cH3'9oo 2\ 1450

AcO

\. Kunieda. J \ol (i. Solladi6. F (-t ftrahedron. 32. 7

rlR.2R)'lr'f.I isoproPoxide.

p

Enantiosclctt hsdes Proceedstr irom the combina

43"/"

5 145"' the pyrazine 6 at intermediatethat forms J' Org'' 57' 6319(1992) I S.C. SmithandC'H' Heathcock'

,t

rvI oxide' -methv r-p-to (R) and ?;ff ,t"#:lf H:ffi1""T,"'.:?te '(^.9q.s (1)

C5H5Cfl(

CrHr'SJ"-tt"' The anionof this C2-symmetric withcarbonylcompoun'ds'2 in contrast reactions Asymmetric high diu'tt"oselectivity "#"U" t*nydes with with react diastereoselectivity' can (1) low reasent wt'i"tt "i"o *ttn to the anionof methyl t*l'ltt'i-'.itoxia" CoHz

c6Hitiit ?1i,,* -;-

(S,S)-1+ C6H5CHo

Ht'f,H\S';. CoHz

(s.s,s)-2 =eo:10 is,s,sln,n'n)

lligh enantiosc .ind also *ith r

ll. Takahashi1 ( le92).

9-BorabicYclol 1,4'HYdnl

or catecholkln respectiveof I

9-Borabicyclo[3.3.1]nonane

(9-BBN)

In contrast,l reactswith an d,B-enal to form a 4-substituted1,1-bis(p{olylsulfinyl)(equationI). 1,3-butadiene (E) foHz BuLi' -\-.\"-S.,*' rHF ' CH3I -o 64y" ,9_-O C6H7 ",..

(E) (l) (S,S)-1 + CH3CH:CHCHO

( S , S ) - 3 ,a s - 2 2 o

In order obtain an

{yv t l H

I N. Kunieda, J. Nokami, and M. Kinoshita, Bull. Chem. Soc.Jpn'' 49,256 (1976)' 2 G. Solladid, F. Colobert, P. Ruiz, C. Hamdouchi, M. C. Carrefro, and J.-L. Garcia Ruano, Tetrahedron, 32, 3695 (1991).

(1&2R)-1,2-N,M-Bis(trifluoromethanesulfonylamino)cyclohexane-Titanium(IV) isopropoxide. allcylationof RCHO.| The reaction of diethylzinc with aldeEnantioselective by the complex(l) obtained when catalyzed enantioselectivity high in proceeds hydes andTi(O-i-Pr)a. disulfonamide C2-symmetric active optically the of the combination from SOTCFT N

)ri1o-i-e4t

(1)

N

SO2CF3

1,coHscHs , -20"_ C6H5CHO

,'t this C2-symmetrlc .- lcctivitY in contrast ,r tlrirstereoselectivitY'

+

(C2H5)2Zn

e8"/"

C6H5yC2H5 H oH (S),98%ee

High enantioselectivitycan also be obtainedwith (cHr)2Zn, (Bu)zZn, and (csHrr)zZn, end also with aliphatic aldehydes. 5691 :H. Takahashi, Tetrahedron,4S, T. Kawakita,M. Ohno,M. Yoshioka,and S. Kobayashi,

(teez). ^ro

)F5

- ;-' F = 90:10

9-Borabicyclo[3.3.1]nonane(9-BBN). 1,4-Hydroborations of enones.t Phenyl l-alkenyl ketones are reduced by 9-BBN ()r catecholbofane(cB) (1 equiv.) in >957o yield to boron (Z)-enolates(>99/1), irwith resoective of the substituents on the alkenyl group. The reaction is more rapid

50

Bomne-DimethYl

sulfide

9-BBN undergo aldol reactions to provide CB. The (Z)-boron enolates derived from (Z)-boron enolates formed from CB show aldols in )96Vo syn-selectivity' However' : lower selectivitY(sYn/anti 3:1)'

g-aeNr -ctt --Y^%Hs oBRz 2'>99:1

cft \/yc6H5 o

jH'9!- CH3.-=.1-C6Hs

o

cH3xH3

e-

"osiR

cHss'!

osiR3

I c6HscHoI 99% V cH2cH3 CuHu*C6H5

o

(r) V'

= 99:1) @Yn/antl

1) BH

2l t+l

OH Alkenylalky|ketonesun
Borane-Dimethyl sulfide, BHj' S(CH3)2' ' of quinone ketals by BHr S(CHr)z C-Aryl gtycosides-t Reductivearomatization providesu**,out"toC-arylglycosides.Thus2-lithiodihydropyran(2)and3rcactto formaquinolketal(4).Reactionof4withBHs.S(cHj)2reducestheglyca|doub|e from p-methylanisole' bond and provides the C-glycoside5 derived

Diastereoselectivc h1 csterswith BHi 'S(CH, oxidation affords 2-alkox

9CH.

C

n'ArV I

CHg CHEO. -

\./

Li +

i

a\

l

,OCHg

r

Vll

l

9cH.

o 3

cHso. /,ocHs

r\."

Ar

!

-\Yt'\./

CHe

ll::;,:8x". A%;i1 50-60%

a"Y-ot \-/4 approachis formulatedin equationII' An alternative

\Z\OCH.

s

The diastereoseleoi \tcreochemistryof the d

K. A. Parkerand C.A. Co r J . S .P a n e ka n dF . X u .J

Borane-Dimethyl

sulfide

5t

r!*r!:l(rns to provide n..l lrom CB show

H- -y"u"t o

(tt)

CHat"'

''osin,

9e 1r

'"osiR3

1) BH3.S(CH3)3 2) H2O2,OH

11 .r rlh 9-BBN, with

al. 'r

BHr 'S(CH3)2

r r . : : rr l ) a n d 3 r e a c t t o lr. titc glYcal double rlr

.t."

(Yo"'" ao)...'\-/

R3sio^*osiR3 : OH Dinstereoselectivehydroboration.2 Hydroboration of a-alkoxy-B, 7-unsaturated esters with BH: . S(CHI)2 (1.05 equiv.) in THF at O - 20" followed by standard oxidation affords 2-alkoxy-1,3-diolswith significant diastereoselectivity.

9CH.

gCH.

1)BH3.S(CH3)2 2) H2O2, NaOH

9CH.

9CH.

o'.Y-t-\

nr-\-rVcoocH3 cHs

cH3 oH

oH

2,3-anti12,3-syn=8:1

9cHt

QCHs

coocH3 --run___*

A,

CHs

z,3-anti12,3-syn= 4:1

\ t

CHs

'OCHr

The diastereoselectivityis independentof the size of the alkoxy group and of the stereochemistryof the double bond. iK.A. ParkerandC.A. Coburn, Am.Soc.,ll3, 8516(1991). :J.S. PanekandF. Xu, J. Org.,57,5238(1992).

52

CH3rCHl

Boron trifluoride etherate

'ilanestoRCHo;tetrahydrofurans'1 trifluoride etherate' Boron ""'";;;;;'setective uddition ailditionof chirat @''*"^"":::#'ffi;;;iective acid promotorfor diastereoselectivr **" "il"*t to form rno" tf't i' aldehydes BF3 etherate (1) to a- una B-utn'yroxy B+ilyr-tei-;;lsilanes of a-substituteo

I "r,/YcozcHg

tt"d'-;o2cH3 ,15';?lB',13t, -B5%-

BzlO---...'\Orf,"r"r.

(cH3)2sic6H5

,% 6

u\<^o" l l \-/

OH

.'-<-cH2cH3 I

CHs

BF3€ i

|

: J . S . P a n e ka n d M Y a n g ' { a : G . H . P o s n e rE ' . M' Shulman' 32 Anieh, Tetrahedron Leners'

96% de

ov,,

(2s,3s)-1 5-Bromo-2'PYrone,

"r.--o..-,flo,"r.

tY;--*

Bzro

"v\

n

96% de

(2R,3R)-1

I

"t3z

cHs'--/'--'(--cozcHs

2, BFgo(czHs)z, ao%

oj

/SiR3

fa

,co2cH3

\ot1"*. Bzlo-.-,...

(cH3)2sic6H5

Diels'AldercYclu&i 15-100' to form adduo llctones.It is thereforea 1

96o/ode

(2R,3s)-1

9*'

"^"-=/?co2cH3

cozcH3

3Yuil-'-

Bzlo CHe

(cH3)2sic6H5

o\r"\

6--2L"

96% de

(2R'3R)-1

l.,''cn,:( es"u'f ziHaLx

involvel'a (1-3 rhis heterocvclization ]:1;'J::[::,'::'l^l"n u'" etherate 2,5-cis-furans' reactio":T;.;;;""0'""t0 This Burgess the tert-aliohols'2 with of Dehvilration higher'ff areusuallv could dehydrat i"ratritzs".Yields **"-i.ntotation When ffi: acid' ."rri,','" reaqent, thionyl chlori*'"tt"t' "n""".,',j" ."ril, in two different

O-

PreParation:

(cH3)2sic6H5

9H'

a

rlt "toluenesulfonic ro.. tt"rnroovnutically

stable alkene predominates'

Noepentyl,ert-alcohols'*"it''"'tl"*resofalkenes'someresultingfromacarbocatron rcafrangefirent'

t'v

o>-\'-r"' d"<

K. Afarinkra and G H Pt

5-Bromo-2-pyrone

cH3/cH3

BF3.o(c2H5)2

V

mhydrofurans.r :lrc:ir c addition dcrr Jcs to form

cHzclz ' 610/o

rt\rAoH I I

(Y

|

S R-.

,.co2cH3 I

n

1n,

t

un3

(Y"t"'""

+ 0 90:1 cH2cH3

OH ./\(

cH(cH3)2

+

-CH2CH3

+

(/

lsY"

|

99.6:0.4

f"'"

l J . S . P a n e ka n d M . Y a n g ,A m . S o c . , 1 1 3 , 9 8 6 8 ( 1 9 9 1 ) . l G . H . P o s n e rE , . M . S h u l m a n - R o s k eC s ,. H . O h , J . - C .C a r r y ,J . V . G r e e n ,A . B . C l a r k , a n d T . E . N . Anieh, Tetrahedron Letters, 32,6489 (1991).

de

o)).-r, R: ...S |

5-Bromo-2-py-n., (1)

,rCOzCHs

i \cH.

Preparation:

oY) /S,R. ,CO2CHs x 'CHs

, C l q ,A 1 ) N B S , ( C 6 H 5 C O ) z OC 2) N(C2H5)s

oY> o4",

oJ

,r-( E:E

1 Diels-Alder cycloadditions.r This pyrone undergoes Diels-Alder reactions at l-5-100" to form adducts that on radical debromination afford halogen-freebicyclic lactones.It is thereforea practical equivalentto 2-pyrone itself.

SrR3 ,co2cH3

' ir \cH.

")) o'?t*

+cH,:6116es,k

P" :e

":Y-cooH #---/ (endolexo = 100:0)

,1""r:""""o o".r^l -''"1

2) NaBH4, cH3oH,25'

rh l'it:, ctherate(1-3 *..; * ith the Burgess r Jihrdration could rl'rrnc Predominates' ! lr,16 n carbocation

ttv

csA,cH3oH

">-\tr>-cH2oH--ffi* #--_/

Br:-Z\..COOCH3

I I----,'-\CH2oH

HO-

K. Afarinkra and G. H. Posner, TetrahedronLetters, 33,7839 (1992).

(5S,6R)-4-r-Butoxycarbonyl-5,6-dipenyl-2,3,5,6'tetrahydm-4II'1,4-oxazin-2-one

54

(5S,6R)-4-t-Butoxycarbonyl-5,6-dipenyl-2,3,5,6'tetrahydro-4H'1,4'oxazin-2'one) 14, 58-59. Asymmetric synthesisof arylglycines.r These glycines are difficult to obtain in optically pure form becausethey readily undergo base-catalyzedracemization.One of the most useful routes involves the Williams glycinate (l). Bromination followed by alkylation with an arylcupfateor an afene (ZnCl2 catalysis)provides 2. Removal of the Boc group (ISiR3),hydrolysisof the lactonering, and oxidative removal of benzaldehyde provides the free amino acid. Even a furanylglycine can be prepared(equationII). 1)lsi(cH3)3

QoHs

QoHs

coHs,. aHs,,, o l]l:?";'"'o ,,"_*-cooH r.,---n f | | 111"1i".""r," -

tr ) aocN\,,\

s6%

nu

eocN-*.-\

*

o

H-"\cuH,

,i\ur,

QoHs caHs,,,.a/\o

2)(o) , zncr,

HzN H2tpd

c6Hs,,. (-o

ao"il-.,.,,\o ,{

trans- ( - ) -2-t-Buty.k1

u)-?

I

90o/"€€

This oxazinoneroute can be usedto obtain bisaryl glycines by a version of the Stille coupling rcaction (equationlll).

goHs

t'3ttli-,,o.,".

CoHs

cuH'\Ao 31il?''"*"cuHu:A. I

( I r r ,

|

BocN:o,\O

|

R. M. Williams and J

CoHs

1)NBS

(rr) eo"rl_ (o--=t-

B2%ee

zv"/o

I

I

This chiral alcoh chloroacetate(reaoio ltvcr acetonepowder :hcn be saponifiedto This alcohol w.ha r\\'mmetric induction icss effective than ti1

BocN---,,\O

s\ B ' H

P. Esser,H. Buschm ,1992\.

\

/

Tfo

r-Butyldimethylsily-l r Intramolecular .1 r rth NEtt can effec r'lvcyclic systemfuv

l-,ot

t-Butyldimethylsilyl

trifluomrnethanesulfonate

l.{
H2N\ -.COOH

-\

H

C6H5

B2/oee

90o/o€€ | . 1r J r \ i o n o f t h e S t i l l e

o

' R. M. Witliams and J. Hendrix, Chem. Rev.,92, 8gg (1gg2).

trans(-) -2-t-Butytcyclohexanol, - -" aY (1R,2s)-(-)-1 \_r.,c(cH3)3 This chirar arcohor (-)-r can be obtained from racemic l by conversion to the chloroacetate(reactionwith crcH2coou), wrriJ is saponifiedby enzyme pLAp (pig liver acetonepowder) at 4?% "onu.rrion'to g*. and the (+)-ester, which can t-Ir then be saponifiedto provide (+)_1. This arcohor when used as a chiral auxiriary in four asymmetric induction than trans-2-phenyrcyctohexan.r test reactionsshows higher or menthor. It is onry srightry less effective than g_phenylmenthol as a chiral uu"iliury.,

i;ril;:t

H' Buschmann' M. Mever-Stork, and H.-D. Scharr, Angew.Chem.rnt. Ed., 3r. ltso

t-Butyfdimethylsilyl trifluoromethanesulfonate (l), 12, g6; 15, 54_55. Intramorecurar Michaer-ardor cycrizstion.t itris sityt triflate (l) in combination with NEt3 can effect cycrization if a,B-enoates substituted by a keto group ro a polycyclic systemfused to a cyclobutane.Thus reaction of (E)-2 with 4 equiv. of l and 7

t-ButYl hydroperoxide

osiR3

/* I

I

l

I

o2'\r"

l

-

l

"'l;3il'i"

il.

coocH3

48"/.

-coocH,

(Bzt)zN, /z-CO PrcH) 1

(E)-2

AcOH, H2O 51o/"

coocH3 4

retro-aldolreaction' can be convertedinto 4 by a equiv. of NEtr provides 3, which Another examPle:

Use of m-chloroPc complete chiralitv tran

H

llf"?ii,'="*"o,"".

cH3o-",^---,'*--'H

6cH.?+

clcc|t cHg

74%

.l

I

-

H ,/t,

H

at^j^ cH3o2c"'V

?''( H

1,NEt3

--sr%-

\ \- / ' \ " H I

I

cn"orc-'\r? R3sio

/l

*-)

il

ll4' and K' Fukumoto'Am' Soc'' I M. Ihara,M. Ohnishi,M' Takano'K' Makita'N' Taniguchi' 4408 (1ee2). i M . T . R e e t za n d E . H

t-':1,:t$,::i#]'!r7.r*rn

y-dibenzvlaminoof chiraty-aminoenoates. Since since

(16, 30a) and reduced with high stereoselectivity can be 'iii-""0**" Reetzr has B_keto esters stereoselective"up'uit addition' r-BuooH with 7-dibenzylaminoenoates epoxidation substrates(1). In this case, as investigated epoxidation oi in.*" hydrolysis ester in results potut'iut t-butoxide' which requires the presence of stereoselectivity' high with epoxidation can proceed well. under these conditions with cuprate also to form is outalned and this reacts Essentially a single O'";;"; lZ; a single Product (3)'

rButyl hydroPerori Sharpless asYrst late on classicalePot dnli-epoxides,but on

r99:l). No reaction Sharplessepoxidatirx

,,

1)t-BuOOH, KOC(CH3)3, THF/NH3

- ,osiR3 -coocH3

(Bzt)2N y'z-coocH3

isopmpoxide

tartrate-Titanium(IV)

,-Butyl hydropemxide-Dialkyl

n

,*H-.._

R.--,,
+ anti-2

I

PrcH)

(Bzl)2N

3

syn-2

(CHg)zCuLi -

>96:<4

OH I

R---,,I-.--COOCH3

l

(Bzl)2N

i

CHs 3

E:: .'idol reaction'

Use of rn-chloroperbenzoicacid provides an amine oxide 4, which rearrangeswith complete chirality transfer to a hydroxyamine(5).

.,

CICoHqCOsH CHzClz,-50" -

.o-

I

(Bzt)zN+,r__Vz- COOC2H5 | . t \ I

R

-r'-\-'H

--Y /l

F.SO

il

. ,nr()to, Arfl. Soc', ll4,

l

7O-80/o

4

R"z"'rcooc2Hs H2,Pd(oH)2R ----.r,-r.COOC2H5 l - - - - - - . - - - -eoo/" --.-_ I 6ru1azt;, OH 95%ee 6

I M.T. Reetzand E. H. Lauterbach,Tetrahedron Letters,32, 4477, 4481(1991\. : :'.: 7-dibenzylamino16. 304) and since ; . ' J , l i t i o n , R e e t z rh a s

r

p,rrJ.rtionwith t-BuOOH It. :rr rrster hYdrolYsisas If ::rqh stereoselectivitY' ari- .uprate also to form

t-Butyl hydroperoxide-Dialkyl tartrate-Titanium(IV) isopropoxide. Sharpless asymmetric epoxidation of B-hydroxy acrylates.t A B-hydroxy acrylateon classicalepoxidation(alkalinehydrogenperoxide)gives a l:1 mixture ofsyn- and but on Sharplessasymmetricepoxidationgives the syr-epoxideselectively arrli-epoxides, t99:1). No reaction occurs in the absenceof the hydroxyl group. The asymmetric Sharplessepoxidationalso is possiblewith cyclic B-hydroxy ketones(secondexample).

,-Butyl hydmpemxide-Dialkyl tartmte-Titanium(IV) isopmpoxide

o H o

r t l

cHsl\y^oc(cH3)3

TBHP,Ti (o-,-P04 cH2cl2,-15' . .., v'

o H o '3

| ll -^--(}OC(CH3)3

7To/o ,.u

CHz

(syn/anti> 99:1)

o H o t t l

o H o

cH3->") "\_,

Butyllithium Diastereosela cthers(l) with Br selectivity,depex hv Petersonelim t rienes.

(CH3)35i-.tzz

(syn/anti= 99:1) Double kinetic resolution.

Davies et al.2 have noted that the enantiomeric selectiv-

ityofSharplessasymmetricepoxidationofanallylicalcoholcanbeenhancedinsome of the allylic alcohol I with casesby use of two kinetic resolutions.Thus epoxidation the epoxide2 and the less (+)-DiPT as the chiral component(58% conversion)provides

*t.-Z>

(cH3)3s

reactiveenantiomer(R)ofl,whichcanberecoveredandepoxidizedwith(-)-DiPT. I in 86% ee. This strategy is Using this technique,the epoxide 3 was obtained from

a

R=H

OH

I

l r l CHs 1

t-BuOOH, Ti(o-iP04, (+) - DiPT , 410/o

R=CHs R = CzHs

CHe

CHs ( R ) -1

eel 2 (5Oo/o t-BuOOH, I Ti(O-iP04, | 59"/. (-) DiPr I

Thus the ethcr product is reducs Jicne5. Acidic cli .clcctivity. In coo 1 7 )w i t h h i g h s e

I

OH

I

f

N^

l v " \,/,,,cHs 3 (86% ee)

on|yusefulwhentheracematesofthea|lylicalcoholdonotdiffersignificantly are available' reactivity and when both optical forms of the chiral reagent Letters'32' 2687(199-l)' I M. Bailey, I. E. Mark
tCHs)sSi V-'

Butyllithium

'oc(cH3)3 > 9 - 41 )

59

Butyllithium Diastereoselective[2.3] Wiltig rearrangement.t Treatment of allylic propargylic ethers (l) with BuLi at -85'provides either syn- or anti-B-silyl alcohols (2) in high selectivity,dependingon the R group. A variation of this Wittig rearrangementfollowed by Petersonelimination provides a stereocontrolledsynthesisof terminal conjugated trienes.

.,2/'si(cHs)s (CH3)3S|,-_z/',.(O,,,r2,r'

BuLi. THF -85" ,

I R

.,,

1 n : r , ' n r c r isce l e c t i v c:.i' .rnccdin some , l r . . r l c o h oIl w i t h rr;.1!I and the less 3; 'rith (-)-DiPT. .* I ris strategy is

I

CHs

OI H

R-.-Z--r\* l \ (cH3)3si

OH

",Fs-l ^

- -si(cH3)3

-si(cH3)3

(cH3)3si syn -2

anti - 2 R=H

90%

R = CHg

6}0/o

96:4

R = CzHs

65/o

97:3

3:97

Thus the ether 3 rearrangesto 4 with high (E)- and anti-selectivityto give 4. This product is reducedby sodium bis(2-methoxyethoxy)aluminum hydride to the (1E,58)diene5. Acidic eliminationfollowed by protiodesilylationgives sarohorneneB (6) in high selectivity.In contrast,basic elimination and protiodesilylationprovides sarohorneneC (7) with high selectivity.

(cH3)3si-Oyo)

-BuLi,

""'ill 3

-85'

CzHs

67"/"

l

si(cH3)2c6H5 anti - 4

si(cH3)2c6H5 s8%lsMEAH OH i r t l : : s i q n i l i c a n t l y in iglL.:hlC.

(cH3)3si r

'

I l()91).

Butyllithium -Potassium

t-butoxide

CHs HO/\v HO--\/-

cz+s-,-rr''\/-'-,/cH2 6

CzHs-.-Z--:.ACHz 1) KH ,0" (99%) 2) F (68%)

7 : T. Matsumoto, M Kat-sut

Scheme r

r2R)-2-r-ButYl-6mahf An imProved PrePan e r R)-3-hYdroxYbutanotc I scale I large a acid on

48' 4087(1992)' Nakai'Tetrahedron' rN. Kishi,T. Maeda,K' Mikami' andT'

c(cH3)3

"*t:#::#-,:;ffi:l-J,:J::;tll''o'^o^^'ion

suchas derivative or ananthracene

or C11; occurs mainly at Ce a problem sin-e attack o;;-;;t' alkyllithium t-BuOlJBuLi an with with 1 "un O" cffected ;; ;'' o'tho-M"tuluti"n give the instead of desired utt"tk with (CHr)lrSnCl to '"u"tion Uy at 190" follo*td treatment on (5 equiv. of each) in fHf tin-lithium exchange itris productcan undergo arvlstannanc2 in 64"yierO' at cq t)r cle' The aryllithium reaction (-ig - 30') without totu"n" in for synthesis methyllithlu. with the side chain required *i,i ura"hyde3 to introduce ,.u",, ester(5)' gencrated methyl thus 82 antibiotic uin"n*ytinone ;";-t*;" of a prccursor(4) to the

1) BuL|/KOC(CH3)3 2) (CH3)3SnCl THF, -90"

I o^o t l cH3'--"\o

Sn(CHg)a

r D . S e e b a c hU , . G1sel.

l-(/-Butylperoxy)'lJ

1) CH3L|, C6H5CH3'

-78'

OHC\/^'--z'CH2

2\

c{'"oart

- 30"

(3)

( \

l-(r-Butylpemxy)- 1,2-benziodoxol-3(lII)-one

5

rT. Matsumoto, M. Katsuki,H. Jona,andK. Suzuki,Am. Soc.,ll3, 6982(1991')' (2R)-2-t-Butyl-6-methyl-4II-1,3-dioxin-4-one(l) (14, 69 -70). An improved preparationof I from the acetal (2) obtained from pivaldehyde and (R)-3-hydroxybutanoicacid, permits preparationof this chiral derivative of acetylacetic acid on a large scale (13 g.).'

c(cH3)3

c(cH3)3 ir .r:rrc such as .': ('q or CItt

: lluOI(BuLi r( I to givc the gi \,n trcatment

2 N B S ,A I B N

o^o

f(cHs)s g^9 + l . t ercHzlt'o

oAo i I cHsl|\o

cHA--\o

Br

Br

2 - 3.5:1

2

l:. .rrvllithium :i l,rr synthesis thrI cstcr(5).

1)Al2O3 2\ H2, Pdlc, NEt3, EIOH 43o/o overall

f(cHo)s o^o

t l cH3,,..,,\\\*o 1

r

- Sn(CH3)3 I D. Seebach, U. Gysel, K. Job, and A. K. Beck, Synthesis, 39 (1992).

a

t -(l-Butylperoxy)-1,2-benziodoxol-3(lll)-one,

-'zcHz OBzl

1, stable at 25'.

OH

/-','r-i,, t i l \-.4-/

o \

o

l-BuOOH BF3.OEt2 85%

/ooc(cH3)3

y'-':r-\,,

w t

l

t

1

o

o

1-(t-Butylpemxy)'1,2-benziodoxol-3(1IO'one Oxidation.

reagent'r is a versatile oxidizing This new iodinane

1,cH2Cl2'25o-t;;c6Hu/s-cH

"

a)

txt

! c6H5l"-cH3

rtr-gf S.r.d :rr*rtutc

o

"t#r"-

cuHuAcH.

C5H5 CH3

Soc'' ll4' IM. ochiai, T' Ito' and Y' Masaki' Am'

,

i;rc

{

'( (.'F{ ':rr'Cn:' I

\,,v'

6269 (1992)'

:c.l-ts

. :r lt$tr

(Y\

cHe-o cn.H

t({c\1t I

o tl

61"/"

:a-.rnlx

: i

{

i IJI\I

: a:.,rr I

. . ( . (

?*' OH

l}rr-

-l

Cr+

t.r I

t.-l

T\T

CH: ''

-4oH

u-Camphor dimethyl acetal (1). Selectiveprotection of myo-inositok.) lnositol derivatives, particularly various phosphates,are involved in various biological processes,but are difficult to prepare in enantiomericallypure form. A useful expedient is to use o-camphor not only as a protective group but also as the chiral auxiliary. Thus o-camphor dimethyl acetal (l) reacts with rnyo-inositol (2) to give the 2,3-protectedtetrol 3 in 3l7o yield. The l-hydroxyl group of 3 reacts selectively with the bulky t-butyl-dimethylsilyl chloride to give 4 in 88% yield. This product reacts selectivelywith pivaloyl chloride to form the C4-protectedester in 78o/oyield. The tetrol 3 reactswith the bifunctional silylating reagent,1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, to give a protected5,6-diol. By use various of acylatingreagentsit is possibleto obtain derivativesof rzyo-inositolsin which hydroxylgroupsare free at C1; C1 and Ca; Cr, C:, and Ca; Cr, C+, and C5; C1, C3, and C,ri Cr, Ca, and Cs; Cr, C2, and Cr,i Cr, Cz,Cq, and C5; and C1 and C6.

"X,

cH3\K.cH3

t\ + /-11 4y'ocH"

HO

(cH3)3sioTf 31o/"

o

OH

C H-A I

ocH3

",oH

2

1

' K. S. Bruzikand M.-D. Tsai,Am. Soc.,ll4, 6361(199r.

Camphor-derived oxazinone (l). The oxazinone I is preparedin severalstepsfrom ketopinic ethyl ester

CHs--o,Ctto a\\

c,Huo3-(o

)e

CHo Several steps

LI--L)'tH
1 m.p. 242",cre-155'

64

(fR)-or(1S)'10-Camphorsulfonamides derivative of I The enolate of the N-propionyl

Asymmetric aldol reactions'.

CaHs'

canundergohighlysylr-selectivealdolreactionstoprovidethe..non-Evans''syn-aldols (16, 48).

1) LDA,-78" 2) clTi(o-t-Po3 3) c6H5cHo 1

-

751"

o q H l l , xJ'\i^cuHu =

*

CHs

? ? '

(c6H..)2

x-l\',^c6Hu CHs

99:<1

(1992)' 1K.H. Ahn, S. Lee' andA' Lim' J' Org'' 57' 5065

(1R)- or (1S)-10-Camphorsulfonamides' realcohots' The a-chloro-a-nitroso Chirat a-nitro'" ";;;;;;-;;1i-p-omi'o oximation by yield I tn 78% l0-camphorsulfonamide agent2is preparedtio'n-tf'e zinc cnolate(a) of an ethyl the with reacts '"ug"nt followedby chlorinatio"'int'

a ( k{\'lrc:. (

ll(

eopborr (hilal P-

.r .i 'n\ CnCd I

:f :sir\-C (rf r.t( *:-s.rx'lcr.ltr I

cH3-.v.cH3 \

/l-)> a\

(C6H11)2NSO2-

o

cH3\'cH3 1)NH?oH

2)(cH3)3cocr, 1ao/o

l\

/) t

2 ", I

(C6H11)2NSO2-

N--O

I (HtO*) of 4 .provides a single nitrone (4)' Hydrolysis and ketone 3 to form essentially reduction converted by hy-drochloride5' which is general and a B-keto N-ttyd'o*ytu*ine This sequenceprovides a hydrogenolysisinto (-)-noreptrlOrl-(O]^i \:Y:" in 96-99'|J"k ee" ,out. io aflti-p-amino alcohols

10-Camphomultam (l)

r .:ltrC Of I

;" . \ n-aldols

1) LiNlsi(CH3)312 2) ZnCl2

o c6Hs-A\7cH3 3

OZnCI l

2

^\,6n5 ,, .\-CHs a

o Hso*

"uruy'ytt'

-2

+NH20H

'-H'l t'

cl5

1 ) N a B H 4C , H3OH 2\ Zn, HCIIHOA: 68% from 3

OH t c.Hu-\icH' : NHe 6, 960/" €e (anti/syn=95:5)

'(t -nltroso fe-

lW. Oppolzer,O. Tamura, G. Sundarababu,and M. Signer,Az. Soc., ll4, -5900(1992).

h.r irrimation | ,,1 an cthYl

(

l0-Camphorsultam (1), 13, 62; 14, 71-72. Chiral B-hydroxy esters,t The N-acetyl derivative I of Oppolzer's auxiliary can bc converted into the O-silyl-N,O-keteneacetal 2, which reactswith aldehydesin the presenceofTiCla to afford aldols3 or 4. Theseare hydrolyzedto B-hydroxy esters5. The stereoselectivitydependsupon the steric demandsof the aldehydegroup R mainly, with

CH.

"t'*"t'

'iLCt

''--o

NI

2

,.11

?#'."o"r,

I OSiMe2-t-Bu

O2 1 = X*COCHg Tict4 FCHO, CH2C|2

rf { provides 1 ' :iJuction and rrJt: a general

X*-,?,CH2

2

X*\..^-r-R

+

l

l I o o H

p-Carboxybenzenesulfonyl

azide

91 : 9 610/o R = CoHs = i-caH7 75o/" 96.4 : 3.6 = c-CoHl 73o/o 95 : 5

-

?-*

I ',o",*,o,

+ 5

/FN.

slight dependenceon the silyl substituents'

o

I W. Oppolzerand C. Starkemann, Letters,33' 2439(1'992)' Tetrahedron

(10-Camphorylsulfonyl)oxaziridines, 13, 64- 65; 14,'72; 16' 6l 62' (LDA) of (+)-3Kinetic resolutionof a lactone.t Hydroxylation of the enolate yield and 6OVoee' methylalerolactone(2) with (-)-1 (0.5 equiv') provides 3 in 58%

cHr.-(c '

t \l (ia1ur

.#

-l>=-

('etcciolbon

Catal-Jur a Rh(l) and

O2

c)-1 CH.

CH.

t -

1) LDA,TMEDA 2 ) ( - ) - 1 , T H F ,- 7 8 '

t l \oAo ( x )- 2

t thc \-hr< --:hrlamirrc.

A,.o' t l \oAo

\$antag6 i:J

I

thc rcgro

i rr-rclic atr 'rl: t{xencd

3, (60% ee)

provides (2S,3R)-(-)-verruFlash chromatographyfollowed by two crystallizations carinolactone(3) in >95Vo ee. I F.A. Davisand A. Kumar'J. Org., 57,3337(1992)'

(l)' 2' 62' p-Carboxybenzenesulfonyl azide, p-HOOCCoH+SOzN: Azi'dationofN-hydroxyp.lactams.|ReactionoflwiththeN-hydroxyp-lactam 2doesnotprovidetheexpecteda-diazo-B.ketoesterbutcompound3,formedbyazide resultsobtain in reaction transfer to Cr with cleavageof the N-hydroxy bond' Similar

Hzc\

I

Catecholbomne

o Trisylazide,2 N(C2Hs)3

,(""^O.^-.--Si(CHs)s

/-"o^

rt l)A) of (t)-3r r : l . i a n d 6 O %e e

5 of the N-hydroxy B-lactam (4) with trisyl azide in the presenceof 2 equiv. of tricthylamine. 1C.M. Gasparski, M. Teng,and M.J.

Miller,Am. Soc.,114,2741(1gg2\.

Catecholborane (CB), 16, 65-66. catalyzed hydroboration r Hydroboration by cB can be catalyzed by a number of Rh(I) and Ir(I) catalysts,particularly RhCt[p(C6H5)3]2and Ir(cod)(pCyr)(pylpFo. Advantagesare that selective hydroborationowing to steric factors can be improved and the regioselectivitycan be enhanced.Moreover, the Rh(I)-catalyzedhydroboration of acyclic and cyclic allylic alcoholsproceedswith high diastereoselectivity, oppositeto that observedwith 9-BBN (equationsI and II).

OH

OH

(r)t"*"H. :..iR)-(-)-verru-

i|.

"#k#;- Ho'^+cH3+ Ho-^\r 9-BBN el%

|

i-:rJroxY B-lactam I -1.ltrrmedby azide ls ,,[1xipin reaction

SOn

|

rHF,2oo

8 1: 1 9 '17:83

,,.-U.CHzOH

cB.Rhfl)g3% |

e-BBN ris"/"

Pr

Pr

syn

/"
OH

\

anti

^.-CH2OH 'l

|

OR

V.On 91:9 54:46

I

I

cH.

68

s1

Cesiumfluoride Inadditionat.ewgroupscandifectRh(I)-orlr(I)-catalyzedhydroboration.Thusan

amidegroupcandirecthydroborationofcyclohexene-derivedalkenes(equationIII),

CONHBzI

coNHBzl 0il)

,\ t

\'2

cB 1) rr(r),

p{hlorol

( tirrnirr IJ.Di :anat1ckrb lnt(\ th€ tf

2\ Ac2O

i --i{renc I

l OAc sYn/anti= 91:9

G C' Fu' and I D. A. Evans,G.C. Fu, andA. Hoveyda , Am. soc.,ll4, 6671(1992);D. A. Evans, (1992)' 114,6674 ibid., B.A. Anderson,

r. ftrrmcd

,b) rs forn JccomFxl

NaNr)' Ceric ammonium nitrate-Sodium azide (CAN, enol ether in cHjcN with NaNr triisopropylsilyl a of Reaction a-Azid.o ketones.r -20" results in an a-azido ketone and (4 equiv.) followed by CAN (3 equiv') at

cpzT

triisopropylazide.Othertrialkylsilylenolethersarelessusefulforthisazidationbecause of their readY hYdrolYsis.

o

-Pr)s

d

NaN3,CAN cH3cN,-20"

.\r'r. (-J

+

(t-P03siN3

72o/o

1P. Magnusand L' Barth, Tetrahedron Letters,33' 2777 (1992)'

CotrTi

CH

Cesium fluoride, CsF. AllcylationofRCooH.|InthepresenceofCsF(1.5equiv.)carboxylicacidsreact withalkyliodidesinDMFatl0-15.toformestersin.To-g|voyield.DMSOcanalso effective' be used as solvent, but less polar solventsare not

!

o * gr1 -c'!'Dvl* 1cH313cAoeu (cH3)3ccooH o il ThisreactioncanalsoconvertBulSnCoRintocarboxylicesters(equationl). (l) coHscooH

Bu3snosnBu3 > Bu3sncooc6Hs

czHsl'csF

riifirrdr r ri\rl

I

r:-f,,rnlrc Ltu -

Tcttx

:r

r rli

r":-: hrnd :: e..llrtIl

'

coHscooczHs

94V" I T. Sato, J. Otera, and H. Nozaki' J' Org', 57' 2166 (1992)'

\v : ii

ft P.

titanium (Tebbe reagent)

p-Chlombis(cyclopentadienyl)(dimethylaluminum)-p-methylene

tr':.i:tttn. Thus an ri-urrtion III).

9 1 . . , - - .G . C .F u ,a n d

69

p -Chlorobis(cyclopentadienyl) (dimethylaluminum)-p'methylene titanium (Tebbe reagent). 1,3-Dienes.l Reaction of the Tebbe reagentwith 2-butyne provides the dimethyltitanacyclobutene1. Aldehydesreactwith I to provide a complex (a) formed by insertion into the titanium-vinyl bond. This complex is unstable and at 60" decomposesto a 1,3-diene(2) and Cp2Ti:O. Ketonesreact with 1 to give two insertion products.One is formed by insertion into the titanium-vinyl bond and correspondsto (a); the other (b) is formed by insertion into the titanium-alkyl bond. This latter complex does not decomposeinto a diene when heated gently. The trend to formation of the undesired

cH2YcH3

( ll ('N with NaNj r - . ! . / l J ( )k e t o n e a n d

Cp2Ti,.ry'CH3

r\ .:./rJation because

I

- CP2T|=O

cH3cHo

cH3 -

tYt.r,

98Yo

CHs

CHs 2

1

o ,SN:

cH.A

CHe

[

,tt' I

cH2\"'cH3

, l"o,'f).r, I - *-* CHs arh,,\\'lic acids react e l.-t I)MSO can also

b .34"/"

- Cp2Ti=O

| 3il.'. ]

I

"tt-4"".

I CHs

o OBU

n r':quationI)'

t':

intermediateb increasesas the size of the alkyl groups of 1 increasesand as the size of alkyl groups on the aldehyde or ketone increases.Even so, this route is useful for preparationof l,3-dienes from simple alkynes and unhinderedaldehydesor ketones. Ketone methylenation 2 A comparison of methylenation of about 10 ketones using indicatesthat the Tebbe reagentor the Wittig reagent(methylenetriphenylphosphorane) rhe yields are consistentlyhigher with the former reagent,and that the yield improves with hindrancein the substrate.Another advantageis that the Tebbereagentis available commercially (Strem and Alfa), but expensive. I K. M. Doxseeand J. K. Mouser,Tetrahedron Letters,32, 1687(199f). rS.H. Pine,G.S. Shen,andH. Hoang,Synthesis,165 (1991).

70

Chlorobis(cyclopentadienyl)methylzimonium

Br

Chlorotris(cyclopentadienyl)hydridozirconium(IV) (zirconium hydrochloride, Schwartz reagent). Conjugate addition of alkenes.t Hydrozirconation of alkenes followed by addition of a catalytic amount of CuBr'S(CH3)2 results in in situ pteparationof alkyl cuprates

OCHz I

N,. Bzl

that undergo l,4-addition to an enone.

I

i

CpzZr(H)CI

rHF'((((

>

CH2=611611r)2OTBS

] [cp2zncr(cH2)4orBs

o ,,\ (/

tcH'

f-V.. l l t

)

\Z^-tri

tazr 3

o

, CuBr.S(CH3)2

CH2:N-(C2H5)2\ 85'

\

G,.r2)4orBS

\

I

,^

fit'

1) Cp2zr(H)Cl 2\ , CuBr S(CHg)z ( FO

-

tl

o

0-o

v

with various active enop

I J.H. Tidwell,D. R. Senn (Z)-Vinylstannes.2 (Z)-Mnylstannanes can be prepared by hydrozirconation of followed by proton quench. stannylacetylenes

B-Chlorobis(iso-2-ethg I Preparation:

1 ) C p z Z r ( H ) CTl ,H F

CH3:SnBu3

\-at'{

2\ H2O. +

92"/"

CHs

SnBu3

\- I

cH3"-'\c t P. Wipf andJ.H. Smitrovich, J. Org., 56, 6494(1991,). 2 B. H. Lipschutz,R. Keil, andJ.C. Bafion,Tetrahedron Letters,33,5861(1992).

Chlorobis(cyclopentadienyl)methylzirconium,Cp2Zr(Cl)CH3,15, 81 Indole synthesis.t A novel route to 4-iodoindoles involves reaction of N-allyl-Nbenzyl-2-bromoaniline(1) with this zirconoceneto form the zirconacycle2, which is converted into 3 by iodination and elimination. This product undergoesene reactions

Asymrnetric reduai campheylborane(lpclB( ketones:they show link alkyl groups are similar i 1l). Thus acetylcyclohe rcduced in 95Voee (6-5

B-Chlombis(iso-2-ethylapinocampheyl)borane

Br .i

:.rincS followed bY addition

OCHz I

f-BuLi Cp2Zr(CH3)Cl

N,. I Bzl

[r :',r.rration of alkYl cuprates

CpzZt,-7

-CH+

/
1l t2,cHzcl2 2) DBU

)

'ezt

,

|

C : - Z " C l ( C H z ) 4 O T B]S

.cH,

..<-J( i l t \ \zL"

C2H502CHC:CHC02C2H5 85"

tgzr

i

r--<'...-co2c2H5

6o,c,Hu

fm \-4N Bzl

3

4 CH2:N+(C2H5)2 85"

-

:-i,)oorBS

N(C2H5)2

Bzl 5 with variousactiveenophilesat 85' to form 4-iodoindole derivativessuchas 4 and5. 1J.H. Tidwell, D. R. Senn,and S.L. Buchwald, Am. Fc:.:'-J hv hydrozirconationof

Soc.,ff3, 4685(1991).

B-Chlorobis(iso-2-ethylapinocampheyl)borane, Eap2tsCl(l). I Preparation: | - - H2Bcr.s(cH3)2 cH2c,2,25" ;fftr,r.,

-C"H.

C H3

snBu3

F6 cHrAcH,

v- , .t-t.5tt6l ( 1992).

( ( . ( H , . 1 5 ,8 1 r -r,'lrcs reactionof N-allyl-Nrr :rc zirconacycle2, which is F1 \:ret undergoesene reactions

H

cn"Ac"l CHe (1)

Asymmetric reduction of ketones.2 Both Arpine-Borane and B-chrorodiisopinocampheylborane(Ipc2BCl) have one main defect for asymmetricreductionof prochiral ketones:they show little enantioserectivity in reductionof diarkyr ketonesin which the alkyl groups are similar in size. This probrem is now sorvedby reductionswith Eap2BCl 1l)' Thus acetylcyclohexaneis reducedby l in 97% ee and isopropyrmethyl ketone is reduced in 95Vo ee (65Vo yield\.

Chlomcyclopentadienylbis(triphenylphosphine)ruthenium

1) 1, cH2cl2'-25"

O

ll

-:1-$i9I'c!:9IL:-

(CH3)zCHACH3

65"k

FL .OH

r..H3)zcH)\cH3 (c|

CuHrA

(e5% ee)

Letters' Tetrahedron and S Swaminathan' A'V' Teodorovic' I H.C. Brown,P.V. Ramachandran' 32, 6691(1991). Acc'Chem Res''25' 16 (1992)' 2H.C. Bro*n, P.V. Ramachandrtn'

Chlorobis(triphenylphosphine)palladium' 1 can be preparedin -fi"-:'+'S{ri-o-(triisopropylsilyl)-o-glucal C-Aryl glucats' f

TIPSO-\

TIPSO-\

rrpso-trVot \ ,'TIPSO

1) t-Buli; ClSnBu3 2\ l'2,QH2C!2

TIPSO-]-Z.-l

85"/o

cl2PdlP(C6H5)312 C5H5ZnCl(excess) 9OY"

rrpso-\-vot

TIPSO-\

\-o

TtPso--\--+' \ ',PSO_\z-c6Hs 2

of a protectedo-glucal' If Ol high yield by stannylationfollowed :tt/t01":^:--change the same converused for prote:ti:n of the o-glucal' t-butyldimethylsilyloxygroups are in low yield (12-30Vo)'l sion to an iodo glucal p'o""td' with iodide pi CiralrlCoHs):lz' this vinyl tutatyst' 'couPles u ln the presenc" or

q

CH B. \1. Trtxt alxl ('hloro(cYcloPa l. preParedtn r

[2 + 2]Ctc irnvlamine2 r ()n additionof ..rn undergo rc: .rcrlation occur rlwr be used tc

ANHz

\---s-\\\ -q 2

m e t a | a t e d a r o m a t i c s , p a r t i c u l a r l y a r y l z i n c c h l o r i d e o r a r y lglucals b o r o n can i c a cbe i dconverted s.ArylGrignard lo* yield. The resultingC.aryl reagents,however,couplein u",y of the enol ether double bond'2 to C-aryl glycosidesby functionalization (1991) rR.W. Friessen and R W' l-ao'J' Org'' 56' 4821 (1990)' 5808 55' ibid'' tn.W. fti".."n andC'F' Sturino' CpClRu[P(CoHs):]z (1)' Chlorocyclopentadienylbis(triphenylphosphine)ruthenium' compounds.t ln the pres,trrt oirio ,oiuroteil carbonyl Isomerizp.tion "t "t'ii saturatedaldehydesor allylic alcohols reafrangeto ence of this ruthenium'""rnpt"-, double bond' with highest nunrL.. of substituentson the ketones.The rate dependson ,h" ratesinthecaseofmonosubstitutedalkenes.l,l-Disubstitutedalkenesrearrangefaster than 1,2-disubstitutedalkenes'

P t- \lc(iru

Chloro(cyclopentadienyl)dimethyltitanium

IH

1, NH4PF6

OH

O ll

d i o x a n e1, O O ' , 2h

CH:

----';-

cut-tu/\2"'r'CHz

73

c6Hs(cH2)2""\c2H5

t€

c:' .".,,lron Letters,

8h

cuHr&cH20H CH2

CHq

3.5 h

i l cH3(cHd8-'\cHo

rf: .c preparedin

c6HscH2cH2cHo

9O/o

t -

cH3(cHr8"'\cHo

I B. M. Trost and R. J. Kulawiec, TetrahedronLeuers, 32,3039 (1991).

I ,,^----,

Chloro(cyclopentadienyl)dimethyltitanium, CpTiCl(CHr)2, l, preparedin situ from CpTiCl3 and 2CHrLi. [2 + 2]Cycloaddition of allcynylamines; heteroannelations.t Reaction of the alkynylamine 2 with I leads to a titanacycle(a) with evolution of mcthane (2 equiv.). On additionof CHrOH the A1-pyrroline3 is formed in 96% yield. The intcrmediatea can undergoreactionsat either carbon or nitrogen with appropriateelectrophiles.Thus acylation occurs exclusively on nitrogen (4). Intramolecular[2 + 2]cycloaddition can also bc used to obtain tetrahydropyridines.

.l

..ilrJ

t)-glucal. If

. l'J \amc COnVefurJi i;.

1-rr, \"ur,;;

1,2s"I fryli(cp)cr "".o" ,f-N q"r,"ur, *".r. nu.o L ] a

II

couPles with -\rvl Grignard

88% | cHsococl

,l

^ ,coocH3 A N -l (

l.,.rn bc converted )c.l

\--\

\

I CoHs

4 CpTiCl3, C6H5N(CH3)2 c6H5cH3,80'

, u t ' r ( . , H s ) r l z( l ) . In the Presnd;. r.r:rJ aldehYdesor 1 \,nti. with highest nc. r.arrangefaster

88o/"

r

r.r

(--.\.-coHs

CoHs I P. L. McGrane, M. Jensen, and T. Livinghouse, Am. Soc., ll4,

5459 (1992).

74

4-Chlom-2,3'disutrstituted-2-cyclobutenones

(-)-B-Chlorodiisocampheylborane, (-)-Ipc2BCl (1), 13' 72; 14' 82'

'utt-/

o tl

ill ,uAc,

Red'uctionofacetylenicketones,RC=CCR.|Alpine-Boranecaneffectthisreducto steric effects' Thus tion in high enantioselectivity,but this borane is very sensitive In contrast' asymmetric it fails to reduce a carbonyl group adjacentto a /-butyl group' reductionofalkylarylketoneswithlisincreasedbyahinderedalkylgroup.The as the steric bulk of Rr same effect obtains in reduction of actylenic ketones(2). Thus increases.the enantioselectivityalso increases'

CHs

l. rCH3)2CHO

OH

,o

n-Oct-----:-{

n-Oct------(

Rr

R1

3

2

I

(cH3)2cHo R1 = iPr

g6k

26o/o @e

R1 = C(CHs)zCzHs

760/o

>99o/o @a

R1 = t-Bu

72o/o

>99% ee

l). K. Krysan.A. (it , Chloromethyl)dir

r P. V. Ramachandran,A. V. Teodorovic,M. V' Rangaishenvi,and H C Brown' J ' Org" 51' 2379 (1992).

Stereoconlrollt .ritutcd 1,3-diener {t para. This int

:hc diene with a d "r a (P-hydroxrc

, chloromethyl)dinx formaldehyde.Thc precusor(4) for an

^t\--/o (1)

4-Chloro-2,3-disubstituted-2'cyclobutenones' ll I

underthe condition :csults in a singlc

'Cl

R2 cH3 ,cHe Regiospecificsynthesisofphenols'|Thesesubstrates,obtainedbyreactionof4si(cHd cH2\.hydroxycyclobutenoneswithP(C6H5)3/CCla'undergoPd-catalyzedcoup|ingwithvari-f transformed are that products form to vinylzirconiums and arylstannanes and ousvinylI \cH, phenols' (100")to tri- andtetrasubstituted on thermolysis

"""Y(

2 (CeH+PdCl)z P(C6H5)3

*

CHltSnBu3

(cH.)rcHoAct CHs -\./

(

i l t A-{

(CH3)2CHO'

,P \,/)t'\

1oo" ,

-SnBu3

CHs

670lo overall

(CH3)2CHO

"T

(Chlommethyl)dimethylsilyl chloride

Bu :11..1this reducni etTccts.Thus

Pd cat. 1) Bu3Sn(EIO)C=CH2, 2) 100"

,o

,14",

"*Y(

rr.l. ]symmetric l\r I grouP. The tcrre bulk of Rl

Cl.-r-1.-Bu cPz

1o-r.yrcHo,^cr ,H

I

I'

t

P(c6H5)3 PdlP(c6H5)314,

(E)

I

100"

>

41o/"

(cH3)2cHo

It.t.,,"tot;Nr,]

CHs

I D. K. Krysan,A. Gurski,andL. S. Liebeskind, Am. Soc.,ll4, 1412(1992).

n | ( )rq., 57, 23'19

tChloromethyl)dimethylsilyl chloride, ClCHrSi(CH3)zCl (1). Stereocontrolled Diels-Alder reaction.l The Diels-Alder rcaction of a 2-substituted 1,3-dienewith acrylatesgives mainly the cyclohexcnein which the substituents {e para. This intrinsic para effect can be revcrsed by joining the dienophilc and rhe diene with a disposabletether. Thus the chloro group of chloropreneis replaccd by a (B-hydroxyethyl)dimethylsilyl group by reaction of the Grignard reagent with lchloromethyl)dimethylsilylchloride (1) followed by a second Grignard reaction with formaldehyde.The product (2) is then coupled with the acrylic acid (3) to form the precusor(4) for an intramolecularDiels-Alder reaction.The product(5) is then oxidized underthe conditionsof Tamao(12,243-245) to the cyclohexenone(6). This methodology "meta" addition. rcsults in a single adduct that is formed by

i.r rcaction of 4ouplinqwith varia: .1ri transformed

CH3 ,CH3 cH3/cH3 ? HOOC-....CH3 tt'Y'---^o\tt' cH2\r-si(cHz)20H Dcc> ll -cH. I \ar, \"r, \cH,

o

2 Fre icl)2

fj'''

CHs

,

180' 6sol.1

o\.^._i"oocH3 -cHe I I $cH.

?CHo

1) cleavage 2) oxid

tt3,'-Yor-o

c4)f-icH. t$CHs 5

m-Chlomperb€nzoic

CH3 ,CH3

acid

CHs Si

?

"t'V'--,,^o\"t.

c4

o.

>o CHg

CHZ

CHs

.\

(,

Chloro(phenylethynyl )dir Stereoselective C-sy4 to styryl C-glycosidesbr r as a silyl ether to an a- ot of the 3,4,6-tribenzylerhc the tetheredsilyloxy preo desilylation(BuaNF) pror.

I J. Shea,A.J. Staab,and K.S. Zandi, Tetrahedron Letters,2715(1991').

m-Chloroperbenzoic acid. Stereoselective epoxi.dation of enoates.t The final step in the synthesis of (+)aphidicolin (4) requires a stereoselectiveconversion of the cyclic norketone (l) to a vic-'1.,2-diol,>C(OH)-CH2OH. Methylenation of the ketone followed by a Sharpless asymmetricdihydroxylationprovides a 1:1 mixture of epimeric 1,2-diols.Reactionwith a chiral oxaziridinealso providesa 1:1 mixture of epimeric epoxides.The transformation is effected successfullyby conversion of the ketone to the enol triflate, which is converted to the enoate(2) by Pd-catalyzedcarbonylationin methanol(13,234).Epoxidationof 2 with ','-CPBA in buffered CH2CI2with a radical scavenger(4,85-86) resultsin a single epoxy ester Q) in 90vo yield. This product is reducedwith lithium aluminum hydride (excess)to aphidicolin (4) in 67Vooverall yield from the ketone l.

.coocH3 1l rtzo, c{zct2, 1oo% 2) Pd(o),co, cH3oH,75%

CHsQ

2

so7"I crcuFqco.H

I

L|AIH4,THF, A

100%

AoocH3

i'q )-,) H

3 (+)-4 1C.J.RizzoandA.B. Smith,III, J.C.S.Perkin1, 969 (1991)

CHo \" C6H5---9i-O-' / CHs

/ '

cH3o !

In contrastcyclization a linkedto the 3 B-hydroxrI I 6. The styryl group of .f ar .i carbinol. Note that a frc uscful for subsequenttrans This overall processis tcquationsI and II).

Chloro(phenylethynyl)dimethylsilane

\-n

-cH. 1-\cHs n

77

Chloro(phenylethynyl)dimethylsilane, C|(CH3)2SiC=CC6H5(l). StereoselectiveC-styryl glycosidation. Storkt has developed a stereoselectiveroute to styryl C-glycosidesby a radical intramolecularcyclization of an ethynyl group linked Thus reaction as a silyl ether to an cr- or B-hydroxyl group of a phenylselenoglycoside. 2 with 1 provides of the 3,4,6{ribenzyl ether of the 2-hydroxyphenylselenoglucoside the tetheredsilyloxy precursor3. Reaction of 3 with Bu3SnH and AIBN followed by desilylation(BuaNF) provides the a-C-styryl glucoside4 in 83% yield.

OBzl .\llhesis of (+)n('ikctone(1) to a 'ci f'\ a SharPless

1)Bu3snH, AIBN 2) BuqNF

BzlO 83o/"

or' CHs-J,

h,,1. Rcactionwith 1 rc rransformation . ir hrch is converted It I poxidationof 2

SeC6H5

"risi-:-..H.

ir r.r.ultsin a single r rluminum hYdride

o

BzlO

coocH3

0

/-1

tr1?cHcuHu

1) Bu3SnH,

c1.

I,

C6H5:3 CeHaCOsH

o COOCHo

2\/

,,/-1

ocH3

ocH3

AIBN 2) BuaNF

,Si-g CHs SeC6H5

F ct1?crcuru 6

In contrastcyclization and desilylationof 5, in which the phenylethynylsilylgroup is linked to the 3 B-hydroxyl group ofa phenylselenoglucoside, providesthe B-C-glucoside 6. The styryl group of 4 and 6 is useful as such and as a precursorof an aldehydeor r carbinol. Note that a free hydroxy group is liberated in this cyclization and can be uscful for subsequenttransformation. This overall process is also an efficient route to C-furanosidein the ribose series ,cquationsI and II).

<>

1-Chlom-1-phenylsilacyclobutane

cH3. /cH3 BzlO (t)

-Si----C6H5 O-

[-.----o-l-t-sec6H5 \-7I BzlO

C\srCHs coHs-bl-o.

ou,)

BzlO

l--o-lJ

OH CH=CHCoHs

?-t'-""' (il) cH.o-lYH

H

CHg

BzlO

"o\

cH=cHcoHs

rN. Auner and J. Grobe. J (i I A.G. Myers, S.E. KePhan. ' ' K. V. Brown et al., J. Ory'.

80% V"-sec6H5;fJ h<"1,

i;.-"l.

the presenceof ClSi(CH,) 'hows significant 1,4-as1

r c . S t o r k , H . S . S u h , a n d G ' K i m , A m ' S o c ' '1 f 3 ' 7 0 5 4 ( 1 9 9 1 ) '

C l .'Si l -Chloro-1-phenylsilacyclobutane' CoHs

C hlorotrimethYlsilane. 1,2-Adtlition of R2Cd .rdditionof cuPratesto eno

(1)

OI M O M

";::"i;:;i;"

of a catalvst' silvl enol ethersordiof atdot reactions'2 In the absence Thus the dimcthylphenyleven at high tem-peratures' narily do not react with aldehydes the silacyclobutane CoH'CgO at 150'' In contrast' silyl ether 2a does not react *itt' and anti-aldols with C6HsCHO at27" to form 'syzanalog(2b), preparedtrorn f, reacts in12:lratio.Thisstereosele",iui.yi.theoppositeofthatobtainedbytheTiCla-cata|yzed effective CH'(CDSi(CHz)r' is even more reaction. 1-Chloro-1-metnyrtiru"i"foUutu*

c-c6H11McH

oMo I

c-C5H11N

thanlforthisaldolreaction.Itispreparedr,oml:-ctrto,opropyl)dichloromethylsilane.3 Itisparticularlyusefulforaldolreactionswithacyclicsilylketeneacetals(equationll).

*"i"

R R

o'"'-coHs o i l l /fcoHu

o'si-cuH,

(t)

A

26, fl = CH3 2b,R=(cH2)3, 100o

+

C6H5CHO

\-,' Qo/o

84"/"

3b(12:1)

\1. Arai, T. Nemoto.\'. o

(' hloro(triPhenYlPhocPl

Preparation.l Stereoselective reocl -tecto provide either Pvn

Chloro(triphenylphosphine)copper

CH=CHCoHs

?-t'-"r, trr)cH3o'/Y

+ C6H5CHO-

tetmmer

230 1000/"

CHs

(syn/anti=19:1)

CH=CHCoHs

I N. Auner and J. Grobe, J. Organomet.Chem., 188,25 (1980). r A. G. Myers, S. E. Kephart, and H. Chen, Am. Soc., 114,7922 (1992) t K.V. Brown et al., J. Org., 56,698 (1991).

7 Chlorotrimethylsilane. 1,2-Addition of R2CuLi to y-alkoxy enals.t ClSi(CH3)? is known to facilitate 1,4additionof cupratesto enonesand enals,but reactionsof cuprateswith 7-alkoxy enalsin the presenceof ClSi(CHr)3 results in exclusive 1,2-addition.Remarkably,this reaction shows significant 1,4-asymmetricinduction.

2 CtSi(CH3)3 THF, _78'

OMOM I

+

cn,'l cthersordiJ rnrcthylphenYl: . rIucvclobutane r- .rntlanli-aldols e I r('11-catalYzed n nt()rc effective or,'mcthYlsilane.3 trl. tcquationII). R , R S i- c o H s

+

(CHg)zCuLi

c-cun,,,Mcno

640h

OMOM

OMOM

I

c-c6H1()\y''\acHs

+

c-c aH.,.,')\'y''-''1cHe osi(cH3)3

osi(cH3)3 78:22

V. Arai, T. Nemoto,Y. Ohashi,and E. Nakamura, Synlett,309 (1992).

o. '

'CuHu

2 '\

Chloro(triphenylphosphine)copper tetramer, ICuCl(CoHs)rP]+(1). I Preparation. Stereoselectivereactions with oxaziridines.2 This reagent can effect N-O cleav.rscto provide either pyrrolinesor aziridineswith markedselectivity(equationsI and II).

Chmmium

aminocarbenes

1) BuLi 2) C6H5CH2X

.CH2C6H5

9t'

iia

1 ,T H F

(r) CoHsAt',1'^ lr\)

(co)5

(R)-1

B:

cuHur

c6Hs/l(cH2)2cH=CH2

>95% de

o C H q-

1,rHF

I

(lr)

--;*

Tlo-"utu 1...t"

cuHu

coHs

lcHi2cH=cH2

Chem'' f f' l8-18^(1972)' r M.R. Churchill, S.A' Bezman, and J'A' osborn' J Inorg' ll4, 5466 (1992)' soc., Am. 2 J. Aub6, X. peng, v. w-g, ""J F. Takusagawa'

(R)-1 can also be convertedtnto ester of (S)-alanine(2) to form th CycloProPanation.t Chromiu gt with unactivated l,3-dienes as vinylcycloProPaneswith high rcg result in a alkylmethoxYcarbenes

occurs selectivelywith the least I with 1,3-dienesthat can adoPt thc Chromium aminocarbenes pentacarThe chromium amino-carbene I' Asymmetric synethesisof tlipeptides't (methyl)carbene]chromium(0)' bonyl [(R-1-az a-2,2-dimelhyl-:-*u-S-pf'"nylcyclopentyl) with amino esters under coupling carbonylative derived from (R)-alanin", und"'go"t (S'S)-dipeptideswith high diastereoselectivity' irradiation (visible lighQ at 0' tolorm

*

cn/6cru,

"^r,

l$o(Co)5

erAocH.

o

CoHs / p

\

(co)scr\ ni;b tcH. cil. cHl (R)-1

H t l * cHog'\o(cHe).

C O ,h v , 0 " THF

H

88V"

I NHz

F- /

B"{'z\c,',

(s)-2

O

CHs

ocH3

cH.JAru\o,"'.t.,. cuHul4N-*-Bn. -cHa \.

o_J

b

i

(R,S,S)-3(s8:2)

Cr(C

c.HrAo

Chromium aminocarbenes

)H:c5Hs

CuHu,,

1) BuLi 2) CoHsCHzX

(R)-1

BzCH2 CH3

R-4

t€

'

(S)-2,CO, hv THF

/:--f

(co)5cr\_ il-" .b / X

CH3

? 9t. ,.-\iAN4-..,1o(cH3)3 b CoHs1,'N;-Bt. -cH' [J

1 ,NfH3

( R , S , S ) - 5( 8 7 : 1 3 )

o€

li.

CoHs

.,tal).

(R)-1 can also be convertedinto the (R)-chromium4, which coupleswith the t-butyl ester of (S)-alanine(2) to form the protecteddipeptide5. Cyclopropanation.r Chromium and molybdenum carbene complexes can react with unactivated l,3-dienes as well as electron-rich or -poor dienes (14,91) to form vinylcyclopropaneswith high regio- and diastereosclectivity.In fact' reactionswith alkylmethoxycarbenesresult in a single diastercomer.In addition, cyclopropanation occurs selectively with the least hindered double bond of the diene and more readily with 1,3-dienesthat can adopt the s-cis conformation.

rr,. ::hcnc l, pentacar5 ,:^rnclchromium(0), f .1nlinocstersunder d.r.,.rcrcoselectivity.

Cr(CO)s

+

cH/6crnu

THF 1000

cH34ocHg

"^"1-^",'u ocH3

Mo(CO)5

Bu

ocHg

H

8€'

,ul'z-",r, o

cHs

- ^,J-- -.o1atr;. :: lt o *-Et. ,

CHS

S S '3 (98:2)

ocH3

Cr(CO)s cuttu^ocH,

92o/o

er"r.

82

Chromium

arninocarbenes

time for synthesis carbeneshave been used for some o-Alkoxyphenols'| Chromium dienylcarbenes' chromium to o-alkoxyphenols employs ofp-alkoxyphenols. A novel route under carbon irradiated when prepared as shown, Thus the chromium carbene r, yield' 90% in 2 to cyclizes *t"pt""ed ketene (a) that monoxide is converted t'" " Cr(CO)s 1)BuLi 2) cr(Co)6 3) cH3orf>

rt orovides the oxazinone 2 in good b-v.ch Optically pure 2 can be obtained the chiral auxiliary, effected by h1'drq Reaction with ketene ketak'! Tt ortlx acyclic ketene ketal 2 to give two In 5' and 5 acid to the butyrolactones I rather group selectivity with an ethyl

.ocH3 (co)scr{ 'CsHs *

cHz-

2 CsHs-

n,,"o I rHF I

CHr-

I

ocH3 I .'r,-.. \

-Z\t l l \,,'

c

ocH

[,.o,0.,

eo%

l

x\.

--o

Le

cslls

cl{:

complex active chromium-carbene arylglycines'3 The optically

Optically activl canbe-used Preoaration lo1 rr.. trs,zn'l]z-ffi"" t''-oto'nt"ttethanol' DMAP l, prepared of 1 in CHrCN containing

Thus irradiation of opticallyactivearylgtyJnes' 1) AcBr

t)cu,'-,'. cuH.

N(CH3)4* /.O (CO)sCra^ ,, \'6n5

HzN oH 7e"/"

CoHs

rcgi The reaction was used for a

rCuHu ,O(CH2)2CH=C(Cl.

,uf,ao'.

(CO)sCr< 'CHs

, (CO)sCr{ 'CoHs 1

I nu,"n."*

81% DMAP I CoHs I

1\ chromatograpny

H2N---,COOH ' "H _ cuntu

,i ilr. r0",, 23oloov€rdll

coHs ),,4o

t*Y^o CeHs

(R)-3 (94'l"ee1

2 ( 8 8 : 1 2)

(CO) sCr-- C (OR) R comPkx a carbene I and the stabilized Phc H'Ovield. HYdrolYsisof 3 with (Z)-l'3dr ellene3 rearrangesto a catalystfor this rearrangement'

Chromiumaminocarbenes 83 mc :rmc for sYnthesis nrunr.lienYlcarbenes. drrlcJ under carbon r I ir 907r yield. (COt5

'ocH3

provides the oxazinone 2 in good yield, but modest diastereoselectivity(76% ee). optically pure 2 can be obtainedby chromatography.The final step involves removal of the chiral auxiliary, effected by hydrogenation. Reaction with ketene ketak,a The chromium carbene complex I reacts with the acyclic keteneketal 2 to give two orthoesters,3and 4, which are convertedby aqueous acid to the butyrolactones5 and 6. In the example cited the carbenereactswith high selectivity with an ethyl group rather than a methyl group.

,ocH3 (CO)5Cr{ 'CeHs *

PCzHs

CHz{

C O ,T H F

OCH3 2

coHs---.-1

.:: ;

,oCHs

I Y cHr)-d'ocH,

coHs--lroczHs * l--6^ocn,

76V" )

CH,

4

( <'lo/o )

\r-

"'-o

| ".o.

Hso*

I

coHs--r1

coHs\r-1

l F o ru::: carbenecomPlex : :..rJ for PreParation ( \ i()ntainingDMAP C;Hs

'CoHs

x

11

f

NH

OH

CHs'/-O

l-oF o 6

5

The reaction was used for a regioselectivesynthesisof eldanolide(6)' 1) THF,co, 80" 2) HCI P(CH2)2CH=C(CH3)2 /OCH3

(Co)sCr{ 'cH.

*

CHz={ 'ocH3

,::{, CeHs

o tl ( ' o

1 hr',CH3CN DMAP

1",

L_/

r

cH;

CoHs I {=r. Ao I

'u _Ao I CoHs 2 t 88:12)

\-cH=c(cHr),

6 (trcnslcis = 24:1\ (CO)sCr:C(OR)R complexes; allenes.s Photolysis of a mixture of the chromium in 6jo/a carbeneI and the stabilized phosphorusylide 2 under CO gives the allene 3 4. The (Z)-enone rield. Hydrolysis of 3 with Hro+ in ether provides the B-substituted effective is an allene3 rearrangesto a (Z)-1,3-diene(5). Pyridiniump-toluenesulfonamide catalyst for this rearrangement.

Chmmium(Il) chloride

(Co)sCrl

hv, CO C6H6,25'

,oc2H5

(c6H5)3Pz\ co2Bzl

c(cH3)3

2

1

C2H5O, Cr(CO)6

selectivity. Reactionsof chiral r configuration of the bromide car can provide accessto compler c

(c6Hs)3PO

fOzBzl

Fcl (cH3)3c

o

H

CHs

-sv"2/PYHrs

HCl, ether

i

-\.-o CHs

4

reactionsinto nephromopsinicr

CzHs? CO2Bzl (aHs)sc-,or'-,-?

CO2Bzl O i l l

K;nd"c)J

I J. Mulzer,L. Kattner,A. R. Strcct Soc., 113, 4218 (1991).

4 IJ.R. Miller, S.R. Pulley,L.S. Hegedus' andS' Delombaerr'Am'Soc''ll4'5602(1992)' 2 D. F. Harveyand K. P. L;und,Am. Soc.,113,8916(1991)' 3 C.A. Merlic and D. Xu, ibid., ll3' 7418(1991)' 4J.-M.Vernier,L.S. Hegedus, andD.B. Miller' "/' Org', 57,6914(1992)' Am' Soc''114'10665(1992)' 5S.L.B.Wang,J. Su,W.D. Wulff,andK. Hoogsteen, 6 M. R. Sestrick, ibid', ll4, 40'19(1992)' M. Miller, andL. S. Hagedus, Chromium(Il) chloride, CrClz. fo crotyl Asymmetric addition of allylic bromides to aldehydes.t The 1,2-addition homoallylic provides reaction) (Hiyama bromides to aldehydes promoted by crcl2 ofbenzaldehyde alcoholswith anri-selectivity(8,111-112). A model study ofthe reaction that this center indicates position 6 the group at with allylic bromideswith a stereogenic give as the major to (7 and centers Bt) controls the configuration at the generated centers' An chiral three at arrangement all-.syn product the diastereomer(2) with the the all-syn increases merely bromide allylic of the at the e position additionalstereocenter

c6H5cHo+ eztolj,Ver

products.)Ester, cyano, or chlo a-substituentcan favor formatr

CzH5OOC(CHj3C=CCH2

c c"Hu/

CrCl2

fl)

Chromium(Il) chloride - Lithi Allenic alcohols. Proparg rn c n c eo f C r C l z ' L i l ( 2 e q u i r ' . 1 (Use of other solvents increas

8O"/"

CHs c[

//',CHc = i

(""

a , ^ , ,

o.,^-N,'1--!-t6t5 o L t v : Y :

en, 6H

+

82:18

Bzro'->aVC6H5 cH3 oH

Addition of y -disubstitutcd halidesadd to RCHO when catr srereoselectivityobtains in add addition of LiI and use of DM? In contrast,addition of 7{isut .rnd stereodivergent(equations

Chromium0l)

iodide

chloride-Lithium

selectivity. Reactionsof chiral allylic bromides with chiral aldehydesindicate that the configurationof the bromide can override that of the aldehyde.This reaction therefore can provide accessto complex chiral adductssuch as 4, which is convertedby standard

I : C

t.25 65'.

oBzt -/cH2

CO2Bzl

CrgHzz

q j )-o

H

CHs

4 steps

Hooc\

.SHt

,,7

c,.Hrr4oAo

CHs

c)-s

rcactionsinto nephromopsinicacid, (-)-5.

CO2Bzl I J. Mulzer,L. Kattner,A. R. Strecker, andP. Luger,Am. C. Schrdder, J. Buschmann, C. Lehmann,

r'

Soc.,113,4218(1991). . ... ,t t 1992),

i

,,,/l).

,l'.'JJition fo crotYl r.r rJes homoallYlic i.'r,,t bcnzaldehyde :;t: ' that this center ril\c itsthe major : .lir.rl centers.An r:.:.ilscs the all-syn

Chromium(Il) chloride-Lithium iodide (l:1). Allenic alcohols. Propargylichalidesreact with carbonyl compoundsin the prescnce of CrCl2 'Lil (2 equiv.) in DMA to form allenic alcohols as the major products.r (Use of other solvents increasesthe formation of homopropargylicalcohols as minor products.)Ester, cyano, or chloro groups have no effect on the regioselectivity,but an a-substituentcan favor formation of propargylic alcohols.

C2H5OOC(CHj3C-CCH2Br+

CrCl2.Lil DMA

C6H5CHO

84"/"

OH | ^.,cHz

c^H^/^'V"

+ CeHsOOC(CH2)3C=CCH2OH

I

(cH2)3cooc2H5 98:2

(""

. Y*tu

cH3 oH 3

Addition of y-disubstituted allylic phosphates to RCHO.2 Both (E)- and (Z\-allylic halidesadd to RCHO when catalyzedby CrCl2 to form anti-homoallylicalcohols.Similar \tcreoselectivityobtains in additions of (E)- and (Z)-allylic phosphates.In this case rddition of LiI and use of DMPU as solvent are usually requiredfor satisfactoryyields. ln contrast,addition of 7-disubstitutedphosphatesto aldehydesis both stereoselective rnd stereodivergent(equationsI and II).

Chromium(Vl)

oxide

I ll (t) HexCHO * er'-,,/VOP(OC2H5)2 I Bu

---

crcl2,Lil 25'

effected with CrO3 in 90% aqueous: dichromate(Na2CrO3)in aqueousH; are obtained with CrO: in CHrCO(

OI H

nr..y'VH.*

"**

vtr2

, \

Bu Pr 99:1

o tl (lf) HexCHO + B]'\a/."'-,'OP(OC2H5)2 I Pr

pr "\

/

OH aoY"

r'^4'{Hex Pr' Bu

v t t /

/

-

CHs

I

'

.-.CHz

1) HBr2B.S(CH3), 2) H,O I

\

rH.C. Brown, S.V. Kulkarni,V.\'

Xl

(ree2).

9B:2 rK. Belyk,M.J. Rozema,andP. Knochel,J' Org'' 57' 40'10(1992)' I. Antes,C.E. Tucker,andP' Knochel'J' Org" 57'6384 2C. Jubert,S. Nowatny,D. Kornemann, ('t992).

Chromium(Il) chloride-Nickel(Il) chloride' lb' when treated with CrClz Cycloenediynols.t The r,r-iodo enediynals la and (14'98)' undergo an intramolecular (5-8 equiv.) and a catalytic amount of NiClz additionofthealkynyliodidetothealdehydegrouptoproducel0-and1l-membered cycloenediynols,isolatedastheacetates2aandZb'Theseproductsareunstable'but2b wasshowntoundergocycloaromatizationto3whentreatedwithl,4.cyclohexadiene. and is believed to be responsible This reaction is typical of .oln" antitumor antibiotics for thc biological activitY.

Cobalt([) acetylacetonate, Co(ace I ntrarnole cular homo D ie Ls- A I a tetheredalkyne group at C2 underg treatedwith 8 mol% of Co(acac):.((

is particularly facile when a 5- or 6 on thermal treatmentof I at l{0-

\

R

Co

\-,.r6na^ (bH,)"cHo lli"i;:)i"'',

,t^\.'t\

i l t l

\/"'aI

OAc

3 1 a ,n = 1 1 b ,n = 2

34o/o 760/o

2a 2b

Letters'32' 31'11(1991)' I C. Cr6uisyand J.-M' Beau,Tetrahedron

Chromium(Vl) oxide (CrOr)' This conversion can be effected in )80% overall RCH:CHz-RCH2COOH'1 H2BBT S(CH3)2' thexylyield by hydroboration of l-alkenes with HBBrz'S(CH3)1' followed by hydrolysis to form torun" lUrefhx), or dicyclohexylborane(HBChx2)' to RCOOH' which can be RCHrB(OH)2. The final step is oxidation of RCHzB(OH)2

1 R=H,n=1 R=H,n=2 R=CHs,n=1

W. Tam,and L.G. Edrl M. Lautens,

Copper(I) iodide-Tetrabutylenr Skipped diynes and triyncs. I rropargylic halides or tosylatess rt

:n DMF or CH3CN.I This reaction

Copper(I) iodide-Tetrabutylammonium

"u^/{Uex . , \

Bd

Pr

99:1

t'F.r, OH

t

87

effected with CrO3 in 90% aqueousacetic acid, pyridinium dichromate (PDC), or sodium dichromate(Na2CrO3)in aqueousHzSOa.In generalthe highestoverall yields (80-92%) are obtained with CrO3 in CH3COOH/H2O.

OH e t t z

chloride

CrO3,

[.ur,.r1ory, ]

CHs

cH,Z)(\He' Pr Bu

cH3cooH, Hzo

1) HBr2B.S(CH3)3 2) H2O

86/"

t'pr"oo,.., CHs

rH.C. Brown, S.V. Kulkarni, V . V . K h a n n a ,V . D . P a t i l , a n d U . S . R a c h e r l aJ, . O r g . , 5 7 , 6 7 7 3

(reez).

98:2 lq.--

J. Org.,57,6384 Knochel,

I l h .\ hcn treated with CrCl2 ::Jcrqo an intramolecular t ..c l0- and 1l-membered ..jucts are unstable,but 2b l( :'.r 1,4-cyclohexadiene. ith rt.l ..licvcd to be responsible N .

Cobalt(I! acetylacetonate, Co(acac)2 Intramolecular homo Diels-Alder reaction of dienynes.t Norbornadienesbearing a tetheredalkyne group at C2 undergoan intramolecularhomo Diels-Alder reactionwhen treatedwith 8 mol%oof co(acac)2,(c2Hs)2Alcl (4 equiv.),and dppe at 25". This reaction is particularly facile when a 5- or 6-memberedring is formed. No reactionis observed on thermal treatmentof I at l4O-170".

\

R

CHz)n

R

Co(acac)2, (C2H5)2AlCl, dppe, benzene, 25'

\.---.16r,r

1s i l

l

7

l

OAc 3

1 R=H,n=1 R=H,n=2 R=CHs,n=1

76/" 64o/o

69/"

\f. Lautens, W. Tam,andL.G. Edwards, J. Org., 57,8 (1992).

rr. ^, rffccted in )80% overall ( l1 , . H:BBr S(CH3)2,thexYl1, .. ,.rcd by hYdrolYsisto form l ( ) l i , l o R C O O H ,w h i c h c a n b e

Copper(I) iodide-Tetrabutylammonium chloride. skipped diynes and triynes. A new route to skipped diynes involves coupling of rrtrpargylic halides or tosylateswith l-alkynes catalyzedby cul, Nacor, and Bu+NCl :r DMF or cH3cN.' This reactioncan be extendedto skipped triynes (equationII).

Copper(I) iodide-Tliphenylphosphine

C u l ,B u a N C l NaCO3,DMF

(l)

Et-----CH2l

,Zuco2cH3 co2cH3

Cyanotrimethylsilane. Cyanosily lation of ald ehy d cs acid catalyst such as Znll or A ethyldiisopropylamineare alst.rh methylsilyl ethers in 90-100'i r tavalent silicate, (CHIIS(CN )\-(( amine. The reaction can proceedi the chiral tin(Il) kwis acid l. pn ( l2-l and 1,1'-dimethylstannocene

H------cH20H

F-cHroH

-;

(tt)

L-CBH1,

CaHrz+CH2Br

T'OS

cBrc/ P(cons)s I

t

7"'"''

11+(CHz)gGOzCHg

-co2cH3

E-QsH17

5'lo/"

--c8H17

The skippeddi- or triynesare reducedto skipped(z,z)-dienesor (z,z,z)-trienesby 4H2O(equationIII)' partialreductionwith NaBH+/Ni(OAc)2' (lll) CsHrz--:\-.-CH2OH

+ (CH3)39(

90o/o

crH,rfficH20H

r S . K o b a y a s h iY , . T s u c h i y a ,a n d T t

fT. Jeffery,S. Gueugnot, Letters,33,5757(1992)' Tetrahedron andG. Linstrumelle, Cyclam (1,4,8,1 1{etraazacvclotctr

Copper(I) iodide-Ttiphenylphosphine. This coupling has been effectedwith Pd catalysts, Coupling of I-allcynes and ArX.t 80-120'. but can also be effectedwith cul/P(C6H5)j (1:2) in the presenceof K2cor at

C6H5l

+

Cul/P(C6H5)3 , K2CO3 DMF,120"

HC=CC6Hs

--;C6H5CH:CHBr + HC=CC5H11-n (Elz=ss'.1)

C6H5C=CC6H5

CoHsCH:Cl-lC=CCsHtr-n (E/Z= 99:1)

1K. Oku.o, M. Furuune,M. Miura, and M' Nomura,TetahedronLetters,33,5363 (1992)'

Epoxidation.t An iron comp of I is an effective catalyst for r or CH3CN. Thus reaction with cr

Cyclam

Cul,BuaNCl D,M F NaCO3

.CC:CH3

82v"

Cyanotrimethylsilane. cyanosilylation of aldehydes.t This reaction has been effected by use of a Lewis acid catalyst such as Znl2 or AlCb (4,542-543). Amines such as triethylamine or ethyldiisopropylamineare also highly effective catalysts, providing cyanohydrin trimethylsilyl ethers in 90-100% yield. Presumably,the reactive intermediateis a penTributylphosphineis as effective as a tertiary tavalentsilicate, (CH3)3Si(CN)N(C2H5)5. amine. The reaction can proceedin high enantioselectivity(907oee) in the presenceof the chiral tin(Il) lrwis acid 1, preparedby reaction of (+)-cinchonine with triflic acid and 1.l/-dimethylstannocene(12,20I -202).

cHz:\i\

7""o^

TfOSnO,,. ttf

---CBHl7

carc/ e(coH5)3 |

-1-.H-

V-CH2Br

/ L-caHrz

: +

.rrcncsor (Z,Z,Z)-trienesbY

I

.llr

l:

osi(cH3)3 /..',-.,..CHO I |

1,c12cl2, -28" + (CH3)3SiCN 630/"

\-/

O^"(90o/oee)

-cH20H

rS. Kobayashi,Y. Tsuchiya,and T. Mukaiyama, Chem Letters, 537,541 (1991)'

-r-r.57s7(1992). Cyclam (1,4,8,1 1-tetraazacyclotetradecane), l.

- , " ' Jrn cffcctedwith Pd catalysts' ts ;.cncc of K2COI at 80-120''

t ' -

l

NH HN

c!-

C6H5C=CC6H5

-

tr.

.) NH HN

CoHsCH:Cl-lC=CCsHrr-n (ElZ=99:1) : ' ' , 1I ( \ t e r s , 3 3 , 5 3 6 3 ( 1 9 9 2 ) '

(1)

(, Epoxidation.t An iron complex preparedby reaction of Fe(CF3SO3)2with 1 equiv. of I is an effective catalyst for epoxidation of alkeneswith Hzoz (30vo) in cH3oH product or cHrcN. Thus reaction with cyclohexeneprovides the epoxide as the main

(RRF erd t!

Cyclobutenediones

OH

I

HzOz Fe(1)(CF3S03)2 -

o"+ 40/"

t i l 17"/o

cHs\--/'o

1) C6H5L| GHs 2) CH3l,Ag2O

"A"

s

6't"/"

o

cHlcH'

CHs

1

cHs

o ceHf\coH,

CeHs

'CoHs + frans-isomer

,Bu

[\-"u^,

o.

bH

3

26%

I L. S. Liebeskind, K. L. Granberg,and J. Zli

high stereoselectivity with only tracesof the allylic alcohol. cis-stilbeneis oxidized with tothecis-epoxide.Iodosylbenzene,CcHolo'cana|sobeusedastheoxidantforthis reaction.

ls,2S-cyctohexanediot. a'])'"o"

\ho"

rW. Nam.R. Ho, andJ.S.Valentine, Am' Soc',f 13' 7052(1991)'

Asymmetric allrylation of P-kao whenprotectedas the acetal2 with tlS selectivealkylation(equationl). Cyclic sulfates,sulfites,15, 105-107; 165' they are now Review.t These products have become of special interest since In addition' of alkenes' dihydroxylation availablc in optically pure form by asymmetric and epoxides of that from differ can the regioselectivityin reactionswith nucleophiles (104 1991 through 1863 from literature covers the yields can be superior.The reference

(t)

p

o$.oo.r.

references). rB.B. t-ohray,Synthesis, (1992). 103-5 2 RX Cyclobutenediones. -98;209-I2O;' 14' 253-254:16' Naphthoquinones from cyclobutenediones (13,9'7 to 2,3-disubstituted t02). Liebeskind et al.\ have devcloped a stereocontrolledroute quinonesfrom2-alkyl.3-alkoxycyclobutenediones(l).ThusadditionofArLitol 2 with RLi followed followed by methylationprovides 2 in 5O-757o yield. Reactionof byaquenchwithtrifluoroaceticanhydrideandNHqClprovidesthccyclobutenone3. followed by oxidaThese products are convertedinto quinones4 by pyrolysis at 140" tion (CAN).

= CH3l = CrsHlgBr

I K. Kato,H. Suemune, andK. Sakai.Icrrd

t R,R)- and (S,S)-1,2-CyclohexaocditL Asymmetric olefination of mahyi cthylidenationof 4-methylcyclohexans

(R,R)- and (S,S)-1,2-Cyclohexanedi(2,2-dimethylprcpyl)amine

""'\1o

OH

I

ll

H

BuLi

61"/"

^/*tutu

oAo

17o/o

cH, Bu,pH

cHs\--/P

1) C6H5Li 2) CH3l, Ag2O

i

bcH.

)L+c6H5 o\ bcH.

87v"

cHf.-cH'

,,|""

cHf.-cH'

1

cHg

c a -r.lv ^ , , 5

2€

1)140' 2) CAN

,Bu

CHg

l\-cu,,

+ trans-isomer

Bu

o b H <27"

3 'L.S. LiebeskindK , . L . G r a n b e r ga , nd J. Zhang,J. Org.,57,4345 (1,992).

c,r .',.1s ith high stereoselectivity - .:.cd as the oxidant for this s

"Ot lS,2S-cyclohexanediol. ab

\)\o|r

Asymmetric allqlation of p-keto esters.l The a-carbomethoxycyclopentanone, when protectedas the acetal2 with (lS,2S)-cyclohexanadiol,undergoeshighly stereoselective alkylation (equationI). x. , l:rtcrcstsince theY are now rc' \ . .,r1()n of alkcnes.In addition' that of ePoxidesand .r :lrr irom t: through1991(104 1863 -.-I r(,m ra:

(t)

p f

LDA, THF, HMPA,RX

coocH3

q- .. lo9- 120;14, 253-254-16, c. -.' ll;J route to 2,3-disubstituted I hus addition of ArLi to I I ilJ :-.r.rr()n of 2 with RLi followed 3. H.t :.r(r\idcsthe cyclobutenone o x i d ab y . . r . at l-10'followed ^-

o /

\,,,\

p \-coocH" R

3

2 RX

H

= CHsl

57o/o

92o/ode

= CrsHrsBr

66/o

>99% de

' K. Kato, H. Suemune,and K. Sakai,Tetrahedron Letters,33,24'7 (1.992). rR,R)- and (S,S)-1,2-Cyclohexanedi(2,2dimethylpropyl)amine. Asymmetric olefination of methylcyclohexanones (12, 396). The asymmetric with the chiral phosphonamideR,R-1, derived cthylidenationof 4-methylcyclohexanone

92

(&R)-and(S,S)-1,2-Cyclohexanedi(2,2-dimethylpropvl)amine

providesthe (S)-ethylidene2 in from (R,R-1,2-cyclohexanedi(2,2-dimethylpropylamine)' highenantioselectivity.Thisproductundergoesanenereactionwith2,3.di-o-benzyl.oglyceraldehyde(3)toformthetriol4(>90:l0selectivity),withtwonewchiralcenters. ozonizationof4providestheopticallyactiveacyclic5with|,5-anti-selectivity.

o

o

CHzC(CHg)s

r-YN. l l \-2,,,(

P/zO ' -cHrcH.

A

+ l

Y

cH2c(cH3)3

"\CHzoBzl OBzl r

1) BuLi 2) HOAo

(-) -tran s -Cy clohexane-(l\2R)-disulfoort

Enantioselective cyclopropanation d propanationof allylic alcohols is possiblc ' by this C2-symmetricdisulfonamide l. R '

(CzFl.)i

CaHs,'/-.-zOt

SnCl4, CH2Cl2

I

63%

t

T

IH. Tokahashi, M. Ohno,andS I M. Yoshioka,

CHs

CHs

(S)- 2, crp+ 23'

( R , R ) -I

(Cyclooctadiene) (cyclooctatriene) ruthcri Coupling of l,3-dienes with acrybc most efficient catalyst for this coupling to the absenceof the Ru catalyst,Diels-Aldt

CH3 QBzl

OCH39H3 : | cH3o'--yv\

),,__,.,.-_.OBzl =

/",zCH, .u ll112'

*

cH/\coN((

o o H 5, (rD- 2.6" 4 (>90:10)

Asimilarreactionwith(R)-6and2,3-o-dibenzyl-l-g|yceraldehydefol|owedby yield'l oxidative cleavageprovides, 1,6-anti-7 in 600/o

o il

+ "'CHs

(\/"'.'con CHs

-\

-.2\

H' Y: 6gzt

-OBzl

[2 + 2]Cycloadditions.2 In the prcrr acrylatesundergocycloadditionto give c1c The reaction involves prior isomerization, undergoesthermal cycloaddition with thc

1)SnCl4 2) os

(R)-6

CHr:6116t2N(C2H5)2

r*

[*r:r

1 T Mitsudo, S.-W. Zhang, T. Kondo. and \. I l T Mitsudo, S.-W. Zhang, and N. Satake.T

x

t S. Hanessian and S. Beaudoin, Tetrahedron Lefters' 33"7659 (1'992)

(CyclooctadieneXcyclooctatriene)rutheniun llD(

2 in c :' '\ idcs the (S)-ethYlidene -. 2,3-di-O-benzyl-owith :.ritrfl ! centers' N;i. * ith two new chiral . i .r:th 1.5-anli-selectivitY'

o CHg

\-cHroezt H A oBzl 3

HSo2R 16'ro2- ro3' (-)-trans-cyclohexane-(1R,2R)-disulfona-ia"', flN --./""ttHSOzR Enantioselective cycloEnantioselective cyclopropanation of allylic alcohols't the Simmons-Smith reagent catalyzed propanationof allylic ut"oiot, is possiblewith : CoH+NOz-P' ty ili. Cr-.y.metric disulfonamidel, R (C2H5)2ZnlCH212

cH#i*" * .-}--.-.oH ---l-,,,..o+ :' caHs c6H5

SnCl4'CH2cl2

'

637"

760/" ee rH.Tokahashi,M.yoshioka,M.ohno,andS.Kobayashi,TetrahedronLetters,33,25'15(1992)'

I i J

v '

*< 2 'ts+23"

Ru(COD)(COT)' (Cyclooctadiene)(cyclooctatriene)ruthenium' the acrylamides't Ru(COD)(COT)is or acrylates with l,3-dienes Coupling of mostefficientcatalystforthiscouplingtoprovidederivativesof3,5-dienoicacids.In areobtained' of the Ru catalyst,Diels-Alder adducts the absence Ru(coD)(coT) 8oo

t", ] i:

cH /YcHz

*

cH/tcoN(cH3)2

-

51"/"

o 5 rro - 2.6"

coN(CH3)2 Z'\Z'\/CON(CH3)2 I CHs

x-

bY : -rllvceraldehYdefollowed

lcl.

+ CHs

80:20 and catalyst and a base' allylamines this of In the presence [2 + 2]Cycloaddilions'z derivatives' to give cyclobutane-B-amino:ttb:Y:"-::O acrylatesundergo cycloaddition which then of the allylamine to an enamine' The reaction involves orror'tro..iration wilh the acrylate' und.r*o", thermal cycloaddition CH2:CHCOOCH3 (

NCHg, 70"

-\*s*r9* cHz:cHCH2N(C2H5)2 [cnacH:cHN(CzHtrtl /coocH3

--1

!r

l

cH;

I

7

'N(czH5)2

^*: y111^o-'; r Kondo' Zhang' rr Mitsudo, 11'"lttltiiil;' S'-w' arf{"!,;:,::^::'',iil: andN' Satake'T' Kondo' t r. rr,ritruAo'S'-W' Zhang'

-^
l

94(Cyclopentadienone)(cyclopentadienyl)dicarbonyImo|ybdenumhexafluomphosphate(1)

Acylation.r These complexes read rc amides or dipeptidesin high yield. The rc:

(Cyclopentadienone) (cyclopentadienyl)dicarbonylmolybdenum hexafluorophosphate (1). Preparation:

o ,\ \ \ / \

(CoHs)gC*PFo

1) Mo(CO)3(CH3CN)3

cH2cl2

2) LiCp

rl

1 , m . p .1 9 0 ' d e c ., air-sensitive

cis-4,5-Disubstituted-2-cyclopentenones.t Although nucleophiles react with uncomplexedcyclopentadienoneB to the carbonyl group, 1 reactswith nucleophilesa to the carbonyl group of the terminus of a diene group. Thus reactionof I with a Grignard reagent provides 2, which undergoesdecomplexationby protonation with TFA to 3. Oxidative decomplexationof 2 with C6HsI(OCOCF3)2providesthe cis 4,5-disubstituted cvclooentenone4.

CpMo(CO)2 CHsMgCl THF. -78"-*25" 1 + 92"/"

.l-zo

cF3cooH

U-.r. 2

o tl rA--cHs \J 3

I

CsH5l(OCOCF3)2 -66.7^ "'- | lcH"cl,. -78'

t

CpTa(O)Cl2

+

I

.Alo, PFo\t=)

CpMo(CO)2

+

Cptvto-(Co)z

o< Br

CpTaC|3[OCOCH(CH3)2]

- -

o tl

A--cH.

\_l

bcocr. 4

I L. S. Liebeskind and A. Bombrun,Am' Soc.,ff3' 8736(1991).

Cyclopentadienyltantalum(V) carboxylates' CpTaCl3(OCOR)' These chemicalsare preparedby reactionof a carboxylic acid with cpTacla.

amides in 75-81Vo yield with little racrmi

1K. Joshi,J. Bao,A. S. Goldman,andJ. Kohr .

Cyclopentadienyltantalum(V)

hr\afl uoroPhosphate(l)

-m

CpTaC|3[OCOCH(CH3)2] + CpTa(O)Clz +

^-9tr.

./=lo, pFo-

o< rl \t4

1 , m.p. 190"dec. , air-sensitive

ruclcoPhiles react with unwith nucleophilesd to :r.rcts ! a I T ' _ :r.rction of 1 with a Grignard to 3' tr lr()tonation with TFA 4,5-disubstituted cis . the rtlcs : ): 0{:i^

- -

C6H5CH2NH2 +

C6H5CH2NHC(O)CH(CH3)2

cptvto-(Co)z ' t

t- J:

f . -

95

Acylation.t These complexes reacl readily with amines or amino acids to form amides or dipeptidesin high yield. The reaction with amino acid complexesprovides

olr Menum

. -

carboxylates

o ll /^-CH3

l

\__,/ 3

.(. ()(OR). ci:\,\\lic acid with cpTacl4'

9Oo/o amides in 75-81% yield with little racemization. I K. Joshi,J. Bao, A. S. Goldman,and J. Kohn,Am. Soc.,ll4, 6649(1992).

rtE

coocH3

a\ t Cp2ZrRz' Dialkylbis(cyclopentadienyl)zirconium'. by reaction of reagents are available These Hydrosilylation of 1-alkenes't -78'' of l-octene with Reaction THF at c'u'Yel'.in cpzztclzwith excessBtM;;;;t n-octSiH(ccHs)z in ot cp2ztBu2results ci'z(c;H5)' HzSi(coHs)z catalyzed W-Iitn"' in13-T5Toyieldwith}ggZaregioselectivity(equationl).

- Hzsi(coHs), #

1) LDA ruEDA 2i t(caHs)clPdl2,

l

84%

coocH3

1) LDA 2) [(cH3caH4)clPdl2 TMEDA,CO

,\

n-Hex-cH2cHzsiH(coHs)z

CH

o ll

and E' Negishi' C' J' Rousset'P' E Fanwick' l T. Takahashi'M' Hasegawa'N' Suzuki' M' Saburi' A m . S o c . ,f 1 3 , 8 5 6 4 ( 1 9 9 1 ) '

t,"i|1:11n[,fids

to but ignitewhenexposed arerelativelystablein sealedtubes,

a i r ; t h e y a r e v e r y " n ' i t l u " t o t o i ' t u ' " ' O n l y d i e t h y l z i n ccan isre a dgenerated i l y a v a i l arelatively b l e i n s o safely lutions be hazardous"otpoundt These nitrogen' under packaged (equationI)'1 Zncl2 ;ith in ether by u'";;;i;tion in siru from Grignard reagents as a complex with MgX2' which is precipitated and reaction *"nt'ut"t-it'n This ether

(l) 2RzMgX + 7nCl2

=:

R2Zn+MgX2+MgCl2

cH.-rrAorr,

L^

I CHe

cl

can be isolated after osmylation to thc l'

) H. M. R. Hoffmann,A. R' Otte'andA \ArLJ

( lR,2R)- or (1S,2S)-/rans'\,2-Diaminal Asymmetric epoxidation't Jacohtn (ll or (S,S)-diphenyl-1,2-diaminoethane alkeneswith NaOCl, but the enantioscl

in the case of cis-alkenes.Subsequcntlr

| ''o""n"

{

X2Mg'dioxane CaHso. ,CoHs further a solution of R2Zn for an inert atmospheregives under Filtration dioxane. Grignard reagents' is slow in the caseof hindered reactions'This transmetalation Chem'Int' Ed'' 3O'1008(1991)' rD. Seebach, L. Behrendt'andD' Felix' Angew'

-J

z:N- .Nr Mn ;-

cn-4 !o'cio{ ts.", t-Bu

l-Bu 1

Di-p-allylpalladuim chloride)' [(C3H5)ClPd]z'- -, and carbon of TMEDA (large excess) 'ft" p"t"n"" a'Cyclopropyl esters-j--in esters to carboxylic of complex reacts with enolates n-allylpalladium this monoxide, minor products of allylic alkylation u' itt" rnulo' product' The form 2-cyclop,opyt t"t'* 96

Jerived from the readily available rra solved by crystallizationwith tananc r

(lR,2R)- or (lS,2S)nrazs-1,2-Diaminocyclohexane

coocHs

o t:

It ;

coocH.

A

" l t

coocH3

84y"

.

::! atailable bY reaction of -\". Reactionof 1-octenewith , z'-llu; rcsultsin n-OctSiH(C6H5)2

1) LDA 2) [(CaH5)CrPd]2, TMEDA,CO

1) LDA 2) [(CH3CaH4)CrPdl2 TMEDA,CO

CH=C1166.

x

COOCH3 +

,Xoor"

\J

,

(14"/") (83olo)

' - Hex-CHzCH25iH(C6H5)2

I

o

9H' I

"t.1Aor,

.,:. P.E. Fanwick, andE. Negishi,

CHe

.'-\. hut ignite when exposedto ri. - :. rcadilyavailablein solutions nrj. ::r hc gcneratedrelatively safely ::r\,n with ZnCl2 (equationI).r n-,cipitatcd . as a comPlex with : r i:

l:Z^-MgXe+MgCl2 t . I Oloxane

O

A/or., cHs

'cHg

can be isolated after osmylation to thc 1,2-diols. ' H. M. R. Hoffmann,A. R. Otte,andA. Wilde,Angew.Chem.Int. Ed., 31,234(1gg1).

( lR,2R)- or (lS,2S)-trans-1,2-Diaminocyclohexane. Asymmetric epoxidation.t Jacobsen'ssalen-basedcatalyst l, derived from (R,R)or (S,S)-diphenyl-1,2-diaminoethane (16,157) can effect asymmetric epoxidation of alkeneswith NaOCl, but the enantioselectivityis generally only moderate(-70% ee) in the case of cis-alkenes.Subsequently,this group has examinedsalen-basedcatalysts

I

X2Mg.dioxane

caHso. ir-. , .,rlution of R2Zn for further r : - :rJcrcdGrignardreagents. -

i-

; -10.l(X)tt(1991).

7:N. .Nr Mri ,--(\ \ l/r\ //

//

6Hs1

cto{ :\ )-o t-Bu

f-Bu 1

t\ll I)..\ (large excess)and carbon s:'- :n()latesof carboxylicestersto k -r 'r,\rproductsof allylic alkylation

a)

,coHs

H,')--(.H i' 7:N. ' Mr .N:.

\\

)-cH.

A r-4,-( !o'cio{ :\l-Bu

\-

_F t-Bu

)-t-a,

2

derived from the readily available trans-1,2-diaminocyclohexane, which can be re:olved by crystallizationwith tartaric acid. Of these new catalysts,2 proved to effect

(l&2R)-

or (lS,2S)-lrazs-l'2-Diaminocyclohexane

epoxidation of cis-alkenes with >907o ee. Thus it effects epoxidation of cis-Bmethylstyrenein92% ee and of a ketal in 94% ee. Even an a,B-unsaturated ester can be epoxidizedinsgVo ee, but in this casethe reactionwas conductedin the presence of 4-phenylpyridineN-oxide.

c6H?_/cH3 847o,92o/oee

aY"l \--J

coHs_rcoocHs

b-'-

63/o,94"/o a@

c6HsscH3+ H2Oz

65%. 89o/oee

3 C

,

Br I

Asymmetric epoxidation of l,3-dienes and eynes. Jacobsen has extended his methodfor effectingasymmetricepoxidationof alkeneswith a chiral (salen)Mn(II) complex (16, 157-158) to conjugateddienesand enynesby use ofthe chiral (salen)Mn(Ill) complex 2.2 Epoxidation of l,3-dienes with Naocl catalyzedby S,S-2 provides only monoepoxideswith only moderateenantioselectivity(-45Vo ee). In the caseof (Z'E)-dienes' epoxidationoccurswith high selectivity(10:1) at the (Z)-alkene(equationI). In contrast, high enantioselectivitycan be obtainedwith cls-enynes(equationII)'

tiYt-.H3

+ Hzoz

\2

I E.N. Jacobsen, W. Zhang,A. R. Muci.J. R [.ri, I N. H. t-ee and E. N. Jacobsen,TetrahedronLcu I M. Palucki,P. Hanson,and E.N. Jacobscn. rlv

(DBU l. 1,8-Diazabicyclo[5.4.0]undecene-7

(D rerora,,y'J

CHs

NaOCI 2

tsBrorc-_ZylcH. = 7: l),66%ee (trans/cis

(cHs)ssi\__ortt' 1rr;

(CHg)sSi.\---. Y,,6 oHs

a-Ailql a, B-enones.t Theseprodrrt: a Michael acceptorwith DBU (0.20 equir I i

o

l l l .

CHr:6g"OOC2H5

(trans/cis= 2.5 : l), 90%ee

E

o tl \,rr3

Asymmetric ortdation of ArsR wilh H2o2.3 The chiral (salen)MnCl complexes derived from this diamine can effect asymmetric oxidation of alkyl aryl sulfides' The highest enantioselectivityis obtained with (R'R)-3.

DAJ rl

| r(

+CH,:CHCN-CHs

60

1,8-Diazabicyclo[5.4.0]undecene'7 (DBU)

ct:-.i\ epoxidationof cis-Bir r: .rn a, P-unsaturatedester I q.1. .()nductedin the presence

:N.

/ Mn

(R,R)-3

dir

c(cH3)3

coHs_rcoocHs

q

3, CH3CN

c6H5scH3+ H2o2 -- **-

65"/",89o/oee

.s'

cuHui5-cH. (-)-S' 47% ee

o\\ ts'

t-ar. + H2o2-r"**

his t!. J.rcobsenhas extended com(II) '' (salen)Mn ., chiral * chiral (salen)Mn(Ill) ! .--, "i the mono1 -. :.S-2 Providesonly (Z,E)-dienes' of case i r-, ln lhe ln contrast' [,-.: renc (cquationI)' I I ) . F -.:u.ttion

,1x1s-cH.

\z-s,

(-)-S, 68% ee

(1991)' I E.N. Jacobsen, W. Zhang,A. R. Muci, J R' Ecker,andL' Deng'Am' Soc''1f3' 7063 r N. H. Ire and E.N. Jacobsen, Letters,32,6533(1991)' Tetrahedron r M. Palucki,P. Hanson,andE.N. Jacobsen, ibid',33,'7111(1992)' (DBU)' 1,8-Diazabicyclo[5.4.0]undecene-7 can be preparedby additionof an enoneto products These a, a-Atlql B-enones.t

uo,o.-Z-
---6"t'

aMichaelacceptorwithDBU(0.20equiv')in1,3-dimethyl-2-imidazolidinone(DMEU)'

o

II

.\. \-/

CH2:611aOOC2H5

CHs-

)a l.l

rhiral (salen)MnCl comPlexes The :r\rn of alkyl arYl sulfides'

185' 80v"

-

,)',-.cn"cH2cooc2Hs

I r l \-/

o A

1a

o

D B U 'D M E U '

o I '\"r. + CHz:CHCN

60"/.

ar.&"H2CH2CN ll-cH,

Diazomethane

Diborane. Diastereoselective reduction of 4-Lc'to. be effected with several reductants.but thc with BH3.THF at -78' in THF.'

o

2l

ll

85o/o

tlt-a", 1,8-Diazabicyclo[5.4.0]-7-undecene hydrobmmide,l.

/ \

\ \\-// / \

oH

-2

N+ 'l-

R1

"lt-"",

' N- - ) t l \

?1"".

B-o^c".

Er

H

R2

o{

_CH.

*'/-;=,d-oX"r, anti - 2

1, m.o. 120- 122"

Preparedby reactionof DBU with Br2 in HOAc in the presenceof HBr. Bromination of arenes.2 This reagent brominates activated arenes at room temperature in DMF/H2O (phenol * tribromophenol, 89Vo yield). Less reactive aromatics are brominated by I in the presenceof HgCl2 as catalyst (mesitylene* 2-bromomesitylene,76Vo yield). Polycyclic arenes are brominated by 1 in refluxing acetic acid (naphthalene- l-bromonaphthalene,65Voyield). rJ. R. Hwu, G. H. Hakimelahi,and C.-T. Chou,Tetrahedron Leuers,33, 6469(1992). 2 H. A. Muathen , J. Org., Si , 2740(1992). Diazomethane. Cyclopropanation.l This reactioncan be conductedwith diazomethanegenerated in situ ftom N-methyl-N-nitrosourea(excess)with KOH in CH2CI2/O(CzHs)2. A number of Pd compoundscatalyzethe cyclopropanationand are equally effective for ex situ and in siln reactions.

R1= CHs,R2= CHg

71%

gt = cHe, R2= i-Pr

8996

R1= iPr, R2= CHs

92:%

:

I G.A. Molander,K. L. Bobbin,andC. K- Murrr

Dicarbonylbis(triphenylphosphine) pelht I,4-Silylstannation of l,34ienes.) T reaction,which can be highly regio- and tE silyl)tributylstannanewith butadiene prorx organosilylstannanes with more bulkr gru obtained in lower yields.

(l) Bu3snsi(cH3),* " 4Yc',

\ /f> r\/

?

+ cHs--*Arr,

(c6H5cN)2Pdct2, KOH,CH2C|2

| NO

I O. M. Nefedov,Y. V. Tomilov, A. B. Kustitsyn,U. M Dzhemilev, and V. A. Dokitchev, Mendeleev Comm., 13 (7992).

(CH3)3SnS|C6H5(CH3)2 * CH Z",ZQ

r Y . T s u i i a n d Y . O b o r a ,A m . S o c . , 113.g-Vs rt

Dicarbonylbis(triphenylphosphine)palladium

Diborane. Diastereoselective reduction of 4-ken-2-alkylborate esters (1). This reaction can obtained be effected with several reductants,but the highest diastereoselectivity(anti) is -78' 'THF in THF.' at with BH:

Ct1. ",_,^

9{-Ci

.!.

x

BHs.rHF

'

rHF'-78' >

o-o'tcH. L I

tlt-,,tt.

,"t3t.*

B-/tcH.

Rr

,,

9H l" ?1"r. -

Ri ///\\,//\"\./t

OnC r,

syn-2

anti - 2

a

'rc of HBr. rr .Prcsence x:r-.::.\ activated arenes at room rf - - l. sqc''r Yield). lrss reactive o: f li( l- as catalyst(mesitylene :r .-. hrominated bY I in refluxing l:

.rcld).

l, - . ::, ,,. 33. 6469 ( 1992).

generated n.:...:rJ wirh diazomethane A number l.li{ rr CHrClr/O(C2Hs)2. nc .,', rquallv effective for ex situ and

Rl = CHg, R2= CHg

71o/o

34:1

R1 = CHg, R2 = iPr

89%

62:'l

Rr = !pr, R2= CHs

92/"

>50:1

I G.A. Molander,K. L. Bobbitt,andC.K. Murray,Az. Soc',ll4, 2759(1992)' (1) Dicarbonylbis(triphenylphosphine)palladium, Pd(CO)2[P(C6Hs)3]2 catalyst for this effective most is the I,4-silylstannation of l,3-dienes.l This of (trimethylreaction the Thus (E)-selective. reaction,which can be highly regio- and I). Other (equation (E)-alkene single a provides silyl)tributylstannanewith butadiene are products the and reactive less groups are with more bulky organosilylstannanes obtained in lower yields.

(CO)2Pd[P(C6H5)312

(l) Bu3snsi(cH3)s+ cHNct'

--ffi-

r

(;

(E)

ti(cH3)3

- (E)

(cH3)3Snsic6Hs(cH3)2 *cn/v"',

D..-

1cr. and V. A. Dokitchev,Mendeleev

-"*-

rY. Tsuji and Y. Obora, Am. Soc., f n, 9368 (1991).

ffitic6H5(cH3)2

102

Di-p-carbonylhexacarbonyldicobalt

Dicarbonylcyclopentadienylcobalt, CpCO(Co)2' presenceof CpCo(CO)z' the mono[2+2+2]Cycloaddilion (cf. 12,163).1 In the mixture of epimers' cyclic enyne (Z)-l cyclizesto the tetracyclic diene (2) as a 2:1 (3), and can be The product has the carbon skeleton present in the diterpene stemodin the diterpene'This converted in three steps to an intermediatein a total synthesisof cycloaddition fails with (E)-1'

The yield of the carbonylation-erpan catalyzed by both Co2(CO)s and Ru.tCC (equationIII).

/^-r-\ l

(il) \.,\ru'

l

)

\

d

+ co

CHzCOOCzHs + Ru3(CO)12

This combined catalyst can also effcrt tones to tetrahydroindolizines(equationllll rearrangement(equationIV).

CpCo(CO)z 55"k

(rrr) cH.-Q-cH,

2 (2:1)

@(col

cH2coc(cH3)3

co | (lv, CH3..\N,'

CHs

Co2(CO)e. Rua(COr. | -----;;CH2COC5H5

I J. Germanas, Am' Soc',ll3' 4006(1991)' C. Aubert,andK.P.C- Vollhardt, Di-p-carbonylhexacarbonyldicobalt, Co2(CO)a' by to Ring expansion-carbonylation.t The ring expansion of aziridines BJactams piperidones to a Rh(I) catalyst(r5,82-83) hasbeenextendedto expansionof pyrrolidines by cobalt carbonyl-catalyzedcarbonylation(equationI)'

(r) +R,.

Co2(CO)6 c6H6,02, 220'> co

R1 R1= CHs, R2= CHzCoHs R l = C H s , R 2= C o H s

(-'{^'

.)

nr AttAo Rr 24o/"

Cyclic enediynes. The realization thr an enediynecore which is essentialfor tlx svnthesisof this ring system.One approa'h eldehydeprotectedas the Co2(CO)6adduc conventionalstepsfrom cyclopentene-l--i{ and N(C2H5! cyclizesto 2 in 69% rield

o

* t\ttAol R1 15"/o

oHc

\cotcor.

i

I

t-BuMe2SiO

cH2oH 56"/"

e{

Di-p-carbonylhexacarbonyldicobalt

r :---.nce of CpCo(CO)r,the monoir:- lr as a 2:l mixture of ePimers. hr .r :Jrpcnestemodin (3), and can be ' ' : \\ nthesisof the diterPene.This

103

The yield of the carbonylation-expansionreaction is generally improved when catalyzed by both Co2(CO)s and Ru3(CO)12, dodecacarbonyl-tri-tr iangulo -ruthenium (equationIII).

/^>-1

t t (ll) \-,^-t'

)

an

tt--AttAo t

Co2(CO)8

+ CO

\ cH2cooc2H5

l

I

CHzCOOCzHs

+ Ru3(CO)12 79/o

c: \

This combined catalyst can also effect cyclization of 2,6-dimethylpiperidinylketones to tetrahydroindolizines(equationIII), and this cyclization can predominateover rearrangement(equationIV).

co

2 (2:11

(lll)

Co2(CO)6, Ru3(CO)12 cH.Af^ar. cH2coc(cH3)3

r

| (lv) c H ". A N 2 t

|

r

c

o

l

a^) l

Ru3(co)12, | co2(co)s, \ruA 77yo ,.-1)

cH2coC6H5 -\ .

I l-r. .l(x)6(1991).

t-

c\: :-.rrrnof aziridinesto B-lactamsby c\: :'r\r()nof pyrrolidinesto piperidones Ir s:

lttt

F:

-* " R1 24o/o

-

t

tR'

o

\rAo

-

CeHs

oHc \colcolu

Bu2BOTf NEt3

t-BuMe2SiO l-BuMe2SiO

cH20H 56o/o

*cH.

1o:1

/-\ lll lII ttt^o

|rr.rrCur, l

Cyclic enediynes. The realizationthat a number of antitumor antibiotics contain an enediynecore which is essentialfor their activity has led to extensivemethods for synthesisof this ring system.One approachinvolves an aldol reactionwith an acetylenic aldehydeprotectedas the Co2(CO)6adduct.Thus the keto aldehyde1, preparedin five on treatmentwith dibutylboron triflate conventionalstepsfrom cyclopentene-1,3-dione, and N(CzHs)r cyclizes to 2 in 69Vo yield. Attempted decomplexationwith N-methyl-

l

R1 15"/o

c(cH3)3

Didlt

104

Di-p-carbonylhexacarbonyldicobalt

o9l R3S|CTCCHO + CHoCH-, Coz(CO)o sc

Q,*'*o

1

2(ElZ= >%

CH2OBBu2 3 to 3' Such morpholine N-oxide (NMNO) in cyclohexene results in aromatization agents'2 aromatizationis characteristicof compoundsof this group of antitumor the antibiotic (6) of structure enediyne tetrahydroquinoline the A synthesis of propargylic alcohol with an dynemicint involves condensationof a co(co)6-protected enol.3 Thus treatment of 4 with triflic anhydride and 2,6-di-t-butyl-4-methylpyridine

The uncomplexedpropynal underqocsI Intramolecular Pauson - Khanl alkynyl allylaminochromiumor lung intramolecularPauson-Khand reac-tx

inCH2CI2/CH3NO2resultsin5in52%yie|d.(Useofnitromethaneiscrucialfor iodine provides 6, which satisfactoryresults.) This product on decomplexationwith undergoesaromatizationwhen heatedto form 7'

(co)sM -coocH3 Tf2o, cH2cl2,cH3N02 43o/o

l,M=Cr,W

M.D. Wang and H. Alper,Am. Sr. ll, r P . M a g n u sa n d T . P i t t e r n aJ, . C . S . C h d ' P. Magnus and S. M. Fortt, ibid.. 5JJ t I 'C. Mukai, O. Kataoka, and M. Hanaob ' F. Camps,J. M. Moret6, S. Ricant. arxl J

52o/"

Dichlorobis(cyclopentadienyl)hrhi c ' p l H f C l 2 - A g C l O 4 , 1 5 , 11 9 - 1 2 0 : l C l

7

6

complex I ofProPYnal Diastereoselective aldol reactions of propynals'a The cobalt almost exclusivelY' aldol syn the form (2) to reacts with O-silyl ketene O,S-acetate

Aryl C-glycosides.t This C-gl1c - )-gilvocarcin (a). An unusual feel ('-glycosidation of the A ring. folk Ihus reaction of the t--acetylfucosc,

t'plHfCl2/AgClOa (2 equiv. each) rn ! in 877ayield. This product was cor

Dichlombis(cyclopentadienyl)hafnium-Silverperchlorate

*"'tI::::,

I

+ cH3cH<

Coz(CO)o

I

1)TiCl4 2) CAN

psiR3

1

sc(cH3)3 2 (Elz = >98: <21

'cH2oBBu,

105

o' Hl ol -\ -\ -SC(CH3)3 R3S|C=C' \a CHg 3 (syn/anti= >98 : <2)

J

rr-.'. ::r aromatizationto 3. Such S ' l , ' t a n t i t u m o ar g e n t s ' 2 n. .::ucture (6) of the antibiotic p:-.'-.1 propargylicalcoholwith an

(95:5). The uncomplexedpropynalundergoesthe samereactionwith high ar?/i-selectivity Intramoleculnr Pauson-Khand reaction. Addition of Coz(CO)a (1 equiv.) to alkynyf allylamino chromium or tungstrum carbenecomplexes(l) at 25" results in an intramolecularPauson-Khand reactionto provide 2 in 7O-75% yield.

r: .: 1.,'-di-r-butyl-4-methylpyridine I nitromethaneis crucial for t.' ,.rlh iodine Provides 6, which l

H

/--CHz

NJ

(co)5M

Co2(CO)8, THF, 25' 70 - 75v"

I,M=Cr,W

:M.D. WangandH. Alper,Am.Soc.,114,7018(1992). : P. Magnusand T. Pitterna, J.C.S. Chem.Comm.,541,(1991)'P. MagnusandS.M. Fottt,ibid.,544 (1991). 'C. Mukai.O. Kataoka,andM. Hanaoka, Letters,32,7553(1991). Tetrahedron ' F. Camps,J. M. Moret6,S. Ricant,an
520k

6

T'

I :rccobaltcomPlexI of ProPYnal - 'rn aldol almost exclusivelY.

Dichlorobis(cyclopentadienyl)hafnium-Silver perchlorate, Cp2HfCl2-AgClO4,15,119- 120; 16'120-121. Aryl c-glycosi.des.l This c-glycosidation was used for synthesisof the antibiotic 1+)-gilvocarcin (4). An unusual feature of this synthesis is that the first step is the c-glycosidation of the A ring, followed by addition of the remaining three rings. Thus reaction of the t--acetylfucosederivative 1 with the iodophenol 2 promoted by -78 - -20'provides the c-glycoside Cp2Hfcl2/Agcloa (2 equiv. each) in cH2clz at five stepsto 4 in 38% overall yield. in 3 in 87Voyield. This product was converted

Dichlorobis(cyclopentadienyl)zirconium

Cp2HfCl2 AgClOa

OBzl

Ethylmagnesiation of alkenes.'' In thc nesium chloride adds to alkenesto sivc.an electrophiles(equationI).

bH. 1

fl)

OBzl

n-CsH17CH=CH2 +

C2H5MgCl

OH

o

OBzl

Hr,,

c,

n-CaH.,z^

1T. Matsumoto,T. Hosoya,and K. Suzuki,Am. Soc.'114,3568(1992)' Dichlorobis(cyclopentadienyl)zirconium. Coupling of |-alkenes with Grignard reagents, TWo laboratoriesr'2have reported that Cp2ZrCl2 can catalyzecoupling of l-alkenes with C2H5MgBr or (CzHs)zMg' Thus l-decene reactswith c2HsMgBr in the presenceof cp2zrcl2 to form the bisGrignard reagent (a) that on quenching with HrO+ provides 3-methylundecane(l) The high

This carbomagnesiationcan also he ag caseof the free alcohol, the reactionafftxd

OR

CH2:CHgH17

+

C2H5MgBr

CP2ZrCl2 rHF

C,H^ -

arrrrro---l.-*,

1) C2HsMgCl. W& Hp2 2) B(OCH3)3:

ncsH2o)\r'cHz R=H R=CHs

70q 8G

**i".o. I

i'"'

CgH17

CH3 1

regioselectivity is notable. Another advantage is that the intermediate is a Grignard reagent subject to further functionalization.

Protectionof the alcohol with a t-bul)ldrrnc ncsiation.The actual catalyst in these rcxt dc, Ethylmagnesiation of homullylic can add to the double bond of homoalllh high stereoselectivity.In the cas€of the aar proceedswith high anli-selectivityin thc cr ln contrastto the reaction of the sln-txrnrq

107

Dichlombis(cyclopentadienyl)zirconium

of Cp2ZrCl2Qnol'%)'ethylmagEthylmagnesiationof alkenes.3 Inthepresence (a) that can react with various intermediate an give to nesium chloride adds to alkenes electrophiles(equationI).

Cp2HfCl2 AgClOa t

87o/"

OH

?T'!i;+ c2H5Mscr (r) n-c6H17cH=cH2 L-"-r,,j]"n''l t t

'y*

ocH3

a

uur"I "*.""o

I

?"'?t

QzHs ,-crHrr/'--'-oH

n-csHlrMcH3

4 ll

:'',. (1992).

Thiscarbomagnesiationcana|sobeapp|iedtoallylicalcoholsandethers.Inthe cascofthefreealcohol,thereactionaffordsthesyn-diolwithg5:5diastereoselectivity. . Irro laboratoriesl'2have reported Thus :':' (';H.MgBr or (C2Hs)2Mg' : ( r-Z-rclr to form the bisGrignard (1) The high 'rJ,- :-mcthylundecane 6

oR

j" oH

ll 3,,5#:;i;i6t'": ?" ?'*r-c"nro)1., r-""rrol

)--=-zcHz#

lzHs l t'"n'c'H"l

n-Cs{2s'

R=H R=CHg

CzHs

CzHs 7O"/o 80o/"

95:5 11:89

I

se'u.n.oI I

?"u CH3^CgH17 1

t\

rhe intermediateis a Grignard

blocks carbomagprotectionof the alcohol with a l-butyldimethylsilyl group completely "Cp2Zr'" be may nesiation.The actual catalyst in these reactions (ethers)'a Ethylmagnesium chloride Ethylmagnesiation oi homoallylic alcohols on catalystswith cp2Zrclz with alcohols can add to the double bond of homoallylic highstereoselectivity.lnthecaseofthearrli-homoallylicalcoholl(R:H)thereaction proceedswithhighanli.selectivityinthecaseofboththealcoholandthemethylether. lncontrasttothereactionofthesyn-homoallylicalcohol3,thereactionproceedswith

Dichlorobiscyclopentadienylzirconium

- Butyllithium

t

2)B(ocH3)3/H2o2,-78' CHz

l

\.^1r-

9H'

l n-Non--1

n-Non-\,cH2oH

r

| L

Bzt 1

3 +svn-4

o\-

5* b,Hu

l

CHZ

anti-4

less in the case of the methyl the anri-selectivityis markedly less cnri-selectivity,and ether (3, R:CHI)' , ..- .^) ^*.-6ac proceeds -.ncee6s sluggishly' slueeishly,the reacof disubstitutedalkenes Although carbomagnesiations regioselectivity'However' pro"."o, in high yield and .'onof endo_5_noruorn"n-z-oi1iy of the methyl ether of 5' ur. O."r.ured in ttr" reaction the reactivity unO ,"gio..tlO"iui(

1)C2HsMgCl,CPzZtCl2 2) H3O*,-40"

,,.\

ZCHz

I I ( tt \.,A^r/

I

97o/o 75"/"

>99:1 97'.3

l\'cPlr'

z)x"o' , 8'*

Bzl

"o'zr s+z"lrr o\-

_AczHs+"&"r,

RO

-'--,

85:15 65:35

55-/o 38o/o

3,R=H R = CH3

s,R=H R = MEM

,,n l\l'""""e s i ( c H 3) 3 [.&"

>99:1 97:3

CHs

l

6rH, 6n anti-2

75o/o 65%

1,R=H R=CHs

OR

+svn-2

" *on-.-,[cH2oH

I

\[!' l t t\-'tN

)

H Bzl

Am' Soc'' ll.3'6266 C'J Rousset'and E' Negishi' rT. Takahashi,T' Seki' Y' Nitto' M' Saburi'

(reel).

'btd'' 113'6268'^(1eel) t)i.s.'il,*n, and R'M' Wavmouth' 'Am' Soc''ff3' 5079(1991)' , e,.*t. tt"i.VA^ and Z' Xu' ibid" 113'8950(1991)' aA.H. Hoveyda,Z'xtt'''t'fr"'"*"] ^Je'u Houri' 14' 122-1'23' "ZtCp2" Dichtorobiscyclopentadienylzirconium-Butyllithium"'ZrCp2"' Reaction of dienes;^p-erhydroindoles't or enynes of is Reductive coupling in a zirconacycle (a) that i in THF at 25" results with the cyclohexenylat;

;"';',ll*:1.11: byHc,(10%;; hydro,yzed I,flil;,Jj ll];ffifi'.;*!i:::,'."#, to gtvesu electrophiles other various i" "r"uu.A by ketone3' oi a wittr Co gives the tricyclic

t Triquinane sYnthesis'2 A highlr zircontu the :.rlenic acid (6) employs group :nyne I with an allylic hydroxyl C I the of Addition :o the A-B rings. e This group' ,'f an allylphosphonate oxidat by followed rinylphosphonate t0 shich is hydrolyzed by a mild base (Z)-crotylphxp rnion (BuLi) of diethyl

Dichlorttliscyclopentadienylzirconium

- C p

CHs '-.,,-,CH2OH + syn-2 cR

si(cH3)3

| .+N'/

31ti-2

si(cH3)3

Cp-)r

lll 't'"0," -

,, 1 ! *.\ 1

czHs

H

Hso* 75o/o

I

H Bzl

>99:1 97:3

Bzl 1

I 30%lco

CHs ,-\--,,.CH2OH

- Butyllithium

+ syn-4

o\-----

I OR CzHs

XIj( l t

anti-4 8 5 : 15 65:35

--\--tN

)

H Bzl 3

. s.s in the case of the methYl . - rroceedssluggishlY'the reaci l r .: .'nd regioselectivity.However, x' - ,.tion of the methYletherof 5.

cHo

4CH, I

.--.1 | (tt \Anr/

1l"Cp2zr" 2)H3O* .

8eo/o

Bzl

I

H 9H'

-^-bt l l \,1-N

)

H Bzl "CP2ZI"

94o611l

l2)co

I o\-

i

H. I H I

a-K \-]-- i

R >99:1 97:3

H Bzl

t

Negishi, Am. Soc., ll3'

6266

f.

!-_ I l.r se50 (1991).

bm. lrCP:"' 14,122-123' "ZrCP2" Fdr,,indoles.tReactionof '(a) that is rn a zirconacYcle F, r-i

ricld). The Zr-C

bonds can

l h - : ' . : : c d p e r h y d r o i n d o l e s .T r e a t m e n t

Triquinane synthesis,2 A highly stereocontrolledsynthesisof the triquinane penralenic acid (6) employs the zirconium promoted bicyclization-carbonylation of an cnyne 1 with an allylic hydroxyl group to provide the bicyclic enone 2, corresponding ro the A-B rings. Addition of the C ring was effected by a novel Michael addition of an allylphosphonategroup. This approach is useful becausehydroboration of a vinylphosphonatefollowed by oxidation provides an (a-hydroxyalkyl)phosphonate, which is hydrolyzed by a mild base to an aldehyde(equationI). Thus addition of the to 2 provides3, which, after protection anion (BuLi) of diethyl (Z)-crotylphosphononate

110

- Butyllithium Dichlombiscyclopentadienylzirconium

(r'

ot l

1) BH3THF

ol l

CHs

2) H2o2,NaoAc> RCH2_.,,,P(OC2H5)2

R'\,-P(oCzHs)z

OH

NaHC03, cH3oH,H2o> 80 - 85% overall

CHs

RCH2CHO several sleos 467o ov€r3ll

Reaction of 3 with pyridinium of the carbonyl group' is convertedto the aldehyde3' p-toluenesulfonateeffectsdeprotectionofthecarbonylgroupfollowedbyaldolization. Dehydrationofthealdolfo|lowedbyhydrogenationprovidesthetricyclicketone5. Thisproductisconvertedinto(+)-6bystandardreactions.Thiscyclopentannelationto providetheCringproceedswithhighstereo-andregiocontrol'Sinceallylicalcoho|s canberesolvedbySharplesskineticasymmetricepoxidation,itshouldbepossibleto prepare optically active triquinanesby this route'

si(cH3)3

3:ii'"'' sr.

CHa CHs

84"/o

followed by protonolysisand cartrx was used for a synthesisof (*)-tn A lle ny lzirc oniu m reage nts.t allenylzirconiumreagent(a) that rt ctherate to form anti-B-acetvlenic . and anti-p-acetylenicalcohols.a si tbrmed.

CHS

OBzl

1, R = CHzCoHaOCH3-P

coHs4 cHs.-1^cHo Li

t

t

o

:;:tpfi

l

1) CH3CHCH=CHP(OEt)2' 2) BU4NF 94o/"

1) 2) 3) 4\

PyHTs MsCl DBU H2,Pdlc

58%

CHsCHs CHs

CHs

o -so.z.*

CHs CHg

Bicyclizationofl,6.heptenynes.3Treatmentofthechiral3-methyl-1'6-octenyne formed from Cp2ZrCltlBufi $:Z)' t, preparedfrom (+)-citronellene, with the reagent

V. Mori. N. Uesaka,and M. Shihas r{;. AgnelandE. Negishi, Am.Su . I 'G. and E. \q Agnel,Z. OwezarczYk, 'll. Ito, T. Nakamura, T. Taguchi.and

Dichlorobis(triphenylphospine)pc Carbo ny latio n of o-allY Ibc aad :hloride (1) in the presenceof tr ralladiumcatalyst(5 mol %) prorr

Dichlorobis(triphenylphospine)palladium(II)

CH.

o !-

lll

1) "ZrCp2"

acHz-.-.,.i51ocrHu;t

lAI

2 ) H a O * :C O , 73"k

I

\

'rfi

OH

F o

2. >9o%de

CHe H : -

1*:

- severalsteps 46o/o overall

d. .r Rcectionof 3 with PYridinium ir',,uP followed bY aldolization' :':,,rides thc tricYclic ketone 5' h r. This cyclopentannelationto t.:. d --- 'crrntrol.Since allylic alcohols (:. \:.:.lii()n.it shouldbe possibleto

si(cH3)3

o HU

c _

F'

(+) - 3, >99o/oee

2. This product followed by protonolysisand carbonylation,providesthe bicyclic ketone was used for a synthesisof (+)-iridomyrmecin (3)' "Cp2Zr" reacts with propargylic ethers to form an Allenylzirconium reagents.a presenceof BFr allenylzirconiumreagent(a) that reacts in sia with aldehydesin thc to the sy'?addition In ctherateto form anti-P-acetylenicalcoholsas the major product. is usually alcohol nd anti-p-acetylenicalcohols, a significant amount of an a-allenic tbrmed.

OBzl

"Cp2zl' THF.-78"

coHs-{

cHs..1^cHo

3::>epfi RJil

t{''

H-,o

cH'. H

H 2

t{Y

- CHs CHs

:hc chiral 3-methYl-1'6-octenyne rmcd from CPzZrClzlBuL\ (1:2),

o

c-CsHrrCHO BF3O(C2H5)2 76"/"

CHs

CoHs

CoHs ?

49:l

J' Org'' 57, 3519(1992) V. Mori. N. Uesaka,and M. Shibasaki, I c. Agnel and E. Negishi,Am. Soc.,ll3,'7424 (1991) 'c. Letters'33' 1543(1992)' and E. Negishi,Tetrahetlron Alnel, Z. Owezatczyk, 'H. It;, T. Nakamura, ibid'' 33' 3769(1992)' T. Taguchi,and Y' Hanzawa,

Dichlorobis(triphenylphospine)palladium(II)' (600 psi) of o-allylbenzyl Carbonylation of o-attylben4yl halides't Carbonylation in the presenceof this and (2 equiv') ;hloride (1) in the presenceof triethylamine (2) in 78o/oyield' lactone enol benzoannelated the ralladium catalyst(5 mol %) provides

rtz

Dichlombis(triphenylphosphine)palladium(II)

.Z\\.,//\r\r

r

t t *cHz

iT

,-,

l

- Copper(I) iodide

CO'N(C2H5)3

Pd(il) 780/"

(') u

Bu2MePy 9 o H Tf2O, cH2ct2,25' _

63v"

orf (D )-.,o,

=cH,

.orf

t_/

c

a

+ Hl

(E)-1

cl

HO-----.

sevefal steps

?tt orr

tr

.

,)fJ:,

(z)-1

of theantiulcer in a synthesis A similarreactionwith 3 gives4, whichis an intermediate agentu-68,215(5).

and 2 equiv. of diethylamineto givc thc tl ,nd (Z)-2 exhibit comparablecytotoxitr K. Arai, K. Yamada, andS. Tcrr K. Nakatani,

rG. wu, I. Shimoyama, J. Or9,56,6506(1991)' andE. Negishi, -Copper(I) iodide' Dichlorobis(triphenylphosphine)palladium(II) be coupling of dienol tlitriflates and propargylic alcohols.t This coupling can dicyclic the used to obtain open-chain (E)- and (Z)-dienediyne diols, analagousto enediyne system of the neocarzinostatinchromophore,responsiblefor the cytotoxity prepared of the antitumor antibiotic. Both (E)- and (Z)-dienol ditriflates (1) can be couple ditriflates from 2-formylcyclopentanoneas shown in equation(I). The dienol of cul, lo% catalyst, with propargylic alcohols in the presenceof 5 mol vo of the Pd

Dichlorodimethylsilane, (CHr):SiCl:. Reductive coupling of RCHO aad cll. uracil (5) involves a novcl coupling of u * ith dichlorodimethylsilane.Thus treatnrr bcnzeneselenoland (CHr)2SiCl: (cxccs:s n 927a yield as a mixture of epimcrs tl *ith Bu3SnH and (C2H5)BI follo*c'd br

ll3

Dichlorodimethylsilane r

I

,dide

-'-\.-O. ^-'--,ry

l F o

(l) tr

nv (cH3)2c=o

Tf2O,Bu2MePy

? o H cH2cl2,25' 63"/"

oTf

?tt orr

tr

(z)-1

( E ) -1

oTf

. X:;" (t)2-.€\^-. 'orr \--l HccH3

P d ( l l ) ,C u l , DMF NH(C2Hs)2, 91"/"

(E)-1

9Hs HO CHs CHe

{

- -oH '{

?tt orr

tr

.,x::"

CHs CHs ,CHs CHs

(z)-'l

rc-- . .:r.llcin a synthesisof the antiulcer

and 2 equiv. of diethylamineto givc the (E)- and (Z)- dienediynesystem 2. Both (E)tnd (Z)-2 exhibit comparablecytotoxity. (1991). :K. Nakatani. andS. Tcrashime,TetrahedronLetters,32,3405 K. Arai,K. Yamada,

y-(,,pper(I) iodide. coupling can be 13tltc alcohols.r This cyclic ditr.'- .lr,,ls.analagousto the cytotoxity trl : :i. rcsponsiblcfor the prepared ir-.:.:r,'l tlitriflates(1) can be dienol ditriflates couple luj' :: rl). The rrf the Pd catalYst,107oof Cul' :'

Dichlorodimethylsilane, (CH1)2SiCl2. Red.uctivecoupling of RCHO and allylic alcoholst A synthesis of tunicaminyluracil (5) involves a novel coupling of an aldehydewith an allylic alcohol, effected s ith dichlorodimethylsilane.Thus treatmentof the alcohol I and the aldehyde2 with benzeneselenoland (cHr)2Sicl2 (excess) in pyridine at 23' provides the product 3 n 92Vo yield as a mixture of epimers (1:1). Radical cyclization of 3 in acetonitrile *.ith Bu3SnH and (C2H5)B3 followed by siloxane hydrolysis provides the protected

ll4

Dichloro(ethylene)platinum

dimer

D

\HAC CH3O,,,./,,--y'lOMEM t l o-r.t\^,.

R3S|O\

/D

A]-'

lCt

(,

l l " "

rBSd brrso

CHz 1

2

o

C6HsseH (cH3)2sicl2 Py,23"

t(

R3S|O\A

,r7c"^u

*'r",

92"/"

CHs

1 ) B u s S n H(, C 2 H 5 ) 3 8 2) oH

AcNHz,,.

oH oH

>

o

o

indicatesthat rearrangementinvolves inre

*'rt,

I K. Ikura,I. Ryu,N. Kambe,and N. SoncJr .

CH3O"''\O : TBSO

t O OTBS

a ( 3- a : 1 )

o 'PMB

Diethylzinc-Chloroiodomethane, (C:H. I Cyclopropanation ofalkenes.t Thc ! from diethylzinc and CH2I2,and presuma reagentpreparedfrom (C2H5)2Znand (l

the usual Simmons-Smith reagent. pan rclvent. Moreover,cyclopropanationof alh t equationI).

OH derivate 4 of tunicaminyluracil (5). rA.G. Myers,D.Y. Gin,andK.L. Widdowson, Am- Soc.,f13' 9661(1991)'

Dichloro(ethylene)platinum dimer, IPt(C2Ho\Clr]2, Zeise's dimer (l)' Isomerization of silytoxycyclopropanes to allyt silyl ethers.t This Pd(lI) complex effects isomerizationof silyloxycyclopropanesto allyl silyl ethers. The last example

(t)

'-\

rc,/{ m

(/

S . E . D e n m a r ka n d J . P . E d w a r d s J. . O r e . . *

Diethylzinc - Chloroiodomethane

D R3S|O\ ]l--D

-"vo \- "J.."-'(. PMB

/

: o ores

lsa

1 , C D C | 32, 0 "

R3S|O. ,H

/-Y"o'

rK]-t (-J

\-,

2 SeC;Ht

?siR3

1,cHcl3

R3S|O-n Pr/

-czHs

11s

,,/tY'"^'

8a"/"

CzHs

) - -: :-\ ^,

cH3\Y.cH3

t\

"tr>_l\

H l osiR3

2v

OH

l . '--r,

-

n -^^/i

:

nssio)-,,'--r. H

indicatesthat rearrangementinvolves inversion of the silyloxy group.

o

rK. Ikura,I. Ryu,N. Kambe,andN. Sonoda, Am. Soc.,ll4,1520 (1992).

'-- o OTBS

4 3 - 4 1)

) F ^

cH3-y'cH3

o 'PMB

rc

Diethylzinc-Chloroiodomethane, (C2Hs)2Zn-ClCHzl (l)' Cyclopropanation of alkenes.r The Simmons-Smith reagentis generally prepared from diethylzinc and CH212,and presumablyis (iodomethyl)zinc,lCHzZnX. The related reagentprepared from (C2H5)2zn and clcHzl in the ratio 1:2 is more reactive than the usual Simmons-Smith reagent, particularly when used with dichloroethaneas solvent.Moreover,cyclopropanationof allylic alcoholscan show high diastereoselectivity (cquationI).

5

OH l H

OH (C2Hs)2Zn- ClCH2l,

(t) r

l l - r . ) 6 f r (l 1 9 9 1 ) .

t r l

ctcH2cH2ct,0'

a'Y.\,{

H

(99% de) r ' u ' 't . c ' . d i m e r ( 1 ) . hl ,tltl erhers.r This Pd(II) complex I , . i . i l r l c t h e r s .T h e l a s t e x a m P l e

1 S . E . D e n m a r ka n d J . P . E d w a r d s ,J . O r g . , 5 6 , 6 9 7 4 ( 1 9 9 1 ) .

116

(BINOL) 2,2/-Dihvdmxv-1,1/-binaphthyl

(Simmons-Smith reagent)' Diethylzinc-Methylene iodide allylic alcohols Cyclopropanation of substituted Asymmetric cyclopropanation't

1)f.41 2) Cfi/

(1)attachedtoacarbohydratederivedfromo.glucosewith(C2H5)2ZnandCH2I2(excess) canproceedwithhighoius",.o,"t""tivity.Thetriflateoftheproduct(2)whenheatedin

OBzl

(C2H5)22n,CH212 -35' - 0" >97"/o

(,?u'u oJ"'

1) t-BuLi(3 equiv.)

"roH OBzl

\/

\.,,

2 (>50:1 de)

1

r* a

OBzl 1) Tf2O,PY 2) DMF, H2O,

Ho,-,..yzcaas 4 (90%,98.4%ee)

3,3/-DiarYl BINOLs can be obtaincd * BINOL followed by Suzuki coupling rth (equationI)'

: 1) BuLi (3 equiv.) 2\ BTF2CCF2BT

(t) 4

\

of the cyclopropylto the aldehyde3 with release aqueousDMF undergoescontraction methanol4.NotethatthepresenceofthefreehydroxylgroupatC2oftheglucopyranoside of the product 2' I is essentialfor the high diastereoselectivity lA.B.Charett,B.C6t6,andJ.-F.Marcoux'Am.Soc.,rl3,8166(1991).

(BINOL)' 2,2/-Dihydroxy-1,1''binaphthyt 3-and3,3I-Substitution.Thedirectedortholithiationroutecanbeusedtoeffect3or carbamates' by use of the MOM or SEM ethers and 3,3'-functionalization of BINOL (THF, -78')' t-Buli of equiv. 2.2 is best lff.",.d with Generation of the monoanion G e n e r a t i o n o t t h e d i a n i o n i s b e s t e f f e c t e d w i t h 3 . 0 e q u i v . o f Bconfiguration' uLi(ether,25").This proceedswith retention of method when applied to lS;-sfNOf-

OMOM

4,4-Disubstitutedbutan4-olidcs'by additionof Gngna cnantioselectivity .ruxiliaryBINOL.The reactioncan prtx

(BINOL) 2,2i-Dihydroxy-1'l/-binaphthyl

tt7

i. :.- ill I

o:' ' "f substitutedallylic alcohols rr .\ '- | ('1H.)2Znand CH2l2(excess) n-.'. : ihc product(2) when heatedin

1) l-BuLi (2 equiv.)

,l qd-

710/o

6,?u'u oJ''' 'rroH

2 ( > 5 0 :1 d e )

HO-=//>.C6Hs 4 (90o/.,98.4"h ee)

of 3,3/-Diaryl BINoLs can be obtained by conversion to the dibromo derivative Pd[P(C6H5)3]a by mediated BINOL followed by Suzuki coupling with arylboronicacids (equationI).

Br 1) BuLi (3 equiv.) 2l BIF2CCF)BI

OMOM

84y"

OMOM

(t) tr ..- -r * irh rclcaseof the cyclopropylh \ . ir(rup at C2 of the glucopyranoside i ',:':,rduct2' nr 11991)

":t.'tion routecan be usedto effect 3'-- \1o\1 or SEM ethersor carbamates' -78")' q I I cquiv. of l-Buli (THF' This 25")' (ether, r: : rquir'. of BuLi 'rl(nti()n of configuration' s

c6H5B(OH)2 Pd(0)

Br

tsi(cH3)3 cH3cN

I

in high 4,4-Disubstituted butan-4-olides.2 Products of this type can be obtained the chiral (R)-1, of esters, inantioselectivityby addition of Grignard reagentsto 7-keto induction. .iuxiliary BINOL. The reactioncan proceedwith high 1,7-asymmetric

ll8

2,2tDihydroxy'1'l''binaphthyl

(BINOL)-Triphenylborate

o&o-cH. o'?o o

"11dll, ry*

+

B(OC5H5)3

(S) - 2' 95% ee

(A".ru

(R)-1

CH2\,,C to the use of 1'1/-binaphthyl is a general introduction Review.3 This review from 1974 to 1992' uu*iUu'lt'; 86""f""n"t' derivatives as chiral

*':?.it;?"it , retrahedron andv. Snieckus 1p.J.cox,w. wang, MiYano"J.t S and 2 y. Tamai.M. Akiyama'A Okamura' 3c. Rossini,L' Franzini'" #;;;;';Jp'

(l)

C6H5CH=NBz|

+

ocH3

ou un rl. l)1,)]).,

s03 (19e2)' sutuuao'i'svnthesis'

ta srnr Jienc promotedby (R)-1' generated ': fhis asymmetric Diels-Alder reaoion comof this organoaluminum

2,2/-Dihydroxv-1,1/'binaphthyl-TFimethvl".t:1tl:l;"

j.""1',"".##*'?i"J"'"hvdes'. *";r::Ixxfx::;;'::::;;[, -2- oxai form cis-4-alk oxY

CH2\,.OS .

( ocH3

)-l A)^o\ocH'

C6H5CHO

1' CH2C|2'CH3CN 0" ---;;;-

cH3o'^\y'

cis-3

,lkaloid derived from nicotinic acid' lbata' Tetrahedron I H. Suga, S. Shi, H. Fujieda, and T

(1991)' Leners' 32' 691 I

',''";:l:::li::;i:::l;I,:Hl:l"Tl"-reac,ioncanbeeff

ectedinT2-e0v.

with reactionof (R)-BINOL io'on reagentr' p'"pJuy "n'J the with Danishefsky and the eeby catalysis Thu-sreactionoi un uldinlin" (jt'ii)"^ii':' triphenylboratein

J' Ort 57 K. Hatltoriand H. Yamamoto'

t)ichloroketene. Ct Indolizidines; quinolizidines't gent'ntt (l) \-bcnzyl-2-vinylpiperidine

Dichlomketene

o

"\Yill,

r9a t: -

ll9

+

B(OC6H5)3

B-CnHq

o

(S) - 2, 95% ee ( R ) -I

l l L . .-l

z

-l-l

( ' t .-

' thc use of 1,1/-binaPhthYl r r r1 9 9 2 .

C6H5CH=NBzl

.

rr5.r(1992).

l r l Bzl

2, B5o/oee

dienepromotedby (R)-1, generatedin situ, providesthe adduct2 in 85o/oee (equationI). This asymmetric Diels-Alder reaction can be used to prepare (-)-anabasine (5), an

r(-'

L.C-o

o

ocH3

:

cH3cN 1, cH2cl2, 0"

1 , 4 4M . S . c{zct2, -78"

cuHu4f-

:tnr. Comm., 687 (1992). , 503 (1992).

!m. F- -. - rrf this organoaluminumcomto ;\, 'JJition with arYl aldehYdes lt:

(l)

cH2Y'oSi(CHs)s /

1

o

71v"

Bzl/N

77.7"/"

poocH3 -\ {:C

)1 oA"uru

'".a) trans - 3

. r 2 .6 e lI ( 1 9 9 1 ) .

5, tts = -79.2"

:lkaloid derived from nicotinic acid. J. Org., 57,3264(1992). K. Hatltoriand H. Yamamoto,

: Ir\ '- i!ri()ncan be cffectedin72-90Vo ;p.--.1 hv reactionof (R)-BINOL with | , : ,:r .tldimine and the Danishefsky

Dichloroketene. Indolizidines; quinolizidines.r Generation of dichloroketene in the presence of \-benzyl-2-vinylpiperidine (l) generatesan intermediate(a) that cyclizes on warming

l2O

Dichlomketene

to the 10-memberedlactam 2. A silnilar reactionwith the N-benzyl-2-vinylpyrrolidine (3) provides the 9-memberedlactam 4' 2,6-Dichloropyridine N-oxide,

CtA

X

o

i'tl

(^l^"t,

25"

cl2c=c=o

Oxidation.l In the presence of ruth RuTMPOz, and a trace of HBr or HCl. 1 secondary alcohols at 25" in high I ield Adamantaneis oxidized mainly to the l-hrt (15-25Vo) and adamantanone-2(7-21 '1zn

\....,.N-.._..C6H5 1

,"--rAcH" t

l

cl

60'

\.--rya"cctt

CI

Bzl I

oCH.

a

t "

z--zl\CH, ( l \--N..,-CuHu

ct2c=c=o

cl cl

25" 64"/"

..) t

l

RuTPP(CO).H& benzene.20'

+

1

*1

ft""u cyclization and Exposureof either 2 or 4 to 12or c6H5SeBr triggers a transannular quinolizidines(5) from 2 or dcbenzylationkr providc iodo- or phcnylseleno-substituted the analosousindolizidines from 4.

OH .\

t

2

-

12,50" 857"

I E . D . E d s t r o m ,A m . S o c . ,f 1 3 ' 6 6 9 0 ( 1 9 9 1 ) .

cl

l

Il. Ohtake,T. Higuchi, and M. Hirobe. .{a .S

CI

ldisilou I J- Dichloro-1,1,3,3-tetraisopropy t(cH:):cHlzSi(cl)osi(cDcH(cH.):l:I lt Regio- and stereoselectivedihfiranl I exclusivelywith the isolatedcvcloallc \\'hereasdirect osmylationof 2 providcs

1,3-Dichloro-1,1J"3-tetraisopmpyldisiloxane

\ -benzyl-2-vinYlPYrrolidine

,-\

/\i -l-l ClN-o*id", 2,6-Dichloropyridine

l2l

l-Cl

o

(1) Oxidation.r ln the presence of ruthenium porphyrin oxo complexes' such as RuTMPOz, and a trace of HBr or HCl, pyridine N-oxide I can oxidize alkanes to secondary alcohols at 25' in high yield. The reactive intermediate is not known. Adamantaneis oxidized mainly to the l-hydroxy derivativc (68Vo);adamantane-1,3-diol (l-2%) are minor products. (15-25Vo')and adamantanone-2

cl cl

CHa

I '

cl cl

.^> l

l

R u T P P ( C O )H, B r benzene,20'

+

1

'x"* (,

94o/o

ri\

",A*A",

o

*1

ft""u cyclizationand t : - - :. .r transannular u--

C6H5COCH3

o

OH

.:rd quinolizidines(5) from 2 or

.\

t

l

a\ t

l

I

H

.-\

l ^ l I z9l

N -.-4.,

:H. Ohtake, T. Higuchi,andM. Hirobe,Am.Soc.,114,10660(1992).

l " ' o 5

I J-Dichloro-1,1,3,3-tetraisopropyldisiloxane(TIPDS-Cl2), 1' [ (CH: ):CH]zSi(CI)OS(CI)CH(CH:)zlz $6,r2s 126). Regio- and stereoselective dihydroxylation.t This reagent adds to the oxepin ! exclusively with the isolated cycloalkene double bond to provide 3 (84Vo yield) Whereas direct osmylation of 2 provides a mixture of diols in low yield, osmyla-

(Diethylamino) (phenyl)oxosulfonium

methylide

CoHs

1

.<;rCHz

1 ) N B S .C O r 2) (CHgO)rP

coHu:A^ t i

86.3%

f-BocN-_,,\O

84V"

2

--CHz

CoHs

""'lA?

1, NaH, DMSO C6Fl5 18- 25'

l-Bo

t-eocll--r.\O Hnn

R = CHs R = CoHs

82/" 96o/o

I usually gives a single product {. tcl dimethyloxosulfonium methylide results l-3:1. Use of diazomethanealso result arc converted into the desired amino rr dcprotectionof the amino grouP' I R.M. williamsandG.J. Fegley, An. -Sa. I tionof3resultsinalmostcxclusiveattackoftheterminaldoublebond.Whenthe presenceof (S,S)-N,N/-dineohexyl-2,2/-bipyrrolidine osmylation is carried out in the but (867o)is(2S)-5' Howevt:'l*:t-: ieaction' (4) (16,i50-151), the rnu3o'p'oOutt yield(1lVo)' (2S)-5 as the major product'but in lower catalyzedby(R,R)-a' ut'o f'ouidtt by and the regioselectivityare controlled These resultsshow that th; diastereosclcctivity group' the sterically demandingTIPDS

705 (1992)' rO. SatoandM. Hirama,Synlett'

Diisobutylaluminum hYdride. a-Trimethylsiloxy aldehydes'i Ttrc r icld by addition of cyanotrimethvlsilanc rcducedby DIBAH (1.5-2 equiv.)in hcu hv dilutesolutionsof 1-1.6N HISO. at l5 can be hydrolyzed by dilute HCI to a-ht

(cH3bsicN

CoHs -CN X -os

?

cuHrAcH.

cH(

I (Diethylamino)(phenyl)oxosulfonium

methylide'

5' 23r' (1),3' 10s-,106: iGr"ir* (c6Hs)l*so(cH1)BF; o,;ia''t Thesecyclopropyl aminoacidscanbe I-Aminocyclop'ooo'-'--iniuoty'ti'' the a, B-dehydro with ylide

yield by rcactionof this obtainedin high chemicuiun.topti"ui lactones(3) preparedtin'n 1SS,On;-4-t-butoxycarbonyl-5'6-diphenyl-2'3'5'6{etrahydroderived from The reaction of 3 with the ylide 4H-1.,4-oxazin-2-one(2, 1+,SS-SO)'

+

1)NH4C| 2 ) 1 . 3N H C I

C6H5r_-Qg(r

63"/"

cH/\orc 2

Diisobutylaluminum

,-rr\..,_r, P-"''o -o ,si-i-Pr \-Pr

CoHs CoHs

cuHrr-J-^

I

1 ) N B S ,C C t 4 2) (cH30)3P

Y

2

I osoo,(s,s)- q

".t'yA?

cuHu:A^ I Y

'"'-

I

| C H-' C |-, ,- 7 8 o Y

,"'in,j'' pi-iPr -o \i_p,

x .-"rtnal double bond' When the 5, r. r Jincohexyl-2,2t-bipynolidine but |.5 il,,scvcr. thc samereaction, yield(7lVo)' ,Juct. lower in but rr :^. -- Ltosclcctivityare controlledby

CoHs 1 , N a H ,D M S O c u H r : - \ o 1 8- 2 5 "

I

t-eocru:rz\O

I

r-eocru-.*,.\o

1 ) L i ,N H 3 H3N*-.--COO2)H3O-_

H, H

4 1 : 0 1:0

82% 960/o

I usually gives a single product 4, rcgardless of R. Cyclopropanationof 3 with dimethyloxosulfoniummcthylide results in two diastereomericproducts in the ratio l-3:1. Use of diazomcthanealso resultsin a diastereomeric mixture. The products arc converted into the desired amino acids by reduction with Li in NH.r followed by dcprotectionof the amino group. : R.M. Williamsand G.J. Fegley,Am. Soc.,ll3, 8796(lggt). Diisobutylaluminum hydride. a-Trimethylsiloxy aldehydes.t The a-trimethylsiloxy nitriles I, obtained in high r icld by addition of cyanotrimethylsilaneto ketoncs catalyzedby Znl2 (4,542-543), are :cducedby DIBAH (1.5-2 equiv.) in hexaneat 0" to imines (a), which can be hydrolyzed rv dilutesolutionsof 1-1.6N H2SOaat 15" to a-silyloxy aldehydes (2). Thesealdehydes ;an be hydrolyzed by dilute HCI to a-hydroxy aldehydes(3).

(cH3hsicN coHs.-.cN Ri""l,*, n ? :.rr^cH.----------.------* cH/\osi1cH.).-------------* 1

: - . . , ).

:.

-.'l.

T'-.- lclopropyl amino acidscan be tr, " I :his vlidewith the a, B-dehydro t' r

r.o-diphenyl-2,3,5,6-tetrahydro: -l rvith the Ylide derived from

R

"K"

R 3

R=CHg R = CoHs

:St -5(majorProduct)

82 - 96Vo

(H3CO)2P.-:O

CoHs

qAo/^

1) NAH 2) ROH

t-eocN\_,.\O :

86.3ol.

t-BocNr_.\O

=CHz I

123

hydride

1) NH4CI

2 ) 1 . 3N H C r 63v"

CoHs.-.OSi(CH3)3

cH/\cHo 2

HCt,H2O

CoHs._-oH

cu/\cno 3

(lsrR-'sJ 124

DiisobutYlaluminumhydride

By appropriatechoice of i-Bu2AlH of terrninal eno1u11.' Regioselectivereduction regioselectivity to the primary "un be reducedwith marked or i-Bu3Al, terminal "po*lO"t i-Bu2AlH mainly ePoxides ate ted"ted by or the secondary alcohot'"i"tufi-J"uttto to the primary alcohol' use of i-Bu3Al favors reduction to a secondary alcohol' **;; epoxides' Phenyl-substituted in the cure silyl-substituted This regioselectivity is ,.;;; Reduction of theseepoxides mainly to primary-alcohols' epoxides are reducedby i-Bu3Al in THF' best effected with LiAIH+ to secondary alcohols is

nYcHs

'

H- P\ R>-

RCH2.H2oH

+

OH

R = (C6Hs)3Si

fl = C6H5

i-Bu2AlH

95"/"

l

o

..ng n-C16H2'1N-oTt

i-Bu3Al

93"/"

iBu2AlH

90o/o

i-Bu3Al

90o/"

LiAlH4

95"/"

i-Bu3Al

90o/o

1 0 0 :1 0:100

?-CtoHrl l

0: 100

:\"^ors o'

18:82

base

l + ..."tD-OMen ' cHa CzHt

2 DIBAL -78" 85"k

o

O H ? ? cH."\'^---"t*i't'", 1

q H 9

(CH3)4N- HB (OAc)3

A

HOAc

cn/-/)1"t;i,

9O"/o

l

l

.

2. >95"/"de

O H 9 H 9 I ' A

CH{/"*"t';'", 3, 88"/. cle

n-C,olf

ss'/"

Reductive cleavage of hbutyUinahy ion' but thc eenerallycleavedby fluoride to )ield th hours 1-2 in CHrClz at23" in

97'.3

oll l

-

65:35

sulfoxides(1)' preparedby of 1'3-diols3 tT.(*) q: 6-diketo by Asymmetric synthesis arereduced p-toluenesulfinate' with (S)-menthyl of thedianionni BlAit"ton"' reaction

l cH.'/\'

I DIBAH cnzCtz,o..p-( s7%

>98o/oae

R = n-CeHrz

o

(2s)-hydroxl keto DIBAH (2 equiv') to the to the 'rt converted be can de). The products (Evans n ammonium triancetoxyborohydride of 2'3-epry Regioselectivereduction pure 3-all enantiomerically "on r"r*d into -15 - l at CH2CI2 in equiv.) (3 oi"O"

Raney Ni

oH 9H l . cH.McH. (R'R) - 4

andN' Ogunr'Srd I M. Hayashi. T. Yoshiga' : t,t. gisct,,Z.-R.Liu, and M' Singh'J t)rt ' La ti. sorruaieandN. Ghiatou'Tetrahedma 'J. M. Chong,ibid', 33, 33 (1992)' t i.'1. cor"ylnd G' B' Jones'J' org" 37' ltt ( I S,2R,4S,5R)-2,5-Diisopropylcyclobcr PreParation.r'

(cH3)2cH\, HO

(D Ior ct Chiral titanium catalYst ansa-bis{tr chiral titanium catalyst,an of I T ith reaction of the dimesylate

(1) 125 (1s,2R,4s,5R)-2,5-Diisopmpylcyclohexane-l'4-diol

a:-

^llopriate choiceof i-BuzAlH ::rioselectivitY to the PrimarY -rJuced bY i-Bu2AlH mainlY

0:

.-.li()nto the PrimarYalcohol' .: :norides. PhenYl-substituted . Rcductionof theseePoxides

Ir lc.

I

2 with high diastereoselectivity (>95Eo DIBAH (2 equiv.) to the (2S)-hydroxy ketone anti-l'3-diol4 by reduction with tetramethylde). The products can be converied to the reagent) followed by desulfurization' ammonium triancetoxyborohydride (Evans These epoxy alcohols can be Regioselective reduction of 2,3'epory alcohols'a by reduction of their tosylates with converted into enantiomericalli pure 2-alkanols -15 - 25"' DIBAH (3 equiv.) in CHzClz at

Illl

I

9H

DIBAH

CHr +

..nQ

RCH2CH2OH

n-C16H21,.MoTs

CH

-/.\ "illBilt, n-crcH21,"-ycH3 + n-C'roHx' ) I s7"^ 6t ,, : 3 CHs >98o/oee

>98% ee

OH

100:1 0: 100

t-"ttlt ^\.,^ors o '

0: 100 65:35

18:82 bY : \fto sulfoxides(1), PrePared bY reduced are :,,lucncsulfinate,

=-

O H ? ? cHa*tti't'* 1 (CH3)4N.HB (OAc)3 HOAC

l:-

.-n-c,0H2.,^-] n-c1oHz1"'\Y,,ltt

sso/'

6H

94:6

cHs

ethers are ethers's /-Butyldimethylsilyl Reiluctive cleavage of t-butytdimethylsilyl DIBAH by cleaved reductively Uut they can also be generallycleaved by fluoride lon' yield' in84-917o alcohols to yield the corresponding in CHzClz at23'in1-2 hours

97:3

h\

---^: +

9O"/"

I M. Hayashi, T. Yoshiga'and N Oguni'Synlat'-41,9 .(1991)' ';;, 57' 1618.(1ee2)' t;.; Z.-R.Liu, andM' Singh'J' org'' 1605(1992)' 33' r G. Solladi6andN' Ghiatou'Tet'ih"d'onLetters' (1992)' t J.M. Chong,ibid', 33, 33 J' Org'' 37' 1028(1992)' ti.l. co..y1nd G B' Jones' (1)' ( I S,2R,4S,5R)-2,5-Diisopropylcyclohexane'l'4-diol , PreParation.r

(CH3)2CH6...OH

t

l

Ho"'\^cH(cH3)2 OH 9H I ' cn3,McH3 ( R ' R )- 4

of alkenes'z The enantioselec.tivekomerization Chiral titaniun catallst Q) for the dichloride (2)' is preparedby conchiral titanium catalyst,t"l"'-OOtt"denyl)titanium is that product form a of r wiih indenytlithium to rcaction of the dimesyrut.

DimethYlsulfoxonium

methYlide

cH30

o

CH3O

Hs o.(

1

cH3o

v e r t e d i n t o 2 b y r e a c t i o n w i t h B u L i a n d t h e n w i t h T i C l l i n Tfrom H F athe t - . isopropyl 7 8 . 6 5 . . Agroup' single indenyl groupsare placedaway product is formed in which the the isomerization of the LiAiH; (4 equiv ) can catalyze This reagent, when rcduced by in 767o ee' product only 1i1 to 1S;-l as the meso-trans-4-butyf-f-uinyf"ytiohexane

NHCOCH3 (! 4)

(""

a\ t YI

1, L|AIH4 mesitylene,23'

l

c(cH3)3 3

(cHt ll

100"/.

-

I

c(cH3)3 (s)-4, 76ol"

l-"tr--.

I (A , ll . I

l

"t"t.,] (R)-4

r M . G . B a n w e l l ,J . N . L a m b e r t ,M . F \ l e c l r t

(teez).

Dimethyl sulfoxide-Triphosgen€' Triphosgene(CCIIO)2C:O. is a rcad Ofidation.3 This combination(l t rs rmall- and large-scaleSwern oxidatttns

H H

crHr-+cH2oH 1Z. Chenand R.L. Halterman,Synleu'142(1990)' 2ldem,Am. Soc.,114,2216(1992)'

DimethYlsulfoxonium methYlide' C y c l o p r o p a n a t i o n ' , T h e k e y s t e p i n a b i o m i m e t i c s y n t h e s iin s oseveral f ( + ) . c osteps l c h i cffom ine(4) reactionof the tricyclic l, prepared is a regio_and stereoselective 5-bromo-2-methoxyphenol,withdimethylsulfoxoniummethylidetogiveasingleproduct ( 2 ) i n l 5 a o y i e t d . W h e n t r e a t e d w i t h t r i f l u o r o a c e t i c a c i d a tproduct 2 5 " , t h i sisp rconverted o d u c t f e a into rlanges O-methyl ether 3' This in 897o yield to the a-tropolone (+)-colchicine (4) in four known steps'

/-*'r*,

H. EckertandB' Forster,Angew'Chen It .tldrichimicaActa, 21, 47 (1988)' C. Palomo,F. P. Cossio,J.M Ontoria'arrJ

l2-Diphenyl-1,2-ethanediamine. lG l: Asymmetric sYnthesisof l)'dbJt rcactionof (R,R)-l with a l,2-dione to

1,2-Diphenyl- 1,2-ethanediamine

127

H2CSO(CH3)2 D M S O ,1 8 '

ltt

*, c

I

I'HF at -78 -. 65". A single :'.\av from the isoProPYlgrouP' :.rlrzcthe isomerizationof the

cH3o

,'nl)' product in 76Voee'

NHCOCH3

cH30

(1 4)

t.\

r M . G . B a n w e l l ,J . N . L a m b e r t ,M . F . M a c k a y , a n d R . J . G r e e n w o o dJ, . C . S . C h e m .C o m m . , 9 7 4

tl

(tee2).

n: 72' ..

I c(cHs)s (R)-4

Dimethyl sulfoxide -Triphosgene. (CClrO)2C:O, is a readilyavailablersubstitutefor phosgene.2 Triphosgene Oxidation.3 This combination(1) is comparableto DMSO-oxalyl chloride for both small- and larqe-scaleSwern oxidations.

H H

czHs#cH2oH

1, N(C2H5)3 -78-0'

l l /FN. O' PMP

(4) n '- -' . .\nthcsisof (a)-colchicine l. prcparedin severalstepsfrom 1. n:.-- 'le th\ lidc to give a singleproduct :rr. ,-rJ et l5', this product rearranges b(' .r lhis product is converted into

H H

c2Hs+_j-cHo l l /FN, OPMP

ll. Eckertand B. Forster,Angew.Chem.Int. Ed., 26,894 (1987). - .lldrichimicaActa, 21, 47 (1988). (1991). J. Org-,56,5948 F.P.Cossio, J.M. Ontoria, andJ.M. Odriozola, C. Palomo,

lJ-Diphenyl-1,2-ethanediamine, 16, 153-158. Asymmetric synthesis of 1,2-diamines.t This synthesis involves as the first step :!'actionof (R,R)-l with a 1,2-dioneto form a dihydropyrazine(1,2-diimine,a), which

lza

1,2-Diphenyl-1,2-ethanediamine

can be reducedto a piperazine2 by various hydride reagents.The highest diastereoselectivity obtainswith NaBH:CN and an acid catalyst,pyridinium p-toluenesulfonate,in CH3OH at -30', which affords the diaxial product (2). Reductionof the C-N bonds can be effectedby acetylationand cleavagewith lithium/NHr. Somewhatbetter results can be obtained by conversion of 2 to the biscarbamate3 by reaction with isobutyl chloroformateand cleavagewith LilNH3. This 1,2-diaminederivative is cleaved to the

-;

cH3"\"'\oi'--t" (E)-2

I

(S, S)-1,N(C2Hs)3 | hexane I C6H5CH3,

bishydrobromidesalt 4 in 68% yield and 99Vo ee.

I

9BR'* I

c6Hs\ NH,

faoHsn-ru1-cHsl | | | \ll CH.l LauHru"

+ C H 3 C O C O C H 3+ l

|

CoHu."'\*r, ( R , R )1 -

PPTS NaBH3CN, cH3oH,20' _ SSYo

1)CICOO-l-Bu 2)Li/NH3

o\ | \

a

H C6H51.-N--7rCHs | I C6Hur..'\;r1l",rata H 2

NHCOO-l-Bu I

cHs\-AcHs : NHCOO-r-Bu (R,R)- 3

1)-2oo | CH"^

ll-cH,

2) H2o _ 650/o

H{

"'

ery

(E,z)_3 H

coHsr..-N._acHs + 15:1

HBr,AoOH 80"

l

l t'-t'-at. CoHs"" H

of allyl alcohol itself, but rearrangemcnrof r: proceedswith high enantioselectivin..

Enantioselective Darzens reaction.-' Rr hvdeswhen promotedby (R,R)-l resultsin ar can be debrominatedby Bu3SnH/AIBN or err

HBr.H2N

tttfcH. t : HBr.H2N (R,R)- 4, 99o/"ee

Asymmetric lreland-Claisen rearrangement.2 The chiral diazaborolidine S,S-1 rearrangementof allylic esters.This can effect highly enantio- and diastereoselective reagenthas previously been used to convert (E)-crotyl propionate(2) into the (E)- or (Z)-enolate(3) dependingon the solvent and the base(16,155).Thus 2 is convertedinto (E,E)-3 by reactionwith I and ethyldiisopropylaminein CH2CI2in CH2C|2at -78". On standingat -20" for severaldays it rearrangesto the threo-acid4 in >97% ee. Reaction of 2 with I and triethylamine in toluene-hexane results in (E,Z)-3, which rearranges at -20' to the erythro-acid 4 tn >967o ee. The by-product of rearrangement is the bis-sulfonimide precursor of 1. Lower enantioselectivityobtains in the case of esters

d

o CnHqCHO +

N'Q

ll

BrcH2

oc(cH3)3

KOC(CH3)3 HOC(CH3)s

CoHs

OC(CHJ3 3, oe-140o

rith base.Theseepoxidesare easill con\cno irc easily reducedto B-amino a-hvdrorr cs

1,2-Diphenyl-1,2-ethanediamine

-l'he highest diastereose:..," 'rum in t\- : P-toluenesulfonate. honds C-N I R-.:rcrionof the rr \ ll,. Somewhatbetterresults r:'. .r hr reaction with isobutYl n: -. .icrivativeis cleavedto the

(S,S)-1,1-Pr2NC2Hr, ?8R.2 cH^cr,.-78o , 6-\.-cHs

o -

t

l

o'A\"-cH3

cH.,.\.,.

%CHs

(E)-2

(E, E)-3

I( S ,S ) - 1 ,N ( c 2 H 5 ) 3 |

I

r,-ro" I ,rr,ol'u"'"

hexane C6H5CH3,

i

l. Hs

3.Hs

OBRr*

t

*Y"'1

-

?- "" )l -cH,

ru^cH'l a

129

1) -20o 2) H2O > 65o/o

I

o

o

,o\.""t.

,o\c"

cHzx-/',rcHs

cHzx2.,rcHs

erythto-4 (>960/"ee)

threo_ (>g7o/oeel

(E,Z)-3

H C6Hs1.N-"eCHs

t

\*'-"t. CoHs*'' H

6r

of allyl alcohol itself, but rearrangementof various allylic propionateand butyrateesters proceedswith high enantioselectivity. Enantioselective Darzens reaction.s Reaction of l-butyl bromoacetatewith aldehydcswhen promotedby (R,R)-l resultsin an anti-adduct(2) in >91Va ee. The product can be debrominatedby Bu3SnH/AIBN or convertedto a glycidic ester(3) by treatment

H B r . H 2t N

e'

l

-

cH.-=AcH. : (R,R) - 4' 99o/oee

(RR , )-1,

o

HBr.H2N C6H5CHO+

Jl-oc1cH.;.

BrcH2/

N(CcH<)r. -78o

ff

O

9H :

cuHrl-y^oc(cH3)3 Br 2 (98o/oee)

l - ;hiral diazaborolidineS,S-1 l : - , . i - n r c n t o f a l l y l i c e s t e r sT' h i s xi '" rpionate(2) into the (E)- or : 16 . 97Vo ee' Reaction c\- '. rn (E.Z)-3, which rearranges is the lr,:: 'Juct of rearrangement trr '. ',htainsin the case of esters

N . O

KOC(CH3)3 HOC(CHds

82/"

f" ll cuHu-^)i^oc(cH3)3 75"/" :

NaN3

coHs

oc(cH3)3 3, ct6-140o

OH 4

with base.These epoxidesare easily convertedto B-azido a-hydroxy esters(4), which are easily reduced to B-amino a-hydroxy esters.

130

(S)-(+)- or tRx - r

(&R)-1,2-Diphenylethane-1,2-diol,dimethylether

Asymmetric synthesis of B-amino acid esters.4 The chiral diazaborolidine I (16,155) also effects diastereo-and enantioselectivereactions of (S)-r-butyl thioproponoate (2) with N-benzyl or N-allyl aldimines 3 to form B-amino acid esters 4, precursors to chiral trans-B-lactams (5) in 9O-99Vo ee.

"r.? lf-*

r--Y -'-O'-O

+ rY'\ \--\,2 I

LJ 2,R=c-CoHrr

C6H5CH=NCH2CH=CH2 3

*

(s,s)-1, N(c2Hs)s

o tl

C6H5CH3, hexane, -78"

cH.cHrAsc(cH3)3

CH2=61611'N O t t l ceHs/-lAsc(cH3)3 = CHs

r-BuMgX

R'N4 ,

O

L_l'cn, c"(,

4 (antilsyn = >99:1)

5 , 9 0 %e e

I M. Shindo, K. Koga, and K. Tomioka. .{r I M. H. Nantz, D. A. Lee, D. M. Bender, and A. H. Roohi, J. Org., 57, 6653 (1992)' 28.J. Corey and D.-H. I e,e,Am. Sac., ll3, 4026 (1991). 38.J. Corey and S. Choi, TetrahedronLetters,32,2857 (1991). a E. J. Corev. C. P. Decicco, and R. C. Newbold, TetrahedronLeuers, 32, 528'7 (1'991)

(&R)-1,2-Diphenylethane-1,2.dio|, dimethyl ether (1)

c6H: CH3O

,cuHu

(S)-(+)- or (R)-(-)-Diphenyl(l-merbla E nantios elective cyanomethy latiu-l action of BTCHzCN with ZnlCu. adds t cquiv.) to give B-hydroxy nitriles in t{'. the optical yield is markedly decreascd 7U7o).Therefore, I servesboth as a licz

qi

( R , R )- 1 ( 1 6 , 1 5 8 - 1 5 s ) .

i

OCH3

CHr

c6HscHo Asymmetric aromatic allqlation; binaphthyls.t The reaction of l-naphthyllithium with a naphthylimine (2) catalyzed by I provides 3, which is hydrolyzed (H2O' CFTCOOH, NazSO+),with recovery of 1, to the aldehyde 4 in 85% ee. The stereochemistry can be improved by use of a bulky R group in 2.

+

BTZnCHfN

K. Soai. Y. Hirose. and S. Sakata.Tetralx$

(S)-(+)- or (R)-(-)-Diphenyl(1-methyl-2-pyrrolidinyl)methanol (1)

c ,.rrrl diazaborolidineI o.. ,,t (S)-t-butyl thiopron: j-.tmino acid esters 4,

cH.?

liu't

r)r.4. r)v'\/ :-a

l3t

(R,R)-1 c6H5cH3,-45'

Li 2,R=c-Q.11" 3

(s.s)-1, N(C2Hd3 hexane,-78' StHsCHs,

85% I H.o.

t -

'la

R

,

O

L-J

c,H{

CH"

5, 90% ee 4 ,gso/oee

. i-

-r: 5lu7 (1991).

v.

6

rn5-j ( 1992).

' M. Shindo, K. Koga, and K. Tomioka, Am. Soc., ll4, g732 ,lg92).

(S)-(+)- or (R)-(-)-Diphenyt(l-methyt-2-pyrrotidinyt)methanot (l). Enantioselective cyanomethylation.l cyanomethylzinc bromide, prepared by reaction of BrcH2cN with znlcu, adds to aryl aldehydesin rhe presenceof (S)-l (l cquiv.) to give B-hydroxy nitriles in 87-93vo ee. If only 0.3 mol% of (S)-l is present the optical yield is markedly decreased(in the case of C6HsCHO ec falls from 93 to 787o).Therefore, I servesboth as a lieand and a catalvst.

poHs Ar,\-cuHu (s)-1 \Nl, bH

' r 8 ' 15 9 ) .

I

CHs ( s )- 1

c6H5cHo :! :. :r()nof l-naphthyllithium r.:'rih is hydrolyzed(H2O' d- { in 85Va ee. The stereon l

+

BTZnCH2CN

T H F ,- 1 3 "

*

RCH(OH)CH2CN (S), 93%ee

K. Soai, Y. Hirose, and S. Sakata, Tetrahed.ronAsymmetry, 3, 6j7 (1gg2)

r32

Diphenylsilane/AIBN

Diphenylsilane/AlBN. into alkenes by Alkenes from vic-diols.r Bisldithiocarbonates) can be converted areequally initiator an and Diphenylsilane (8,499). reactionwith tributyltin hydride/AIBN particularly gives reaction radical This effective and avoid use of toxic tin compounds. high yields in reactionsof nucleosidederivatives' 1 ) N a H ;C S 2 ,C H 3 l

R3Siq

2) (c6H5)2siH2,AIBN 80- 1100 > 911"

\)-e"s" Hd

R35iq \)-4"""

OH

lD.H.R.Barton,D.O'Jang,andJ.Cs.Jaszberenyi,TetrahedronLetters,32,2569(1991').

Enzymes. The earliest use of enzYmesr common bakers' Yeast (Sacc/rarv in the wine industrY.Although tt

by fermenting Yeastto benzvl-l' reactionwas viewed as a challcq as the biochemical one. Indeed t reportedin Organic Synlfteses.Ho

ways as shown bY two exhaust reports, more examPles from I cnantiomericexcessis at least)9

tbr preparation of enantiomerice The recent decisions of the Fo cnantiomericdrugs ratherthan to

ro use of enzymesor other as1Bakers' Yeast is used almo h-v a dehydrogenasewhich usrl

reductions,highest enantiosele ketones.B-Keto estersare also p-keto acids can also be reducc Yeast contains a varielv of cnzyme is preferable' These art and liPases.I lvases,isomerases, Purified reductasesusuallYrequ can be used as biocatalYsts.A

available.5These reductionscar The most widelY used enzrr nitrilases,ProbablYbecausetk commerciallY.TheY are Partic Esterasescan also .r'nthesis.s'e

Enzyme-catalYzedtransesterific and diols.lo A promisingnew areaof enz rcdox systemsthat are not PY-ri benzylviologen(commerciallr I

eas,formate, or carbon monorr sourceis a 2-enoatereductase.c

-.1:rbc convertedinto alkenesby - . ..rlanc and an initiator areequally ry': l' - :.'Jical reactiongives particularly tt..

>

::..

Enzymes. The earliestuse of enzymesas reagentsfor enantioselectivereactionsemployed the common bakers' yeast (Saccharomycescerevisiae), which had been used for centuries

R 3 Soi

\y

Base

. 'n Ldters, 32,2569 (1991).

in the wine industry. Although it was known in 1966 that benzaldehyde-l-dis reduced by fermenting yeast to benzyl-r-d alcohol in looro ee, this example of an asymmetric reaction was viewed as a challenge to chemists to develop chemical systems as efficient as the biochemical one. Indeed only two examplesr of enzymatic reactionshave been reported in Orgonic Syntheses.Ho'vre\er, Jeast reductionshave proved usetu) in numerous ways as shown by two exhaustivereports listing nearly 700 references.2 Since these reports' more examples from 1988 through 1991 have been listed if the reported enantiomericexcessis atleast)95Vo.3 This last review coversthe general useof enzymes for preparation of enantiomerically pure compounds (gg0 references). The recentdecisionsof the Food and Drug Administrationto give preference to single enantiomericdrugs ratherthan to the racemateswill undoubtedlyprovide further impetus to use of enzymesor other asymmetricreactionsin drug design.a Bakers' yeast is used armost excrusivery for reduction, principalry of ketones, by a dehydrogenasewhich usually follows the prelog-cram rule. As with chemical reductions,highest enantioselectivityobtains with aromatic aldehydes and aryr methyl ketones.p-Keto estersare arso reduced with high eanantioserectivity by yeast. some B-keto acids can also be reducedefficiently to (R)_B_hydroxyacids. Yeast contains a variety of enzymes, and in some cases use of a single purified enzyme is preferable.These are divided into oxidoreductases, transferases, hydrolases, lyases'isomerases, and lipases.Many of theseare commerciallyavailable(but expensive). Purified reductasesusually require expensivecofactors.In addition individual microbes can be used as biocatalysts.A general review of microbial asymmetric reductionsis available.5These reductionscan be the oppositeof those of yeast. The most widely used enzymesare the hydrolytic enzymes: lipases,proteases,and nitrilases,probably becausethese enzymes do not require cofactors and are available commercially. They are particularly useful for resolution of esters,6,? and for organic synthesis.8'e Esterasescan also catalyzeesterificationif the water concentration is low. Enzyme-catalyzed transesterification can be used for resolution of secondary alcohols and diols.ro A promisingnew areaof enzymaticreactionsis that of anaerobes. Theseorganismsuse redox systemsthat are not pyridine nucleotidedependent,but can use methylvirorogenor benzylviologen(commerciallyavailable)as mediators.Erectron donorscan be hydrogen qas' formate, or carbon monoxide rather than glucose.rl The first new enzyme from this sourceis a 2-enoatereductase,effected with stereospeclfic trans-addition of hydroeen. An

134

EPhedrine

additionaldoubleortriplebondinconjunctionisnotreduced.2-Enalsalealsoreduced, butreversibly.A2-hydroxycarboxylateviologenoxidoreductamhasalsobeenidentified. Carboxylicacidreductase.f,o,nunu",obescanreduceacidstoaldehydesinthepresence of methYlviologen. Anothernewdevelopmentinenzymaticreactionsistheuseofmonoclonalantibodies ascatalysts.Theseantibodiesshowregio-andstereoselectivity'substratespecificity,and rateacceleration.Hilvertl2hasdiscussedthreedifferentreactionsthatalecatalyzedby theseantibodies:decarboxylation,Diels-A|derreactions,andClaisenrearrangements. possibilities' This catalysis is a new field with tremendous (1990). 1 (1985);K. Mori andH. Mori, ibid.,68,56 1D. Seebach et al., organic Synthesis,63' (1991)' 49 9f' Rev'' 2S. Servin,Synthesis, I (1;qi; R. CsukandB.I' Glanzer'Chem' 1071(1992)' 3 E. Santaniello,P. Ferraboschi, P. Grisenti,and A. Manzocchi,chem' Rev',92' 4 "Chiral Drugs,"C&EN, Sept' 28, 46 (1992)' 5 H. Yamadaand S' Shimizu'Angew'Chem'Int' Ed'' 27' 622 (1988)' 6C.-S.Ch"nandC.J.Seh,Angew'Chem'lnt'Ed'28'695-707(1989)' 1047(1991)' 7 W. Baland,C. Frescsel, and M' Lorenz'Synthesis' 8A.I.M.Janssen,A.J.H.Khunder,andB.Zwanenburg,Tetrahedron,47,4513,7409,7645(|991). PureAppl. R. Sumayev,and M. Schneider, 9U. Ader, P' Andersch'M. Bergu'U. Goesgens, Chem.,64, 1164(1'992)' '753(1990)' r0H. G. Leuenberger,PureAppl' Chem'' 62' (1992)' rrH. Simon,PureAppl' Chem',64' 1181 12D.Hilvert,PureAppl' Chem',64' 1103(1992)'

l' I J
-oH a . . ( .-NH .., + CoHs"' Bzl

6HsQ

/CHCOOC2H5 HO

(

(R)

y; CeHi

(2Sr

a-Amino esters.t (2S,4R)-l is clearcd The diastereomcrst high diastereoselectivity' I by flash chromatography' Bisdebenrv-lalton (3) in >987o ee'

ether

o' (2S,4R)-1 + (CH3)2Zn

-

'/ HO

Ephedrine. Enantioselective addition of Bu2cuLi

to enones.t

Preliminary results indicate

t h a t t h e p h o s p h o r u s d e r i v a t i v e l o f e p h e d r i n e c a n s e r v e a s a c h i r a l l i g a n d f oHighest rdibutylreactionof (-)-ephedrine with HMPA' cuprates.The ligand (+) is obtainedby cuprate two equiv' of I for one equiv' of the enantioselectivityis oUtainedby use of

H

CoHs CHe L-n"-eru1CH.;,

V4x

CHs 1

andbyadditionof4equiv.ofLiBr.Howevertheenantioselectivitycanvaryfrom0to T5voeedependingonthesourceofCul.Severalrelatedchiralphosphorusligandshave also been known to show moderate enantioselectivity' lA.Alexakis,S.Mutti'andJF'Normant'Am'Soc''113'6332(1991)'

rC. Andres,A. Gonzillez'R' Pedrosa'A Pcrc Leuers' 33' t' Tetrahedron F. G6mez-Beltr6n,

Ethyl (S)Jactate. tx:t Chiral sulfoxides'l These have routc this but (n'53)' oxidationof sulfides morc E3 sulfoxides (ee up to 92-96%)' A

Ethyl (S)-lactate

D{.

F

-.J. l-Enals are also reduced, .-:.im hasalsobeenidentified. . :o aldchydesin the presence

'-.

:r\c of monoclonal antibodies

c l - . : \ r r \ . s u b s t r a t es p e c i f i c i t y , a n d !.' 'J.ictions that are catalyzed by .rnd Claisen reaffangements.

B.-.

(2S,4R)-2-Ethoxycarbonyl-4-phenyl-1"3-oxazolidine (1). Preparation:

,oH

cH3o CH2Cl2,MS r(.... * -C6Hr"' .. -NH lHcooc2H5 HO

Bzl

(R)

rl:::..

. . __ . ' r \ S ) . - -rl()ttg). F u -,. :.,,,1.17, 4513,7 409,7645 (1991). , ure APPI. F . . . . . r n d M . S c h n e i d e rP

coHi

T^ \e/-cooc2Hs 'Bzl

c6Hi ag,rz

(2R,4R)-1

(2S,4R)-1

a-Amino esters.t (2S,4R)-1is cleavedby dialkylzinc reagentsin ether at 0' with The diastereomerscan be obtained as optically pure products high diastereoselectivity. by flash chromatography.Bisdebenzylationaffords pure ethyl (R)-a-aminocarboxylates (3\ in >987o ee.

(2S,4R)-1 + (CH3)2Zn Preliminary results indicate r.\. ?:-.- .,\ a chiral ligand for dibutYl- , .nhcdrincwith HMPA. Highest r.: I l()r onc equiv. of the cuprate

?3ot"'.

\efrt'B.l

o : , - . : :l l M o r | i b i d . , 6 8 , 5 6 ( 1 9 9 0 ) . '. r , .r Rt't., 91,49 (1991). r, - r hL'm.Rev., 92, lO71 (1992).

C6H5 COOC2H5

ether 0'

t

l

(^f^t"' HO

Bzl 2

*

c6Hscooc2Hs t l "'ctts

(\N/ HO Bzl

86:14

I H2,PdlC

{ cooc2H5 HrN^cH. (R)-3

h

I C. Andrbs,A. Gonz6lez, M. A. Salvado,and S. Garcia-Granda, A. P6rez-Encabo, R. Pedrosa, Letters,33, 4743 (1992). F. G6mez-Beltrin,Tetrahedron

I t r - - ,.clcctivity can vary from 0 to

ligandshave a : : , : -riral phosphorus tlr .

rq9l).

Ethyl (S)-lactate. Chiral sulfuxides.l These have been prepared by a Sharpless-type asymmetric oxidationof sulfides(13,53),but this route is only efficient for preparationof aryl methyl sulfoxides(ee up to 92-96Vo). A more generalroute involves reactionof a pure chiral

(E)-Ethylidenecyclopmpanone

136

ketal

cyclic sulfite (2) with organometallicreagents.It is particularlyuseful in the caseof the sulfite2, preparedas shown from ethyl (S)-lactate.The reactionof 2 with an alkyllithium

cH3 ,cH3 ^ oxo *

cH1;lrocttr

^J

->

2c6H5Mscr "tt1r"utu >

C6H3C>+ 60'

8ar

soct2,N(c2H5)s

,J rd'cut,

\

cHcoocH3 cHcoocH3

CHs 50% overall

cH3(

1

1

CHe poHs *C^H.

d.'s-.b l"o 'tr"nr-z

CHs

,CoHs cH3Mst ,K"utu -HO p 7O/" CH"-S.

-

6!

"'..

n-OctMgBr, A

-'100o/o

CHo

./

n-Oct

- s'o l

+1

(R)-4(100%ee)

cH3od

cts -2460 |

1 ) n - O c tM g B r( 6 1 % ) 2) cH3Msl (-100%)

|

I n-Oct. ,CH3

:csult in productswith four chiral ccnta

+ 1

.('.o (S)-4(100%ee)

or alkyl Grignard reagentproceedswith marked regioslectivityand complete Inverslon of sulfur to provide a sulfinate(3), which on reactionwith a secondorganometallicgives a chiral sulfoxide (4) in quantitativeyield togetherwith the chiral auxiliary diol l. The method is particularly useful in preparationof alkyl l-butyl sulfoxides since t-BuMgCl reactswith trans-2with a selectivity of 95:5 in contrastto that of CHjMgCl (80:20). I F. Rebiere, O. Samuel,L. Ricard,and H. B. Kagan,J. Org., 56,5991(1991).

(E)-Ethylidenecyclopropanoneketal (l). [3+2]Cycloaddilion to alkenes.r The ketal I when heated (60-100") can undergo regio- and endo-selective[3 + 2]cycloadditionto electron-deficientalkenes.Since hydrolysis of the adduct proceedswith >90% stereoselectivity,this cycloaddition can

{r S. Ejeri,S. Yamago,and E. Nakamura.

(E)-Ethylidenecyclopmpanone

-:;lrrlv usefulin the caseof the ,.rion of 2 with an alkYllithium

F ft

CHs ,CHs

.1

o--.-o + cHcoocH3 cHcoocH3 /\

->

i.

SOC|2, N(C2Hs)3

CHg -rr

50% overall 1

| "oo", "ro I .r l^Q'

'

l0oo

CH3 ,n-Oct

..t"'o

?"

+1

(R)-4(100%ee)

O-\--OCH29CH20H l

l

cH" I z\--cHs \ / cH3o2c'

borcH, >9:1

rcsult in products with four chiral centers with high stereocontrol i S. Ejeri, S. Yamago, and E. Nakamura,Am. Soc., 114,8707 (1992)'

t\f . i

lr

i

..;itrvitv and completeinverston "r .r \cc()ndorganometallic gives r rhc chiral auxiliarYdiol t. The ''utrl sulfoxidessince l-BuMgCl -' :Lrthat of CHsMgCl (80:20). s 6 5 e 9 l( 1 9 9 1 ) .

il I .\ hcn heated(60-100') can unrlcctron-deficientalkenes.Since u. -ricctivity, this cycloadditioncan re'-

ketal

137

Ferric chloride. Perylenequinone(2).t

A novel route to this quinone (2) involves double coupling (1), prepared as shown, by treatment with FeCl3 of the 5-bromo-1,2-napthoquinone

o /'\/-\

t

l

l

equiv.) is most satisfactory,and CH.1NO; rs tl

OAICb

1 ) S e O z ,H O A o( 7 1 " / . ) 2) NBS, H2SO4(41%)

l

This is a fairly generalanomerization.tetn are labile to FeCl3, but reactionsare fa^steru with furanosides.The reaction of the glrcos temperatureand is complete in 15 minutc'st.r Oxidative coupling of ArOAlC12.' Otxt plicated mixtures, but oxidative coupling of , route to hydroxylatedbi- and tetraaryls.The s phenolswith AlCl3 in CHTNOz and need nt{ I

coocH3 coocH3

A

2 | \/

FeCl3 CH3N02,25'

I

I

CHg

CHg

l0ol. FeCl3/CH3CN 25' 910k

FeCl3 CHsNOz,80'

cH3o cH30

CHs

ocH3o 2 in anhydrousacetonitrileat 25". Anomerization catalJst.2 In the courseof debenzylation/4-methoxycinnamoylation of the a-glycopranosideI promotedby FeClj, Nakanishie/ a/. observedthat the anomeric p-methoxyl group is anomerizedto give a-glycoside 2 (a/B : 95:5).

BzlO

ocH3 BzlO

"'oBzl

1) FeCl3 AgOTf 2) 4-CH3OCinnCl,

OR t

^

vo)*...ocH3

t l RO/Y,,OR

OR 2, R = CHzOCinn

tf$. -15I I Z. Diwu and J.W. lnwn, Tetrahed762, \. Ikemoto, O.K. Kim, L.-C.l-o, V. Satlanan ! etters,33, 4295(1992). (i. Sartori,R. Maggi,F. Bigi, A. Arienti.G (est ,r1r.t3 (1992).

lluorosilicic acid, H2SiF6. Desilylation.l This acid is less acidic rh jffcct on acid-labileprotectinggroups.A funL ,i r-butyldimethylsilylethers in the Prcs.'nct .rhers. The selectivity of HzSiFr,can be enh :ficctive than DMAP). The cleavageis effccr .ifter one hour.

RL t A. S. Pilcher,D. K. Hill, S.J. Shimshock. r 1992).

Fluomsilicic

rr- - . i 2) involvesdoublecoupling s . rn. hy treatment with FeCl3

acid

139

This is a fairly generalanomerization.tetracetyl,Acetonidesand benzylidine acetals are labile to FeCl:, but reactionsare faster with acetyl derivatives.The method fails with furanosides. The reaction of the glycoside I is carried out in CHzClz at room temperatureand is complete in 15 minutes to 5 hours. oxidative coupling of phenols results in comoxidative coupling of AroAlcl2.3 plicated mixtures, but oxidative coupling of dichloroaluminum phenolatesis a useful route to hydroxylated bi- and tetraaryls. The starting material is obtained by reaction of phenolswith AlCl3 in CH:NOz and need not be isolated.Of severaloxidants,FeCl3 (1 equiv.) is most satisfactory,and CH3NOz is the preferredsolvent.

ocH3o

"-'-)-'-ro

QHs FeCl3 cH3N02, 25'

i l l )\z\/coocH3

h:

Br CHs

rsomers

+ 98:2

lFl FeCl3 cH3N02, 80'

coocH3 'coocH3

+

tsomers

98:2

CH

r-- r .,:r()n-l-methoxycinnamoylation thatthe anomeric .',i1.rrhserved n:. N l , c - 1 , (Br : 9 5 : 5 ) . OR

: ! -

\,.o{'.ocH3 | | eo/'{""oR t

l

I OR 2, R = CH2OCinn

' Z. Diwu and J. W. Lown, Tetrahedron, 48, 45 (1992). I N. fkemoto,O. K. Kim, L.-C. l-o, V. Satyanarayana, M. Chang,and K. Nakanishi,Tetrahedron Letters,33, 4295 (1992). t 48, G. Sartori,R. Maggi,F. Bigi, A. Arienti,G. Casnati,G. Bocelli,and G. Mori, Tetrahedron, e483 (1992).

F-luorosilicicacid, H2SiF6. Desilylatian.t This acid is less acidic than HF, and can effect desilylationwithout c-ffecton acid-labileprotectinggroups.A further advantageis that it can effect desilylation of r-butyldimethylsilylethers in the presenceof l-butyldiphenylsilylor triisopropylsilyl cthers.The selectivity of HzSiFe can be enhancedby addition of triethylamine (more cffectivethan DMAP). The cleavageis effectedin CH:CN at 0" and is usually complete after one hour. J. Org.,57,2492 andP. DeShong, R.E. Waltermire, D.K. Hill, S.J. Shimshock, A.S. Pilcher, \t992).

+ (CH3(CH2)aCO)20

Gallium(Il) chloride, GaCl' GaCl: (Ga2Cla)' ReductiveFriedel.Craftsreaction.|Reactionofaniso|ewithGazCla(2equiv')and anaromaticaldehydeinCS2atloomtempelatureresultsindiphenylmethanes.Similar reaction involves the reducing resultsobtain with ketonesand aliphatic aldehydes.This ability of GaCl and the Lewis acid activity of GaClr'

'ffi cHo Ga2Cl4 cs2,25"

,\

i l l

cH,o)J

47v"

Y

+

11 ,"\a/\/\

i

OCHs

\2\ocHs 89 .

l

t

i

l

\z\ocn\Z\o*r.

T. Ohno,T' Nishimura'S S T. Mukaiyama, : T. Harada,T. Ohno,S. Kobayashi, andT I

Grignard reagents. Modified Grignard reagents, RUg) hv reactionof RLi and Mgtz [L:OSO: ligand can exert a marked effect in ad rcactsexclusivelywith an aldehydein tl .rldehydein high selectivity (equationl

l

o (r)

c6H5cHo *

"rru^

CHsQ

?""'

U

cHo ..\

l

l

33' 6357 I y. Hashimoto, K. Hirata, N. Kihara, M. Hasegawa, and K. Saigo, Tetrahedron Letters'

(1ee2). Gallium(IlD chloride-Silver perchlorate' Friedel.Craftsacylation.ThisreactionisgenerallyeffectedwithAlClr'buta stoichiometricamountisrequired.SinceacombinationofLewisacidsissometimes et al.t have examined the reactivity more effective than a single t-ewis acid, Mukaiyama AgCloa and report that the combination of of several lrwis acids in combination with AgClOawithGaCl:,AlCl3,orBCl3resultsinacatalystthatcaneffectFriedel-Crafts when Agcloa and Gacl3 are present uilution in good yield. Highest yields are obtained presumablyGacl(clo+)2, and high is in the ratio of 2:1. The altual catalytic species catalyst'2 yields are obtained by use of I0 mol 7a of this

c6H5YcHo

cH3MgL

CHs

L=Cl'Br'l L=OTs L=OAc

The ligand has a marked effcc :'chiral aldehydes(equationIl). lt can .:lohexanones(equationIII).

Grignard

+ (CHg(CHz)rCO)zO

reagents

?"r'

G a C l 3/ A g C l O 4( l : 2 ) cH2cl2,35'

,t\

VI

9'1"/"

oA(cHr)o CHs .{,lc with GazClq(2 equiv') and Similar . rn diphenYlmethanes' rc.rctioninvolvesthe reducing

' : (

ocH3

hC

Aq

. 't1 -.,-\.'\. l

+ t

i

I T. Mukaiyama, Chem.Letters,7059(1991). S. Suda,andS. Kobayashi, T. Ohno,T. Nishimura, : T. Harada,T. Ohno,S. Kobayashi, 1216(1991)' Synthesis, andT. Mukaiyama,

Grignard reagents. Modifi.ed Grignard reagents, RMgL.t These Grignard reagents can be prepared bv reactionof RLi and MgL, [L:OSO2CFr, OSO2CHj, OCOCHI, OCOC(CH3)r]' The ligand can exert a marked effect in addition to carbonyls.Thus cHrMgococ(cHl)l rcactsexclusively with an aldehydein the presenceof ketone to form the adduct of the .rldehydein high selectivity (equationI).

l

l

o

l

-ocn\Z\ocn,

(l)

C6H5CHO

+

CH3MgOcoC(CH3)3

cuHrAcH.

- n3v,

?*. c.HuAoH

cH3lcH3

*

cu"u^o"

99:1

li

\

\.irtl(). TetrahedronLetters' 33' 6351

c6H5YcHo

CH3MgL

"utuyo"".

i ' , : , . 1' t . l

-.

U6nS -- -,,\^,

CHs

CHs

but a ; .,':-i.rllv cffectedwith AlCl3' sometimes is ni ::rr,nof kwis acids a" t . : ,tl.r haveexaminedthe reactivity of 1"o. .rntl report that the combination Friedel-Crafu : - :i.,lrst that can effect are presenl tx.: .\ tcn AgClOa and GaCl3 '-i:urritbly GaCl(ClOa)2'and high 1 -

9H :

OH I

L = Cl, Br, |

8Oo/"

70:30

L = OTs

76/o

92:B

L = OAc

83o/"

9 1: 9

I CHs

, \.rr3

The ligand has a marked effect on the reaction of Grignard reagcnts with :.chiral aldehydes(equationII). It can also affect the addition of reagentsto substituted .',:krhexanones(equationIII).

Grignard

reagents

_o (llr)(cfthc-H OH

?ut' (cH3)3c=JA?oH

1cH.;.c-AfcoHs

lM.T.

C6H5MgBr

94o/o

49:51

C6H5MgOTf

87"/o

73:27

C6H5MgOTs

9O/"

85:15

l. l, 1,2,3,3,3-Heptamethyltrisilane,( CH t, I I Preparation. Radical reductions.2 This silane is I :cduction of substrateswhen the produo r tcneral procedureit is used in combinatioo ,r 75-90'. It is effectivefor reductionof ha

\1. Kumada,M. Ishikawa,andS. Maeda../ () : t'. Chatgilialoglu, A. Guerrini,and M. Luc:ru

Reetz, N. Harmat, and R. Mahrwald, Angew Chem.Int. Ed., 31,342 (1992).

Hexamethylditin.

[4+IlRadical annelation.t Inadiatro 'rJone 1, phenyl isocyanide(5 equiv.).ari :: tl0'results in the tetracycle2 in -l{X? 1

"

z^r)

o tl +

C6H5NC

,r/\-/

[ .s

'\-1

o

| \z\')'-("<, \-/

|

\ modificationof this radical annclatio '. radical annelationof the pyridone 3 *i ":;ursOf to 5.

?utu ctr.yrc=rA/-oH 19 :'

rc.':

l:

l

CH: (CH!)3Si-S iH-S(CH3)3 1,L,1,2,3,3,3-Heptamethyltrisilane, Preparation.I Radical reductions.2 This silane is less reactive than Bu3SnH, but is useful for reductionof substrateswhen the product is formed by slow hydrogen transfer. In the generalprocedureit is used in combinationwith AIBN (lO-zOEo) in tolueneor benzene at 75-90'. It is effectivefor reductionofhalides, selenides,thionoesters,and isocyanides. rM. Kumada,M. Ishikawa, Chem.,2,478(1964). and S. Maeda,J. Organomet. : C. Chatgilialoglu, A. Guerrini,and M. Lucarini,J. Org., 57,3405(1992).

'

| ,t . 3r.342(1992). Hexamethylditin. [4+1]Radical annelation.t lrradiation of a mixture of the N-propargyl bromopyridone l, phenyl isocyanide(5 equiv.), and (CH3)rSnSn(CH:): (1.5 equiv.) in benzene at [ifO"results in the tetracvcle2 in 4O% vield.

o n

.z^y) gr-'\-'

[(CH3)35n]2,hv c6H6, 80'

+

C5H5NC

[*^lr"] 4O"/"

A modificationof this radical annelationprovides a synthesisof (+)-campothecin(5) 'r radical annelationof the pyridone 3 with phenyl isocyanideto provide 4, a known ::ccursorto 5.

t44

5-Hexen-l-Yllithiums

9H' cH.J

o

f"t.-".

-78' 1)r-BuLi, 2)'7a"'>25" -

IL

I

z^l^l H'

[(CH3)3Sn]2, hv, C6H6, 80"

,,/*co2cH3

CHc

cHxH3

il-

CzHs

f^-cn' V1l

C6H5NC

_

+ TMEDA

1o%*

\_f

77"/"

T \ ( ; w. F. Bailey,A. D. Khanolkar, K' Gavaskar' .1m. Soc.,ll3, 5'120(1991)'

Dimerization of

catalyst' particularly l'3'dienes'2 In the presenceof a Pd(0)

Hydrogen Peroxide. Hydroxylation of naphthalene't Rcacttr or in HF (lovo)lpyridine (307a)at 10" to ltl' rield in which l-naphthol is the major pndu pcracid(HF/SbF5'HF/BFr), 2-naphtholis ot'ta

bis(dibcnzylideneacetone)palladiumIPd(dba)' ]'1'3-dienesreactwithltoaffordadducts (2) of dimcrization-doublestannation'

a6y'YcH2

* [(cHs)ssn]z

Pd(dba)2,0' 89%

(crtdrsn*Sn(CH3)3 2

I Hror,Hr/sor..-za', 50"/" fD.P. CurranandH. Liu, Am Soc.,f14' 5863(1992)' (1992)' 2 Y. Tsuji andT. Kakehi,J.C.S. Chem.Comm''IOOO

5-Hexen-I -yllithiums. prepared by cyclization to (cyclopentyl)methyllithiums.t 5-Hexen-l-yllithiums, (cyclopentyl)-78", to cyclize 25" on warming to iodine-lithium exchange at methyllithiums.CyclizationcanbefacilitatedbyadditionofTHF'TMEDA,or Substituted substrates show considerable pMD'TA (pentamethyldiethylenetriamine). stereoselectivitY.

1

:r()ta result of rearrangementof the hldrotr .uperacid may involve a naphthaleniumn-n Allql hydroperoxides.: Direct al\rlatr ROOH is usually unsatisfactory,but alkrl pc rvdroxymercurials2 proceedsreadilr. .{fia :rre demercuration(NaBHa) followed hr d h"'droperoxide3 in 30-557o overall f icld

Hydrogen peroxide

.l "t,t'

ll:;?:!;1$ [ -.------------------* l"t.-./) \_J r [

| -]

cH3oH --'*cH.*

cH2Li

,u",rrr,H,.r,r1

CHz CH3\-.CH3

-1rt

/*," (,,..--;

\_l

+ TMEDA

lW.F. Bailey,A.D. Khanolkar, T.V. Ovaska,K. Rossi,Y. Thiel' andK.B. Wiberg, K. Gavaskar, Am. Soc.,ll3,5720 (1991).

o C

l'.i{ll) catalyst,particularly ,it *ith I to afford adducts

Hydrogen peroxide. Hydroxylation of naphthalene.t Reaction of naphthalenewith H2O2 (907o) in HF in HF (7\%o)lpyridine(30%) at -10" to 20' gives mixtures of naphtholsin 26-43% or yield in which l-naphthol is the major product. If the reaction is conductedin a superacid(HF/SbF., HF/BF.), 2-naphtholis obtainedalmost exclusively.The differenceis

OH I

H 2 O 2H , F , - 10 - 0 '


oz',-.Sn(CHs)s | "ror,"r/soru,-rr'

i

9 8 . 4: 1 . 6

?

1 . 8: 9 8 . 2

C\-

tu

-l rllithiums, PreParedbY .relizc to (cYcloPentYl):' ,rf THF, TMEDA. or .:rirrcs show considerable

not a result of rearrangementof the hydroxyl group. Thc reaction in the presenceof a superacidmay involve a naphthaleniumion. Allql hydroperoxides.2 Direct alkylation of hydrogen peroxide as a route to ROOH is usually unsatisfactory,but alkyl peroxymercuriationof alkenes(l) to provide hydroxymercurials2 proceedsreadily. After protection of the peroxide group, selective demercuration(NaBHa) followed by deprotection (HOAc, H2O) provides alkyl hydroperoxide3 in 3O-55% overall yield.

Hydrogen pemxide- Peroxotungstophosphates 1) H2O2(3Oo/.), Hg(OAc)2

2) KBr C 6 H s C H : C H 21

"utu1^rnr..

,ocH3 CHz:C.^..

^

u ru-u-r^HgB,. " I ooH

OH

NaOH

"'#o""'

cnscooH, Hzo

I O-^

NaBH4,

o-o

90%

PYHors

C6H51 -.CH3 Y

cH3(cH2)5cH(oH)cH20H

c13

\J

| cHs-^ocHe CHs

C6Hs -._.,CH3

cH.AoHtoH)(cH2)4cH3

I ooH

38"6 overall

3

OH OH r c . A . o l a h , T . K e u m i , J . C . L e c o q ,A . P . F u n g ' a n d J . A . o l a h , J ' O r g ' , 5 6 ' 6 1 4 8 ( 1 9 9 1 ) ' 2 A. J. Bloodworth, C. J. Cooksey,and D. Korkodilos,J. C' S' Chem' Comm', 926 (1992)'

Hydrogen peroxide - Peroxotun gstophosphates. acid with H2O2 The metal catalyst is preparedby reaction of 12-tungstophosphoric and cetylpyridinium chloride' Oxidations with H2O2,t In the presenceof this catalyst, internal alkynes are

I Y. Ishii andY. Sakata, J. Org., 55,5549( lgq)L

oxilt Hydrogen peroxide-Rhenium(Vll) Oxidatrr alkenes.t of Dihydroxylation H1O2at 90' catalyzedby RezOr results in r'

oxidizedby H2O2 (35%) to epoxidesand a,B2-enones'

H2O" F Dortr

ClaH2e

PrC=CPr

cat. HzOz, cHCr3,25"

? lt

.ceHs

3&

CH2

O ll

o 620/o

15o/"

PrCH=CHPr

60

Klaas,and M. St1\r i \. Warwel,M. Ri.ischgen under the sameconditions,a primary-secondaryvic-diol is oxidized to a 1-hydroxyoxidized. 2-alkanone in 45-9OVo yield, whereas a primary-tertiary vic-diol is not Secondary-secondaryvic-diols are oxidized to a-ketols in modestyield or overoxidized to carboxylic acids.

H1'drogenperoxide-Tirngstic acid' H;O; Oxidation of cycloalkenes to diadcht' 'zone,but can also be effectedwith H;O; c

Hydrogen pemxide-T[ngstic

,OCHg CHz:C.'CHg

CH3(CH2)sCH(OH)CH2OH+

acid

cH3(cH2)5cocH20H 9Oo/"

HnRr

PyHOTS )F

o tl

OH -,cooH, i'O

I

C6Hs\\,,,cH3 I

cH3

cH(oH)(cH2)4cH3 85%

cH.

2:3 O tl "'\- (cH2)4cH3 cH3cH (oH) +

ooH

_i8," . eratl

3

;F

cHloH)(cH2)4cH3

o +

oH

,{ t

tL.

, rr(.,56,6148(1991). -: ( omm.,926(1992).

.:,,phosphoric acid with H2O2

OH

rY. Ishii andY. Sakata, J. Org., 55,5549(1990);idem,ibid., 56,6233(1991).

Hydrogen peroxide-Rhenium(VlD oxide, H2O2- Re2O7. Dihydrorylation of alkenes.t Oxidation of terminal, internal,or cyclic alkenesby H2O2at 9O" catalyzedby Re2O7results in vic-diols in 60-80% yield.

r f - . ,r.tlvst, internal alkYnes are r..

c,,oHrnAcH,

OH

H2O2, Re2O7 Dioxane, 90"

broHrr-l-'---oH

aYo' \ o H

o f

327o

- pr-[--jc'Ht OH 15o/"

PrCH=CHPr

,r\tt OH

Klaas,and M. Sojka,J.C.S. Chem.Comm.,1578(1991). S. Warwef,M. Riischgen \ . .rrt'lis oxidizedto a l-hydroxy'- '- -'r.rr\ vic-diol is not oxidized' ntodestyield or overoxidized :t -

Hydrogen peroxide-Tirngstic acid, HzOz-WO:' nH2O. oxidation of cycloalkenes to dialdehydes.' This reaction is usually effected with ,)zone,but can also be effectedwith H2O2 catalyzedby tungstic acid in l-butyl alcohol

t-Hl

(R,R)or(S'S)-6'6i-(1-Hydmxy-2'2'dimethylpropyl)-2'2'-bipyridine Since a cycloalkene by the cycloalkane-1'2-diol' probably accompanied is n::':::: 'nt:::t:tl at 35". The dialdehyde under these*"it""tt' further O'"id"n'd" " t" oxidi'zed t* t''-ott'or oxide is also oxidized nl1':y":;;o 80Vo in ':p;;;]*nnn: th' reaction t" uv tttit involves oxidation is obtained ntl ;;;"nt' crutu'#-ti'v? to the dialdehva"' h 41Vo yield' from cyclohex ane is "b;;i-J yield; adipaldehyde 48' 3503(1992)' and J' Anren' Tetrahedron' 1D. Jingfa,X. Xinhua' C' Haiying'

148

Ilydrogen peroxide/Urea-Phthalic RrsR2 -

ll nB nr.'

pyridine (R)-2 Surprisingly,the simple high as1-m show can .ututy.t. Mo,"ou"t it with s' adduct an ".'-"i *C" can provide of R2Zn u aildition Enantioselective effected by catalvsts to .hul"on"' can be or propionitrile as' this caseuse of acetoNr(a tcttt')

O li

-,\-: -,\- -CoHs C.Hs-

anhydride'

to a sulfone' ' r^* "'ith this this conversionis overoxidation one problem with with urea in H2o2 of ll Theuseot tt " complex

with mostoxidants' prouio.*sulfoxides ""r.""t, observed il,5il;-;;i thisproblemandprovide overcomes unnya'iO"' ptrtnaiic wittr combination

than (S'Stl ine (R)-2 is more effective til-' the same adduct in 19-) p.oau"ts reactton' also observed in this Sd rC. Bolm,M. Ewald'M' Felder'andG Harms-& ';. ;i;, C. s"t'tingtoff'andK' t i. e"r*, M. Ewald'andM' Felder'Btz

-Tiffi*##;*i:i'1";:,"*'d',".":X'lJl#"'ii"'N.he'eroaroma'ic adduct with the H2o2lurea iigtt vi"ro o' *-*iJn """ o" "o#*ii'i" compounds (1'1)' ;;; in combinatio"*un oitn"i""""nio'iot >8o%' Yields are generally t"t^i" "Jtoride'

aceticor more effectivethan

l -Hvdroxy-3-isothiocyanatotetrabut]l 'Acetalizltion'' Distannoxanesof activateboth d can they 115,89)because 1 is found Of a number of stannoxanes' ethvlerx with ketones ,lf aldehydesand usuallr t which of cvclic a,B-enones'

andP'Nantka-NT:':lt'#'ri8;ilil?? rR.Balicki, L.Kaczmarek, A: "?:),:.,";r;,iri. P.A Giguere' and 26..Lu, E.w. Hughes. i' euti't.'i'andP' Nantka-NamrrsKr' t;. ;;;;;"'ki'

tonr,tuntl.

(l)'

o

(R,R) or (S.,S)-6'6'-(1-Hydroxy'2'2-dimethylpropyl)-2'2l-bipyridine a/oof this of 5 mol Preparatton' . . ,: -.L,.r-;-" n RCHO.2 ln the presence

.,':iii*;,;ff:;;::I::if#iltffiil (equationl)'

ll

a\

'r ardehvdes 'oi'i.,"*'0"varie'v

+ HOCH{

\-/

with high enantiosetectivity

o

c!-lell

-^j,'\ t t

C(CHs)s CoHs

0)

C(CHg)s

(cH3)3c

OH (R)-2

(R,R)- 1

1, toluene -25 -> 00

Zn(C2H5)2

80 - 97%

,

RCHO

\..e"

gf-c2H5

2',/-"r/

o

HOCFtPTT

l

'1 I'iitrl. Sincea cycloalkene 5. i:r rr\ crall processprobably b. l.l-diol or oxidizedfurther ir::!:'.-bv this reactionin 8O7o r:.lJ. B

149

l-Hydroxy-3-isothiocyanatotetrabutyldistannoxane

Itnt

, . , . 1( 1 9 9 2 ) .

Surprisingly,the simple pyridine (R)-2 is almost as effective as (R,R)-1 as the chiral catalyst.Moreover it can show high asymmetricamplification.Thus use of R-2 with an ee of 14Vocan provide an adduct with 87% ee. Enantioselective addition of R2Zn to enones.s This conjugate addition of R2Zn to chalconescan be effected by catalysiswith Ni(acac)2-(S,S)-1 in the ratio l:20. In this caseuse of aceto-or propionitrile as solvent is essential.In this reaction,the pyrid-

o

CzHsQ

Ni(acac)2,(S,S)-1 (C2H5)22n, CH3CN

cuHu4JcuHu

cunu,,,+cuH,

(R), 72o/oee n :. ,\ croxidationto a sulfone, ) " : l ( \ o f H 2 O 2w i t h u r e ai n rl. r'l and provides sulfoxides

ine (R)-2 is more effective than (S,S)-1 as the chiral ligand. Thus use of Ni(acac)2(R)-2 producesthe same adduct in 827o ee. Asymmetric amplificationwith (R)-2 was also observedin this reaction.

o : . : 1),i c e . n,--\ ()r of N-heteroaromatic r- .rrllt the HzOz/ureaadduct :r :J cf'fectivethan acetic or

I C. Bolm, M. Ewald,M. Felder,andG. Schlingloff,Ber.,125,1''l'69 (1992). rC. Bolm, G. Schlingloff,andK. Harms,Ber., 125, 1191(1992). I C. Bolm, M. Ewald,and M. Felder,Ber., 125,1205(1992). (1). l-Hydroxy-3-isothiocyanatotetrabutyldistannoxane,HOSn(Bu)2OSn(Bu)2NCS Acetalizatian,r Distannoxanesof this type are useful catalysts for esterification ( 15,89)becausethey can activateboth alcoholsand carbonylgroupson the sametemplate. Of a number of stannoxanes,I is found to be the most efficient catalystfor acetalization of aldehydesand ketoneswith ethyleneglycol. In particularit can promoteacetalization

,._). l:.: , .. r1992). ;

of cyclic a,B-enones,which usuallyproceedsin low yield. l - h i p r r i d i n e( l ) . tl^- :-:.\cnceof 5 mol % of this : , * idc variety of aldehYdes

1-l

o

A

(-j

001 1 X

+ HocH2cH2oH ""L

(-l

o

CHsll

^

z-\ I

OH

68/"

i-1-'-2-.....-,>

^\*,/\-.,.C(CHs)g

''

a--.-H\ l l l

+

( 1 0e q . ) HOCH2CH2OH

\--O

+

1

(R) 2

\..et nG-czHs

93/"

150

N-HYdmxYurethane

1 J. Otera, N. Dan-oh, and H' Nozaki, Tetrahedron' 48' 1449 (1992)'

14, 179- 180; 16' l7 9' [Hydroxy(tosyloxy)iodolbenzene, is usually conductedin refluxing a-Tosylorylation of ketones'\ This reaction acetonitrile.Therateofthereactionismarkedlyincreasedbysonication.Thusitcan beconductedundersonlcationat55.in10-30minutes.Thisversioncanbeusedto evenalicyclicketones' tosyloxylate

,OBzl BzlO-\YOr -O- -COOCzHs BzIOW--N' BzlO H 2

HMPA (82%) 1) NaH, (C2H5)2O, 2) NaOH{s), CH3OH (80%)

B'C Bz

I D. Yang, S.-H. Kim, and D. Kahne,Az. -kr

C6H5|(OH)OTS cH3cN.((((

O ii

A CHe-

v

-CHs

91o/"

O

O

A ..cHs+ rso=.,\.cH3 CHs- Y 5:1 611

o

a\ t

1

OTs

l

r A . T u n c a y ,J . A . D u s t m a n ,G . F i s h e r ,c . I . T u n c a y ,a n d K , S . S u s r i c k , T e r r a h e d r o n L e t t e r s , S 3 ,

7647 (r9e2).

(1)' Available from Aldrich' N-Hydroxyurethane, HONHCOOC2H5 N_oLinkedglycosides.|Thetrisaccharidegroupofseveralpotentantitumor linkage. A general method for stereoselective antibiotics contains an unusual N-o The N-hydroxyurethaneas the key reagent' synthesis of such saccharidesemploys selectively occurs glycosylation that group so carboethoxy group deactivatesthe nitrogen withthehydroxylgroup,butitfacilitatesdeprotonationofthenitrogentopermit s u b s e q u e n t S p 2 d i s p l a c e m e n t w i t h i n v e r s i o n . T h e r e q u i s i t e g l y c o s y l u r e t h aof n e2s s u c h a s 2 glycosyl.sulfoxidewith 1' Deprotonation can be prepareddirectly by reactionof a ( N a H ) p r o v i d e s a n a n i o n o n n i t , o g " n t h a t r e a c t s w i t h a t r i f l a t e ( 3 ) w i t h i n v e- r s 25" i o n ito nhigh by NaOH (solid) in CH3OH at 0" yield. The coupled product is def,rotected disaccharide4' provide thc N-O

I

N-Hydmxyurethane

tt9 qt.

,oBzl

ezo-\vQ

o_N-cooczHs

BzlO--r*/ BzlO

) tr.-.,11\conducted in refluxing q J \r sonication.Thus it can r I:r. versioncan be used to

H 2

1) NaH, (C2H5)2O, HMPA (82%) 2) NaOH1el, CH3OH (80%)

o

tl )H, - TsO--.../A-..-,-CH3 . ' 5 1

ls

\

Letters, 33, : -trck. Tetrahed,ron

i: ". \ldrich. o-:- ,l scveral potent antitumor nr:, rncthodfor stereoselective rr-:'- its the keY reagent.The 6 s. .., r:r lationoccursselectively l:: - ,)l thc nitrogen to Permit suchas 2 r.:'- :lrcosyl urethanes of 2 o\ .:, \\ ith l. DeProtonation high in r:.:' ,:r (3) with inversion s :, rn CHrOH at 0' * 25' to

\-\-O

BzloS

Btlobcu. 3

BzlO

BzlO

r D . Y a n g , S . - H . K i m , a n d D Kahne, Am. Soc., ll3, 471.5 (1.991);Idem, in press

l5l

BocO

cHrZ-\')'-"-'

r

CHs

.a

1

water or Indium. 1 indium is stable to boiling Unlike most metals' a water" in AllYlntion 25' with no need for aldehvdesin water at effecl il;;;;";;; can alcohol. Indium promotor'

o tl

o^o t

l

-y' r^ -(cxz lcH2" -\

iH. H2O,25"

c6H5cHo * ,rNc^'

In, -G**

2a

?t

c6n5*cH2

lz, CHgCN'-20' lBr, C6H5CH3'-80-85'

OH OH

*

cuHuAcno

erNcH,

-a*

cuau/\1,-'-zcH' OH = 67:33) @Yn/anti

Thereactionwhenextendedtoacrylatesprovideshydroxyacrylicesters'whichare precursorsto methylene TJactones'

The generallY higher selcorr homoallylic carbonates. lJ.J.-w. Duan,P.A. Sprenger. and I

Iodine/Pyridine. a-Iodination of cYclulLcz cquiv.) dissolved in PYridineCO

oH 9Hz

. r,-y::;. c6H5cHo

1 C.J. Li and T.H.

rHl

"uruScoocH3

32"1.017 (1991)' Chan, Tetrahedron Letters'

"^t"ir#,iii**[)]i;t'"rl;""'"'

ncO,,,.O

or the rhe conversion ol no\latttr.carbonates''

atNtemperatures c a r b o n a t e l t o 2 h a s n ' O i t i " * i f y b e erBr n ein f f etoluene, c t e d * uparticularly it'inCHrC a t - 2 0 ' ' l t c aofn b e with ;.;;i, higher carriedout with -80-85".

C . R . J o h n s o n ,J . P . A d a m s . M P Ukokovi6, Tetrahedron Leuers. 33

Iodine/Pyridine

153

BocO I

Cuzr'"f'VOgzt CHs 1 m . rtable to boiling water or : .ir 25" with no need for a l.l

o tl o^o l

o,

l

o tl

l -\ -\ -(CHz)zOBzl + IcH2-'-\a-'\ lCHz' Y

OH )"'r.

o r

(cH2)20Bzl

CHs

CHs

2a

2p

*CHz t2,cH3cN,-20" -80-85" lBr,C6H5CH3,

OH

7g%

5.7:1

8oo/o

14.9:1

I

- ,, )--,r'----ZCHz -

l

OH = 67:33) \syn/anti

The generally higher selectivity of IBr was observed with a number of other homoallylic carbonates. I J.J.-W.Duan,P.A. Sprenger, andA. B. Smith,III, Tetrahedron Leuers,33, 6439(lgg2).

hl.:- ,\\ acrylic esters,which are

oH

c.,i.

Iodine/Pyridine. a-Iodination of cycloalkenones.t This reaction can be effected with 12 (1-4 equiv.)dissolvedin pyridine/CCl+(1:1) at O - 25".

CHe

o

'-l\AcoocH3 A

(A"r.

nco,,, cro trnalt'r.i The conversion of the I ::: ('HICN at -2O".It can be n. :.lrricularly at temperaturesof

o t2,pytccta)-'.'

1*-

t.*CHsr l

77o/"

nco,,, 1^7o

a,

C . R . J o h n s o n ,J . P . A d a m s , M . P . B r a u n , C . B . W . S e n a n a y a k aP, . M . W o v k u l i c h , a n d M . R . Ukokovid, Tetrahedron Letters, 33, 917 (1992).

154

Iodine-Silvertrifluoroacehte

'u':;i,:';;:"i";X:;;;?:;,;:li:,:ihtdroruransLip**1'hasprepared choice by a r' unor'u"shownthat

n'jJ"tr''""'il*t thefour isomers"r tr't

CHs 1,,CF3COOAg

"t')t)r

-l

\cH.

oH

/l

\ I

CHs

II c.nus"ct

\-<

r

87"/"

syn-(E)-1

2,5-cts

"r,$"*'

zzv"

CHs I

proper

tl t' (lodomethyl)zinc iodide' ICH:Znl' clon cs"l a'M ethyten e- y' butyrola of a ctp; addition involves stereoselective that on [661rlge alkenylcopperreagent2 to form an a-methylene-7-butvrolaett'o

HC=CCOOC2H5 + C6H5CH2Cu(C

,SeC6H5

2',-trans

cnr-l-o)--cHt

c6H5cH2 CHg }1

tr\

,'l 2'5-cis

cunuAoAo

at.-''-oFt*'

?n' cH.fr

CHs \--<

oH/

g (cisltrans= g2 g1

,SeC6H5 -cHt

CHs

is algt I An intramolecularversion

2's-trans

cH.-(o)

o

sYn-(Z\'1

(r) CHe

.'l

t

oH

i

cH3-{o}--cH3

et"r"

cHe-A, l

\cH.

_-l

CHs.\---< ,SeC6H5 c"Hus"cl

t

-

2'S-cis >

cH.-(o)-cH'

91"/"

anti'(E)-1

CHg.

,/l

b, CFgCOOAg .-P

9H' CHg\.rr'\ l l l oH ,/ CHs anti-(Z\'1

: A. Sidduriand P. Knochel'Am 'Srr- l

\

II

\

osz'

t

c^Husect -

86o/"

2's-trans

perchlan lodonium di'syn-collidine ctoaigir iodola e ctiv E nantio sele htgn with effected be rcaction can as thc chiral acid o-camphorsulfonic )98% ee' but cffectedwith Kl/Iz in CH3\,CH3

cH3-{o}--cH3

__l

II

tl

cunuA(cHz)scu(cN)

2'5-trans

1,,cF3cooAg

9Ht

zcH'

CHs. / >

,SeC6H5 \ 2'5-cis

"r.-{o}tt.

or 2'5-transchloride' the 2'5-cisiodine or phenylselenyl either of the electrophile' can be preparedselectively' tetrasubstitutedturan (1992)' Arn'Soc'' 114' 1084 I B.H. LipshutzandJ C' Barton'

'l\ r"t' ( r ) e-N I 6" )-\ -ci I \.r, 2

155

Iodoniumdi-syz-collidineperchlorat€

>!urans. Lipshutzr has PrePared F .- ,\\n that by a ProPerchoice ^ ev

to form an a-methylene-y-butyrolactone(3) with cls-selectivity.

l

--a

(Iodomethyl)zinc iodide, lCHzZnl, (l). A new one-pot preparation of these lactones a-Methylene-y-butyrolactones.t involves stereoselectiveaddition of a copperlzinc reagentto an acetylenic ester to form an alkenylcopperreagent2 that on homolgationwith I reactswith an aldehyde(or ketone)

r I

./'

2'5-crs

o)-CHe

,-' ,

HC=CCOOC2H5+C6H5CHzCu(CN)ZnX cB - -.

|

/:\-

I Bzl

/ SeCnHq

' l fooc2HsI -

-

|

Cu(cN)znX I 2

r

-

)-cH.

2's-trans

I' c6HscH2f
,,| \

c6HscHo

2.5-cis

,l-cHs

-ct. ' o) -

z's+rans

An intramolecular version is also possible (equation I)'

\', \ o) - C H s

L- -

2.5{rans

1) HC=CCOOC2H5 2) C6HsCHO;Zn(CH3)2

O lt

...

c*

-\ cuHut \1cttr;.cu1cllt1znl

76/"

rA. Sidduriand P. Knochel,Am. Soc.,ll4, "1579(1992).

f x

,SeC6H5

f ,.

' o)_-cu"

,-. -

-_''2, \ o) - - C H s

C-

c'

CH2Cu(CN)ZnX

Bzl

,SeC6H5

h

{.

78v"

cunuAoAo

COOCTHs - -

3 (cisltrans= 92:8)

c*

l -.

/

2'5-cis

z.s-trans

Iodonium di-syn-collidine perchlorate, (l)' 10, 212; 11,269. Enantioselective iodolactonization of a bis-y,i-unsaturated chiral amide.' This reaction can be effected with high enantioselectivityusing a sultam derived from o-camphorsulfonicacid as thc chiral auxiliary. The cyclization of 2 to (-)-3 can also be cffected with KI/I2 in >98Vo ec, but the chemical yield is only 39o/o.

"'$' rc

,rSeC6H5

o

)-cH.

2'5'cis

- .r-. thc 2,5-cis-or 2,5-trans'

H

""rJirlo".o: 87o/o

cH2=//'" f-\ O/'.O,\CHrt

O2 (-) 3 (>98o/oee)

156

anhydride lodosylbenzene-Ttiflic

I T. Yokomatsu, J'C'S' Chem'Comm''728(1992)' H. lwasawaand S. Shibuya, Iodosylbenzene-Tliflic anhydride (C6H5IO/TfzO)'l' Glycosid'ationofthioglucosides.Reactionofthesetworeagentsinthepresence glycosidationof tetrabenzylof +A VtS in CHzClz provides a reagent(1) that promotes methylthioglucotetraacetyl-protected of reaction The protectedmethylthioglucosides.r

Iodosylbenzene-Ttimethylsilyl azide, C"H. lt Cyclic o, B-enones. Reaction of tnisopr with the combinationof C6H5IO and trimethrl p-azide,which on treatmentwith BurNF at O Examples:

q"'?t'tt

.>

sideswithlproceedswithmarkedB-selectivity,particularlywhenSiO2isalsopresent.

("-|--f, H \,-o

1, cH3cN 810/o

scH3

(o-

\--c

BzlO,,,. BzlO

TIPSO

o^ro-.]..€cHa

d^""'

"'OBzl

azro"'f

OBzl ( c / B= 1 . 1 2 )

TIPSO .'t1

7ai orit

(oo"

O.Or.a?

c BzlO,,,

1, cH2cl2

) 77"/"

ncol\:'nscHg : 0nc

BzlO

\

rP. Magnus,A. Evans,andJ. Lacour,Tetrahedm

(p, 100o/o) (|992) 1K. Fukase, |. Kinoshita,andS. Kusumoto,TetrahedronLetters,3S,T|65 A. Hasuoka,

lron powder. Aerobic oxidation of alkanes.t \anous trridation of unactivatedC-H bonds. \luretr .rnd iron complexesare useful catalvsLsftv .rldehydeand an acid. Iron powder is th< r can b RuCl:'HzO, and RuCl2[P(C6H5).r]. .. even acetaldehrde. and l-methylpropanal, preferred usins ttx acid. By to chloroacetic r\

Imn

-:4..128(1992)'

F

r t .l . I ^--- t\\o reagentsin the presence nf tetrabenzylr''-'-\ gllcosidatioo methylthioglucol-protected r:',,--:r e" -.-i.1rl\when SiOz is alsopresent'

powder

157

Iodosylbenzene-TFimethylsilyl azide, C6H5IO/N3Si(CH:):. Cyclic a, B-enones. Reaction of triisopropyl (TIPS) enol ethers of cyclic ketones with the combinationof C6H5IO and trimethylsilyl azide in CH2CI2at -15'provides a p-azide, which on treatmentwith Bu+NF at 0'is convertedinto the a,B-enone. Examoles:

q".?t'tt .'-\Z\ ^l | | ("\-f--'

CH

\-.-O

,*-

H

qtft't' /'\-'\ ro_I I l r r-.-.ft-..{ H L-O

1, CH3CN

l

qt'3

t

a1"/" ,t-\-^\

ocH3

:

.o-l

ocH3

( I. \ q -

I

( l:--f.'t.' H \-.-o

CEzt

TIPSO

d^""

OBzl

ll

"-|\1.ur.

TIPSO

.'''[j.uru lANa

6:1 \-'

780/o overall

OH

o

1, cH2cl2

r\

",ocHs

77"/"

a

SBzl

ocH3

C

'OBzl

l

O3zl

. a lr,'rlron Letters, 33,'7 165 (1992)'

o tl (^f"u^u

O^"" \-,

I P. Magnus,A. Evans,and J. Lacour,Tetrahedron Letters,33,2933 (1992).

lron powder. Aerobic oxidation of alkanes.t Various metal complexes are known to catalyze air oxidation of unactivatedC-H bonds. Murahashiet al. have found that both ruthenium and iron complexes are useful catalystsfor aerobic oxidation in combination with an aldehyde and an acid. Iron powder is the most effective catalyst, but FeCl3'6H2O, RuCl: .HzO, and RuCl2[P(CrHs):]: can be used. Useful aldehydes are heptanal, 2-methylpropanal,and even acetaldehyde.A weak acid is suitable; thus acetic acid is preferredto chloroaceticacid. By using the most satisfactoryconditions,cyclohexane

158

Imn powder

is converted to cyclohexanoneand cyclohexanol (2.3:l ratio), and alkylarenes are oxidized selectively at the benzylic position. This system is clearly different from the bond selectivity differs Gif iron system (14,184-185); the tertiary/secondaryC-H markedly in the two systems. I S.-I.Murahashi, Y. Oda,andT. Naota,Am. Soc.,114,7913(1992).

Iron(III) oxide (FezO:). Baeyer-Villiger oxidation ofketones.t This oxidation can be effected in high yield by oxygenationin the presenceof an aldehyde(3 equiv.) and Fe2Or. Benzaldehydeis the aldehydeof choice but heptanalis also useful. Benzeneis the only suitablesolvent.

o ll

{ \J

Asymmetric Wittig - H orner react* volved phosphineoxides,phosphonarc finationshavenow beenachievedbr uQ-BuLi) reactswith 4-r-butylcyclohera triflate/2,6lutidine provides the alkl li& The reactionwas shown to be applicab t-&.{,r .70'

961

? ..i'i"o1i"".-f^p s,o/o rl

02, Fe2O3

\-,

otr'

ocH3

)-o-r.-s, cHs ll I \-.Z\ocH3

t's'!f--rrococ6H5

R"S|O u

)-iJ"oc5H5

C -H e l l /FN, o ' H

C "H " l l /FN, o . H

I S. C. Denmark and C.-T. Chen. Azr. .!r

I S.-1.Murahashi,Y. Oda, and T. Nasta, Tetrahedron Letters, 33,'7 557 (1992)

o -tgrt

1,3,2-oxazaphosphorinane, N-Isopropy!-(25,6S)CH.1|];f

s \cH(cH3)z

NHCH(CH3)2 c2H50Pct2 CH2C|2,A

?c'Hu CHI-7-]:O-/P - ' N.

Bzlors

'cH(cH3)2

5go/o

1

I

N'Isoprcpyl-(2S,6S)'1,3,2-oxazaphosphorinane

-.rrrrr).and alkylarenesare . .lcarly different from the ll bond selectivitY differs

l

(

159

have usually inAsymmetric Wittig-Horner reactions.r Wittig-Horner reactions oleenantioselective Highly or phosphonamides' volved phosphineoxides,phosphonates, the anion I' Thus finationshavenow beenachievedby use ofthis chiral phosphonamidate with trityl (-BuLi) reactswith 4-l-butylcyclohexaneto form 2 in >98Vo de. Elimination stereospecificity' complete triflate/2,6-lutidineprovidesthe alkylidene3 with essentially Thereactionwasshowntobeapplicabletoavarietyof4-alkylcyclohexanones'

..rn bc effectedin high Yield is r,l FclO:. BenzaldehYde :. the only suitablesolvent'

lll

]\ 7-

r *t-au$o

r-6uLl -70"

96"/o

o o H

cH3'|s+-{-J,-au-t ";i 6uHu" 2 (98o/" de)

c (c6Hs)3cort, 2,6-lutidine cH3cN,60'

..CeHs

ll I

\.

I

c(cH3)3

"i ,ococoHs I

-N

o

'

- -r.t

-<
H

I S. C. Denmark and C.-T. Chen, Am. Soc., ll4,

11992).

ll

;F

c

----o-ljezt .'------.-N .CH(CH3)2 S

oc2H5

/-

(s)-3

Bzlors )'P N-' c H ( C H 3 ) 2 59"/"

(1)

10674(r9e2).

Lanthanide(Ill) alkoxides.r Lanthanide(Ill) isopropoxides can be prepared in 75-85% yield from hydrated '4CHrOH' lanthanide(Ill) chloridesby reaction with methyl orthoformateto give MCl3 which is convertedto MClc .3i-P2oH by reaction with isopropanol.After removal of the liberated cH3oH, MCl3 .3 i-ProH is treatedwith 3 equiv. of BuLi to give M(o-i Pr): .LiCl. This procedurehas beenusedto preparethc isopropoxidesof La, Ce, Sm, and Yb. These isopropoxidesas obtained without removal of LiCl, can replaceAl(O-i-Pr)r as the catalyst in oppenauer oxidations.The most effective for oxidation of 1-phenyland l-ethanol with 2-butanoneis Yb(o-i-Pr!, followed by La(o-l-Pr)r, Sm(O-i-Pr)r, reaction, Ce(O-i-Pr)r.They can also be usedfor Meerwein-Ponndorf reductions.In this and ce(o-l-Pr)r, Sm(o-l-Pr)r, by followed La(o-iPr):, is catalyst effective the most yb(o-;-Pr)3. The lanthanide alkoxides are also effective catalysts for epoxidation of geraniolwith l-butyl hydroperoxide.Highest yields (96Vo)are obtainedwith Yb(O-iPr)3 reactions as catalyst.Addition of 4 A Ms to remove water usually improves yields in with lanthanidealkoxides,which are very sensitiveto water' I A. Irbrun, J.-L. Namy, and H. B' Kagan,Tetrahedron Letters,32' 2355(1991)'

(s)-(-) Cx

s I

I H. Sasai,T. Suzuki,S. Arai, T. Arai. and !

Lithium/Ammonia. Reductiveelimination of BujSn fiv

cles can be reducedefficiently bv treatn and NHr. This reductionpermits use
Lanthanum(III) l-butoxide, La3(O-r-Bu)e(l). aCatalytic asymmetric nitroaldol reaction.t In the presence of this alkoxide, II)' I and (equation chloro ketonesor nitro alkanesundergoaldol reactions

o H o (t)

C6H5CHO

ctcH2cocH3

"uru$"r.

o tl

1) CH3SnCu(SCsH3 2) CH3l

l l l CH,N 1

CHg

(il)

c6Hs(cH2)2cHo

Sn(CHJ3

cH3N02 3

Asymmetric nitroaldol reactionsare possibleby use of the optically active lanthanum with oxide 2, preparedfrom (S)-(-)-2, 2t dihydroxy-1,1/-(S)-(-)-binapthyl (BINOL) La3(O-t-Bu)e.

:,'llowed by addition of Li,/t{Hr reductd t :,' give 4. The trimethyltin group u'as cs

Lithium/Ammonia

La3(O-f-Bu)e

-i .5'i yield from hYdrated D t l ' - 1 : ct o g i v e M C l 3 ' 4 C H 3 O H ' ir: - ,rropanol. After removal of i ,...;rr. of BuLi to give M(O-l' . 1:,,poxides of La, Ce' Sm' and Al(O-l-Pr)3 replace I : I r('1.can l-phenylof . oxidation - lirr LS m ( O i - P r ) ra, n d Ir I.'rO-i-Pr)j, -: reaction' this ln rctluctions. n- : and t . :::rtO-i-Pr)3,Ce(O-d-Pr)3' of ePoxidation for c: ., ..rralYsts Yb(O-j-Pr)3 with ,:. obtained 6 rnrpfovesyields in reactions u.: [

\::.r.

8 . . . r : : . 1 5 5( 1 9 9 1 ) .

r\

:rc\cncc of this alkoxide, a.ruation I and II).

-

(s)_2

(s)- (-)

"3i?,

cHo

91%

90o/o €€

I H. Sasai, T. Suzuki, S. Arai, T. Arai, and M. Shibasaki, Am. Soc-, ll4'

o

1) CH3SnCu(SC6H5)Li 2) CH3l

o l"sn(cH3)3

2

CHe

OH

I-c.Hu

1) DDO 2) alkylation

,,\,.CHs r T

cHsN

o H o t l l I --: ,\ Aar. coHu- Y -:

&ruo,

4418 (1992)'

Lithium/Ammonia. Reductive elimination of Busn from carbocycles.t The Bu3sn group of carbocycles can be reducedefficiently by treatmentwith lithium (excess)and r-BuoH in THF and NH3. This reductionpermits usc of this group as a directing group in annelationreactionsas shown in Scheme(l). Thus reactionof the enone I with lithium (phenylthio)(trimethylstannyl)cupratefollowed by methylation provides 2 as a single product' This product was converted into an enone and alkylated to give 3. cyclization of 3

t

CI

l6l

1) LDA (93%) 2) L|/NH3(91%)

'Sn(CH3)3

CHs 4

u\., : rhc optically active lanthanum :,'t - )-binapthYl(BINOL) with I

rollowedby additionof LilNH: reducedthe keto group and removedthe tributyltin group :o give 4. The trimethyltin group was essentialfor control of the chiral centersof 4.

162

Lithiumaluminumhydride-(s)-2,2/-Dihydroxy-4,5,6,4/,5/,6/'hexamethoxybiphenyl

1E. Piersand J.Y. Roberge,Tetrahedron Letters,32' 521'9(1991)' Lithium aluminum amides' LiA(NHR)4 (f)' Thesereagentscanbepreparedbyaddition(dropwise)oftheamine(5equiv.)to asuspensionofLiAlHqirranhydrousetherorTHFwithstirfinguntilprecipitationiS /-Bu, or CHzCoHs' beI CPr, can complete. , R l C oRo R 2.R u Ni-Pr' HR+R2oH}Lithiumaluminumamides(1)canconverl

Asymmetric reduction of ketones.' A with I and C2H5OH(1 equiv. each)in THF et ketonesor alkyl aryl ketonesin 53-93Q rr is generally greater than that obtained *ath

particularlyin reductionof dialkyl ketonestr effects. I D. RawsonandA. I. Meyers,J. C.S. Chem.( rt

estersinto amides in essentiallyquantiativeyield'

cH3YcooczHs

i, ether,25" CH3-=',,CONHR

t"t-y'-Ot

t

OH

+

l

OH

OH

1000/"

O"h

LiAl(NH-t-Pr)4

Lithium (&R)-bis(l-phenylethyl)amidc.

HO(CH2)4CONH-i-Pr

Kinetic resolutoin of a B-lactam.' ..\d p-lactam 2 at -90" followed by quenching (3R,4S)-3,formed by silylation of (S)-2. Thr

Gt of aryl epoxides These reagentscan also effect regioselective opening

o

cunrA

T H F ,O '

+

LiAl(NH-l-P0a

(

coHsf I OH

100"k

NH-r-Pr

.SC6H5

F'".

(98:2)

I A. Solladi6-Cavalloand M. Bencheqroun,J' Org'' 57, 5831 (1992)'

-4,5,6,4|,5|,6|.hexamethoxybiphenyl Lithium a|uminumhydride-(S).2,2/-Dihydroxy (1).

1) 1,THF,-90' 2) (cH3)3sicl

(cn

19oloConversion

(t) - 2, Rg = l-BuMez

hv controlling the amount of base.The rccr l|lJo/o ee. Similar resultsare obtained in an aldol n .clectivity in this caseis about l0:1. uhera

OH .SC6H5 111 I 2i cHscHo CHs-\ r--f t ' )-N

(s)-1

{

'siR.

o (t)-2

4(r0 r

Lithium (R,R)-bis(l'phenylethvl)amide163 \l -: ^ -he\amethoxybiphenyl r -l

l .

( 5 e q u i v ' )t o t1 -.':.c)of the amine is {l '::: stirringuntil precipitation can convert 6 , .-::tinumamides (1)

:ONHR

+

o!

""a-r,a-O,-. l OH 0o/o

of LiAIH+ Asymmetric reduction of ketones.l A reagent 2, pteparcd by reaction of dialkyl with I and C2H5OH(1 equiv. each)in THF at 20"' effectsasymmetricreduction enantioselectivity ketonesor alkyl aryl ketonesin 53-93Vo yield and 6o-97Va ee. The (9,\69_|70)' BINAL-H reagent Noyori,s with obtained that than greater generally is similar steric have groups particularly in reductionof dialkyl ketonesin which the alkyl effects. I D. Rawsonand A. I. Meyers,J. C.S. Chem'Comm',494 (1992)'

CHq " CH:r

= . | ^u6 -nsANAC^H^ v6' 's Lithium (R,R)-bis(l-phenylethyl)amide, i, 'l

:-

"

-

Ho(cH2)4coNH-i-Pr

(\:.,'.:rg of arYl ePoxides'

coHsf

F.

-

..:

NH-iPr I OH (98:2)

the N-protected Kinetic resolutoin of a p-tnctam.r Addition of this chiral base to (R)-2 and provides _ 90" followed by quenchingwith excessClSi(CHj! 6-lactam 2 at to 72Voee in up be obtained (3R,4S)-3,formed by silylation of (S)-2. This product(3) can

.SC5H5 r--{ t

l

/FN,

O'

1 ) 1 , T H F ,- 9 0 " 2) (cH3)3sicl

(CH3)3S|\

y'-t'.,".

197"conversion

SiR3

(t) - 2, Rg= FBuMez

.SCoHs

l" '1

+

(3R,4S)'3,72o/oee

--/sc6H5 l l /-*'.,*. ee (R) - 2, 100o/o

11 9 9 2 ) .

n r -1.5.6.{'.5',6/-hexamethoxybiphenyl

(s) 1

in essentially hy controlling the amount of base.The recovered(R)-2 can be obtained l\OVo ee. but the Similar resultsare obtained in an aldol reactionof (+)-2 with acetaldehyde, reaction' silylation in the 7:1 about selectivity in this case is about 10:1, whereas it is

----rsscoHsll 1".""ocr.{

-

/il'r,r. ( x )- 2

scoHuoxidation CH3

F.r,*. a(10:1)

Lithium 4,4/-di-t-butylbiphenylide

Regioselectivedeprotonation of a ketone; regioselective resolution.z Treatment of (R,R)-ketone 2 with (S)-1 provides the A6-enol silane 3, whereasa similar reaction the (S,S)-isomer of 2 provides the As-enol silane 4. Since 3 and 4 are difficult to the of separate, they were identified from their corresponding enones. In contrast treatment

BocN

NBoc H

(s,s)-2

(R, R)-2

I

-nr" |,.,-.,,,"*.,..,",,

-nt" {"".).t,",, tr)-r, osi(cH3)3

o

1, BF3.O(C2H5)2 -80'

Li(cHr

ketones to form l,5-diols, which are rcad tetrahydrofuran is cleaved to the most suh

""t

I, BF3O(C?||, -80'

(cH3)3sio

4 (79:21)

3 (9a:6) -70o (s)-1,(cH3)3sicl,

rac-2

3 + 4 60:40

of racemic-2 shows only slight regioselectivity. 1 P. Coggins and N. S. Simpkins, Synlett' 31,3 (1992). 2 K. Bambridge,N. S. Simpkins, and B. p. clark, TetrahedronLetters, 33, 8141 (1992).

Lithium 4,4/-di-t-butylbiphenylide (1, LDBB). Reductive lithiation of tetrahydrofurans.t Tetrahydrofurans can be reductively -80" in the presenceof 1 equiv. of BF3 etherateto give cleavedby this radical anion at by 2. This lithium reagentleacts with aldehydesand represented best a 4-lithiobutoxide

2-Mnyltetrahydrofuran(neat) is readilr rion provides the (Z)-alkenyl alcohol (51 r

d)^"',

1) I 2\ t+l

B. Mudryk and T. Cohen, Am. Soc.. llJ.

lrl

Lithium diisopropylamide. Anionic Fries carbamoYl nusfen' * hich the ortho-positior is protected br LDA results in transfer of the carbamorl

Lithium diisopropylamide

rc/r ctile resolution.2 Treatmentof .: ,-, 3. whereasa similar reaction n- { \ince 3 and 4 are difficult to nJ:-- .nones. In contrasttfeatmenl

o

1, BF3.O(C2H5)2 -80"

Li(cH2)4oBF3-Li+ 2

\or.lr*rcno 75% \

OH

I

(CHg)z HO(CH2)4cHcH 3

NBoc H

(s,s)-2

ketones to form l,5-diols, which are readily cyclized to tetrahydropyrans.2-Methyltetrahydrofuranis cleaved to the most substitutedcarbanion(4).

I

-n'" | (s)-t,(c*.).s,c', * H h,SO

CHg\,r0..

1, BF3.O(C2Hs)2 -Bo.

CHq

t -

t-iA(cHr)30BFa-Li+

\_f

(a)

u,* | ,"*r,r"*"*o

I

OH

H cH. -.-,-1.,.- (cH2)30

4 (79:21)

t

l

cHs cHs |e 3 + 4 60:40

2-Mnyltetrahydrofuran(neat) is readily cleavedby I to a dianion, which on protonation provides the (Z)-alkenyl alcohol (5) as the major isolated product.

d7^"', !.:'

i , t r t ' r r ,3 3 , 8 1 4 1 ( 1 9 9 2 )

I - ::.'hr drofurans can be reductively :n.- I I cquiv. of BF3 etherateto give u--' :i.iqcnt reactswith aldehydesand

;l) 1 2l H2O

HO(CH,).CF\H,

B . M u d r y k a n d T . C o h e n ,A m . S o c . , 1 l 3 , 1 8 6 6 ( 1 9 9 1 ) .

Lithium diisopropylamide. Anionic Fries carbamoyl transfer,t Treatment of the biphenyl 2-O-carbamateI in nhich the ortho-positionis protectedby a methoxyl or triethylsilyl (TES) group with LDA results in transferof the carbamoyl group to form the biphenyl 2. Cyclization of

166

Lithium

diisopmpylamide

LDA,THF

ocoNEt2 ocH3

r\

HoAc' Q.-o"

Q"o**,

"i:lt /yu

^y"' %ocH.

Yon.

V'-. tl

r'\ \fru' i i

l l

LDA -300

'\

[-=

v'

o

| l

-*

\z'-

A ' H ,|

2 results in the dibenzopyranone3 tn 68Vaoverall yield. This carbamoyltransferwas used to synthesizethe fluorenonedengibsin(6) from the key intermediate4. An anionic rearrangementprovides 5. Methylation and desilylation providesan amide that cyclizesto a fluorenonethat on dealkylationwith BCl3 provides6.

I W. Wang and V. Snieckus,J. Org., 57. J:r I r B. G6mez, E. Guitirin, and L. Castedo.S|aLr

Lithium diisopropylamide/Butyllithiun p-Lithio ketone enolates.t B-stannrl

i-PrO ocoN(c2H5)2

3 LDA, T H F ,A

I-

to the enolatefollowed by LilSn exchang the B-lithio ketone(Z)-enolatea. This spco a-alkylation; B-alkylation followed br a-r

61"/"

1) Ll

o tl

TES

a 8

r-guMsnBu3 1

1) CH3l;2) TFA (87%) 3) 2.5 LDA; 4) BCl3(56%)

HO

? u r-guA(cHs)ocHs

n-C5H11Br a 71%

i

cH3o

H. Nakahira,I. Ryu, M. Ikebe, N. Kambe. anl I I. Ryu, S. Murai, and N. Sonoda,J. Ors.. 31.

Intramolecular aryne cycloaddition.z A new approach to the basic skeleton of ergot alkaloids involves an intramolecular cyclization of the amide I to form 2, effected with LDA at -30'.

Lithium perchlorate. [ 1,3]Sigmatropic rearrangement ol d :enge in 3M lithium perchloratein diethll

Lithium

HOAc,

)\ E: {

LDA -300

680/" overall

perchlomte

ra> \r'=.t

l(

r\ ll

I

\Z^-r'i

4'1"/"

)-oLi

1

lr . . t . dengibsin(6) from the : : . :r:r()rL-none

rW. Wang and V. Snieckus,J. Org., 57, 424 (1992). 28. G6mez, E. Guiti6n, and L. Castedo, Synleu., 9o3 (1992).

. 5 Methylation and desilYlation with BCl3 provides6. - :-.rlkvlation

,1:.1

t

Lithium diisopropylamide/Butyllithium. (LDA) B-Lithio ketone enolates.r B-Stannyl ketones2such as I on deprotonation -78 to 0" are convertedinto to the enolate followed by LilSn exchangewith BuLi at the p-lithio ketone(Z)-enolatea. This speciesundergoesB-alkylation more readily than

coN(c2Hs)2

a-alkylation; B-alkylation followed by a-allylation is also possible.

OH TES Ol-Pr

FC

Lir. o--Li

0"

,-rr-v

t-BuMSnBu3

5

\

1) LDA, -78" 2) BuLi,-78'-

o tl

a

1

o r-euAlcHs)ocHs

1) n - C5H11Br n - C5H11Br

71"/"

a

2) cH2=cHcH2Br 700/o

o .rr\tcHs)scHg

\'-zcu,

{.c I I H. Nakahira,I. Ryu, M. Ikebe, N. Kambe, and N. Sonoda,Angew. Chem.Int. Ed.' 30' 1'77(1991) r I. Ryu, S. Murai, and N. Sonoda,J. Org., 51,2389 (1986).

a'i tll,'

rproach to the basic skeleton of ,'t rhc amide I to form 2, effected

Lithium perchlorate. [1,3]Sigmatropicrearrangementof allyl vinyl ethers.t Allylic vinyl ethersrearin diethyletherat 25'to homoallylicaldehydes. rangein 3M lithiumperchlorate

Lithium

Perrchlorate

cHa?

QBzl

cH.

cHo

* cnlvsn(cH3)3

LiClO4,ether 90"/.

HO'

r il-

,CH2CHO

CHs'l-OH

I

H

HO-

t

CHs'

-

H

\oH

CHa

l oAcH,

I

al t$ctt.

Aldol reaction of silyl enol ethcrs'' ketal I at 25' in the presenceof LiCIO' tUnder these conditions a chiral a-alkorr :

&::

psiR3 c6H5cHO +

cHz{

!

ocH3 ConjugateadditionoJ'o-silylketeneacetalstoenones.2Additionofl-methoxy-1(r-butyldimethylsilyloxy)cthylenetocyclohexenoneproceedsinlowyieldwhencatalyzed in 95% yield when catalyzedby 1'0 M by TiCla or TiCl+/Ti(O-i-fr;, Uut is effected LiClOa in diethYl ether'

osiR3

o

A

(A

* cHg

""ryOSi(f-Bu)Mez ocH3

LiClOa,Et2O

737"

U

CHs..--,.CHO : * 6azt

CHzl

/osiR3 ocH3 1

a\

s"rr"oocH3 osiR3

o .,\

1

I

*

"t."tYosi(t-Bu)Mez OC2H5

B7v"

\--\.".

cooc2Hs

to a-hydrory aldehydes'3 This reaction syn-Selectiveadtlition of allylstannanes (Ticla, MgBr2). It can also be effected by is usually effected with rcwjs acid catalysts use of 5 M LiCl4O in ether'

:helation control.

Substilution of allylic alcohok by s$ .ubstitution with 1-methoxy-1-(t-bunldtr Jicthyl ether.

Lithium

perchlorate

QBzl

QBzl -,\ -CHO * cHf'-,/Sn(cHs)gry CHs'

cn"r,\:,^"-r'cH, 0H ( 2 5: 1 )

,CH2CHO

CH Z"'-,.sn(CH3)3

Q--'"to H

t-BuMe2si6 6vort'r =cH, 6tr,tOlvt

f-BuMe2SiO

Aldol reaction of silyl enol ethers.a Benzaldehyde reacts with the silyl ketene ketal I at 25' in the presenceof Licloa (3 mol vo) to give the aldol 2 in 860/oyield. under these conditions a chiral a-alkoxy aldehyde reacts with I to give the aldol of

c '.:cocH3

'CHg

psiR3

* .t'1"r. c6H5cHo Additionof 1-methoxY-lr,,fr. \. r .. . ..r. in low yield when catalyzed i .:,lJ u'hen catalYzedbY 1'0 M

.

C . : ' J

: OBzl

a\

Uk#:oocH3 OSiRJ

o

+

frnel

/

PSiR3

ocH3

Liclo4' etnet.22o -

CHg

ocH3

: OBzl II I H F I V

ocH3

A

htd,r,trt' aldehydes.3 This reaction . \tillr-). It can also be effectedby

Resio

"urr/t-Ao"r.

1

W"t'cooc2Hs

-#*

1

CH3--.--.CHO

osiR3

Liclo4'

chelation control. substitution of allylic alcohols by silyt ketene acetals.s Allylic alcohols undergo (1) in 3M LiClOa in substitutionwith 1-methoxy-l-(r-butyldimethylsilyloxy)ethylene Jiethyl ether.

Lithiun pyrrolindobomhYdride

OH

I

ar \',

OSi-t-Bu(CH3)2

Licto4,o(c2Hs)2

I

I'

I ,2\

eo"/o

cH<\ocH" cHs

1

cH3ooc)

r^\

coocH3

a\

ur1, (-k

(A"r.

I G.B. Fisher,J. Harrison,J.C. Fuller.C T (i.c 4s33(lee2).

.

Lithium 2,2,6'6 -tetramethylpiperididc t |.t('rrr (E)-selective enolate formation't s'lect high lithium enolatesare formed with dialkylamidefollowed by trappingwith OSi of LiCl formed on trapping, since the adJr in (E)-selectivelithium enolates.The hcst

with crystalline 2,2,6,6-tetramethylpiperid and LiBr under anhydrousconditions'

OH

a^'J

(-J[/

1 860/"

edcoocH3

? il

'+lYi-?' ^,

(

C2Hu/^"tt'wns

caution!

A violent explosion has been reported from contact of cyclooctatetraene

with LiClOq in refluxing ether.6 I P. A. Grieco, J. D. Clark, and C. T Jagoe,Am' Sac', 113, 5488 (1991)' 2 p. A. Grieco, R. J. Cooke, K. J. Henry, and J. M. VanderRoest,TetrahedronLetters,32,4665 (1997)' 3 K . J . H e n r y , J r . , P . A . G r i e c o ,a n d C . T . J a g o e ,i b i d ' ' 3 3 , 1 8 1 7 ( 1 9 9 2 ) ' aM.T. Reetz, B. Raguse,C.F. Marth, H'M' Hngel, T' Bach' and D'N'A' Fox'Tetrahedron' 48'

Vinylcyclopropanes.2 Allylic bromr& deprotonationwith LiTMP (THF.20') arc alkenesto provide vinylcyclopropanes

s'/3't(1ee2).

5 P. A. Grieco, J. L. Collins, and K. J. Henry, Jr', Tetrahedron Letters' 33' 4735 ('|t992)' 6 R. A. Silva, Chem. Eng. News, Dec. 2 (1992)'

Lithium pynolindoborohydride. L|H3B-N

*

I

(1)

of a number Lithium aminoborohydrides.l The reagent I is a typical member in amine.boranes with of lithium aminoborohydrides,prepared by reaction of BuLi quantitativeyields.Thesereagentscanbestoredat25.underN2foratleastsix as reductants'Thus months; they are not pyrophoric. They are comparableto LiAlHa and anhydrides yield. l-actones I reducescarbonyl compounds(including esters)in high epoxides' amides, 1 reduces are reduced,but carboxylic acids are not reduced. In addition oximes, nitriles, and even halides.

(CH3)2C=CHCH2BT+ C6H5CH=CHz

Anthracenes.3 A convenientroute to dropyran of LiTMP with benzocyclobutcm

Lithitm 2,2,6,6-tetramethylpiperididel7l

u,ClOr,O(CzHs)z

)oocH3 'cH,

1G.B. Fisher,J. Harrison,J.C. Fuller,C.T. Goralski,and B. Singaram, Letters,33, Tetrahedron 4s33 (1992).

Lithium 2,2,6,6-tetramethylpiperidide (LiTMP' l). (E)-Selective enolate formation.t Corey and Gross (12,285) have noted that (E)lithium enolatesare formed with high selectivityby treatmentof ketoneswith a lithium dialkylamidefollowed by trappingwith ClSi(CH3)3.The (E)-selectivitymay be the effect of LiCl formed on trapping, since the addition of LiCl or LiBr to LiTMP also results in (E)-selectivelithium enolates.The best experimentalconditions involve metalation bromide, which generatesboth l-iTMP with crystalline 2,2,6,6-tetramethylpiperidinium and LiBr under anhydrousconditions.

f-coocHs

U O ii

oLi

L|TMPL|BT r'HF,-78"

-.t\ -cH" CzHs' \'/

oLi

I

CrH^'\

I

+ I CHs

C2H5"\-'CH3

(z)

(E) 50:1

f: -' .()ntact of cyclooctatetraene

<:..

tr)91).

,'.iht'dronLetters,32,4665(1991). ,r9l) l\ .: l). N. A. Fox, Tetrahedron,48, c: r

Vinylcyclopropanes.2 Allylic bromidesor chlorides,particularlyprenyl halides,on deprotonationwith LiTMP (THF,20) are converted into a carbenoid that reacts with alkenesto provide vinylcyclopropanes.

" r\. 33.4735 (1992).

CoHs-LITMP,THF, 20"

1)

(CH3)2C=CHCH2BT+ C6H5CH=CH2

\----7

\/

T

CH=C1611t;t 'rpical member of a number in l : liul.i with amine'boranes l'' under N2 for at least six [ r , , l-iAlH4 as reductants.Thus r rcld. l-actonesand anhYdrides lti: 'r,'n I reducesamides,epoxides, rl; :' t . :

(cis/trans= 74:26)

Anthracenes.3 A convenientroute to anthracenesinvolves the reactionsin tetrahy(precursorsto benzynes). and halobenzenes dropyranof LiTMP with benzocyclobutenols

172

tit

triethylbomhydride

Lithium

o

H

lVo of LiBH(C2H5)3is present,hydroboration rate and in good yield. Lithium triethllbnroh BH(OR)2.

9cH' \

/

*

+

1 , T H P ,^ 62"/"

,,)-"-)

9cH.

CH3(CH2)3CH=CH2

A;oH

YocH3 +

lA. Arase,Y. Nunokawa, Y. Masuda,and Il ll.rr

ocH3

I P. L. Hall, J. H. Gilchrist, and D. B. Collum, Az. Soc., l13, 9571 (1991); P. L. Hall, J. H. Gilchrist' A.T. Harrison, D.J. Fuller, and D.B. Collum, ibid., ll3,9575 (1991). 2 I. Jefferies, M. Julia, J.-N. Verpeaux, and T. Zahneisen, Synleu., 647 (1991). 3J.J. Fitzgerald,N.E. Drysdale, and R.A. Olofson, J. Org., 57,7122 (1992).

Lithium

tetramethylthallate,

Conjugate -40"

addition

This ate complex

reacts with

"1[:i4lt A

---70"-

o cHaA(\cH, cooc2Hs

cyclic

enones at

high selectivity. Note that a mixed ate complex

o

o

(/

Lithium tris(diethylamino)aluminum hy..dr Preparedby reactionof LiAlHr with H\( RCONH2 - RCHO.| Reduction of cr useful only with N,N-disubstitutedcarbnre primary carboxamidesto aldehydesat 1i' rn

Li(CHr)aTl.

to enones.r

to form the 1,4-adduct with

A

LiHB(C2Hs)3 HB(OBu)2 > THF, 20'

(/-"r.

tXt' l l l

* >95:<5

\-/

?"? cH3,'/\,AcH3 cooc2Hs

such as (CH3)2TlCl'2BuLi deliversthe butyl ligand more readily than the methyl ligand. Surprisingly, the mixed ate complex (CH3)3CT|'LiC=CCsH1 delivers the acetylenic ligand exclusively. I I. E. Mark6 and F. Rebidre,Tetrahedron Letters,33, 1763(1992).

Lithium triethylborohydride. Hydroboration with dialkoryboranes. Dialkoxyboranes, prepared by reaction of BHr in THF with an alcohol (2 equiv.), react very sluggishlywith alkenes.However if

o il ,/YruH, i l \/

l

L Tl{f

9rt

rJ.S. Cha,J.C. Lee, H.S. Lee, S.E. tre. J \l L e t t e r s ,3 2 , 6 9 0 3 ( 1 9 9 1 ) .

173

Lithiumtris(diethylamino)aluminumhydride

t

l% otL|B}{(C2H5)3 is present,hydroboration with BH(OR)2 can proceed at a reasonable rate and in good yield. Lithium triethylborohydridecan also promote the formation of BH(OR)2.

.

cH3(cH2)3cH=cH2

OH

LiHB(C2H5)3 HB(OBu)r

I

+ CHs(CH2)3'"\CH3

THF, 20"

(5v")

95"/o t

ocH3 . r - , , I q9l ); P. L. Hall, J. H. Gilchrist, !.-. ,t99l). r r . . ; : r r J T( 1 9 9 1 ) . -llr (1992). " :-

p l - r r c a c t swith cyclic enones at \ , t r l h a ta mixed ate complex

tXt' +

(/

'95: <5

r

CHq O

t " l l

cg-

-^\r'l\cH^ I

cooc2H5 rr :- :e.rdilythanthe methylligand. ( ( ( .Hil delivers the acetYlenic

.

i

,

,

-

|

r\\':.rncs. preparedby reactionof J:iir.hlv with alkenes.Howeverif

rA. Arase,Y. Nunokawa, (1992). Y. Masuda, andM. Hoshi,J.C.S.Chem.Comm.,51

Lithium tris(diethylamino)aluminum hydride, Li[N(C2Hs)2]3AlH. Preparedby reactionof LiAlH4 with HN(C2H5)2(3 equiv.) in THF. RCONH2 - RCHO.I Reduction of carboxamidesto aldehydeswith LiAIH+ is useful only with N,N-disubstitutedcarboxamides.This new hydridc (1) can reduce primary carboxamidesto aldehydesat 25" in 12 hours in yields of 5O-9O%.

o

tl

fY\NH' \2

1 ,T H F , 2 5 ' 91o/"

r J . S . C h a ,J . C . t r e , H . S . I r e , S . E . L e e , J . M . K i m , o . o Letters, 32, 6903 (1991).

[aY"o \/

Kwon. and S. J. Min. Tetrahedron

4

OH

CzHs Magnesium(Il) bromide etherate, MgBr2' O(C2H5)2. anti-Aldol selectivity.t a/,ti-Selectivity can be increased by transmetalation of the lithium enolate of the aldehyde or ketonc. Note that the anri-selectivity requires

I

85o/"

C5H5COC2H5

o H o : t l cunu/-f\c.H, CHs

CrHuA

l t'1

OBzl

,r4 1) LDA; MgBr2.O(C2H5)2 2) C6H5CHO

I

Mgl2, -60"

o

these alcohols (acetyl, benzyl). The high rc chelation.The reactioncan also be used to gl

(antilsvn= 98:2)

(cH3)3ccoc2H5

o H o i t l cuHr-f\cuHu CHs

9t' ,a^\-,'-\

lt lt

-crHu

Mglz

1", o vl

(antilsyn= 99:1)

1-16 hoursofequilibrationofthe enolates,and this equilibriumis highly dependenton thc substitutionpatternof both the ketone and aldehyde.However, the order of addition of MgBr2'O(C2H5)2(1.25 equiv.) is not important. I K. A. Swiss,W.-B.Choi,D. C. Liotta,A. F. Abdel-Magid, J. org.' 56' 5978 andC.A. Maryanoff, n 991).

C. Bonini,G. Righi,and G. Sotgiu,J. Org.. Sa

\tanganese(III) acetate. Oxidative cyclizption by addition to C-! r i o n i n t h e p r e s e n coef M n ( O A c ) r ' 2 H 1 O1 t t 2 (30-5OVo),which is evidently formed br h

o Magnesium iodide, MgI2. Iodohydrins; 1,2-diols.t The reactionof 2,3-epoxyalcoholswith MgI2 in toluene at -60" results in 3-iodo-I,2-diols in 85-95% yield. These iodohydrins are reduced to 1,2-diols by BurSnH in 5O-85% yield. The method is applicableto derivativesof

/.4-.2-COOCH3 -cH2cN | <''azCHz I CHs 1

Manganese(Ill)

OH

4

CeHs

Mgl2,-60" 85o/"

r o H l l czHs/'{

acetate

OH Bu3SnH

crHr/tY/

: OH

6H (97:3)

): : a

:.rscd by transmetalationof : thc cnli-selectivity requires

4

OBzl

oBzl

I

er/-y'I

Pr

OH

(>99:1)

o H o l t l c6n5lfc5H5 CHs

these alcohols (acetyl, benzyl). The high regioselectivity is attributed to magnesium chelation.The reactioncan also be used to generatesecondarydiols (last example).

(antilsyn = 98i2)

o' Hl ol

cuHrlt'cuH, CHs

9Bt

9t' ,t'\.'^\

l t t -crHu

1 "o, w

+

fan'o'

Mglz

cHg

\"rru

90"/"

(antilsyn= 99:1) (98:2)

(-. ri.

rhriumis highly dependenton ll,,*gv.r, the order of addition

J. Org.,56,5978 r ..\.Maryanoff,

P \ . ,lcoholswith MgI2 in toluene r l - . :c.c iodohydrins are reduced - .rpplicableto derivativesof rl

I C. Bonini,G. Righi,andG. Sotgiu,J. Org., 56, 6206(1991).

Manganese(Ill) acetate. The acetoacetateI undergoes cyclizaOxidative cyclization by addition to C=N.t '2H2O (0.5 in CH3COOH to give the ketone presence equiv.) tion in the of Mn(OAc)r (30-5OVo), of an intermediateimine. which is evidently formed by hydrolysis 2

o A,coocH3 -cH2cN |

,,,zcu" I

CHs 1

cH3ooc/ Mn(OAc)3

o>/K

/,--E\" 2

r76

Mercury(II)

acetate

This reaction can be used for synthesisof a decalindionesuch as 4 from 3, or for cyclization to cyclopentanones.

cH3cHo

CHr i l -

"r.\oot CH3 CH3

o ll

COOCH3 v -cH2cN

Mn(OAc)s +

|

13"/"

CeHs 3

'B.B. SniderandB.O. Buckman, J. Org.,57,322(1992).

Manganese(Ill) acetate-Copper(Il) acetate. Radical cyclization of polyenes.t Radical cyclization of the tetraunsaturatedBketo ester1 with MnO(OAc)7/Cu(OAc)2(2:l) affords the o-homo-5a-androstane2 with seven chiral centers in 3lVo yield.

CH3CHO +

cny'YooH I

z

CoHs Mn(OAc)3,Cu(OAc)2 ACOH,25' 3'1"/"

r P . A . Z o r e t i c ,X . W e n g ,M . L . C a s p a r a , n d D . G . D a v i s , T e t r a h e d r o n L e t t e r s , 3 2 , 4 8 1(91 9 9 1 ) .

Mercury(Il) acetate (2) can be preparedby reactionof hemiperoxy1,2,4-Trioxanes. 1,2,4-Trioxanes acetals(L) with Hg(OAc)2(1 equiv.) catalyzedby HClOa.This route can show high Thus the trioxane3 has the chair conformationwith all three diastereoselectivity.

substituentsequatorial. I A. J. BloodworthandN. A. Tallant.J. ('..s ('rk!.

Manganese(Il) acetate

,-J ^.tr,,nc such as 4 from 3, or for

OH

cH3cHo

CH, i l -

"t,\oot

t

,fr.\o H

l

l

cH.

-

1

cH3 cH3 1

l I 42o/^ -- | +

I CzHs 4

rYHs1on"1, 2)NaBH4 CH.

I ' o^o cHs>tr- _o

CHe' X cH3 cH3 2

pl:.',:i,,n of the tetraunsaturated lr'-- :r-homo-5a-androsta 2 nwei t h

CH"

cH3cHo* "rrzYo CoHs

I ' o^o

1)CF3COOH 2) Hg(OAc)2

O"Ornarr\6 CoHs uo-ru"r. | *"""o { CH. I

'

oi{o t - , 1 cH"-*do - t CoHs

. ,' n L e t t e r s 3 , 2, 4819 (1991).

3 (e,e,e >97o/o)

rr,-..i br reactionof hemiperoxyl{t t t- This route can show high ci : ' .()nformation with all three

"

"t.\o

cH3 cH3

coocH" " *.J-.\

cH, o

cF3cooH

substituentsequatorial. ' A. J. Bfoodworthand N. A. Tallant,J. C. S. Chem.Comm.,428(1.992).

178

l-Mesityl-2,2,2-trifluomethanol

Mercury(Il) trifloummethanesulfonate-N,N-Dimethylaniline' Hg(OTflr'C6H5N(CH3)2 0), 12, 307. polyene cyclizations.l This reagent (1) is particularly useful for cyclization of polyenes containing various oxygenated groups that can function as terminating groups' In this case cyclization occurs on oxygen rather than carbon, as observed with kwis the acid catalysts. Subsequentto cyclization, reduction with NaB&/NaOH eliminates mercury substituent.

Example: CHs CHs

o

1 ) 1 , C H 3 N O 2- ,2 0 ' 2) NaBH4,NaOH

?H'9r' ?

/f"-\ cH3l+cH3

cHz

2

\

q ?'.?" o^o'Y)

cu/-........ .Z-.c 3,>97:3

24o/"

I A. S. Gopalan, R. Prieto, B. Mueller, and D. Peters, TetrahedronLetters, 33' 1'679(1992)'

I -Mesityl-2,2,2-trifluoroethanol,l. Preparation:l

'8.J. Corey,X.-M. Cheng,K.A. CimPrxt' I : E.J.Corey,X.-M. Cheng,andK.A- (-tnq

Metal halides. Cleavage of terminal ePoxidcs: hd (l) can result in two halohydrins.Br p halohydrinscan be obtainedwith abou

H

9oHs

(r-|{coHu r o \-,N-e' Bu

(2)

o

A

n-C6H17

cH. - o I

ll

4t\/t"r, I ll cH3"'^\.,,^..-cH3

ce,z' coHscHs.-78", 100%

TiCl4,C7Hr6,-25"

>951

TiBrz(NRz)z , C7H16,0'

>951

CFs

ee 1, 100o/o

ester Asymmetric Diels-Alder reactions of a, B-unsaturated acids.2 The acrylate in cyclopentadiene (2) of this alcohol (l) undergoeslrwis acid-catalyzedreactionswith >97:3 diastereoselcctivitY.

HCt,H2O,25'

>954

-\ J . J . E i s c h ,Z . - R . L i u , X . M a , a n d G

2

Metal halides

o

! laniline,

(cH3)2Atcl -7A'

A rl

:ul.,rlr useful for cYclization of n :.-rction as terminatinggroups. ci:a,\n. as observedwith lrwis itl- \.rUHr/NaOH eliminatesthe

CHz

?" ?'.

\

H20-DME,

DI

o-)l( F

coo

CHr#

CHs

4

3,>97:3

t'

! . r t t : . 3 3 . 1 6 7 9( 1 9 9 2 ) .

rE.J. Corey,X.-M. Cheng,K.A. Cimprich,andS. Sarshar, Letters,32,6835(1991). Tetrahedron rE.J. Corey,X.-M. Cheng,andK.A. Cimprich, ibid.,32,6839(1991).

Metal halides. Cleavage of terminal epoxides; halohydrins.t The cleavage of a terminal epoxide (1) can result in two halohydrins.By proper choice of a metal halide either one of the halohydrinscan be obtainedwith about 95% regioselectivity.

r2)

o

.+

RCH(OH)CHzX +

RCH(X)CHzOH

n-C6H 1 7

CH" OH

r " l

ffcF3 t t l ll.-,,,,,,.*cH.

1 , 1 0 0 %e e

T i C l r , C z H r o ,- 2 5 '

>95o/"

5:95

T i B r 2 ( N R 2 ) 2 , C 7 H 1 6 , 0 ' >957"

94:6

HCt,H2O,25"

89:11

wotrd acids.z The acrYlateester in with cyclopentadiene r,.:-| 1,\DS J.J. Eisch, Z.-R. Liu, X. Ma, and G.-X. Zheng,J. Org.,57,5140 (1'992).

180

(rS,2R)-2n r}|.rra

(S)-or(R)-2-Methoxy'2/-diphenylphosphino'l,l/'binaphthyl

Methanesulfonyl chloride/Sodium hydrogen carbonate. p-Lactams.t Treatment of the B-amino acid I with 1 equiv. of CH:SOzCI at 45. in CH3NO2 containing suspendedNaHCO: furnishesthe B-lactam 2 in the highest yield reported to date for this cyclodehydration. The cis-isomer of I also undergoesthis

OH cH^)'..

+ HSiCl3

Pd-rRr'

99i

MsCl,NaHCO3 CH3N02,45'

/cH2coocH3

97%

HotcArun, 2

b+HSicr3;b reaction to give cis-2 (75Voyield). Yields are lower when applied to simple B-amino acids,probaLrlybecauseof lower solubility in CHTNOzand higher temperatures,75-80''

exo.1

I Y. Uozumi,S.-Y.Lee,andT. Hayashi,Terrohc

I M. F. Loewe,R.J. Cvetovich,and G. G. Hazen,Tetrahedron Letters,32,2299 (1991)' ( I S,2R)-2-(p-Methoxyphenylsulfonyl)emin Enantioselective addition of (CzH:t:Z

(S)- or (R)-2-Methoxy'2/-diphenylphosphino-1,1/-binaphthyl(l)'

N-sulfonylaminoalcohols, I was found to tr additionof diethylzincto aldehydescatalvzcdI chloride. Addition of calcium hydride or r cnantioselectivitybut can increasethe vield

c p-CH30C6H.Sq

ocH3

(R)-(+)-1

P(CoHs)z

I

c6HscHo + (C2H)2Zn

Asymmetric hydrosilylation of norbornene (2).t This reaction can be effected by in high regio- and enantioselectivityby reaction of 2 with clrSiH catalyzed to be converted product can The (R)-1. with complexed dimer (allyl)chloropalladium 96Va ee. (4) in (1S,2S,4R)-norbornanol

c-C6H11CHO +

(C2H5\2Zn

c*{:

I -phenylpropanol

(f S,2R)-2-(p-Methoxyphenylsulfonyl)amino-

lrl ate. ..:::

I cquiv. of CH:SOzCI at

\r-::

trr'. :hc P-lactam 2 in the highest L l - : . , ' m c r o f I a l s o u n d e r g o e st h i s

+ HSicl3 t

\ 7l_^.'-SiCf. z-'.\,/

ojll)r_ nn"

3 (exo,10O/"1 eo"/.I IH:KHco3 n'u' I \

zl1-oH z_\\,/ (1S,2S,4R)-4(93%ee)

5

b+HSicr3;rb,-ticr'; ..:.n appliedto simPle B-amino 75-80'. ' j:r.: hiqhcrtemPeratures, T

"'

(1R,2S,4R),95oloee

exo,1O0"/"

I Y. Uozumi,S.-Y.Lee,andT. Hayashi,Tetrahedron (1992). Letters,33,'71,85

::t r\. 32,2299(1991). ( f S,2R)-2-(p-Methoxyphenylsulfonyl)amino-1-phenylpropanol (l).

i n a p h t h Y l( l ) .

Enantioselective addition of (CzH)zZn to RCHO.| Of a variety of chiral N-sulfonylaminoalcohols,I was found to be the most effective ligand for asymmetric additionof diethylzincto aldehydescatalyzedby titanium(IV) isopropoxidein methylene chloride. Addition of calcium hydride or 4 A molecular sieves does not affect the enantioselectivitybut can increasethe yield.

CHs

-CoHs

/-R=\

p-CH3OC6HaSO2 NH

OH

(1)

r -1+)-1 1 , Ti(O-'-P04

C6H5CHO

+

(C2H5)27n

C a H 2 ,C H 2 C | 2, 0 '

tutu)a"r. H O H (S) , 97%ee c-C6H11fCHe

). I hi: reaction can be effected I *ith ChSiH catalYzedbY t - nroduct can be convertedto

c-C6H11CHO +

(C2H5\2Zn 77o/o

H O H (S),90%ee

182

(Danishefsky's diene)

,rdns-l-Methoxy-3-trimethylsilyloxy'I,3-butadiene

1 K. Ito. Y. Kimura,

and H. Okamura,

and T. Katsuki,

Synlett, 573 (1992)'

,aCuHu tl * CH3OOC-.._..N

Cl-h

,

t..

i-P{'H

c

1

f _ \ o

(1)

(S)-2-(Methoxymethyl)pyrrolidine.\""\""-CHt

?)

H 2-Methylenecyclohexenones.l A diastereoselective synthesis of a 2-methylenethe chiral cyclohexenone(5) involves use of (S)-2-(methoxymethyl)pyrrolidine(1) as group. exo-methylene the of generation auxiliary and as the leaving group for

I

///

Eiu",4

c6Hs{}LocH3

i-Pr''

l-Pr""f-6g6611.

(Y

coocH3

1)NBS, ccr4 2)1

>^

CHe

/'1..COOCtlt

<,t_-*.) t ocH3

ocH3

\

1) Li/NH3,I-BUOH 2) CH3l

ocH3

CuHr/

3

2 CHe

/'J-Cooca" t

Vv\ t

l

ocH3

i

I

1 ) T s O H ,H 2 O 2) ctc6H4c03H 83V" overall

coocH3 CHz

OCHs

4

The chiral auxiliary can be recoveredhr i H. Waldmannand M. Braun,J. Org.. 57. tttt' Methyl acrylate.

l2+2+2lCycloadditions.t The anrm *'hen treated with methyl acrylate un&retr cyclization to form the spirobicyclic crckrhc tliastereomers(4lVo yield). Decarboxrlatxn

cHc

rA.G. Schultzand R.E. Taylor,Am. Soc.,114,3937(1992)' /rons-1-Methoxy-3-trimethylsilyloxy-1t-butadiene (Danishefsky's diene). (l Reaction wilh imines derived from a-amino esters.t In the presenceof zncl2 2,36-substituted form to diene this with reacts t--valine from 1 derived imine the equiv.) (92:8). This reactionis 2 and3 with high diastereoselectivity didehydro-4-piperidinones Michael cyclization undergoes which form a, to reaction a Mannich involve to believed 92:8. ratio in the 3 2 and form to

1) LDA. THF 2) CHz=CHCOOCT+r 41%

1, R3 = Me2-f-Bu

diene)

..f.lr'.

Methyl acrylate l:

'-r

rl99f)

cH2)

,acuHt

cH3ooc\.-N

il

+

ZnCl2 THF, -20"

( ocH3

iP/'H 1

L-

osiR3

r83

(1)

ir - .r nthesisof a 2-methylenet!r ,rrrrolidine (l) as the chiral group. x r ,-nrcthylene

",,$o",, l-Prt"'f.6g66t. 2

seueral I sTeps +

occH3 \

1) L|/NH3,t-BuOH 2) CH3l

o tl

a\ t t

ocH3

l

cuHuAfH 4

!

coocH3 The chiral auxiliary can be recoveredby a Curtius reaction.

CHz

rH. Waldmannand M. Braun, J. Org., 57,4444(1gg2\. Methyl acrylate. The anion of the methyl cyclopentanccarboxylateI [2+2+2]cycloadditions.t when treated with methyl acrylate undergoessequentialMichael-Michael-Dieckman cyclization to form the spirobicyclic cyclohexanonep-keto ester2 as a mixture of two diastereomers(41% yield). Decarboxylationof 2 followed by addition of cH:MgBr

CH

9cHo Dani.hefsky'sdiene). Ir thc presenceof ZnCl2 (l 5 6 .rr-:rr t() form 6-substituted2,3. h i s r e a c t i o ni s r.-.':r itr'(92:8)T Michael cyclization * .-::,jcr,qoes

1) LDA, THF 2) CH2=CHCOOCH3

1 ) N a C l ,D M S O( 8 1 % )

2) CH3MgBr(7s%) ...'............................'..'.'.......................* 41"/"

osiR3 cH3 cH3 1, R3 = Me2-f-Bu

2

Methylaluminum bis(4-brorno-2,6-di-r-butylphenoxide)

(c6H5)3siq

coocH3 (CH3)2CuLi BF3.O(C2H5)2

several steps

41"/"

n

eu-?>4 =

CHs

syn-2

CHs

Nirsunoou I Inversron

CHs 4

I

';A8

(C"H.)"SiO

o

A ry!"tT 77"/"

:

i l l

-.>
'

(t)-6

eH. anti-2

syn-(S,R)-3. Since the enantiomcn c asymmetricepoxidationwith (- FDIPT are availablefrom this rearrangemcnr(

This rearrangementProvidesa Prr cven those possessingan asymmclrlc i

to dehydrogenation provides3. This productwas convertedby dehydration,oxidation' and trienone This hindered the trienone4 with only one chiral centerat thc spiro carbonatom. followed by methylation by conjugatc 6 sesquiterpene B-vetivone was convertedto the decarboxylation. 48, 46'7'7(1992)' I G. H. Posnerand E. M. Shulman-Roskes, Tetrahedron,

{coHs)osi! e,..

,ur_r-"t

^

CHs

206; 16' 209-212' Methylaluminum bis(4-bromo-2,6-di-l-butylphenoxide),I' 15' to B-hydroxy alderoute A novel Asymmetric synthesisof B-hydroxy aldehydes't rearrangement stereoselective effect to reagent hydes is based on the ability of this of this restereoselectivity The aldehydes. oi o, B-epo*y silyl ethers to B-silyloxy ethers triphenylsilyl with highest being arrangementdependson the silyl substituents, s}',-epoxy the Thus ethers. triisopropy|silyl and neg|igible with the more hindered allylic alcohol with silyl ether 2, preparedby Sharplessasymmetricepoxidationof the (+)-DIPTfol|owedbysi|ylation,isrearrangedbyltotheanti-B-hydroxyaldehyde (40:1).Theanti.epoxysilylether2,obtainedbyMitsunobuinversion'rearrangesto

osi(c6H5

o

Rearrangement of epoxides.: Tl ment of trisubstitutedepoxidesto aldr

Methylaluminum

:

(CH3)2CuLi BF3'O(C2H5)2 817.

185

(c6H5)3siQ

(c6H5)3siQ

coocH3

bis(4-bmmo-2,6-di-/-butylphenoxide)

f

)

Bu.GycHo +

er-Gg: eHt

40:1

CHe anti(S,S)-3

syn-2

syn-(R,S)-3

.'-CHg

IttitsunoOu I inversion I

;ts

";.f8

4

(c6H5)3sio

(C"H^).SiO

o

II

fi

eH.

-\ct" -

(t)-6

anfl-(R,R)-3

f

12:1

CHs syn-(S,R)-3

anti-2

,'\]cH3 CHs

/ CHs

,r4-i-"ro

z

syn-(S,R)-3. Since the enantiomers of syn- and anti-2 are availablc by Sharpless asymmetricepoxidationwith (-)-DIPT, the four possiblealdolsof a B-hydroxy aldehyde are availablefrom this rearrangementof a, B-epoxy triphenylsilyl ethers. This rearrangementprovides a practical routc to a number of B-silyloxy aldehydes, even those possessingan asymmetricquaternarya-carbon.

cHo to anddchydrogenatlon il.: ::r{)r1. trienone hindered This ,:\)nr. r.-' bY U-i.1:emethylationfollowed

anti/syn= 100:1 (C^H^).SiO I

(c6H5)3siQ , - - ., r . ) l ) .

er/"r'c'o E{ cHs

Bu

anti/syn -- 2OOt1 r,. I l.i. 206; 16, 209-212' \ - '.rl routcto B-hYdroxYaldei . ,:eosclcctive reafrangement 0f this reP. -'crd()sclectivity rl rr!- - \\'ith triphenylsilyl ethers lr .:hcrs. Thus the sYr?-ePoxy li: ': ,rf thc allYlic alcohol with aldehYde rr '-c urtti-B-hYdroxY ,ru to rearranges inversion, s-:

osi(c6H5)3

o

osi(c6H5)3

cHo anti/syn = 100:1

Rearrangement of epoxi.des.2 This aluminum reagent (1 equiv.) effects rearrangement of trisubstitutedepoxidesto aldehydeswith very high selectivity.Lewis acids are

MahybH f86

Methylaluminum

bis(4'bmmo-2'6-di-t-butylphenoxide)

but,the ordinary kwis generally used tbr rearrangementof epoxides'

acids rearrange

trisubstitutedepoxidestoa"mixtur"ofaldehyde.andketones.ofvariousmetalfluorides' antimonypentafluorideisthemosteffectiveforselectiverearangementoftheseepoxides to ketones.

a-Allqlation of enol silyl etherc *'ith R directly with primary alkyl halides is limitcd in the presenceof 1'.1-2equiv. of MABR. c primary alkyl triflates(2 equiv.) in moderate1 ethersof ketones,esters,and some aldehldc for reactionswith ketene silyl acetals.

clt'

9H'

L-O/ _/\ Bu' \ s Bu

cH3xcHo +

,u\*

Bu Bu

o

MABR,CHzClz,0'C

75o/o

0:100

-78"C SbFs,C6H5-CH3,

86"/"

82:18

c.7 Un3

t

osi(cH3)3

w

-

MABR sbFs,-78'c

.)

B u +

cHo

\_,.f

Bu

o

aY"'

0 : 10 0 85:15

73o/" 79"/o

ri

Y

osi(cH3)3

Therearrangementoftri-andtetra-substitutedepoxidesbythisreagentinvolves arti-migrationof thc alkyl groups'l

CHe | 9Hs

Ao

CHa

( osiR3

ffx,:

?", 1, cH2cl2

crr&ct' 'cHo (

osiR3 Pr "r.Y,

cH.Ao

1z-)/.$snBu3


t (

I K. Maruoka,J. Sato,and H. Yamamoto. .{a .! : K. Maruoka,R. Bureau,T. Ooi, and H. \'ame t K. Maruoka,T. Ooi, and H. Yamamoto. IrrroA t K. Maruoka,J. Sato,and H. Yamamolo. .{a -l

Methylaluminum bis(2,6-di'/-butyl{-acd Asymmetric Diels-Alder reactiots ol formed from f-butyl methyl fumarate(l ) trtt to form the adduct2 in 937oyield (99: I t. Srn

Methylaluminum

(,-.:tr.rr\ L,ewis acids rearrange tr.:- . ( )f variousmetal fluorides, ' r,.::rrn{€mefltof theseepoxides

Bu Bu

187

a-Alkylation of enol silyl ethers with RCH2OTf.a Alkylation of enol silyl ethers directly with primary alkyl halidesis limited to allylic and benzylic halides.In contrast, in the presenceof 1.1-2 equiv. of MABR, enol silyl ethers undergo a-alkylation with primary alkyl triflates(2 equiv.) in moderateyield. The reactionis applicableto enol silyl ethersof ketones,esters,and some aldehydes.t-Butyldimethylsilyl groups are preferred for reactionswith ketene silyl acetals.

cH3xcHo

B-

bis(2,6-di-t-butyl-4-methylphenoxide)

1, CH3OTf cH2ct2, -40'

O=-"si(cH3)3

Q"", cHo

: 100 .2 18 1, C2H5OTl

CHg

.B-

t

l (,..'...fcHo

*

a-\

-l- )"c,n, cHs- Y .cr, o (87 : 13)

Bu : 100

CHs

1, HexOTf

8 51 5

-Hex

o

osi(cH3)3

(9a :6) bv this reagent involves

/ffsnBu3

t t \-.2

l

1,cH3orr 72/"

CHe I K. Maruoka,J. Sato,and H. Yamamoto, Am. Soc.,f 13, 5449(1991). I K. Maruoka,R. Bureau,T. Ooi, and H. Yamamoto, Synlen,491.(1991). I K. Maruoka,T. Ooi, and H. Yamamoto,Tetrahedron, 48,3303 (l9g}). 1K. Maruoka,J. Sato,and H. Yamamoto, Am. Soc..ll4, 4422 Ogg2\.

CHs

Pr

cHo-__l,.Pr I CH3

O

Methylaluminum bis(2,6-di-/-butyl-4-methylphenoxide)(MAD). Asymmetric Diels-Alder reactions of unsymmetrical fumarates.t The complex formed from l-butyl methyl fumarate(1) with MAD reactswith cyclopentadieneat -7g' to form the adduct2 in 93% yield (99:1). Similar high discriminationis shown in reaction

188

lGlkrt+

Methyl (R)- or (S)-mandelate

of the complex with 2-methylbutadiene(Slvo yield, 86:14). In contrast, Diels-Alder reactionof I catalyzedby (C2H5)2AlClshows practicallyno selectivity.MAD can even distinguishbetween a methyl and an ethyl ester group.

endo-2-Methylbicyclo[2.2.1]hept-S.en1'l

al

N

,("o'"'"./\ .

t_euozc)

MAD r-[----"o"-t'

\Jd\ co2CH3

1

",-l\-_/.CorCH3 1

+ 99:1

CO2f-Bu 3

The MAD-mediated Diels-Alder reaction of /-menthyl methyl furmarate with cyclopentadiene(2 equiv., cH2cl2, -78") proceedsin 86vo de with an endo-exomethoxycarbonyl ratio of 98:2. I K. Maruoka.S. Saito,and H. Yamamoto, Am. Soc.,f 14, 1089(1992).

Methyl (R)- or (S)-mandelate,CoHsCHOHCOOCH3(1). Asymmetric synthesisof B-lactams.l The 12+2lcycloaddition of benzyloxyketenes and imines 2 derivedfrom (R)-1 resultsin 3,4-cis-disubstituted B-lactams(3), which can (5). acids be convertedto optically active 3-amino-2-hydroxybutyric

Stereoselective aldol reactions of o-a this ethyl ketone (l) reactswith various a-m protection as silyl ethers and thermollsis {51 ketones 2 and 3. The diastereoselectivirrrs 1) 2) 3) 4)

LiNlSi(CH3)312 RCH(CHs)CHO CrSi(CH3)3 s00"

o

6H.W tl cH2 cl

syn s 2 R = CoHsR = HzC=CHR = BztOCHzR = (,-P43S|OCH2-

?utu

cttrctr,zo"

Bzlo

oc(cH3)3

_ (-octcHg)s + BzloCH=c=o 88v" N Bzl/

1-aryl- and 2-vinylpropionaldehydesreacl r benzyloxyaldehydesand B-triisopropl lsilr lor

M. Ahmar,R. Block,G. Mandville,and l. Ronre

2

HCI ,or" I (CH"),CHOH I { CHrCnHs - - I

./\

-coocH(cH3)2

HzN- Y = OH

(2R,3S)-s

HO,,,.,.C6H5 Several steDs

t

Hrruy'YcoocH(cH3)2 =

I 0-Methyl-9,1O-dihydroacridene/Sodiun

br

aY\.'\ t=*N-V l l l l I

CHs

OBzl 4

rY. Kobayashi,Y. Takemoto,T. Kamijo' H Harada. Y. Ito. and S. Terashima, Tetrahedron, $. 18s3 (19e2).

Photocatalysis of radical cyclizotioa. Jc-halogenation of aliphatic bromidesand ant elso effect radical cyclization of l-allr.lorr-l-l r ield.2

l0-Methyl-9,10-dihydroacridene/Sodiurn

k ." l{), In contrast,Diels-Alder 1r.., i n()selectivity.MAD can even

endo-2-Methylbicyclo[2.2.1]hept-5-enyl ethyl ketone,

n-:

A;"",

N CC't-Bu

Ol\-.cozcns

+ oql

CO2t-Bu

):C-.

3

borohydride

stereoselective aldol reactions of a-methyl aldehydes.t The lithium enorate of this ethyl ketone (l) reactswith various a-methyl aldehydesto form aldors, which after protection as silyl ethers and thermolysis (500') were isolated as the a,B-unsaturated ketones 2 and 3. The diastereoserectivityis highry dependenton the R group. Thus

-:-,^:lI

m e t h y lf u r m a r a t ew i t h c Y Jc with an endo-exomethoxy-

.. r)992).

1) 2) 3) 4)

LiNlsi(CH3)312 RCH(CH3)CHO CrSi(CH3)3 500"

osi(cH3)3 g osi(cH3)3 ? cH, cHr * \rA.-r,^r.rn \zA,-.,-\.-R lcH2 l . r i l l i I cH3 CHs

,I t. > :

. - I , ) a d d i t i o no f b e n z y l o x y k e t e n e s

[\.

.'riutcd B-lactams (3), which can .:rc acids(5).

t-

oc(cH3)3 N'Bzl 3 (15:1)

Hcl ,or" I (cH3)rcHoH I HO,,,.r.C6H5 | -r'i::

I

syn, syn 2

OBzl 4

Tetrahedron, 4t, 'nd S. Terashima,

syn, anti 3

R = CoHs-

98:2

R = H2C=CH-

80:20

R = BzlOCHz-

t2:BB

R = (l-Pr)3SiOCH2-

15:BB

2-aryl- and 2-vinylpropionardehydesreact with .syr, syn-selectivity, whereas the Bbenzyloxyaldehydesand B-triisopropyrsityroxyaldehydesreactwith syn, anti-serectivity. I M. Ahmar, R. Block,

G. Mandville,and I. Romain,Tetrahedron Lerters,33,2501 ogg2\.

l0-Methyl-9,lO-dihydroacridene/Sodium

affill

l.

Yru-\Z

,rrruy')icoocH(cH3)2 :

cu" cH3 cH3

ll

borohydride,

| / NaBHo

(1)

CHe Photocatalysis of radical cycrization. This system, when irradiated, can effect dehalogenationof aliphatic bromidesand aryl halidesvia a radical intermediate.rIt can also effect radical cyclization of 1-allyloxy-2-halobenzenes (equationl) in 76vo isolated vield.2

(2R3&5R)-4-Methyl-5'phenyl-3-phenylthio'2-morpholinol

rC. Agami, F. Couty, L. Hamon, B. Prince. and (' I 2 C. Agami, F. Couty, B. Prince, and C. Puchcx.r?v

CHr

zYt

l^i;

ll l. -$OCH2CH=CH2

76"/"

t

i

l

t

(Y) \_,,^-o

-

Methyl(phenylseleno)malononitrile,

t M. Ishikawa and S. Fukuzumi, Am. Soc'' 112' 8864 (1990)' 2 G. Boisvert and R. Giasson, Tetrahedron Letters' 33,6587 (1992)'

ro-r.ot'l

# lor,"(i' I cur,u"l'-*" cH. I L cHs Asymmetric synthesisof N-methyl'a-amino

I

cH.4 This reagent is prepared by reaction of

(l)' (2&3&5R)-4-Methyl-S-phenyl-3-phenylthio-2-morpholinot' glyoxalwith (R)-NThis chiralmorpholineis obtainedin 85Voyield by reactionof in water'r andthiophenol methylphenylglycinol

..oH gHo I

NC

C6H5SeBr. Radical additions to alkenes,t Unlike rcd containing OR, SR, or NR2 groups (l6.ltt-1 of AIBN undergoes1,2-additionto alkenes p alkenesproceedsin high rick 1,2-disubstituted

CsHsSH

Bu

cH2

1 ,A I B N cHct3,60'_ 97%

esters'2 This morpholine can be used

asachiraltemplateforsynthesisofN-methyl-a-aminoesters.Thusreactionwithan group by an alkyl group by the alkylcopper involves displacementof the phenylthio reactionwith an alkylzinc contrast, In 90:10). (about usual Sn2 processwith inversion possibly via an iminium retention, complete iodide involves substitutionwith essentially

C6Hu"\.CHs

intermediate.Thealkylatedproduct(2)isthenoxidizedtoanoxazinone(3),whichon provides N-methyl-a-amino treatmentwith vinyl chloroformatefollowed by hydrolysis esters(4)inhighopticalpurity.Thisapproachtochiralaminoacidsisunusualinthat dependingon the choice of the either enantiomercan be formed from the sametemplate (expensive)is not recovered auxiliary chiral the organometallicreagent.Unfortunately,

c2H56'\.''cHa

--

r2..*

for reuse.

'

Prznt ,OY"

aoYot C6Hr,."

\rAr, r

CHs 2 (>96%de) 1) cH2=cHococl 2) HaO+. CHaOH -8O"/o

-

!"ror?'60-80'/'

(oYo cuH;"\ry e' CHs 3

r D . P . C u r r a n a n d G . T h o m a ,A m . S o c . , l l { . 1 J . \

CH3O--.7,O

r I

HtrtAPr CHs 4

Methyl trifluoromethanesulfonate, CH.OTf . A new route to o f5+2]Cycloaddition. activation of an unsaturatedpyrone such a:s a pyrylium salt (a), which undergoes[5-1)cr to give 2 in 84% yield.

Methyl trifl uorcmethanesulfonate 1 C. Agami, F. Couty, L. Hamon, B. Prince, and C. Puchot, Tetrahedron,46,7003 (1990)' 2C. Agami, F. Couty, B. Prince, and C. Puchot, ibid.,47,4343 (1991).

NCVCN

Methyl(phenylseleno)malononitrile,

cHr

(1)

secuHu

This reagent is prepared by reaction of the anion of methylmalononitrile with rpholinol (l). tr :-.rctionof glyoxal with (R)-N-

C6H5SeBr. Radical afulitions to alkenes.r Unlike iodomalonitriles which do not add to alkenes containing OR, SR, or NR2 groups (16,183-184), this malononitrile in the presence of AIBN undergoesl,2-addition to alkenes possessingthese groups. The addition to 1,2-disubstitutedalkenesproceedsin high yield and with high regioselectivity.

,.O,J|OH -

-

t|

i!

l

|

E e l - .i *c6Hr'."l=lnscuHu

I,A|BN

CHs 1

Bu

cH2

"+#*

NC

cH./fsec6H5

'this

Bu

morPholinecan be used t r\ |'r.- c:tcrs. Thus reaction with an r, --'up bY an alkYl grouP bY the . -':.r\t. reactionwith an alkylzinc tc -. .ntron,possiblyvia an iminium il..-.: i,, an oxazinone(3), which on i: . ..rr providesN-methyl-a-amino ;i^ ': .rnrinoacidsis unusualin that rpi,'. Jcpcndingon the choiceof the [\:. ::\ (cxpensive)is not recovered

CN

Nc\

cH.

/cN

SeC6H5

(\cH,

CoHs syn/anti=80:20 NC 6p SeC6H5

\ / t

^ ,, ^.'\-CHg U2H5U

92"/o

CH3"/\"\cH3 oc2H5 syn/anti -- 25 :75

: t. ,'i+ ^ :': -: -

.'O'-ZO | I | I ^ . . * t \ N A'iP r CoHs CHs 3

I D. P. Curran and G. Thoma, Am. Soc., ll4,

4436 (1992)-

Methyl trifluoromethanesulfonate, CH3OTf. A new route to complex seven-membered rings involves [5+2]Cycloaddition. activation of an unsaturatedpyrone such as 1 with CH-:OTf (2 equiv., 20") to form a pyrylium salt (a), which undergoes[5*2]cycloaddition at 25" when exposedto CsF to give 2 in 847o yield.

Methyltrioxorhenium

hydrolysisof epoxidesto trans-1,2-diolsThrs additionof amines. 2 cH3oTl, cH2cl2,20'

1Hp --.: 'Fr

^,, .-\--CHt UH3 CHa

I

a\ t

I c'r sa7"I orrr/cFl2ct2 I ru'

I xrc 6'

l

7CA

1 H?C 6'

cHZ"".'oH

I

$a

Aldehyde olefination.a CH-rReO. (lt rs aldehydeswith a diazoalkaneand a phosphtr The actual catalyst may be CHTReO:OPR' I aromatic aldehydesand also to enals' Somc rn only moderate Yield.

2 (3.8:1) of phoboids such as tigliane (3)' Phoboids Note that 2 correspondsto the B/c ring promoters' are of interestas highly potenttumor J' Org'' 56' 626'1('1991) 1P.A. WenderandJ.L. Mascarefras,

CH3-..,/.CHO

in cH2cl2 or coHscl at 25"' neous catalystfor metathesisof alkenes

CH3CH=CHC2H5

CaHeCH=CH2

1 Al2O3/SiO2 -***

Nlta

CHg\...\--COOCzHs l CHs (E/Z= 85 : 15)

(1)' Methyltrioxorhenium, CHrReOr with HSn (CH.r)3and purified by vacuum This oxide is preparedby reactionof Re2O7 sublimation'ltissolubleinorganicsolventsandalsoinwaterandisstabletoairand .-._otefinmetathesis.2CHrReormixedwithAl2o3/Sio2isaneffectiveheterogeacid.r

+

I

CHg

ficHo

*

Nza

ozN*

fi*cooc4 ozNV

cH3cH=cHcH3 CaHeCH=CHCaHe +

C2H5CH=CHC2H5

CHr=611t

catalyst for epoxidation of alkenes with Epoxi.dation.3 CHrReOr is an effective or water at -10'to 80"' It also can c^tzlyze H2O2 in l-butyl alcohol, tetrahydrofuran'

"31 (Elz=s7 * .\. Herrmann,J. G. Kuchler, G. Weichsclhlu ntm., 372,351 (1989). \\'.A. Herrmann, W. Wagner, U.N. Flessmr' I' r.J., 30, 1636 (1991). \\. A. Herrmann, R. W. Fischer,and D' \A \|er ' \ \ . A . H e r r m a n na n d M . ' V ' l a n g ,i b i d ' . 3 0 ' l r ' r l

Methyltrioxorhenium

193

hydrolysisof epoxidesto trans-1,2-diols.This secondaryreaction can be suppressedby addition of amines.

CH."\'-CHs

o -

OH

1, H2O2 -10" 100"/"

No

cHs/YcHs OH cH3/oH

CHe

I '

a\ t

1, H2O2 25"

l

/-Yo \-l

70v" 1, H2O2 25" . 90"k

cHNoH

ot>-rot

Aldehyde olefi.nation.a cHrReor (1) is an efficient catalyst for condensationof aldehydeswith a diazoalkaneand a phosphineto form an alkeneand a phosphineoxide. The actual catalyst may be cHrReozoPR3. The reaction is applicableto aliphatic and aromatic aldehydesand also to enals. Some cycloketonesundergo this olefination but

li.o

in onlv moderate vield. 2 (3.8:1)

CH3-- -,CHO Y

l. ..r.h as tigliane (3). Phoboids

I

rurz\coocrHu

ir ( ll.), and PurifiedbY vacuum '- .\.rlcrand is stableto air and

82lo

CHs CHs\..\_-COOCzHs I CHe ( E / Z= 8 5 : 1 5 )

I

1, P(C6H5)3 C o H o2, 0 ' ,

+

O=P(CoHs)s +

Nz

1,PBu3

[aY"'o

l\tr^coocrH,

z*cooc2Hs I ll orNV

+

'*#-

orN& \r( )- is an effcctive heteroge< lt.('l at 25'.

C2H5CH=CHC2H5

ih,

+

CH2=CH'

l : : ipoxidation of alkeneswith ' ttr t10".It also can catalYze

o=PBuo

N2

(ElZ--97:3) :W.A. Herrmann,J.G. Kuchler, G. Weichselbaumer,E. Herdtweck, and P. Kiprof, J' Organomet. C h e m . ,3 7 2 , 3 5 1 ( 1 9 8 9 ) . rW.A. Herrmann, W. Wagner,U.N. Flessner,U. Volkhardt, and H. Komber, Angew. Chem' Int' Ed., 30,1636 (1991). 'W.A. H e r r m a n n ,R . W . F i s c h e r ,a n d D . W . M a r z , i b i d . , 3 0 , 1 6 3 8 ( 1 9 9 1 ) . 'w.A. Herrmann and M. Wang, ibid., 30, 1641 (1991).

194

carbene complexes

Molybdenum

Molecular Sieves. Stereoselectivity effects.l There are several recent reports that molecular sieves can improve the stereoselectivity of various reactions such as the Sharplessepoxidation (e.g., f3,51). The beneficialeffect has been attributedto water-scavengingby the sieves. of the Pd-catalyzed Molecular sievesalso show a markedeffect on the diastereoselectivity I). ln thesereactions, (equation chiral acids with cyclizationof cis-1,2-divinylcyclohexane the diastereoto increase in some cases additions of molecular sieves wele found

,ocH3 (Co)sMol Bu

CH2=66611

molecular cyclization of the carbene complcr

bene I with methyl acrylate in THF ar 6-i' pn 2 in 71.Vo yield.2

H /fl \'/

f/'\+,'\CH, | | :"2 |

1) BuLi 2) Mo(CO)6 3) cHqoSO^cFl -

eo1on.1,,o{:!o

|

,,\LJ

+

v/|"gzvrt2 H

Mno"'(CHq)^c=O

R*COOH

*

|(CHj3C=CR

.v

R = (CH2)2CH3

'*o"ot

ocoR'

CHz

>

T .t(Rl I

Y.T..--/

6 H

selectivity, in one case from 0 to 54Va ee. In more cases,the addition of molecular The highest selectivity obtains with sieves could even reversethe diastereoselectivity. Lancaster4 A and 13X sieves,both of which have sodium as the counterion.The steric effects do not result from elimination of water, since sieves containing ZOVoof water show improved stereoselectivity.No explanationis available at present,but a surface effect is one possibility.

[

r

I .r - rHF,6s" | ,#uo(co)o - l ( i l l\--,/'.. ocHo L

l

I q iI I

The processhas been extendedto the drr molybdenum carbene4 at 60" results in a r [3.3]sigmatropic rearrangementto hexahrdr analogouschromium complex with 3 also rc lower yield. An electron-withdrawinggroup r

I L. Tottie,P. Baeckstriim, Org.'S7'65'79(1992). andA. Heumann,J. C. Moberg,J. Tegenfeldt, H_

\- -*co@ Molybdenum carbene complexes. Thesecomplexescan be preparedin about55Voyield by reactionof RLi with Mo(CO)e followed by methylation (equationI). .l) RLi,ether,0"

Mo(CO)o

+

2) cH3oso2F,o' 55%

3

cooc2H5

/ocH3 (co)sMol

t

R

Cyclopropanation.r These carbenesare particularly useful for cyclopropanation of electron-poor olefins. The reaction occurs under milder conditions and at a taster rate with molybdenum carbenesthan with chromium- or tungsten-derivedcomplexes'This cyclopropanation has been used to trap a molybdenum vinylcarbene generatedby intra-

5

D. F. Harvey and M. F. Brown, Tetrahedroa l.ctt, Idem, Am. Soc., 112,7806 (1990). D.F. Harveyand K.P. Lund, ibid.,113.5{x6 rt,

Molybdenum carbene complexes

:p,n. that molecular sieves 3. :hc SharplessePoxidation tc: .eavengingby the sieves. el;irivity of the Pd-catalYzed qi.r:r\)nI). In thesereactions, i :. increasethe diastereo-

raj o<

/ocH3 (co)sMol

-''T'.-,/I

O

H

r. :hc addition of molecular g:..r rclcctivity obtainswith | .t. 'nc counterion.The steric rr. ;rrntaining2OVaof watet lh.. .rl present,but a surface

r..'

cH3o,n ar-"ctt 35%

molecularcyclization of the carbenecomplex (1) of an alkyne. Thus reactionof the carbene I with methyl acrylatein THF at 65' providesa mixture of the vinylcyclopropanes 2 in 7l% yield.2

|(CH2)3C=CR

1) BuL, 2) Mo(CO)6 3) cH3oSo'cF1 -

CH3o--v..-

(CH2)3C:cR

tl

Mo(CO)5 1

H ','

\t.-\ " l

*

27"/o

R = (CH2)2CH3

)CO I

cH3or n er,Actt

Bu

\:./ Fo

:- :!:)ze=O-

CHr=611611

I i""(co)l cHz=cHcoo""., 1 rHF'6s'> CIK^, ,',,?n*""i"oocH3 Le(""r, I The processhas been extendedto the dienyne 3. Reactionof 3 with butylmethoxymolybdenum carbene4 at 60" results in a divinylcyclopropane(5), which undergoes [3.3]sigmatropic rearrangementto hexahydroazulenes6 in 877a yield.r Use of thc analogouschromium complex with 3 also results in a hexahydroazulene, but in much lower yield. An electron-withdrawinggroup in the diene is essentialfor formation of 5.

(1992). i Org.,57,65'79

Mo(CO)5 Bu

ocH3

rr r-1ionof RLi with Mo(CO)o

,H

--cooc2H5 5Mo

,o" "

cooc2H5

R u..:rl for cyclopropanationof a,:Jrtions and at a fasterrate This B.:: r-dcrived complexes. bY intragenerated nr le.rrbcne

195

ocH3 (1 : 4.8)

5 : D. F. Harvey and M. F. Brown, Tetrahedron Letters, 31, 2529 (1990). : Idem, Am. Soc., 112,7806 (1990). ' D. F. Harvey and K. P. Lund, ibid., 113, 5066 (1991).

196

imidoalkylidinecomplexes Molybdenurn

Molybdenum imido alkylidine complexes' heterocycles' Schrock's group has develOlefin metathesis; oxygenand nitrogen of this type for olefin metathesis' A typical oped a number of molybdlnum catalysts catalyst is l.t

This cyclization also affords a route to nll amines and -amides. Pyrrolines can be obatn -azepines'r also form tetrahydropyridinesand

Bzl I

.-N\ i

r\ i l

t

l "'\-cH(cH3)2 (cH3)2cH r

N

cH"--\ 'CHz ' 1

toHs

) ( 'CHz CHz

CFg bFs

withlossofethylene.Thisreactionisapplicabletoformationoftri-andtetrasubstituted oxygen heterocycles'2 and seven-numbered alkenesand to synthesisof dihydropyrans

e2o/o

//

CHs

\

C" CHg

\

\ /

---------> 75o/o

cH{r tar"u cH3"V"-o5,ar."u"u cH.-.-2...--d

€(F

8r

"r1-""\t, o

1o>-cuHu

CHS

7-o1-coHu

(

)

d)--t"'

" "*- ><

(oY"u^u

.t.-\r,

+ cH2:cH2

CHs

2

t

tt't*\

( 1, cuttu'zoo.

5

o

Reactionofadiallylether(2)withlat20.resultsincyclizationtoadihydrofuran

(

:cHz

a*)

cHs/rcHs

\

-: \

cocF3

.';+oJ""-\;l'

O-.'.C6H5

\

ezr:*\cHs -cH, \

71

CHz

CHS

o""' ll l**t

'i'^ot

7i"/"

\,.oH

R.R. Schrocket al.,Am. Soc.'112,3875( lgq tl{ G.C. Fu andR.H. Grubbs,ibid',ll4' 5'116 --rl: Am Soc, ll4' (i.C. Fu andR.H. Grubbs,

\tonochloroalane, AlH2Cl (1' 595- 59qt' Azetidines. (12, 333)t These ochc t Jrrectly,but can be obtainedby reductionof 9-lactamswith cleavageof the 1,2-bondttt d

-ut monochloroalane(AlH2Cl) or dichlorrnb r high yield (85-l0o7o). Azido groupc' i ''Butyl estergroups are reducedto hvdrorrr

Monochlomalane

qrc/ar. Schrock'sgroup has develrp. : ': olefin metathesis.A tYPical

191

This cyclization also affords a route to nitrogen heterocycles from acyclic dienylamines and -amides.Pyrrolines can be obtained from diallylamines.This reaction can also form tetrahydropyridinesand -azepines,as well as lactams.3

Bzl

Bzl 1

/N: 85%

"'{*\""

;F.

CHs

cocF3

tt

t.l

'cHz

cHz ui:. in cvclization to a dihydrofuran f,,:-r.rtion of tri- and tetrasubstituted n-: :nrbcred oxygen heterocycles.2

tt't*\

-C6H5

+ CH2:CH2

83o/o

at)

o

( ' /] "

?ocF3

)

81/o

.r1-tt\r, o

t'''-T\tt' .

o

-cuHu

) CHs

-c"'

o tl

Bzl-N;-CH3 770/o

\__l/

CHz

i R.R. Schrocket al.,Am. Soc., 112,3875(1990). :G.C. Fu andR.H. Grubbs, lbid, lt{,5426 (tggz). 'G. C. Fu and R.H. Grubbs,Az. Soc.,ll4, 7324(1992).

F +

4oH "---OH

Monochloroalane, AlH2Cl (f, 595-599). Azetidines. (12, 333)r These cyclic trimethyleneamines are difficult to prepare Jirectly, but can be obtainedby reductionof p-lactams. Metal hydridesgenerallyreduce 8-lactamswith cleavageof the l,2-bond to afford 7-amino alcoholsas the major product, lrut monochloroalane(AlH2Cl) or dichloroalane(AlHCl2) reduces B-lactamsto azetidines rn high yield (85-100vo). Azido groups, if present, are converted to amine groups. :-Butyl estergroups are reducedto hydroxymethylgroups,and acetatesare convertedto

198

Monochlomborane-Dimethyl

sulfide

ctBH2.s(cH3 1

hydroxygfoups.ChiralB-lactamsarereducedwithoutlossofenantioselectivity.The by Pd/c or Raney 2-arylazetidinesobtained in this way on hydrogenolysis catalyzed

o cunrA H2, BzlO. BzlO. ,,CaHs ,CoHs Pd/C,CH3OHcuHu^(\nH, H ArH2cl \-{ + l l s4o/o L-N OH e6% 'Bzl /FNBzl O'

N3 )

{

t l ,FN,

O'

HzN.. H

,CoHs

,rCuH,

Lil 'Bu-f _tr

87"/o

Bu-t

OH

-;;

1

/

\ coHs- \

H

68/"

qHul-t'-NHBu{

CHs

CHe

NHz

c6HsocH3 +95"/.

c"H.oH

nickelundergocleavageofthel,2-bondtoaffordthecorrespondingacycltcamtno alcohols or diamines. (2), preparedas shown from a This reduction has been extendedto bis-B-lactams benzy|idineaminoB.|actam(equationl).TWoisomersareformed'whichareseparab|e bychromotography.Thesebis-B-lactamsarereducedbyCIA|H2toanti-andsylr-bis.p-

ROa coH5..-----N.. zcaHs (f)

|

|

,t--N { ' R

RocH2cocl 7o-Boo/"

n JcoHs

I't

Thts I Epoxides - chlorohydrins.: The same cleavageof a-hydroxy epord

,.9

c.Hu'a

(cH3)2s-BHp

oH

c

h^',-t"uH'u t l

?-^.^

2 (antilsvn - 2t1l

open-chainpolyamino alcoholsand azetidines,which in turn undergohydrogenolysisto polyamino ethers. andR' Abe,J' Org', 56' 5263(1991)' M. Yamashita' I I. Olima,M. Zhao,T. Yamato,K. Nakahashi, (1)' Monochloroborane-Dimethyl sulfide, CIBH2' S(CH3)' Cleavageofepoxides,ethers,ketals'rThisboranecleavesepoxidestochlorohy' drinswithmarkedregioselectivity.Itisa|sousefulforcleavageofethersandacetals.

..nQ

cuHr-'\1..^.-ou

I P. Bovicelli,E. Mincione,andG. Onagglr' P. Bovicelli,P. Lupattelli,andM.T. Bcrsu

\lonoperoxyphthalic acid (MPPA). ! Epoxidation of allylic alcohok.t \aHCO: can effect epoxidation of su :cagentshows slight regioselectivitl in d -.acts with clc6H4co3H to give a mrx

Monopemxyphthslic

acid

ctBH2.s(cH3)2

The u: ,.. of enantioselectivitY. nr. ..rtalyzedbY Pd/C or RaneY

1

o cunuA

-;; r

OH I A c CaHu'Y

cl l

+

c6H5^---oH 6:94

F C-

x,:-

]H

cuHu^(\NH, OH

"){

t

l

\."

cuHrl-Y^NHBu{

cH3 /cl

CH3 ,OH

a-'r""'

68V"

v

cHAcH,

cH.AcH,

.\o' o+*so V I cHgAcHz

NHz

ri,

.orresPondingacYclic amino

n. , I t. prcparedas shown from a r\ ::J ti)rmed,which are seParable t r ( I..\lH: to anti- and sYn-bis-B-

RO,

.rCoHs

T_T

2 (anti lsYn - 2:t'1

95o/"

Epoxides - chlorohldrins.2 This reagent converts epoxides into chlorohydrins. The same cleavageof a-hydroxy epoxidesresults in azli-chlorohydrins.

,o cuHr-
/-*L'"u"

?-*,^

c6H50H

** "' -;;d:1"-" o"y q:r^" C6H5OCH3

(cH3)2s.BH2cr ?'

?t

oH oH

98:2

cl

cl

.nQ

cuHrsoH

I c6H5"^>a"\oH : OH

96% ee o:'- - ihain polyamino alcohols and

Lr,

I,l

.: R Abe,J- Org.' 56'5263 (1991)'

tl).

!lcaves ePoxides to chlorohYh,: ,ie.rvage of ethers and acetals. xr.:

I P. Bovicelli,E. Mincione,andG. Ortaggi,Tetrahedron Letlers,32,3719(1991). :P. Bovicelli,P. Lupattelli, (1992). andE. Mincione,ibid.,33,6181 andM.T. Bersani,

Monoperoxyphthalic acid (MPPA). Epoxidation of allylic alcohols.t Although z-chloroperbenzoic acid in aqueous NaHCOT can effect epoxidation of simple allylic alcohols in 80-95% yield, this reagentshows slight regioselectivityin the case of polyolefinic alcohols.Thus geraniol reactswith CIC6H4CO3Hto give a mixture of the diepoxide and both monoepoxides.

Monoperoxyphthalic

acid

In contrast epoxidation of geraniol with monoperoxyphthalicacid in the presenceof cetyltrimethylammonium hydroxide (surfactant) effects almost exclusive epoxidation of the allylic doublebond to give 2,3-epoxygeraniolin9O7o yield. Epoxidationwith MPPA in NaHCO: solution shows the oppositeregioselectivityand provides 6,7-epoxygeraniol in 72% yield. I F. Fringuelli,R. Germani,F. Pizzo,F. Santinelli, andG. Savelli,J. Org.,57, 1198(1992).

1,4-Naphthalenedicarbonitrilc t I [ 3 + 2]Cycloaddition of a:irit DCN (f) forms a radical cation ll

N

cuH,{\cuHu

c6Hs v,N.

F. Miilfer andJ. Mattay,Anger ( A

\ickel(If

acetylacetonate,Nila

Coupling of aryl O-carha ;an be effectedby catalysis*ith ( )-carbamatescan direct ortho-nu :rves for coupling to complex su

,r'r-..-.OCON(C2H5)2 s. &

\."

c,"

rr

Ni(ec-

1 + TMSCH2MgCI#

<>aorl l- ll +( BocHN(CH2)2'/\/l

S. Sengupta,M. Leite, D. S. Raslan

p:':,lic acid in the Presenceof i .:.:r',,\tcxclusiveepoxidationof rr '.r:lJ. Epoxidationwith MPPA r , .: providcs6,7-ePoxYgeraniol

r\ -

| ()re.,57,1198(1992)'

1,4-Naphthalenedicarbonitrile (DCN' 1). the azirine 2 in the presence of [3+2]Cycloaddition of azirines.r Irradiation of (4). by DCN (1) forms a radical cation (3), which is trapped imines to form imidazoles 1, cH3cN hv' 350nm .

N // \

cuHu!\cuHu

l

.

l

l Lc6Hsc:N-cHc6H5 3

ls.-zN-pr, CoHslN;.-CoHs 87L

/)-N \ CoHs Pr 4

I F. Miiller and J. Mattay, Angew. Chem. Int' Ed, 1336 (1991)'

Nickel(II)

acetylacetonate, Ni(acac)2.

coupling coupting of aryt o-carbamates and aryl triflates with RMgCl.l This is that coupling of this value particular The can be effectedby catalysiswith Ni(acac)2. derivauseful into be converted can thus and O-carbamatescan direct ortho-metalation, tives for coupling to complex substitutedarenes'

ocoN(c2Hs)2

OCON(C2Hs)2 s-BuLi/TMEDA clcoN(c^H4^ -

coN(c2H5)2 Ni(acac)2

.Zr",v.CH2fMS

-c+g l' 1 + rMSCH2Mscr 600/"

ll

VocoN(czHs)z

(Y":c6H5Msc, r vb' '5'!'vv' -ffi 3ov" BocHN(CH2)2-\t/

-(Ytu"

BocHN(CH2)2"\l

I S. Sengupta,M. Leite, D.S. Raslan,C. Quesnelle,and V. Snieckus'J. Org'' 57,4066 (1992)'

Nickel acetylacetonate-Diisobutylaluminum

hydride

hydride' Nickel acetylacetonate-Diisobutylaluminum with aryt isocyanides't iliynes and dienynes, enynes, of Cyclizntion

This combi-

nationofreagents(1:2)generatesaNi(O)catalyst(l)whichiseasiertohandlethanthe Ni(coD)2. Reactionof 1,6-enynes(2) with air-sensitivebis(1,5-cyclooctadiene)nicke(O), catalystcombined with Bu:P (2 equiv') an aryl isocyanidein the presenceof this Ni(0) resultsinbicycliciminocyclopentenes(3)whichcanbehydrolyzedtothecorresponding ketone(4).TheoverallreactionisanalternativetothePauson-Khandreaction.

* CHe

/-:cuHr hCn,

poHs

Pt, 1,Bu3P r-), c6H5cH3,60'_ Ct I 92% \/--t=J CHs H

Pr

2

FUnr 3

I csn'

I rHF/H20 t 25'

Pr. '

9oHs /

h-a^ o l F

o

Organoaluminum reagents. St ere osele ctiv e ac etal c learwl by RLi, RMgX, RzZn, and a n rrf configuration.This reaclionr t 12.375-378).Surprisinglv.remr \tereoselectivealkylation can be c preparedin situ by reaction of -,

.rluminum reagent is obtained f almost as effective. Of equal int proceedswith high retention (9' CH3r,,..,.',.-1tCHl (l)

I I O-.*,-O

I (cH3)zAroqF 70%

-"\'C6H13

H

A

1

4 of a phosphinecan provide The samereactionbut with a l,n-diyne and in the absence Yields of bicyclic 1,3-diynes. with obtain yie|ds Highest bicyclic iminocyclopentadienes. increases' atoms carbon productsdecreaseas the number of intervening Thisnickel(O)cata|ystcanalsoeffectcyclizationsofl,T-diyneswithhydrosilanes. 1,6_DiynescanundergoaNi(0)-cata|yzedhydrosilylationtoabicyclicsilacyclopentadiene (equationII).

(t)

c=cH

''3*u,

+

HSi(OC2H5)3

-ffi*

(?si(oc2H5)3

This cleavage usually also 1 -r an intramolecularMeer*etnJ-Alkoxy ketonesof this tl'p€ (a

I .rrals (5) with diethylaluminum ,quation II). Note that the rcdrx

\,AcH,

C=CH

(tl)

cH3ooc cH3ooc

9eHs CoHs toHs

1.Plc2H5)3 CH3OOC

Hsi-cl - =::;oq-/o cH3ooc 6t. CoHs

CHgt,,..,.-,-7tCH3

,t)

t l o_o

a

l K . T a m a o ,K. Kobayashi,and Y. Ito, Synleu,539 (7992)'

--t\

CH3 C5H5 5

L. r anl isocyanides.t This combiur:-r is easierto handlethan the )1 R,.rctionof 1,6-enynes(2) with s: - mhinedwith Bu:P (2 equiv.) . r. Jr()lvzedto the corresponding r l' :.r.()n- Khand reaction-

P1' f >

a.:

poHs 1

,

/---aa..

o

I

\//+-J

il

Frunr

3 I csn, Irrrrnro | 25"

poHs

Pt, , /-->=\

o

l

t

F

o

Organoaluminum reagents. Stereoselectiveacetal cleavage.t Chiral acetals such as I are known to be cleaved by RLi, RMgX, R2Zn, and a number of organometallicnucleophileswith inversion of configuration. This reaction is a useful route to various optically active alcohols but highly (12,375-378). Surprisingly,reactionof I with Al(CHrh is not stereoselective, alkylation can be effectedby reactionwith an (aryloxy)dimethylaluminum stereoselective preparedin situ by reaction of Al(CHr)3 with 1 equiv. of a phenol. The most reactive aluminum reagent is obtained from pentafluorophenol,bvt 2,4,6-tril-butylphenol is almost as effective. Of equal interest,alkylation with these organoaluminumreagents proceedswith high retention (97-99:3-l).

CH3\r/^\y')CH3 CHs,,,.r,.1tCt:^-, CHsr, ",^^ _ ,.,^yCHs I l l ( c H 3 ) 2 A- r o c 6 F 5 _ l l + l l (l)

O.,*-O

7oo/o

OH

O

-.\

H, CoHrs

fi

Z

4

O

S

/C6H13

)C H s

I

tl..i rlc of a phosphinecan provide Yieldsof bicyclic * r:^ 1.3-diynes. nr .::{,nlsincreases. r. : 1.7-diyneswith hYdrosilanes. l-::: ,:r l() a bicyclic silacyclopenta-

OH CH.*'

f:L,, 4

This cleavage usually also provides, as a minor product, the ketone 3, formed bv an intramolecularMeerwein-Ponndorf-Verley reduction and Oppenaueroxidation. p-Alkoxy ketonesof this type (6) can be obtainedas the major product by rcductionof (2.4 equiv.), ketals(5) with diethylaluminumfluoride (1.2 equiv.) and pentafluorophenol lequationII). Note that the reduction is again effectedwith retention.

^si(ocrHu). 'ocH, 9oHs lH30oc

O /'C6H13 t, (\ vev s' /: 1 ) CHs

,CoHs tcH

3H3ooc

Col-t

m-

CHgz, a,.'ry',CHg t l (il) o_o cH-.\cuHu 5

(c:Hs)zArF,ceFsoH C6H5CH3,0' ,

CHo--a,.yrCHo ll I O O..-...'C6H5

I

CHs 6(98:2)

reagen Organobarium

2o4

'aY"'

(esters).2 Both RzAlcl and stereoserective addition to 2-methyr-3-oxo amides with high anliselectivity' R:Al add to ketone groups of these substrates

l8/ zt Qli..C

CHg

I

(c2Hs)Arcr c2HsPH ? -HcH./l'\N(cH3)2 I

?

"r./-a\N(cH3)2

+

CHs

CHs

svn-1

99:1

1i Bt

2) C*tl

anti-1

o o i l l l c.H'x\'\oc2H5

c2Hq /oH ?

t#-

cu"

YAoc2H5

99:1

CHg

CHs

CHs

+ sYn-2

anti-2

rA. Yanagisawa, S. Habaue,and H- Yamanr.r

Am' Soc''113' 7074(1991)' I K. Ishihara, N. Hanaki'andH. Yamamoto' Letters'33' 4353(l'992)' 2 M. Taniguchi,H. Fujii, K. Oshima,and K. Utimoto,Tetrahedron

OrganoantimonY comPounds' use of organoantimonycompounds'In Review. Huangl has reviewedthe synthetic

Organocerium reagents. Addition to RC=N and >C:\'H. double addition to nitriles to form lert-amta addition is about four times slower than th

additiontowittig{ypereactions.,hislaboratoryhasreportedsevera|novelusesforthese compoundssuchasaselectiveacetalizationofaldehydes(equationl).Acetalizationcan alcohol in almost quantitativeyield' also be effectedby the system SbClr/Al and an (l)

RCHO

+

Sb(OC2H5)3 + CH2=QHCH2BT

RCH(OCzHs)z+

o jl

(ll) gt'l

\q2

+ Al + C2H5OH

sbcrr,25.

?

c6H5cN

C6H5COCH3

THF {6

&JC€O +

crHuoFR;;AcH, c2Hso\

PC'rlu RrARz

r"-}cocH3

4 &rc€

C6H5CH=CHCN +

The reaction of anhydrous BaI2 with

lithiumbiphenylide(2equiv.)inTHFprovidesareactivebariumspeciesthatreactswith -7g. to iorm allylbarium chlorides.These reagentsreact with high allylic chl,oridesat a-selectivitywithcarbonyl"o'npound'toformhomoallylicalcoholswithretentionof configuration.

3 BuCeCl2

1a"t-

I Y.-2. Huang, Acc-Chem.Res',25, 182 (1992)'

Organobarium reagents. Altylbarium reagents;homoallytic alcohols't

C6H5CN +

3 CH3CeClz

Bu ,FNH

t-Bu

+

3 CH3CeCl2

6ar

Organocerium

OH

'l ) Ba* 2) C5H11CHO

'(Y"'

rd\rersl.r Both RzAlCl and ,:'::: rclectivity.

I 4vc^H,. t -

.......................................-".,'........* 560/o

" CHs (Z/E=99:1, o,lY= 77 1231

CHs p1 o ^'tt(CHg)z + cH:

r€agents

s4n-1

QoHs

99:1

OH

i 1

)Ho -

^-OCZHS

+

sVn-2 (ZlE= 98:2, crly=92:8)

99: 1

CH,. t1'..2

rA. Yanagisawa, Am. Soc.,f13, 8955(1991). S. Habaue,andH. Yamamoto, l-:

r()ql).

h .: ! , ttt'rs, 33,4353

(1992)'

compounds.In {,:r.rn()antimony r:..: .cvcral novel usesfor these s , ,.iLtittionI). Acetalizationcan r: .,lmostquantitativeYield.

Organocerium reagents. Addition to RC=N and >C:NH.| Organocerium reagents (RCeCl2) undergo doubleaddition to nitriles to form /ert-aminesoften in high yield. The rate of this double addition is about four times slower than that of addition to a carbonyl group.

C6H5CN

+

Bu I

rHF'-65- 25'

3 BuCeCl2

C6H5-f-NH2

eoo/o---_

Bu quant.

o

C6H5CN

+

C6H5COCH3

BUCECI, -----' >

BU ?' ... . + CoHs-fNH2

CoHs-fOH CHa

CHs

78:22

crHroFR;;AcH, ,

C2H5O',roCrHu

r.+cocH3

+

4 Bucectz--iu*

RrARz

C6H5CH=CHCN

+

3 CH3CeCl2

?' ,r:t

HrN-t-\ Bu

cH? ?t'

-46%-

/--J-NHz

C6H5CH2 i '- Ltion of anhYdrousBaI2 with rc ^.:nurTlspeciesthat reactswith i I rc.c reagentsreact with high ol..,re alcoholswith retentionof

Bu

Er.rH t-Bu

Bu -+ 3 CH3CeCl2 62%- t-tr-f*t, CHs

?u

/-l-o{ Bu

CHg

206

Organocerium reagent

Thelastexampleshowsthattheseorganoceriumreagentsalsoreactwithketimines tertiarY amines' form to a-Silytketones.'Organoceriumreagents(15'221)addtothecarbonylgroupof enolates(a)' which undergo alkylation on trialkylsilylketenesto to,,n- B-'ityt cerium ketones.This tandemalkylation can be used reactionwith RI and HMpA to form a-silyl ketonesby the choiceof RCeClz and RX' to prepareeitherone of the two possiblea-silyl

R3sicH:c:o

OC"1ffll NHacr

Prcecrz- f rHF'-78'> ln.si./e,

? R3si---Apr

)A

Rs= t-BuMez

^-^,I cn.r

or-r.

I HMPA

V

o

tl RsSi-...,_Ap.. I CHs

(3).3 The synthesis Asymmetric synthesisof tll-l,3.diphenyl-1,3-propanediamine of CeHsCeClz addition by amines chiral of of 3 is an extension ot a synthesis of CcHsCeClz to the addition Thus (C6H5Li/CeClr) to hydrazont" 1tl'Zl'l-218)' be cinnamaldehyde'provides 2' which can dihydropyrazoleI' preparedas shown from

t) H2NNH2(-60%) 2) (l - BuOCO)2O(-90"/')

t-Boc.'N-N

/ \ r\\ ceHs-'^\,,/ /

C6H5'"\'-CHO

(dl-trans)'2

1)rFA

2) Hr. RaneyNi -'-;;-so'/"-

CeCt

rE. Ciganek,J. Org., 57,4521'(19921: Y. Kita, S. Matsuda,S. Kitagaki,Y. Tsuzu\r.|| -1S.E. Denmarkand J.-H.Kim, Synthesi-s. llr tl a N. Greevesand L. Lyford, Tetrahedron Lenat

Organochromium reagents. RCrClzt Reagentsof the type RCrCI; r -J by reaction of CrCh(THF)r in THF at reagentsalkylate aldehydesin yields of { aromatic aldehydes.They generalll do rxr I hydroxyl, methoxyl, or dimethylamino Iru4 CHrCrClz(THF)r in good yield with rcn lacking such grouPs'

o C8f,rC

X cH3cH3

c6H5Li/cecl3 rHF, -78' oc - 94"/"

1

cunu--(.zlcuH,

rHF, (((( +

Jt -oH CHs-

converted into 3'

H Boc.. N-N

CeCl3.7H2O

NHu - NHz | i

c6H5Sc6H5

o o H i

l

l

cH3"AY\cH3

lsr

CHs C. Beirich,A. Hamsen.T \l'{ T. Kauffmann, t57 /L992).

dl-3

Ultrasound-assistedpreparation'aCeCl:isnotsolubleinTHF'buttheheptahydratewhensonicatedlnrnpisconvertedintothesolubleCeCI:.THF.Reactionof in srtu' CeCl: 'THF with RLi provides RCeCl2

Organocopper reagents. Stannylcupration of proparglanitct ,mines (1) react with BurSn(Bu)CutC':-i :-substituted 3-(tributylstannyl)allllamtrrs ..]-disubstitutedallylamines (3).

Organocopper r€agents

!s::. irlsoreactwith ketimtnes

THF, ((((

C e C l 3 .7 H 2 O +

Rut I

CeCl3'THF -:

.,,:.1lo the carbonYlgroup of , .,rrch undergoalkYlationon i r:-.1ifl] alkYlationcan be used r ':, choiceof RCeClzand RX'

'.-.ct 4 ^ ^ , ':'"

I BuCeCl2 |

77v"l n | \ - ro i Bu. ,OH \./ \-.-

? HSDI\/,,/\pf

.l

r

l l

rE. Ciganek,J. Org., 57, 4521(1992). 2 Y. Kita, S. Matsuda,S. Kitagaki,Y. Tsuzuki,and S. Akai, Synlett,401 (1991,). I S.E. Denmarkand J.-H. Kim, Synthesis, 229 (1992). 4 N. Greevesand L. Lyford, Tetrahedron Letters,33, 4759(1992).

ncdiamine (3)'3 The sYnthesis r. hr addition of CaHsCeClz a.l.:::r(tnof CoHsCeClzto the :f ..:-. providcs2, which can be

t - 3c c N-N \\ la.-"J

C6H5Li/CeCl3 THF, -78" > 85 -94"/"

1

Organochromium reagents. RCrCl2t Reagentsof the type RCrClz can be preparedin situ or in crystallineform by reaction of CrCh(THF)r in THF at -2O' with RLi, RMgX, or (C2Hs)rAl. These reagentsalkylate aldehydesin yields of 4O-90Vo, being highest with CH-lCrClz and aromaticaldehydes.They generallydo not alkylate simple ketones,but ketonesbearing hydroxyl, methoxyl, or dimethylaminogroups on the a- or B-position arc alkylated by CH:CrClz(THF)3 in good yield with very high selectivity in the presenceof ketones lacking such groups.

o l- -oH cHs' X cH3 cH3

o o H i l l cH."'^\*cH. l CHg

\N: NHt

A"uru

CH3CrCl2,20o

cH3/oH )( -oH CHs- X cH3cH3 cH3pH 9H

cH.#cH" l CHs

: T. Kauffmann, Ber., 125, C. Beirich,A. Hamsen,T. Mijller,C. Philipp,and D. Wingbermiihle, t57 /L9921.

d t- 3

s" .'lc in THF, but the hePtahYr , . . ' l r C c C l r ' T H F . R e a c t i o no f

Organocopper reagents. Stannylcupration of propargylamines,t Boc- or Si(CHr)r-protected propargylrmines (l) react with BurSn(Bu)Cu(CN)Li3 and then with an electrophile to form :-substituted 3-(tributylstannyl)allylamines(2). These products can be converted into 1.2-disubstitutedallylamines (3).

OrganocoPP€r rcag€nts

1) Bu3Sn(Bu)Cu(CN)Li2 2) cH3l

H-------\

gu"sn-YNHBoc " l CHe

NHBoc

Allylic organocopper reagcnts.' by reduction of CuCN' LiX. reacts r organocopperreagents,which couplc

2

1

"nt)^"o"' CHs BzlPdCllP(CoHs)slz,

c'l

CHs,,-/-,,-...Onc

710/o

CH::Z

3 Cyclica-alkoxyorganocuprates.3Acyclicopticallyactivea-alkoxyorganocopper reactions'In contrast' reagentsunfortunatelyundergo racemizationduring 1,4-addition acyclica-alkoxyorganocopperreagentcanbestableat-Ts".Enantiomericallypure acid (15,171) via reagentsof this type have been preparedfrom (R)-3-hydroxybutyric

1) Cu' 2) C6H5CO

CHe

t -

cttr,,,,.^ycl

thealdehydeltogive4-(tributylstannyl)-1'3-dioxanes(3),whichareseparableby

CHs-

OMOM | -\ v -cHo

1) LiSnBu3 -2\ t\4O1M9!*

OMOM MOMO I I CHsSSnBu3

BF3Et2o

The particularvalue of this routc t range of functional groups: enonc. cp

2

1

o^o r l

o^o l

l

+

*

(R,R)-3

(R,S)-3

l

flashchromatography.Thecorresponding4-|ithio.l,3.dioxanes,formedbytransmetalaThe axial isomer' derived tion with BuLi, differ markedly in conformationalstability. fromthe(R,R)-3isunstableabove-TS.andrearrangestotheequatoria|isomer'The with BuLi' then CuI' and a-alkoxycopper reagent4, formed from (R,S)-3, by treatment finallyTMEDAat-78.'reactswithethylpropiolateinthcpresenccofClSi(CH3}to form a single adduct (5) in 92o/oyield'

o^o | | cHsscu-TMEDA-Lil

+

'9 H---< bc2Hs

4

cHa

"'snBu3

cH"*

cH3/-*snBu3

clsi(cH3)3' rHF'-7g'cs2"/"

Y

cHl"v

o

l

z

cl

Amide cuprates;B-lacnms.' .l ':act with 1,3-dienoates to give rrrth rquationI). This reactioncanbc crta

,, CuHu*co2CH3

o^o

"r"&oc2H5 o

r I with the dienoate2 follo*cd tn :calmentof 3 with (C6H5)1P?rSt;

209

Organocopperreagents

N SN-VNHBOC I CHs 2

}c:

Allylic organocopper reagents.a The activated copper species (Cu+), produced by reduction of CuCN .LiX, reacts with allyl chlorides and acetatesto afford allylic organocopperreagents,which couple with various electrophilesin good yields'

CHs\/'..-..oAc

^-*,,*

CHs-.,/'-,,,.Cu*

--cH,

n-"-:6HsCHO

-

syn/anti=70:30 lr .:.tirc a-alkoxYorganocopPer f-.,.:Jrtionrcactions.In contrast, -So. EnantiomericallYPure a: r ; : , ' r r b u t y r i c a c i d ( 1 5 , 1 7 1 )v i a -l r. which are separablebY

:

or,,toM :

'

BF3'EI2O

snBu3

CH:r

t cHr,,,,,ycr

1) Cu* 2) CsHsCO

=cH,

74"/"

The particularvalue of this route to organocopperreagentsis that it toleratesa wide range of functional groups: enone, epoxide, carbamate,nitrile.

r\

- "'snBue

-

1) Cu* 2) C6H5CHO

lFa.3 h r.,ttcs.formed bY transmetala'Ihe axial isomcr, derived h,:::r ',, the equatorialisomer.The 1c. :J:r'-nt with BuLi, then CuI, and rr :'rr prcsenceof ClSi(CHr)r to

c cC2H5

clsi(cH3)3, THF.-78oc > 92v"

CoHs

CHz

Amide cuprates; B-lactams.s Amide cupratessuch as [BzlSi(CHr)3N]rCuLi (l) react with 1,3-dienoatesto give with high or exclusive rcgioselectivitythe l,4-adduct coupling.Thus reaction lcquation I). This reactioncan be extendedto a three-component

NHBzI

(l) CuHr*CozCHs

+

1

#

cuHu*Co2CH3

'f I with the dienoate2 followed by trapping with CoHsCHO gives 3 in 77Vo yield gives the B-lactam4. Treatmentof 3 with (C6H5)2P/PyS)2

Organocopper r€agents

+ H--+ Bu3Sn(Bu)Cu(CN)Li2

CHs\/\4CO2i-pr+C6H5CHO+1

pu(Bu)(CN)Li2

Bu3Sn, BzINH OH

/)

CHs

cH.

\

H

$cuH.

<

1

CH(OC2H5)2

CO2i-Pr

BusSn,

/l

l2

1' - . . . . . _ 720/0

using a This reaction has been extendedto asymmetric three-componentcoupling

1 +

H

CH(

H----._COOCH3

( - )-bornane-sultam. to enones tn chiral lithium amidocuprates.6 Lithium amidocuprates can add such as (R)modest to high enantioselectivityif they bear a chiral ligand, LicuL*R, or(S)-N-methy|.1-pheny|-2-(l-piperidinyl)ethanamine(L*).TheadditionofLiCuL*Bu is with 2-cycloheptnonehas been examined in detail. Although the enantioselectivity yield the increases satisfactory,the yield isonly 54Vo.Use of3equiv. ofthe cuprate of clSi(cHr)3 Addition enantioselectivity. the on effect appreciable no with to 827o enantioselectivity has little effect, but addition of HMPA lowers both the yield and the Ether and dimethyl unsatisfactory. are cucN and S(CH1)2 of cuBr. use significantly. obtain in sulfide are the best solvents;low yields and completeloss of enantioselectivity mesodimeric the THF. The report suggeststhat these cupratesreact as dimers and that unreactivc. are complexes

o

a\ (_)

cuH.i') cH.-*l,ttJ H ether,-78o LiCuL*Bu, 54"/"

(s)-L*

a/-a

CHs

1 )1 . 2 L o ?IQ

p- and y-Amino acids." t-Buq p-amino ester 2 without racemizatra the amino group to the CH2OTs or ()rganocuprates affords N-proteocd p-

o

/

cis-2 -Trib uty Ista n ny lv i ny I (cyarc tc eq. of LiCl undergoes conjugate adJrt

to glutamic acid provides7-amirrc r

\

\__f'u 960/oee

NHBoc trC t 2 --_-,r-COOC(CH3)3 HOOC- \,2 7 BU2CUU THF. -5O' _ 90%

Vinyliccuprates.Mareke/al.lhavepreparedtheversatilevinylcupratel,which can function as the dianion of acrolein'

B!

Organocopper reNgents

-H*

+ H-CH(OC'H')2 Bu3Sn(Bu)Cu(CN)Li2 pu(Bu)(CN)Li2

Bu3Sn,

HO

)<.

,i l|o-"t'

H

,iro*'".,

1: cH=c-cHo

CH(OCzHs)z BuaSn --"-

1

--r*-l 2

I

tri:(\ can add to enones in g.':.1.LiCuL*R, such as (R)'r I hc additionof LiCuL*Bu is r.-.:: lhc cnantioselectivitY hf .uprate increasesthe Yield T1r:\ ..\ddition of ClSi(CH3)3 rcl.: .rnd the enantioselectivitY tr.:.,!r()rv.Ether and dimethyl obtainin , : . n.,ntioselectivitY

787o

o a\

-r"**

Bu3snv/

\

H

CH(OC2Hs)2

JcoocH3 CH(OC2H5)2

( E l Z =8 7 : 1 3 ) cis-2-Tributylstannylvinyl( cyano)cuprate.E This cuprate (l) in combination with 2 eq. of LiCl undergoesconjugateadditions to enonesin high yield.

CHg

-4s' 1)1,2 LiC|,THF, 2) CtSiErs ------rr%-

B- and y-Amino acids.e /-Butyl N-boc-aspartate(1) can be converted into a p-amino ester 2 without racemizationby conversion of the free acid function a to the amino group to the CHzOTs or CH2I group. Coupling of these products with affords N-protectedB-amino acid esters.This procedurewhen extended organocuprates Io glutamic acid provides y-amino acids.

\ \ _./-Bu 96% ee

H

CH(OC2H5)2

i + H:cooCH.

rr.'. rnrl that the mesodimeric

)-L'

lz, ether ,

\-J H

1',,nrp()nentcouPling using a

- - -..\ HOOC-

NHBoc | \'z -COOC(CH3)3

1)ctcooczHs,NaBH+ 2)Tsct/Pv:orNat .-----a-r-::-jj=:+>

NHBoc I ---. .l- -\'/ .COOC(CH3)3 lCHz'

1 Bu2CuLi

ttrL r r : . . : t r l 0v i n y l c u p r a t e1 , w h i c h

2tl

NHBoc

ar-._-1.--cooc(cH3)3 2

rcagen

0rganocoPPer

212

B - A m i n o a l c o h o l s , | o A d d i t i o n o f R L i o r R M g X t o t r i m e t h y l s i lof ylimines(1)of alcohols'probably because chelation' In a-hydroxy aldehydesprovides syn-B-amino give derived from Grignard reagentscan contrast, addition of orguno"opier reagents mixturesofsyn-andantt-B-aminoalcohols.Thehighestan/i.diastereoselectivityobtains w i t h B u C u M g B r l 'l ' B F . t .

i -N (cH3)3si-

l

t

tu--,Ac". : ttH,

t-.A"t"

-

E(CH2)nC=CH E = C N ,C l ,C O O R

o

OSiRe

OSiRr f -

OSiRr f -

2t t (f)

*

tuJ^tt'

-

1

l l r

E = OCOCoHs n=2

NHz

1 2:98

BuLi,THF

Biaryl synthesis." Diaryl highc to form unsr 2-methyltetrahydrofuran

>99:1

BuCuMgBrl'BF3 THF,s(cH3)2 >99:1

1)CuCN

Bu(CN)CuMgBrBF3 THF,2 Li

zl r-i$ocx ..\r-Li ll

also undergosubstitutionreactionscan Vinylcuprates.Lr Vinylcuprates(2) that can vinyl cuprates can convert a l-alkyne be prepared as shown in equation(lI)' These

Y

3)Or

|

I ocH3

ocH3

I

R

l \ (l) lll ce' zr(H)cr'

iH

/

Bzl

/--

+

1)2 cH3Li 2) (2-ThlCu(CN)Li

",'''"0'

N)Li2

'cu(c

ws

,,^\r\2

<'\

i l l

+

cH3o

cHso)\2 2

zcHs

\-J

-v o

,Cu(CN)Li2

G

2

into an (E)-1,2-disubstitutedalkene' Vinyliclithiocyanocuprates.lzThesecuprates(1)canbepreparedbyreactionof with (CHr)2Cu(CN)Li (equationI)' L-alkyneswith the Schwartzreagentand then

Li

I

rm \/':/

2rL

3,0

Organocopperreagents

:,, rrimethylsilylimines (1) of 1.. :: ,hablybecauseof chelation.In r :- :r Grignard reagentscan give obtains 1l-- - .;,rri-diastereoselectivity lli\

(l)

CHs

1) Cp2zr(HlCl 2) (CH3)2Cu(CN)Li2

E(CHdnC=CH E = CN,Ct,COOR

2t3

pu(cN)Li2 E ( C H2 l n 1

t

I

:

o tl

OSiRq

f SrR:r

* t'1^cr.

CHs

-

1 + E = OCOCoHs n=2

NHz

tt-

a) \-/

870/"

ococ6H5

2:98 >99:1

Biaryl synthesis.tl Diaryl higher-ordercupratescan undergooxidative coupling in 2-methyltetrahydrofuran to form unsymmetricalbiaryls in good yields.

>99:1 1 )C u C N

2)r-i0ocH.

r..\.,.u [. tr

-'rJcrgosubstitutionreactionscan - .nrittescan convert a l-alkYne

ll

3)oz

|

YocH3 ocH3

tC-

?"tt

)'-

R ', u

cu(CN)Li2

<>(ocH"

/-\ .'a)-v .^A-j cfto'/'-z t.=A/

cn"o)''2

,\S 2

Y

ocH3

93o/"

3.5%

3.5o/o

OH 1)CuCN

Li

r-,r.Ot

r l , ;.rn be preparedbY reactionof l r ( f t rlCu(CN)Li (equationI).

I

2)Li< 3)Oz

O

)-cH. F

-r"Y

n

F/Y

cHs

214

Organocopper reagents

a-Allenic alcohols.ta The reaction of RM$VCuI catalyzed by BF3 etherate with the cyclic carbonates or sulfites of benzyl ethers or propargylic alcohols proceeds in a S*2/ fashion to afford a-allenic alcohols in high antl-diastereoselectivity'

oR'

n3sio.--J---4.-coocH3 (s) -1, R3 = (CH3)3C(C6H5)2

// ,//

BzlO-'\

n o'"'o

BuMgX,Cul THF, -78" BF3.O(C2H5)2,

\

L^ --

-

,/-w----.\

n

tl

H

3't% 79o/o

=c

anti/syn =97:3 = >99:1

Conjugate addition to acyclic (E)- or (Z)-enones.t5 Lithium dimethylcuprate reacts with both the (E)- and (Z)-steroidal22-ene-24-ones(1) to form only the (22R)- methyl adduct (2). In contrast the same reaction but with added ClSi(CHr)r and HMPA with (E)-1 providesthe (22R)-methyladduct,and with (Z)-1 providesthe (22S)-methyladduct'

CC

ox.

-Bu

o X =S

OR' t R3SiO..-..{-.../,-\ :

pH

BzlQ

anti - 2 R'= BOM R=CHs

87o/o 88o/o

Bzl-.r.Boc

(cft)f4 THF -i

cHsMcoocH3

E

(s)-3 (CH.)"CuLi

OR

CHs,,. liF, o. ..-...........'.....................................*

(22R)- 2 (98:2)

1 , E o rZ

(CH3)2CuLi, ClSi(CH3)3 THF/HMPA,O'

Conjugate addition of BuCu.t' &( tonateI with excellentdiastereoselectir rrr are highly dependenton the exact compa

CHs',,

(22S)-2(97:3)

OR 1

cH3 cH3 ( E )- 1

(l 22 22 H R-))2- 2( 1 l o0u0::u0))

Conjugate addition of (CH)zCuLi to y-alkoxy- and y-ureido-a,B-enoates.t6 Lithium dimethylcupratein combination with chlorotrimethylsilaneadds to 7-alkoxy a,B-enoates with anllselectivity. The highest anrl-selectivityobtains with a benzyloxymethyl (BOM) ether such as 1. In contrast,when the 7-substituentis a ureido the cuprate addition proceedswith very high syr selectivity.

+ BuCu.tSi(CH3)3 LiBu2Cu,20'

Cl S,

can result in (S)- or (R)-2 as rhe ma;or 1 Conjugate addition to y-hydmx-ren catc addition to y-hydroxyenonessrrh I rrc highly dependenton the type of cug

Organocopp€r reagents

'ul -.rl.rllzedby BF3 etheratewith a tr, :'.:rrr\lic alcohols Proceedsin -ir.1.:rrcoselectivity'

oR' RaSio..'J-vz\coocH3

215

(CH3)2CuLi, ClSi(CH3)a THF, -78" - 2O'

(s) -1, R3 = (CH3)3C(C6H5)2

oR'

BztO,

,pH

.H

eut

,Fc-(;"

I rthiumdimethylcupratereacts .: | : : l(,rm only the (22R)- methyl r:-.: t'lSi(CH3)3and HMPA with 'I :' r rrlcsthc (22S)-methyladduct'

CHs syn-2

anti - 2

H

anti/sYn =97:3 = >99: l

oR' R3sio--\,,\coocH3

t R35iO-..-.,.(,.....,,\COOCH3 :

R'= BOM R=CHg

1 41 1 9.9:1

87"/o 88/"

Bzl..-*-Boc

(CH3)2CuLi, ClSi(CH3)3 THF,-78'- 20'

cHs,,.-..........Z-.coocH3

81"/"

Bzl..t*-Boc

cHsl-:,^coocH3

eH.

(s)-3

syn-4

C113,,,

(22R)'2(98:2) CH.

Conjugate addilion of BuCu.tT BuCu activated by ISi(CHr)r adds to the chiral crotonateI with excellentdiastereoselectivity. In contrast,additionsof lithium butylcuprates arc highly dependenton the exact compositionof the reagentand on the conditions,and

O

3H:,

(22S)-2(97:3)

(s)-2

1 ( 2 2 R 1 - 2( 1 0 0 : 0 ) loxt - and y-ureido'a , B-enoates't6 adds to 7-alkoxy n: '- j.-lcthvlsilane rI; -, -.tivitv obtainswith a benzylh<: :r 7-substituentis a ureido the

+ BuCu'lSi(CH3)3 LiBu2Cu,20"

93% 95o/o

98% de 18o/"de

can result in (S)- or (R)-2 as the major product. Conjugate addition to y-hydroxyenones.ts A variety of cuprates undergo conjugate addition to 7-hydroxyenonessuch as I to give mainly the anti-addtct.The yields rre highly dependenton the type of cuprate. In contrast,Grignard reagentsgenerally

OrganocoPPer reagents

216

A

A >< /

CoHs

o

q>

i l l

coc(

o

o

l r l X"* / o H

o

CoHs

)G

Li2Bu2CuCN Bu2CuLi BuMgCl,DMPU

o

o

CzHs

*

A t

l

q^<^c2H5 / o H

/ o H

CoHs

CoH5

o

syn-2 93:7 95:5 0:100

93"/o 22o/" 83o/o

o tl

r\<'\

o(

C6H5-vz^y.C6Hs

CoHs

anti - 2

1

I

A "2C

CzHs

CoHs

syn

2

cuprate. Asymmetric conjugate additioa o tion of the chiral bornane l. (lR.:S u rtl trimethylbicyclo[2.2.1]-heptanol-1. (3) to form tl (E)-cyclopentadecenone-2 is replacedby CH3MgCl, onl-'"thc l.l

anti

cH3xcH3

10:90

2 Li2(CH3)2CuCN

is obtained in only 2Voee. The superxr group and the phosphorus atom to crxr

with almost reactwith the same 7-hydroxy enoncsto give 1,4-adductin good yield and complete .syn-selectivitY. benzylic Conjugate addition of BzlCu to a,B-enoates.te Although the usual to addition conjugate ready copper reagents[BzlCu(CN)MgCl, Bzl2CuMgCl] undergo instability. of thermal because a, B-enones,they do not reactwith a, B-enoates,probably with Mg Thc preferrcdreagentfor this reactionis Bzlcu, prcparedby reactionof Bzlcl obtained are results The best followed by transmetalationwith cul or cuBr'S(CHr)2.

/ l \ D ( tr1 - H O\--A' H b".

byadditionofClsi(CHr)3(5equiv.)andTMEDA(l.1equiv.)inTHFat-78"-+40..

CHoO.-n-\.CoHs

o

BzlMgCl,Cul ctsi(cH3)3,TMEDA 860/"

cH3oy.^y,c6Hs O

Bzl

3 ' L. Capella,A. Degl'lnnocenti.A. Iltxdrr

from Enantioselective coniugate addition.2o The bidentate ligand 1, prepared to dimethylcuprate lithium of l-proline, can effect enantioselectiveconjugateaddition adduct the methyl, by _ 20" replaced in 84Vo ee.When the acyl group of 1 is chalconeaI

(l ee1). r B. H. Lipshutz, E. L. Ellsworth. S. 1l Dl ( 1989).

Organocopperrcagents

217

o

C

A )G

]H

CoHs

\rFr(coHs)z I

coc(cH3)3

svn-2

z

(CH3)2CuLi, 1 o(c2H5)2,- 20'

CoHs--1CoHs

o

C6H5$..^-.",.C6H5

cH3 o

79o/o

93:7 95:5 0: 100

84o/o @a

o

CrHs

-

"{.,,,

CoHs

is obtainedin only 2o/oee. The superiorityof I is ascribedto the ability of the carbonyl group and the phosphorusatom to coordinatewith the lithium and copper atoms of the cuprate. Asymmetric conjugate addition of CHjLi.2l The cuprate 2, prepared by reaction of the chiral bornane f, (2R,25,3S,45)-3[(1-methylpyrrolyl)methylamino)-1,7,7trimethylbicyclo[2.2.1]-heptanol-2, with Cul and then CH3Li, undergoes1,4-additionto (E)-cyclopentadecenone-2 (3) to form (R)-muscone4 in 8O%yield and 91.Voee.If CHILi is replacedby CHrMgCl, only the 1,2-adductof 3 is formed.

anti

cH3\K.cH3

cH3\K.cH3

10:90

t\ !- , : ..: in good Yieldand with almost

lt...-t

/--\ // \

N---AN' ct-i. " H \O H

Although the usual benzYlic rcadY conjugatc addition to :-:,:,t t 'li of thermalinstability' hccause F' , p:, :' ,'- J hv rcactionof BzlCl with Mg !r li r- The best resultsare obtained . q L r i r ' .i)n T H F a t - 7 8 ' . . 4 0 ' ' A rrt.

t\

/D

C u l ,C H 3 L |

cl-i.- \ N--.AN' 'oH

\ CHs

LiCH3Cu'

1

.----\ // \ \ CHs

2

CH3Li c6H5cH3,-78"

_

80%

CH3oy,^y,c6H5 O

Bzl

h< '..t.ntllc ligand l, preparedfrom to aJ.:: r,,n of lithium dimethylcuprate adduct p : I rr rcplacedbY methYl,the

3

( R ) - ( - ) - 4 , 9 1 o / oe a

I L. Capella,A. Degl'lnnocenti,A. Mordini, G. Reginato,A. Ricci, and G. Seconi,Synthesis,'|'201

(1ee1). 2 B. H. Lipshutz, E. L. Ellsworth, S. H. Dimock, and D. C. Reuter, Tetrahedron Letters, 30, 2O65

( l e8e).

218

r€ag€nts OrganocoPPer/zinc

3 R.J. Linderman and B.D. Griedel, J. Org', 56,5491 (1991)' 4 D . E . S t a c k ,B . T . D a w s o n ,a n d R . D ' R i e k e ,A m ' S o c ' ,l l 4 ' 5 1 1 0 ( 1 9 9 2 ) ' 5 Y. Yamamoto, N. Asao, and T. Uyehara, ibid', 114,542'7 (1992)' 68.E. Rossiter, G' Miao, N.M. Swingle, M' Eguchi' A'E' Hernandez' and R'G

selectivemonocouplingwith various elcortrp with a second electrophile to give polr:furrrt Patterson'

Tetrahed.ronAsymmetry, 3, 231 (1992)' 7I. Marek, A. Alexakis, and J.-F. Normant, Tetrahedron Letters' 32' 6337 (1991)' 8J.P.Marino,M.V.M.Emonds,P'J'Stengel,A'R'M'Oliveira'F'Simonelli'andJ'T'B'Ferriera' ibid.,33,49 (1e92). e A. El Marini, M. L. Roumestant,P' Viallefont, D Razafindrambora'M' Bonato' and M' Follet' Synthesis,1104 (1992). 10G. Cainelli, D. Giacomini,M. Panunzio,and P. Zarantonello,TetrahedronLeners,33,7'/83 (1'992)' 11B.H. Lipshutz and K. Kato, ibid', 32, 564'1 (1991)' 12B. H. Lipshutz and R' Kell, Am' Soc', ll4,'791'9 (1'992) 13s. H. Lipshutz, K. Siegmann'and E' Garcia,ibid', r13' 8161 (1991)' taS.-K. rung, S.-G. Kim, and D.-G. Cho,TetrahedronAsymmetry'3' 1509 (1992)'-15K. yamumoto, S. Yamada, and K. Yamaguchi, Tetrahedron Letters, 33,7521 (1992)' 16S. Hanessianand K. Sumi, Synthesis,1083 (1991)' 17M. Bergdahl, M. Nilsson, T' Olsson, and K' Stern' Tetrahedron'47'9691 (1991)' t8f.e.S*ir.,W.Hinkley,C.A.Maryanoff,andD'C'Liotta'Syntlresis'127(1992)' lgP.S.VanHeerden'B.C.B.Bezuidenhoudt,J.A.Steenkamp'andD.Ferreira,TetrahedronLetters,

1) Z n ,T H F 2) CuCN 2LiCl

tzntC

t(cH2)41

c6HscHo 1...........-..--------------------_

OM

c6Hs'-cH(cH2)'

o>-\ (,

(cHs)3sicl

os

33,2383(ree2).

20M. Kanai,K. Koga,and K. Tomioka,ibid',33,7193 (1992)' PerkinI' 1193(1992)' 2rK. Tanaka, J. Matsui,H. Suzuki'andA' Watanabe,J'C'S'

Organocopper/magnesium neagents' to RLi and R2culi, which Reaction with chiral 1,3-diaxolan-4-ones.t In contrast preparedfrom (R)- or (1)' L,3-dioxolan-4-ones chiral of react with the carbonyl group react with the diox(S)-mandelic acid and an aldehyde' RCu(MgBr2) or R2CuMgBr olanoneltoprovideethersofmethylmandelate(2)in9o_g4voee.Removalofthe

11

t""1\

P-(" 'l

'r) R,cuMoBr '';i#'''"'

,)ii;.r,

"^76

coocH3

oz Koc(cH3)3

cH2cu(cN)Znl ll:#

oH

g- -cuHu r-#,za";-. I 75/o csHrrT.-R "ur,,A, -J-

CH27nl

7ar

2

z, 90 - 99% de

to provide chiral secondary chiral auxiliary is eff'ectedwith Pb(oAc)a or 02 + KO-l-Bu' alcohols 3. 5201(1992);B' rB. Heckmann, C. Mioskowski,J Yu, and J'R' Falck' TetrahedronLetters'33' Fa|ck,ibid.,33'5205(1992)' J.R. and Chandrasckhar' S. Mioskowski, C. Alayrac, C. Heckmann'

OrganocoPPer/zinc reagents. be prepared from primary Heterobimetallic reagents.t Reagents of this type can by transmetalationwith followed (2 equiv') zinc with l,n-diiodoalkanesby reaction these reagentsundergo groups' CH2 4-6 by separated CuCN'zLicl (l equrv.). When

The unique selectivity of reagentsI atrJ , of the C-Cu bond comparedto thc (--2 bimetallic reagentsare useful for preparatx (RCOCH:CH)Cu(CN)ZnI.) Zinc rc. -cnoatesto form a moderately stablc orerl

in the presenceof a Pd(O) catalyst can c-rlu also be converted to moderately stablc all Tl CuCN'2LiCl in THF/S(CH3)2at -{r' than alkyl copper/zinc reagents.Thcl dr n rlkyl halides,but they do reactwith (CH,r,l

Organocopper/zinc reagents

selectivemonocouplingwith various electrophilesto give intermediatesthat can couple with a secondelectrophileto give polyfunctional products.

,).)t).

l.

219

L:

l{-- ,ndcz.and R.G. Patterson, (1991). : .r: ,,.r.17 I . ^ r , ' n c l l i ,a n d J . T . B . F e r r i e r a .

1 ) Z n ,T H F 2) CuCN.2LiCl

lZn(CN)Cu(CH2)aZnl

t(cH2)41

1 n - - , . \ t . B o n a t o ,a n d M . F o l l e t ' tr.., . .:tt )n Letters,33,7783 (1992).

c6H5cHo

OH

l2 59o/o

I

1 . s 0 9( 1 9 9 2 ) . . 1 - 17. s 2 1 ( 1 9 9 2 ) .

I ^ ,, ,.CH(CH2)41 \16n5

o

o\r'\

r .l- 't691(1991). i r - , : . . t r .1 2 7( 1 9 9 2 ) . Letters, [ .r I crreira,Tetrahedron

(,

(cH3)3sicr

osi(cH3)3

A I

. ) l -\..'\(CH

t t l 64o/o

)aznl)

-,,t|93(1992).

o re.: :,, RLi and R2CuLi,which n.. , | ). preParedfrom (R)- or ( ..\lcUr react with the diox.. r ()-l.i ec. Removalof the H

o.

t.

" oct6n.). rHF,24"

,u**

OH I

C u Hi1^ R 3

Ft.. ,' providechiralsecondarY

/ r'ttt'rs,33, 5201(1992);B. I .rlck.ibid, 33,5205(1992).

.c preparedfrom primary 1 . . r .i . hv transmetalationwith i... these reagentsundergo

.Y t \-'\

CH2Cu(CN)Znl

t CH2Znl

2

1) Cyclohexenone 2) Allyl bromide

74"/"

.YYY" \...

cH2cH=cH2

The unique selectivityof reagentsI and 2 can be explainedby the higher selectivity of the C-Cu bond comparedto the C-Zn bond toward electrophiles.These mixed bimetallic reagentsare useful for preparationof polyfunctional products. (RCOCH:CH)Cu(CN)ZnI.2 Zinc reacts at 25' with p-iodo-a,B-enones or -cnoatesto form a moderately stable organozinc iodide reagent.These zinc reagents in the presenceof a Pd(O)catalystcan couple with alkenyl and aryl iodides.They can also be converted to moderately stable alkenylcopperlzincreagentsby reaction with CuCN'2LiCl in THF/S(CH3)2 at -48". These copper/zinc reagentsare less reactive than alkyl copper/zincreagents.They do not react with aldehydes,acid chlorides, or alkyl halides,but they do react with (CHr)rSnCl, l-iodoalkynes, and allylic halides.

OrganocoPPer/zinc reagents

220

o

o

ll RAcH=cHZnl

tcH=cHcoHrs

cucN'2Licl rHF.s(cH3)2

? a\

Pd(o)

+

lcHltr

(I)

A

55% -

(

RC=CCu(CN)LI

(E,E 100o/')

(E)

(CH3)3SnCl

,

93"/" Cu(CN)Znl

t i l 9Znl

,r*\

Sn(CHs)g

tC=CBu

I

o

Reagents wilh amino or amido grrl type can be preparedwith only slighl dct such as primary or secondaryaminesor

which Propargyliccopper|zincreagents.3Reactionofalkynylcopperswithiodomethylcopper/zin-c^reaBents' reagent)provides p'npu'gylit yield' zinc iodide (Simmons-Smith 80-95% in alcohols ketonesto form hornop'opu'gylic react with aldehydesor

CoHsCOCHs -=;-1 rcH2znr - [(cH3)3sic=ccH2cu(cN)Znll (cH3)3sic=ccu(cN)Li

t

fu@

( ) \

1)z^ zi cucNzuicr

\' /

*', \

H

H

OH (cH3)3sic=ccHzCCH3 CoHs

iodide resultsin insertion with 5 equiv' of iodomethylzinc alkynylcoppers of Reaction of type 2' which can be organocopper/zincreagents prouid" io groups of four methylene (equation l)' irupp"O uy attytic hatides

Addition to allcynes's The polrfun by reaction of organozinchalides rrrth alkynes to provide syn-adducts.uhrch alkenes (equationI). An intramoleculn lequationII). In contrast, attempts to

Organocopper/zinc reagents

o tl

)

q46H=cHcH=cHC.Hrs

t,

lCH2Znl(5 eq.)

(t)

RC=CCu(CN)Li

,(CHz)zCu(CN)Znl

cl-\H,

b

(E,E100%)

50-74o/o -

/cooc(cH3)3 CHz:C. CH2Br

>nul 33co

nz-

(CH2)2CH2C:CH2

t,

Sn(CHs)s

l-\ cHz

cooc(cH3)3 cHz

Reagents with amino or amido groups. Knochel et al.a report that reagentsof this type can be preparedwith only slight deprotonationof groups bearing acidic hydrogens such as primary or secondaryamines or amides,or 1-alkynes(equationI).

B,

p : :

.rlkvnylcopperswith iodomethyl::lr lic copPer/zincreagents,which rlic alcoholsin 80-95% Yield'

Ou(CN)Znl (

Zn CuCN 2LiCl

BUC=Cl

( 60/"

*Tfi c =ccHzcu(cN)Znrl

\

,-z--t\r,

H

OH I (CH.) SiC=CCH2CCH3 I CoHs

nr.thvlzinc iodide resultsin insertion 'rr. rcagentsof tYPe2, which can be t(:

Addition to aWnes,s The polyfunctional zinclcopper reagentssuch as 1, prepared by reaction of organozinchalides with (cHr)2cu(cN)Li2, reactsslowly with activated alkynes to provide syz-adducts,which can react with various electrophilesto provide alkenes(equationI). An intramolecularversion can result in alkylidenecyclopentanes (equationII). In contrast, attempts to use this intramolecular cyclization to obtain

Organocopper/zincreagents

222

(CH3)2Cu(CN)Li2

C2H5OOC(CH3)3Znl

C2H5OOC(CH3)3Cu(CN)Li.Zn(CHg)z'Lil

s S.A. Raoand P. KnochelAm. irc.. I13. 5-li r , 6A. Sidduri,N. Budries,R. M. l-aine.and p hn<

1

1 EIO2C(CHj3 pu(CN)'Zn(CH3)2'Lil'"

---------* (l) auc=cscHs

)<

Bu'

-

75o/o

ScHr

EIO2C(CH2)3

/l

aunscH. z1 PoocrHu

pr cnlcnrar (cH3)2 1"J- "" t"N)Li.Zn \._BU

ocH3cH3 l

Bu3Pb- \-/

1)25'C

(ll)

Organolead compounds. Stereoselective aldol reactions riri c-r The a-methoxy lead reagent lr reactssrrh . with high diastereoselectivityat three conrrg four possiblealdolsare formed and theser*o I correspondingto I shows similar diasteretxc

gHs l '* -,\ -CHa -cHo CeHu. l

1

f' 11

(-/-ru

/tcH' cooc2Hs

?H3?cH3c c6H5/fr OH

four- or six-memberedrings were not successful. 3,4-Disubstiluted cyclobutene-|,2-diones.o These products can be prepared by with functionalized organocopperlzinc reaction of 3,4-dichlorocyclobutene-1,2-diones

2, syn, syn

The reaction of (S)-1 with the srerord the syn-product 3 as a single steroisorncrr

reagents.

"\7" ",4",

cHo rO. 2 BuC=C(CH2)3Cu(CN)ZnX -78" -- 0"

+ (S)-1

9 1a

81"/"

-60" - -40' 1)c-C5H11Cu(CN)ZnX, -,^, t+-/o| 2\ czHsooc(cHz)scu(cN)Znx | f

(Czo,Czz,and C23).2The side chain of 3 is che hormones). I T. FurataandY. Yamamoto. J. C.S. Chem.( ,a : Idem,J. Org., 57, 2981 (1992).

cooc2H5

fS.A. 2C.J. 3 M.J. aH.P.

R a o a n d P . K n o c h e l ,J . O r g . , 5 6 , 4 5 9 1 ( 1 9 9 1 ) . R a o a n d P . K n o c h e l ,i b i d . , 5 6 , 4 5 9 3 ( 1 9 9 1 ) . Rozema and P. Knochel. TetrahedronLetters, 32, lS55 (1991). Kroess, M.T. Furlong, M.J. Rozema,and P. Knochel,J. Org., 56,5974 (1991).

Organomanganese reagents P entacarbonyl(triailcllsilyl)manganc* tl synthesisof [4,5]- and [5,5]spirokeralsfrm with TBDMS-Mn(CO)5 affords the m:rneac with methyl acrylateto form a manganmck i followed by treatmentwith camphorsulfonicrc

r€tgents Organomanganese

O O C( C H 3 ) 3 C u ( C N ) L i ' Z n ( C H 3 ) 2 ' L i l 1

)l'. Zn(CHs)z'LilI -; EIO2C(CHd3 ,l x

Bu'

5 S.A. Rao and P. Knochel, Am. Soc., 113, 5735 (1991). 6 A. Sidduri, N. Budries, R. M. laine, and P. Knochel, TetrahedronLetters, 33,7515 (1992).

Organolead compounds. Stereoselective al.dol reactions with a-methory organolead reactians (ct. 16,242). The a-methoxy lead reagentlr reactswith 2-phenylpropanalin the presenceof TiClr with high diastereoselectivityat three contiguouscenters(equationI). only two of the four possiblealdolsare formed and thesetwo are formed in the ratio 95:5. The tin reagent but the total yield is only l9Vo. correspondingto I shows similar diastereoselectivity,

/

SCHg

ocH3cH3 * au.engcH.

fc*

0Hz

!'u'

?H' c.HuAcHo

Tict4,cH2ct2,-78' 74"/o

CH.

CH3 OCH3CH3 l

l

l

cnHol^ffcHs

cooc2Hs

r

l

-

OCHaCH.T t

'

'

l

l

c6H5l^\/YcH3

I OH

95:5

OH 3, anti, syn

2, syn, syn !.c products can be PreParedbY t unctionalizedorganocopper/zinc

-

The reaction of (S)-l with the steroidal aldehyde 2 catalyzed by TiCla gives the syn-product 3 as a single steroisomerwith control at three contiguous centers,

cHo Tict4

+ (S)-1

'rr

a:

91o/o

(plant growth (Czo,Czz,and C21).2The side chain of 3 is characteristicof brassinosterols hormones). I T. Furataand Y. Yamamoto, J. C.S. Chem.Comm.,863 (1992). l ldem,J. Org' 57,2981 (1992).

rl I

-r-

\

s55 ( 1991). . e l . J . ( ) r g . ,5 6 . 5 q 7 4( 1 9 9 1 ) '

Organomanganese reagents Pentacarbonyl(triallcylsilyl)manganese (15,235). These reagents are useful for synthesisof [a,5]- and [5,5]spiroketalsfrom tetrahydrofuran.Thus cleavageof THF with TBDMS-Mn(CO)5 affords the manganesecomplex 1, which undergoesinsertion with methyl acrylateto form a manganacycle2 in TlVo overall yield. Photodemetalation followed by treatmentwith camphorsulfonicacid (CSA) resultsin a spirolactone(3). This

Organomanganese Feagents

224

wasp by methylenation pheromones (5) of the common lactone was converted into the

is comparableto that obtained with CH'Tr similar manganesc'cerium.or magncsiumn

and hYdrogenation'

CH3MnOCOCTC THF _78'

.-*4o

(CHs)gC-l----l

95\

\

1

(CH3)3C.--^

1) hv

)

R3Sio-

\

,z-'- .co2cHs

I

Y

o----Mn(co)+

ii6'sn

' [-^r\^l v o-\o 83"/o

cp2ri(cH3)2' I

"

83"h

"

a-h) -Hz'Pd(Bacog)g, fi^-) to1-L -cHs \^,{ I u bAcH, ..Y. 5 (4:1) o

The organomanganesereagents are c-om in almost complete addition to aldehldc-su Acylfurans-3 2- and 3-Acylfurans car furoyl chlorideswith RMnCI catal;-zedbr furanyl ketonesnaginataketone (l) and pt

66% from '

(7) of the olive fruit fly by convertedinto the pheromone The enol ether 4 was also epoxide that rearrangesto to provide a very unstable reaction with dimethyldioxirane NaBHa/ceClr provides the cto. Reduction of 6 with the ketone 6 0n treatmenr-*,in of epimers' oheromone7 as a l3:1 mixture

--1" "

*

,)csA 4 78/otrom3

-

f-Y-!o \_d

bJ 6

+

( \-g

?". cH,-\-*no

(\.o.,

1 )9-',,CHs o--cHg

CHr

X g---r) o t + e P i m e r 13:1

7

more complicated sysbe useful for synthesisfor This route to spiroketals may is cleaved by indicate that 2-methyltctrahydrofuran tems since preliminary results TBDMS_Mn(Co)5withaboutl0:lregioselectivityandinsertionofmethylmethacrylate regioselectivity' "otpf"" 1lroceeds with complete RMnand methyl crotonate*itn or arylmanganese pivalates alkylThe Selective addition '" '"'i*yt': add to pivalate' of organolithiums with manganese ty ""ot" OCOC(CHj)3 1f1, prepareA stereoselectivity The I). the ax-ialalcohol (equation 4_r_butylcyclohexanone,"!tJ"'.J"t,

ocl

qi"

+

cH3-=-,cH3 l \-Mtto

Another route to these furanyl ketoncs (cql catalyzedby iron(Ill) acetylacetonate

Organomanganese reagents

c\,:-nr{)nwasp by methylenation

CHz=CHCOzCHg

. ao,r]

))a

is comparableto that obtained with CHjTi(OC6H5)r, but higher than that shown by similar manganese. cerium,or magnesiumreagents.

.---/o (cH3)3c-l---J

CH3MnOCOC(CH3)3 (1), THF, _78.

71o/o

cHs

oH

(cH3)3c-A+cH, + lcHr;.c-$oH

h)

Cp2Ti(CH3)2

o b_\ o

CH:r 1 ---e3;__

cH.

-f:f----7oH

,

, ) ^--L .CHS \,

n -. 17)of the olive fruit flY bY to x.:"., cpoxidethat rearranges u:"' \aBHa/CeCl3 providesthe

C\.o", -o

o.-

/--oH

92o/ode

The organomanganese reagentsare comparablcto ceriummagnesiumate complexes in almost complete addition to aldehydesin the presenceof ketones. Acylfurans.3 2- and 3-Acylfuranscan be preparedin excellentyield by reactionof furoyl chlorideswith RMncl catalyzedby cucl. This reaction can provide the natural furanyl ketonesnaginataketonc (l) and perilla ketone (2).

/cH"

'

I

-,

cHe 'r i

THF.10" CuCl(1"/o) ---;A-----

CHs

cH."'\-"nc' CHg

+ ePrmer 13:1

/cocl /-\ ht-i. tor more complicatedsysr l:. :r.rhl'drofuran is cleaved by t r::.r rtion of methyl methacrylate )r:'ll Jr!' rcgioselectivitY. ' .,-.lnranganese pivalatesRMnpivalate,add to r. .i r:h manganese I r;.:.rrion I). The stereoselectivity

-o'

o

tt.'-l-tt. *

\

(--,rvrncl e4"/o

-1r.,cHg

O 2

Another route to thesefuranyl ketonesinvolves acylationof furylmanganesechloride catalyzedby iron(III) acetylacetonate(equationI).

Organosilver reagents

Li

(l)

-J

ll

\^2

\\

,MnCl

Mnctalir -1 -------------ll \\

o

o ,)--r,

BuCocl Fe(acac)3(3"/.)

82"/"

\-,2

o

A

(CH3)2CHCOCI+ HePtMgcl

Br(CH2)5COC|+ BuMgCl

qH

/-\

-o'

o cuHuY-\ 81o/o

CHe

ryl

rT. Kauffmann,C. Neiteler,and S. Robtrc.8a

HeptCOCH(CH3)2

94o/o

MnClaLi2 THF

(CH3)2Ag(CN)Li2 ether

CoHs

MnCteLiz G) This soluble ate complex (1) is prepared by mixing MnCl2 and 2LiCl in THF at 20".4 ln the presenceof the complex, Grignard reagentsreact with acid chlorides to form ketones in high yield. MnClaLi2(3%) THF

o

Br(CH2)5COBu

86"/"

I P. Deshongand P.J. Rybcezynski, J. Org., 56,3207(1991)2 M.T. Reetz,H. Haning,and S. Stanchev,Tetrahedron Letters,33, 6963(1992)3 G. Cahiez,P.-Y. Chavant,and E. Metais,ibid., 33, 5245(1'992). a c. Cahiezand B. t-aboue,ihid., 33, 4439(1992).

Organothallium reagents. Trialkylthallium reagentshave reccircd I haps becausethey are sensitive to air. *atc compoundsare. However, they are readilr ari nard reagentswith stable and unreaclive di: reactrapidly at room temperaturewith acid h the dialkylthallium halide. Even in the prcsc

o

Jt - C l +

(CH3)3rl

CsHrsOrganosamarium(IlI) reagents,l Reactionof a primary or secondaryalkyl halide with SmI2 resultsin an alkylsamarium(III) reagent,which is moderatelystableand which reactswith various electrophiles. These reagentsare undoubtedly intermediatesin the Barbier reaction of alkyl halides with ketonesinitiated by Sml2, and in fact higher yields are often possibleif the Barbier reaction is conductedby reaction of the alkyl halide first with SmI2 and then with the carbonyl compound. fD.P. CurranandM.J. Totleben, (1992)' Am. Soc.,1f4,6050

Organosilver r€agents. cyano(methyl)argentates.t A number of these silver complexes have been prepared by reaction of CHrLi or CH:MgBr with AgCN including: CHjAg(CN)Li' (CH3)2Ag(CN)Li2,(CH3)2Ag(CN)(MgBr)2.In comparisonto similar reagentsprepared from AgBr, these cyano(methyl)argentatesare less sensitive to light. All these react more readily with aldehydes than with ketones, with cyano(methyl)argentates (CH3)Ag(CN)(MgBr)z showing the highestselectivity.In addition, B-hydroxy ketones and p-amino ketonesare methylatedpreferentiallybecauseof chelation.These reagents also react with complete selectivity with the epoxide group of epoxy ketones. Styrene oxide is methylatedpreferentiallyat the position a- to the phenyl group.

to the carbonyl group are formed. Tlr m acetenyl)thallium(Ill),preparedas sho*n. rce of the acetylenic group.r

cuHrc=cH lg!d{L- [cH.;rl - c =cc These RrTl reagentsalso transferalkr I gr halideswith formationof R2T|X.:

(C6Hs)3CCl +

(c6Hs)3Tl mi

-o

+ (cHs)zTr-c=ccsH,r ct

Organothallium

o L.-: r Ea:

3'.)

82.-

o

\\ /--Bu

(CH3)2Ag(CN)Li2 ether

cunrA

fi-<

?"' -

*

c6H5-/---"oH

/ \ \o'

?" cuHu-\'--cH'

(65%)

o cuH')A

rc:.,rcd by mixing MnClz and i::.::.'rd reagentsreactwith acid

reagents

(13%)

cH3/oH 81o/o

CHs

C6ttutX---'-CHs

'T. Kauffmann, C. Neiteler,and S. Robbe,Ber-, l2S,2409 (1992\.

HeptCOCH(CHg)z Organothallium reagents. Trialkylthallium reagentshave received little attention from organic chemists,perhaps becausethey are sensitive to air, water, and light, and are toxic as all thallium Br(CH2)5COBu

, .r.r r,u03(1992).

compoundsare. However, they are readily availableby reactionof alkyllithiums or Grignard reagentswith stable and unreactivedialkylthallium halides. These R.lTl reagents react rapidly at room temperaturewith acid halidesto form ketoneswith regenerationof the dialkylthallium halide. Even in the presenceof excessR:Tl, no productsof addition

q.l

o

o

-Jj--Cl + CgHrgh :nrl- resultsin an alkylsamar;. * ith various electrophiles. ;r1.,. L:;rrr rcactionof alkyl halides r:. 'Jttcnpossibleif the Barbier n: rith Sml2 and then with the

I

.i.rcr complexes have been {( \ rncluding:CHrAg(CN)Li, s..:: :,' similar reagentsprepared \..rrive to light. All these lhr,:r. than with ketones,with - l: .'J,jition,B-hydroxy ketones lu.- ,'1 chelation.These reagents !' .-n ,rf epoxy ketones.StYrene ri:, rhcnvl group.

(CH3)3T|

Jl-cH3 + (CH3)2rlCl CeHle/ 85o/o

to the carbonyl group are formed. The mixed R.TI(III) reagent, dimethyl-(phenylacetenyl)thallium(Ill),preparedas shown, reactswith acid halideswith selectivetransfer of the acetylenicgroup.l

c6H5c=6sl9Id{L-[cHorr-c:cc6H5]3==! 77"/o

CeHle/

i

C=CCoHs

These RrTl reagentsalso transferalkyl groups to reactivesecondaryor tertiary alkyl halides with formation of RrTlX.2 (C6Hs)3CCl

+

(C6H5)3T

(C6H5)4C

+

(C6H5)2TtCl

8O"/"

a) -o

+ (cHs)zr-c=ccsHrr ct

66/"

[".,1.-

C=CC5H11

228

Organozinc rcagents

Thedialkylthalliumchloridescana|Sobeusedascatalystsforcondensationofalkyl reagent'3 halides with alkyllithiums as the stoichiometric

cuHu3

"".rf-r^ cHe- b','),-r

(CH3)2TlCl (cat )

+ (C6Hs)3cCl

C6H5C=C'' tT

CeHs Ce

(coHs)3cc=ccoHs

CoHsCHO +

(RCHdln

I I. E. Mark6 and J. M. Southern,J' Org'' 55' 3368 (1990)' 2 I. E. Mark6, J. M. Southern,and M' L' Kantam' Synlett'' 235 (1997)' 3l.E.Mark6andM.L.Kantam,TetrahedronLeners'32'2255(1991)'

Organozinc reagents. Erdik has reviewed reactions of Reactions catalyzeil by transilion metals't and by various N(0), N(II), Pd(0), Pd(II)' organozinc reagents that are cataryzed C u ( I ) c o m p l e x e s ( l 4 4 r e f e r e n c e s ) ' P d a n d N i a r e p a r t i c u l a r l y e f f e c t i v e f oconiugate rcouplingof reagents'Nickel catalystscan promote allyl-, benzyl-, propargyl-,and arylzinc additionoforganozincreagentstoenones.Thereportincludesalistofmorethan35 reactionsof Reformatskyreagents' examplesof transition metal catalyzed are pyrophoric and moisture-sensitive' (RCH)Zn from RCH2MgX'2 Dialkylzincs

Allylethytzinc.3 A reagent(2) of th with dicyclohexylborane(1 equiv') to f< to form 2 on treatmcntr' transmetalation in the presenceof the catalyst(-!'-1-crr -(r-q a secondary(E)-allylic alcohol in

Buc=cH. G,*

o n l y d i e t h y l z i n c i s r e a d i l y a v a i l a b l e f r o m c o m m e r i c a l s o u r c e s , b u t i t i s to e xform pensive'A of RCH2MgX with ZnCl2 in ether new route to dialkylzincs in'roolu"'reaction The removedby precipitationwith dioxane' (RCH2)2Znand MgX2' The latter product is

8u,,,/'-.,..CoHs ether 2 RCH2MgX +

ZnCl2

=+

=-'\-..

(RCH2)2Zn +

MgX2

H O H (R,96o/oee)

3s gA

g11

or--.ro

o

p I Msx,'d \-J by Seeadd to C6HsCHO when catalyzed dialkylzincs obtained in this way in alcohols give to (R,R){artaric acid, bach's sPirotitanate (1)' derived from )95Vo ee.

Dimethylzinc can replacediethrla aldehydesreact with 2 in 80-9lQ cc' Allylic dimetallic zinc reagcrtB'' oarcd in silu as shown in equatttxl

0rganozinc

rcagents

rr'*ffi,"&:r,

cJ:.:r\\l\ for condensationof alkyl

I

- - rC6H5)3CC=CCoHs

OH

1, Ti(O-l-Pr)4

I

?no

(RCHz)zZn

c6H5cHo

4Q - 83/o

r , )I ) . , r t )I ) .

C.Hu,. cHrR >95% ee

L:.:rx has reviewed reactionsof \r' rt. Ni(ll), Pd(0), Pd(II)' and u:r.:.lrrly effective for coupling of can promoteconjugate \i -.rt.rlvsts r:: r:lcludesa list of more than 35 [,,:':matskY reagents. :.',phtrric andmoisture-sensitive' but it is exPensive'A s I :Lrurccs, - \ 1 i \ * i t h Z n C l 2 i n e t h e rt o f o r m J ^ ' nrccipitationwith dioxane'The

Altylethylzinc.3 A reagent(2) of this type is preparedby hydroborationof l-hexyne with dicyclohexylborane(1 equiv.) to form an (E)-1-alkenylborane1, which undergoes transmetalationto form 2 on treatmentwith diethylzinc.This reagentaddsto an aldehyde in the presenceof the catalyst(-)-3-exo-(dimethylamino)isoborneol(DAIB, 3) to form a secondary(E)-allylic alcohol in 70-95% yield with 79-98% ee.

BUC=CH

B'-z-a("-n"r)

G,,,,

1

I etzn { CoHs

3, 00

C6H5CHO +

<-87o/o

qCHz)2Zn + MgX2 (R, 96o/oee)

,r-,/-an=, 2

CHs

oa---ro N(CH3)2

OH

CHs 3

H.( ll() when catalYzedbY Seel::.:::. acid, to give alcohols in

Dimethylzinc can replacediethylzinc. Aliphatic straight-chainor 4- or B-branched aldehydesreact with 2 in 8O-91% ee, but pivaldehydereactsin low yield and 737oee. Allylic dimetallic zinc reagents.a A typical reagent (1) of this type can be prepared ir sirz as shown in equation (I). This reagent can undergo attack with two

Organozinc reag€nts

1) BuLi 2\ 2CH2:CHCH2ZIBT

(t) (cH3)3si-c=c-cH2oR

Vn t

vn-F? (cH3)3si

R = CHs,t-Bu

OR l

Substirute d diallE lzinc reatc tE -^ of functional alkyl iodides with (C: electrophilesin the presenceof CuC

l'o"r,

16, pl = CH3 lb, R = t-Bu

while the electrophiles, but the first reaction always occurs on the carbon a to oxygen, and regiois reaction the cases, In all second is on the carbon a to the silyl group. carbonyl step: first in the be used can A wide variety of electrophiles stereoselective.

Cl(CH2)4f + (C2H5)2Zn

45-s5'-

[Cl(CH2)a]2Zn 1

-

lb

C6H5COCI

The reaction of these dialkllzinc: of Yoshiokaand Ohno (16,103).dem 86-97Vo ee.

t2 n.o- / \ 781" / \ 78% t \

f-Bu-O, t-Bu-O, 1.. H. 2-COC6H5 />-coc6H5 \-cH=cHz (cH.).sinCH=CHz (cH3)3si/

lCl(CHz)alzZn 1

3 (97:3) even aryl or compounds,alkyl bromides.The secondelectrophilecan be H3O+ or 12or an acetoxy to converted be group can /-butoxy vinyl iodides with a Pd(0) catalyst.The group by treatmentwith Ac2O/FeClr. In the presence of Pd[P(C6Hs):]a (3 Dialkenylzinc reagents, (RCH:CHa)2Zn's react with cyclic a-iodo- or a-tribromide mol %), dialkenylzincsor an alkenylzinc are reducedby LiAIH(ocHr)3 products These flyloxyenonesto give a-alkenylenones. results can be obtainedwith Similar a-alkenylketones. and CuBr to the corresponding alkenylaluminum reagents.

'-.-/\

o tl

\_J

* (eu-!rzn

Pd(0) DMF

86%

Bu

a 4Phenllthio) alke ny lzinc re4

can be obtained by reaction of an : (1 equiv.) at -10 - 20" to form I

Organozinc rcagents

Vn t Vn-f"-/

,-=. l- -

OR l

1 c H r 1 3 S iI' \r'CHZ la, R = CHg lb, R = t-Bu

hr . 'rhon a to oxygen, while the ..,.-.. the reactionis regio- and r '-rJ in the first steP: carbonYl

231

Substituted dialkylzinc reagents.b Reagentsof this type can be obtained by reaction of functional alkyl iodides with (C2H5)22n.These zinc reagentsreact with various electrophilesin the presenceof CuCN'zLicl.

cl(cH2)4f

+ (czHs)2zn

+s - 55'

- cl( cH)aZnC2H5

a' 0 1 mmHs

o

lCl(CH2)al2Zn 1

> lCl(CH2)al2zn

o

A

CuCN.2LiCl

86/"

,.\

$,"r,,o",

R - -aa^t{.

9

The reaction of these dialkylzincs with aldehydesin the presenceof the catalyst2 of Yoshiokaand Ohno (16,103),derived from (1R,2R)-cyclohexanediamine, proceedsin 86-97%o ee.

:

HY(cH,)4cl

t'a

:-Bu-O \

. 5S

2. 50"

rcoc6H5

lCt(CH2)al2Zn

\-cH=cH,

1

3 (97:3)

-

cHi

^/"r" 97o/o@e

C:: -c HrO+ or 12Or even arYl Or uF ..'n hc convcrtedto an acetoxy

sozcF3 N

(3 th, :rcscncc of Pd[P(CaHs)r]+ c-:.: *ith cyclic a-iodo- or a-tric:. ,:c rcducedbY LiAIH(OCH3)3 n:: :: rcsultscan be obtainedwith

'rtN

)rilocHlcHr;11,

SO2CF3 2

ZnBr ay'Phenylthio)alkenylzinc reagents,T RCH:C| 'SC6H5

Reagents of this type

can be obtained by reaction of an alkynyllithium I with phenyl benzenethiosulfonate (1 equiv.) at -10 - 20" to form a phenylthioalkyne,which on Pd(0)-catatyzedcis-

Organozinc reagents

hydrostannylationaffords an d-(phenylthio)alkenylstannane (2). This tin reagent can undergoStille coupling,but the correspondingzinc reagent3 obtainedby transmetalation is more reliable.

[aY'"

NC'/-v 1)(CH3)3CLi 2) C6H5SSO2C6H5

2 RC=CSCoHs

:

CHg

eH. ,r.an",

H

ZnBr

R

SC6H5

1 ) B u L i ,T H F 2\ Zn*2

t.

o /\t'ro'

SC6H5 2

PdlP(c6H5)314, THF, 60" 73o/o

3+

.

,snBus

R

3

3 + lC6Hs

l\Z\-,"\opiv

PdlP(c6H5)314

o"or^ | ""'" c6H6, 25" I

= R C=cH

Tfo. \/--\

ll ) cH3ooc"'-'-/

H

CoH.

R

SC6H5

at\ i

9cr(cr.r)znr

\-/""

Pd2(dba)3, As(C6Hs)3 THF, 20'

Transmetalationof a vinyl iodide to n

1) &r! 2) MgA

coocH3 SC6H5

(l)

NC\-r-\-,L2l

c-HexCHO 71o/"

'fhese Substituted aryl- and alkenylzinc reagents.s are difficult to prepare directly by zinc insertion, but the alkenyl- and aryllithiums are readily obtained by halogen-lithium exchange.Reaction of these with Znl2 or CuCN .2LiCl in THF at -100' provide stable solutions of the organozincor organocopperreagentsor CufZn organobimetallics.

Rtl Organofinc carbenoids,

,C:7J1 R2' tion of carbonyl compoundswith l.l-br: zinc in ether.These can be trappedhr dl

Organozinc reagents lnl

!c:

r. (2). This tin reagentcan .l , 'htainedby transmetalation

[-r''

BuLi

,-\.-x

i l l Nc'/"2

Znl2

NC,/''V

[aY'"'

CuCN 2LiCl

;\cu(cN)znx i

NC'/"z

l

l

NC""-'z

RC=CSC6H5 Bu3SnH,PdlP(C6Hb)314 c6H6,25'

F. .

81o/o

Nc\r\ i.....*,,,%ot,u l l

I

ts

SnBu3

o

Noz

sc6Hs

.\

I

Cu(CN)Znl

I

ll

70/"

, C .H , q,a , f..l-

Transmetalationof a vinyl iodide to magnesiumis also possible(equationI).

1) BuLi 2) MgBr2,THF, -100"

coocH3 sc6H5

(l)

NC...-,-r.,_..1--l

NC..._..^.,.,-,,1--

MgBr

c-HexCHO 71o/"

k.- .irc diflicult to prepare dilh:..::r. are readily obtained by ni 'r CuCN'2LiCl in THF at reagentsor cufzn )rr.::'''urrPPer

tt)":rn.' organozinc carbenoids,

These reagentscan be generatedby reacR2' tion of carbonyl compoundswith 1,2-bis(chlorodimethylsilyl)ethane and amalgamated zinc in ether.These can be trappedby alkeneswith formation of cyclopropanes.

Organozinc/zirconium

rcagents

CH9,CH.

crsi) Z n -

C6H5CHO +

| "ut, I I Fzn I L H J

ether

crsia

(ll)

R-----

cH3 cH3 68"/"

O*

CoHs

H

H

CoHs

(c,s)

o

al

1) [ClSi(CH3)2CH2]2Zn 2) C6H5CH:CH2

t*CHs

CoHs

Reagentsof the t1-pc aldehydesor ketonesto is useful becausethis ok and in fair to sood viek

,"'"

\^_l

59o/o

Br I 7n

(cisltrans = 11:'l)

n-cznrs{r)ct 'E. Erdik, Tetrahedron,48,9577 (1992). 2 D. Seebach,L. Behrendt,and D. Felix, Angew. Chem. Int. Ed., 3O,1008 (1991). 3 W. Oppolzer and R.N. Radinov, Helv., 75, l7O (lgg2). 4 L. Labaudiniere,J. Hanaizi, and J.-F. Normant, J. Org., 57,6903 (1992). 5 E. Negishi, Z.R. Owczarczyk,and D. R. Swanson,Tetrahed.ron Leuers, 32,4453 (1991). 6 M.J. Rozema,A. Sidduri, and P. Knochel, J. Org., 57, 1956 (lgg2). 7 A. Pimm, P. Kociefski, and S. D. A. Street,Synlett, 886 (1992). " C . E . T u c k e r ,T . N . M a j i d , a n d P . K n o c h e l ,A m . S o c . , 1 1 4 , 3 9 8 3( 1 9 9 2 ) . e W. B. Motherwell and L. R. Roberts, J.C.S. Chem. Comm., 15t12(1992).

Organozincl

zirconium

cpz Br I Zn n-crH1r{ )ct Zr CPz t

reagents.

Reagents of this type are readily available by hydrozirconation

of alkenyl- or

alkynylzinc halides with Schwartz's reagent, H(Cl)ZrCp2, in CH2CI2 at 25" (equations I and II).

regioselectivity.The rci aldehydesto form allcn I C. E. Tuckerand P. Krn

Br I Zn

H(Cl)ZrCp2 cH2ct2

(l)

RCH:CHZnBr

RcHr-< )cl Zr cPz

1

Osmium(III) chlorilc. Oxidation oI ph oxidized by a peracid ir with peracetic acid. tr

Osmium(III) chloride

R (il)

CoHs

)

X ,

\nr zv'

\-----l /----\

R:ZnX

i l z r

Fzn

cPz

H

2

""IU L"t'..

CaHs I

H 4'.1

Ox:.,., (trans)

Reagentsof the type I or 2 areunstableat 25', but they can be trappedas formed by type 1 aldehydesor ketonesto give alkenes.rThe reactionof aldehydeswith reagentsof (94-100:6-0) selectivity high with is useful becausethis olefinationprovides(E)-alkenes slight and in fair to good yield (49-897o). A similar reactionwith a ketone shows only

9Hs

Br I Zn n-c7H15-( )ct Zr 1 cqz

a / s / t r a n=s 1 1 : 1 )

!

-

/,..',-,..CHO

--,*-

25'

(,

a1lr\,.n-C7H15 (,

Elz= 1oo:0

1 , / . 3 0 , 1 0 0 8( 1 9 9 1 ) .

ts_ 5- he03 (1992). . t r t r t I ' e t t e r s3, 2 ' 4 4 5 3 ( 1 9 9 1 ) ' li' s- ;r, (1992). Ioe3). I l 1 :es3 (1992). r 5 f { 2( 1 9 9 2 ) . h.

or il. ^r hvdrozirconationof alkenylI (equations It i,/r('p:. in CHzClzat 25"

Br Zn n-Cru,r{ )Ct 7r CPz t

?r.

c6HscocH3 7O/o

CeHsNn-C7H15 EIZ=86:14

with regioselectivity.The reagentdoes not react with esters.Reagentsof type 2 react (>7O%)' aldehydesto form allenesin satisfactoryyield iC.E. TuckerandP. Knochel, Am. Soc.,lf3' 9ft88(1991)'

t :-, : F:l

-.lBt Zn

RcH2-< )cl Zr cPz

1

Osmium(IID chloride, OsCl3. Oxidation of B-lactams.r In the presence of OsClr (catalytic), B-lactams are Highest yields obtain oxidized by a peracid in acetic acid to give 4-acetoxy-B-lactams. $ith peracetic acid, but C6H5IO and C6Hsl(OAc)z can be used. This oxidation is

236

0smium tetmxide

n ,,-NH (

OsCl3 cHecogH,HoAc

a(oo" /FNH

78o/"

o'

R.SiO

R.SiO "

cH.+{oA"

l H cH3,,\-l

o/-*^

o/-*'

2 (>99%de)

1

intermediate in the of I into the acetate 2' a key particularly useful lbr conversion presumably an oxoosmium(V) complex is involved' synthesis of carbapenemantibiotics. Letters'32' S Akutagawa'Tetrahedron I S. Murahashi,T. Saito,T' Naota'H' Kumobayashi'and 214s (19er).

Note that the mirror-imagereciprocitl ber* basesthemselves. A further improvement can be effected t'r basedon olefin),which accelerateshl drolr srs<

is useful if the alkeneis trisubstitutedor l 'l'lr terminal alkenes.Addition of the sulfonamr& cnantioselectivitY. Use of these phthalazineligands and adJ selectivitiesof 95-99.5Vo in the caset'rf nont ligand 1 are somewhatmore enantio6elL'clt\ However, the use of these dihldrtrlutnt gands does not improve the enantitrtlcct problem in this case can be solved t'r u DH(X) indolinylcarbamoyl)dihydroquinidine'

CHs \-/ H

Osmium tetroxide 16' 249)' In the (L4' 237-2.39; l5' 240-24I; Asymmetric catalytic osmylation of estersof dihydroquiasymmetry was obtained by use early versions or tni. ,.u"tion tlie obtainsby use enantioselectivity Markedly higher nine and dihydroquinitti"" l' ti'"ni*' with dihvdroquinidine 1'4-dichlorophthalazine of ligands 1and2,o'"ot;;;;-;;;"ti'l :: (ligand 2)'' fliganO f) and dihydroquinine

Et

o{

goHs

oso' K!F€( 1. K2c-o3r-&o

H

Asymmetric monodihydroxylation of I J I pl with use of [1,4-bis(9-O-dihydroquinidrnr the products with few exception ut. .n6 dxr{r

electron-richdouble bond. Some regimclctrn with a preferencefor trisubstituteddouhk h

Et N:N

) o( fo,,,

I

--9s'-I4

CuHu*cons

O

I

cHsMcHz

4;

cH3" I

cH30

cr "".X'-.--"'=cH, -il

Osmiumtetroxide

,oAc

r-l /-NH

R -r SLi O,

-,--\i

n )-NH

,oAc

o'

2 (>99/o de) ci.:ii 2. a keY intermediate in the rr "'.mium(V) complex is involved. \

\\utaqawa, Tetrahedron Letters, 32,

Note that the mirror-image reciprocity between I and 2 is greater than in the cinchona bases themselves. A further improvementcan be effectedby addition of methanesulfonamide (1 equiv. basedon olefin), which accelerateshydrolysisof osmateesterintermediates.This catalyst is useful if the alkeneis trisubstitutedor 1,2-disubstituted, but is not useful in the caseof terminal alkenes.Addition of the sulfonamidepermits osmylationsat 0", with enhances enantioselectivity. Use of these phthalazineligands and addition of a sulfonamideresults in enantioselectivitiesof 95-99.5Vo in the caseof nonterminalalkenes.In general,reactionswith ligand I are somewhatmore enantioselectivethan those with ligand 2. However, the use of these dihydroquinidine and dihydroquinine phthalazine ligands does not improve the enantioselectivity of cis-disubstitutedalkenes.2 The problem in this case can be solved by use of carbamate ligands such as (9-Oindolinylcarbamoyl)dihydroquinidine, DHQO-IND (f).

cHs H

15. 140-247; 16,249). In the ar:rJ hv useof estersof dihydroquiobtainsby use k: rnantioselectivity

poHs

OsO4,K3Fe(CN)6 1, K2CO3,I-BuOH/H2O

H

to\,

./ot

CH.t"'/1",'6u9u H H

l

r,,:rthalazinewith dihydroquinidine

237

72o/oee

Asymmetric monodihydrorylation of 1,3-dienes.t This osmylation can be effected with use of [1,4-bis(9-O-dihydroquinidinyl)phthalazine (1) as the ligand. In this reaction the productswith few exceptionare ene diols; generallyosmylationoccurswith the more electron-richdouble bond. Some regioselectivityis observedwith nonconjugateddienes, with a preferencefor trisubstituteddouble bonds over terminal ones.

\ . .N)

t ) \ ,

OH I

1 OsO4,K3Fe(CN)6,

ocH3

c6Hu'-\-A--coHs

"urrl-f'\-"u

84%

OH >99%ee OH

cHrM

-G""./f:cH, cHz

*.r.-.1if-oH

OH

3 :l 72o/" Ae

9oo/oee

?t' cH3-'\.."\--\

cH2;

ct'.'ot "t.-Ji*"t, 98o/oee

t

238

Osmiumtetrcxide

Asymmetric dihydrorylation of enol ethers.a This reaction can be effected in high yield by reaction with K2O3O2(OH)+,K:Fe(CN)6, or K2CO3 catalyzedby either (DHQD)2-PHAL or (DHQ)2-PHAL. The dihydroxylation can be carried out on the

Asymmetric synthesis of hydmn-1 p, y- and 7, D-unsaturated estersis accom y-lactones, generally in 96-98'? ee. scrystallization. mtx

R3SiO

Z\r\,-cH3 l t l cH.oA.'

60 - 851

cH3o 99% ee K2OsO2(OH)4, K2CO3 K3Fe(CN)6, (DHO)2- PHAL

R3SiO

-A

,"oA-.\-*

94o/o

(ZE=99:1)

"r.oV

CHs

(r Oa f,

cH3soy'{H2 HP I t-BuOH.

o

K2OsO2(OH)a, K2C03 KsFe(CN)6, (DHQD)2- PHAL

R

o 2

cHg

(E)

.ROU 997o ee

qude EIZ mixture obtained by conversionof ketonesinto enol methyl ethers or enol silyl ethers. Asymmetric dihydroxylation of enynes.5 Even though alkynes can be oxidized to a-diketones by osoa, 1,3-enynescan be convertedto ynediols exclusivelyby osmiumcatalyzedasymmetric dihydroxylation using a dihydroquinidinecatalyst. The enantioselectivity in this reaction can be markedly enhancedby use of a new ligand l, in which two dihydroquinidinesare connectedby a phthalazinespacergroup. Using this new ligand, 1,3-enynesin which the ene group is ,rans-disubstitutedare convertedinto 1,2-diolstn 73-97o/oee.

60 - 85a

A symmetric dihydroxy lation of allct vlation, can accelerateOsOa-dihvdrorr DABCOs have been shown to bc usefu DABCOs of this type availablefrom (S.S is l.

,#ra"H20

cH2oTBPS (s,s)-1

Nr K-'Feo C^H^'/; " " -'-t' -CsHs ,

Review of asymmetric dihydrox-vbn *as initiatedby Criegee'sobsenatronrn

Osmium tetmxide

ff :. rc.tction can be effected in ,- K:CO3 c talYzedbY either ! a:r :' can be carried out on the

Asymmetric synthesisof hydrory-y-Iactones.6 Asymmetric dihydroxylationof estersis accompanied by spontaneous lactonization to hydroxy B,y- andy, 6-unsaturated generally in 96-98% ee, which can be increased, to l00Va by a single TJactones, crystallization.

o CHs

,*oA-'x-t

mix a or p, cH3s02NH2 t-BuOHH , 2O,0"

'oF(* or

....."................'..'...,-..........................* 60 - 85o/o

Y" o

ar-.r^r)

(R,R) 100o/o ee

99% ee

o

-

('(Y"

(S,S) 10Oo/o ee

o

"

tl

\\

OH

60 - 85%

Aol (

o \--^\.\_,-R

-n3v

r

l

:- .rr:halkYnescan be oxidized to r r "r.liols cxclusivelyby osmiumd:'-Lrinidinecatalyst.The enantioc..: 'r\ use of a new ligand I' in r::.,i.1/inospacergroup' Using this u,:. Jr.ubstitutedare convertedinto

: HO

HO (R,R) 100o/o ee

99o/o €€

e. r:rl()cnol methyl ethersor enol

239

(S,S) 10oe/o ee

Asymmetric dihydroxylation of alkenes.T DABCO, known to acceleratedihydroxvlation, can accelerateOsOa-dihydroxylations;new C2-symmetrical2,3-disubstituted DABCOs have been shown to be useful for asymmetric dihydroxylations.Of several DABCOs of this type availablefrom (S,S)-threitol1,4-dibenzylether,the most effective is l.

/ l-N. rl'-)-cn2oTBPS

'*a,,orr* (s,s)-1

1-,

3ir \

O s O a ,( S , S ) - 1 ,

coHs-.-Z\"uru@#&

OH

"uru*"^r. | OH

" "

(S,S),41olo ee Review of asymmetric dihydroxylation. t-ohray8 has reviewed this reaction, which - rs initiated by criegee's observationin 1936 that pyridine can acceleratethe rate of

240

Osmiumtetmxide-Bis(3-methyl-2,4-pentanedionato)nickel(ID

reaction.As a consequence other tertiaryaminesand diamineswere examinedas catalysts, and were found to also effect enantioselective oxidation of alkenesby Sharplessin 1980. Further searcheventuallyled to bisdihydroquinidineand bisdihydroquinine1,4-ethersof phthalazine.l-ohray and Bhushan(1992) havefound that the bisester(1) of a dicarboxylic acid is an excellentchiral auxiliary for asymmetricdihvdroxvlationof trans-disubstituted alkenes.

CHq

t -

cH.Moe.l

cn/\pnrecHi

'T. Takai, T. Yamada,and T

o ll

Oxalyl chloride (ClC)2. N-AllEl maleinides.t A sha anhydride(l) wirh amines ro fcr thcse products with oxalyl chkrn HCI affords the desiredmaleimrd

F\

o4oAo ' K. B. Sharpless,W. Amberg, Y. L. Bennani, G. A. Crispino,J. Hartung,K.-S. Jeong,H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu, and X.-L. Zhang,J. Org.,57,2168 (1992). 2 L. Wang and K. B. Sharpless, Am. Soc., ll4, 7568 (lgg2). 3 D. Xu, G.A. Crispino, and K. B. Sharpless,ibid., 114,75i0 (1gg2). aT. Hashiyama,K. Morikawa, and K.B. Sharpless,J. Org., 57,5067 (lgg2). s K.-S. Jeong, P. Sjci, and K. B. Sharpless,ktrahedron Letters, 33,3833 (1992). 6 Z.-M. Wang, X.-L. Zhang, K. B. Sharpless,S. C. Sinha, A. Sinha-Bagchi,and E.Keinan,ibid., 33, 6407 (1992). ? T. Oishi and M. Hirama, ibid., 33, 639 (lgg2). 8 B. B. Lohray, Tetahedron: Asymmetry, 3, l3l7 (1gg2).

Osmium tetroxide-Bis(3-methyl-2,4-pentanedionato)nickel(II), OsOa/Ni(mac)2. a-Hydrory ketones.l In the presenceof OsOa (l mol Vol and Ni(mac)2 (3 mol Vo), variousalkenesare oxidized by molecular02 and an aldehyde(usually isobutyraldehyde) to a-hydroxy ketonesin good yield, which can be improved by addition of 2,6-lutidine (2 mol Vo) to suppressepoxidation.

+ CHz:CF

1

o4"A cHl a

3 -A ry I -3,4 -dihy drois oqu i n olint chler-Napieralski reaction,bur rhi isoquinolines.In a modified proccd sith oxalyl chloride to form r.

liminium ion b. This ion cyclizesro hv treatmentwith sulfuric acid in m

i\cl

ll

Oxalyl chloride

h.,: ::r. \\crc examinedascatalysts. r.,: : .,lkcncsby Sharpless in 1980. a:.r ^r\Jihvdroquinine1,4-ethers of h :' '-, l-'iscster (l) of a dicarboxylic h..:- rr lationof rrans-disubstituted

HO\/CH3

02, OsOa,Ni(mac)2 (CH3)2CHCHO, base

QHsI

----

CH3-'\."\

Og.t

ctr---f-otr' o

A2%-

67o/"

o HO. JI -(cHr8cH3 v

CrH" n

o

rT. Takai, T. yamada, and T. Mukaiyama, Chem.Letters, .1499 0991\.

Y-l N' ./

Jo""

o tl

Oxalyl chtoride (ClCt:. N-Allql maleimides.l A short route to these compoundsinvorvesreactionof maleic anhydride (l) with amines to form mareamic acids (2, >95o/o yierd). on treatmentof theseproducts with oxalyl chloride, the hydrochlorides 3 are obtained.Elimination of HCI affords rhe desiredmareimides(4), which arc obtainedin 55-i3vo overail vierd.

/

\

O4OAO 1

ov:\zo cH.cr^ ""'"'! + CHz:CHCH2NH2 I f CH2:CHCH2NH OH 2

. r r 1: r l u n g ,K . - S .J e o n g ,H . - L . K w o n g , . 51. t76u (1992).

II crcococr

+ 0* 2so : ' < r 1 6(71 9 9 2 ) . (1992). r. -r-r..1833 r ' ,-llagchi, andE.Keinan, ibid.,33,

/

on*Ao

\

I

CH2CH=CH2 4

o, n ickel(II), OsOa/Ni(mac)2. | ::,,l .i) and Ni(mac)2(3 mol Vo), Li, r r rlc (usually isobutyraldehyde) g: ,r cd by addition of 2,6-lutidine

,rCl

N(c2Hs)3,25o

*E'2.

r^rrrr o4rAo I

CH2CH=CH2 3

3'Aryl'3,4-dihydroisoquinolines.2 Isoquinorines are generaily preparedby the Bischler-Napieralski reaction,but this crassicar route is not usefur in the case of 3_aryl_ isoquinolines'In a modified procedure,the precursor,(phenyrethyr)amide (r), is treated with oxalyl chloride to form a, which on treatment with Fect3 forms an N-acyliminium ion b. This ion cycrizesto 2, which is convertedinto 3,4-dihydroisoquinorine 3 by treatmentwith surfuricacid in methanor. overat yierdsof 3 are in the ,ung" 55-.s,vo.

Oxazabomlidines

(\1coHs

,.\./.--.,.CoHu

(crco)2

\2 r" o

l

l l

l

I o

\? t'1oAo i<

cH2cl2

a

1

(l) BH3.THF + CF3CH2OH

| ,"". l -

l

,.\,,.^---.,,CoHS

firycoHs

\/

WIr" o-\

rt?o o-\

re -H2

Hro*

Enantioselective synthesis of a ari a-amino acids involves enantioselectir with catecholborane(CB) in the presen to give (R)-alcohols 2. The (R)-alcolxrl

72o/o ave'all

o

(\1cons \l\r'N

(s)'

3

I T. F. Braish and D. E. Fox, Synleu, 979 (1992)' ' ' J ' R e i d e r 'a n d I ' S h i n k a i ' 2 R . D . L a r s e n ,R . A . R e a m e r e , . G . C o ' I " y , P ' D a v i s ,E J ' J ' G r a b o w s k i P J. Org., 56,6034 (1991).

253-255' Oxazaborolidines,19, 110-111; 15,239-242: 16' Theseusefu|heterocyc|eswerepreparedoriginallybyreactionofaminoalcohols withBH:.THForboronicacids'butthesemethodscanrequirelengthyreactiontimes in the caseof hinderedpyrrolidinessuch as 1, (S)-2-(diphenylhydroxymcthyl)pyrrolidine' 2 at 110' for 30 minutes' generates Reactionof I with a bis(trifluoroethyl)alkylboronate if desiredin 95Voyield'l isolated be can which situ, the desiredoxazaborolidine 3 in

cB,(s)- 1,

RCOCCI3

-78" - 23' +

H',.2oH ( R

cct

( R )- 2 92 - 98%ee Nt,2H

n^coct

80- 91%

lt

(S)

PoHs

!/rcutu .

bH

t1

\--NH

BuB(OCH2CFt\z -

11 0 0

2

1 yield (equationI)' The boronate(2) is preparedin two steps in 827ooverall

r.l equiv.)and NaN3 (2 equiv.)to (SFo-i .rmino acids (4) by catalytic hydrogenrt Enantioselective aldol reactiots.' rlso effect enantioselectiveMukairanre.ilyl ethers.

0xazaborolidines

1) BBu3 - CeHs ( - t . o \.--_//

FeCl3

(t) BH3.THF+ cF3cH2oH #-

B(ocH2cF3)3 #

BuB(ocHzcFs)z 2

oAo

r _ -CoHs 'N

Hgo* t=O

Enantioselective synthesis of a-amino acids.z A practical and general route to a-amino acids involves enantioselectivereduction of alkyl trichloromethyl ketones with catecholborane(CB) in the presenceof the oxazaborolidine(S)-f (0.1 equiv.) to give (R)-alcohols 2. The (R)-alcohols (2) are converted on treatmentwith NaOH

72V" ove'all

).-_; 2

s QoHs

l-r.

(

r-;

|

kcuHu b

\--N-B'

Bu ( s ) -1 cB,(s)- 1,

I . . . i i . P .J . R e i d e r ,a n d I . S h i n k a i ,

-78" - 23"

RCOCCt3

'o.ro' n^cct.

NaOH cH3ocH2cH2ocH3 - H2O,-NaCl

(R)-2 92 - 98o/oee

_:
f,r rcaction of amino alcohols r :rquirc lengthYreactiontimes c r r Ihvdroxymethyl)pyrrolidine. l . , t ' t i l r 3 0 m i n u t e sg, e n e r a t e s rr'.: rt dcsiredin95% Yield.l

*",.,2'

*t.2'

R^coct

80 - 91"/o

n^coott (s)-3

H2, Pdlc 88 - 98/o

NaN3 NaOH

:,4":l g"No..2H

R^coott (s)-4 (97 - 99% ee)

, QoHs --i--*''coHs

t

o

_.-N-B'

b, 3 'c', 1 iicld (cquation I).

(4 equiv.) and NaNr (2 equiv.) to (S)-a-azido acids (3), which are convertedto (S)-damino acids (4) by catalytic hydrogenation. Enantioselective aldol reactions.3 The tryptophan-derived oxazaborolidine I can .rlso effect enantioselectiveMukaiyama-aldol reactions of aldehydes with trimethyl:ilyl ethers.

Oxazabomlidines

/YCH" /

\

.(r

o-\-cH.

5

SrF. I

V'1"

,-P'2ll

g

CHs (t)-1

(cH3)3sio\ c-C6H11CHO+

1,C2H5CN' -78o

fCHz CoHs

H"A\"uru qJ o c-CoHrr

----,,zCHs -\r I

04\ 93%ee

/

4,cB.

\\\ \ v r "Lg

rfcHt

c6HscH3 --;;6

88%

CHs 3

+ C6H5 96:.4 o/oee 94:6olode

catalyzedby Reactionof aldehydeswith 1-methoxy-3-trimethylsilyloxy-l'3-butadienc product' I provides an aldol as the major

OS|(CH3)3 c-C6H11CHO

(cH3)3sio,.. fr ? c-CeHr#oCHs

+

t'"''t;:*'

Enantioselective reduction of ta by catecholborane(CB) in the prcs to trichloromethylcarbinols2 in 9l-

cH?6ocu" CF3CO2H

CI

(

o/{"lt.r,' 760/"€@

and triterbiosyntheticprecursorto steroids (35)-2,3-Oxidosqualene,(S)'1'a This conversion involves steps first (1)' The penescan be preparedtiom 1*l-oxiaosqualene to an a-fluoro ketone 3 by Swern converted is of (+)-1 to a fluorohyd'in 1i;,'*t'i"t' (cB) catalyzed by the is reduced by catecholborane oxidation. This a-fluoro ketone final step involves The ee' 927o 5 in (R)-oxazaborolidine 4 to the (S)-fluorohydrin base' conversionto the (3S)-oxide I by

RCOCCI3

but particularlY becausethev can a-aryloxy acids (3), and c-hvdroxt

Oxazaborolidines

CHs

CHs

I

SiF4, BU4NF l-Pr2NEt

I

HO

,

CHs

CHs

95o/"

82o/o

Bu

(cocD2 DMSO

(r)-1 CHs

Ho'.| I- -i *c-c.H1.,$CoHs ?

\

4, cB, c6HscH3

93%ee

CHs

H QH ?

3

CHs (3S)- 1

5

*qnu$ g QoHs

/-'-i'\-c6Hs ( R I b \--N-a,

o/o A@ 4

96 94 6 o/" de

\.au 4

catalyzedby .:. r l,,rr'-1,3-butadiene

1,c2H5cN, -tto a

l: 'ocH3

I

4o l

Enantioselective reduction oftrichloromethyl ketones.s These ketonesare reduced by catecholborane(CB) in the presenceof 0.1 equiv. of the chiral oxazaborolidineI to trichloromethylcarbinols2 in 92-98Vo ee. These products are useful in themselves,

l

^AA"H v

b-c6H11 76o/o9e

lrccursor to steroidsand triterI - - lrrst stcPsinvolvesconversion t ' :n a-fluoro ketone 3 bY Swem bY the l c - : ibrrritre (CB) catalyzed cc. The final steP involves n I

RCOCCt3

CB, 1, CoHsCHs -2O - -78"

OH

I

R,

cct.

2,92 - 98o/oee

but particularly becausethey can be converted into optically active a-amino acids, a-aryloxy acids (3), and a-hydroxy esters(4), with inversion of configuration-

Oxazabomlidines

246

QC6H5ocH3-p

oH ""BlTi[f*" i ec6H5ocH3-p I Hso. | , , r I n- -cocl .,l ; ; * R - - c o o3H n^cct. I 2 cAN,DMF'H2oQC6H5OCH3-P--86-' 0%*

;;fr

n^coocH.

t E.J. CoreyandJ.O' Link, Tarahcdm, 2E.J. Coreyand J.O. Link, Az. S{r - I I 3 E.J. Corey,C.L. Cywin,andT. D R.rg aE.J. Corey,K.Y. Yi, andS.P.T.\lasr s E.J. Corey and J. O. Link, Tetrahedna 6 E.J. CoreyandT.-P.Loh, Am. Sa - I I

9H

R^coocu' 4

is AsymmetricDiels-Afuerreactions.6Theoxazaborolidinela,preparedbyrcaction (2:1) with removal of HzO' BuB(OH)z in toluene-THF of N-tosyl-(S)-tryptophanwith reaction same The reactions' tn-tiot"ftctive Diels-Alder a highly effective catalystin' lb' provides uut"wlitr BHr'THF at 23'

Oxazolidinones, chiral. Stereoselective anti'aldol rezta natural products.Evans el al.l har isobutyraldehydewith the chiral p-

syn-selective aldol reactions.r Surpr from dicyclohexylchloroboraneand to give the anti, anti-aldol 2 arrd obtainswith tlr diastereoselectivity

o

LAv

u''t

\<" orr-*.?,o I

1a

o il

oAru

1b,R=H

Y

CHs

CHs Br

*

"sr\

crAcr.

CHs Bzl

1a,R=Bu

t

"^ )-"ro

*

o

q^,la/'-"*

Y

R

o

i l i l i l ^ .

1 a ,- 7 8 ' 95o/o

b""' 2 = 96:4' @xo/endo R/S=200:1)

Br

lb,-40'

"')"'o

76q"

cHO (n,,,r,

anti, anti - 2e (78/o)

o ll

o il

o ll

oAN'\u"--'-t"-t \ , u+ eHt Ezl

^,,

o

cnf

from N{osyl-(S)-valine provides Significantly,a catalystprepared la or lb' the alducts formed by use of

(92oloee)

the enantiomerof

Under the same conditions.slm other chiral ethYl ketonessuch as

Oxazolidinones,chiral

!/

QC6H5OCH3-P

H-.)+

66-84"/" n

-;\ _^^OH vv

3

-

o

I E.J. 2 E. J. 3 E.J. aE.J. 5 E. J. 6E.J.

247

Corey and J.O. Link, Tetrahedron Letters, 33, 4l4l (1992). Corey and J. O. Link, Am. Soc., ll4, 1906 (1992). Co.ey, C. L. Cywin, and T. D. Roper, Tetahedron Letters, 33, 6907 (1992). Corey, K.Y. Yi, and S.P.T. Matsuda, ibid., 33,2319 (1992). Corey and J. O. Link, Tetahedron Letters, 33, 3431 (1992). Corey and T.-P. Loh, Am. Soc., 113, 8966 (1991).

H a

F.

n^coocH.

Oxazolidinones,

chiral.

Stereoselective

4

anti-aldol

reactions.

As part of a synthesis of polypropionate

natural products, Evans et al.t have studied the stereoselectivity of the reaction of

1,.,.,'rtrlidinela, preparedby reaction rc. l tlF (2:1) with removalof HzO, is s \lJcr reactions.The samereaction

isobutyraldehyde with the chiral B-ketoimide la, which has been shown to undergo syn-selective aldol reactions.a Surprisingly, the (E)-boron enolate, generated in ether from dicyclohexylchloroborane to give

the anti,

anti-aldol

reacts with isobutyraldehyde

and ethyldimethylamine,

2 and the syn, anti-aldol

2 in the ratio 84:16. Similar

diastereoselectivity obtains with the reaction of the isomeric B-ketoimide lb.

9

0

o

(CH3)2NC2H5 1) (c-Hex)2BCl, 2) (CH3)2CHCHO

,'',4^,\'Jl-'-'tt' " r ) ' l -''t

CHe Bzl 1a

o tl

o

o

oAtt

U

t

s'.

8 4 :1 6 anti, anti - 2a (787")

syn, anti - 2a

Br

2 (exo/endo=96:4, R/S=200:1)

tb

eH. CHs

tB=l

N ll>\r''cHo 4-\./,-

:

CHs

+

:

cHo ('1,,,o

-:J

|:':

il I' "' CHsN (92o/"eel

1. :, r rlrne providesthe enantiomerof

9

0

o

o

oArA-Jl.=-"t. :

'B=l

\rn3 1b

+

oAt'l

:

'B=l

eH. CHe

anti, anti - 2b (74V")

CHg 83:17

Under the same conditions,similar anti-selectivealdol reactionsobtain with several other chiral ethyl ketonessuch as 3.4

OxodiPerorlrrll Oxazolidinones, chiral

Asymmetric reduction of ketinirct found to achieve high enantioselecr of ltsuno, preParedfrom BHr and (S derived from (S)-valine,(12'31). is thc Like Corey's oxazaborolidinesderir cd

(c-Hex)2BCl (iHg)zcHcl-lo

o

89%

ezrol)/-cH3 CHg

amounts. The highest enantioseledtr aromatic ketones (as high as 88cr ct of N-t-butylimines of aryl ketones(gl

3

?? "

e,o-?-aYcH'

6H. 6H. cu.

dialkyl ketoneswith 1 resultsin l(l-,

+ Bzlo CH3 CH3

>30:1

anti,anti - 4

srn, anti - 4

cHsl

,CHI

c f----

N'B'o Asymmetricaldolreactions,sThechiralN.propionyloxazolidinone(1),prepared highly -diastereoselective steps from (1R)-(-)-camphorquinone' 'undergoes several in for improving the J'y"utlinity high of uo"uniugt "io)ttlJ aldol reactions with the

H

ilcut'r "o*"i'0,,,,",T:r*:Jl#,1*:*;','I:*:ilffi;:i!i:11?::'.::: Aarru facial preparedbY transmetalatto crystallization'lne oleled of 98-99% after one by (supported with diastereomericpunties (Z)-enolates chelationof intermediate *tin .ot consistent is exhibits also selectivity enolate silyl enol ether)'The lithium an X-ray crystalstructur";;;;;;o;d

r

CoHs

tc(cH3)3 c6H5

cH3

I D. A. Evans, H. P. Ng, J. S. Clark. anJ f, : D. A. Evans, J. S. Clark, R. Metternx-t-

(leeO).

I M. P. Bonnerand E. R. Thornton..{n I r B.T. Cho and Y. S. Chun,Tetrahednt

o

',,*5tt' O

OBzl

(rl) I lt -'--',cHs " + cH.^cHo x{

CHs

-X6 92:8

chiral highlydoubleasymmetricinductiononreactionwith(R)-2.benzyloxypropanol(matching chiral auxiliary provides ttOu"tiut removal of the pair, equation II)' Hydrolytic o' carboxYlic acids or alcohols'

Oxodiperoxymolybdenum (pyridir t lVcdejs reagent.MoOPH). (3R)- or (35) -3-HYdroryas4rtt by hydroxllatitto diastereoselectivity Thus this derivative 1 of L-aspanic I

with MoOPH Providesthe 3-hldror of this hydroxylation is highlv dcg wn-selectivity is obtained with t.}l! THF-HMPA. The highest anti-selcct then with LHMDS in THF.

Oxodipemxymolybdenum(pyridine)(hexamethylphosphoric -- *ex)2BCl

:-,:cHcHo 890./o

CHs lzO

triamide)

Asymmetric reduction of ketimines to sec-amines.4 of the various hydride reagents found to achieve high enantioselectivereduction of ketones, the oxazaborolidine I of ltsuno, prepared from BH3 and (s)-(-)-2-amino-3-methyl-1,1-diphenylbutane-l-ol, derived from (S)-valine,(12,31), is the most effective in terms of asymmetricinduction. Like corey's oxazaborolidinesderived from (S)-proline,I can also be used in catalytic amounts. The highest enantioselectivitiesobtain in reduction of N-phenylimines of aromatic ketones (as high as 88Vo ee). The enantioselectivitiesare lower in the casc of N-t-butyliminesof aryl ketones(80vo ee).Reductionof N-phenyliminesof prochiral dialkyl ketoneswith I results in 10-25% ees.

CH3 CH3 CH3 syn, anti - 4

cH.1

(1), prepared -f ',nr()nvloxazolidinone

tCHs

zCuH, KCuHt Nt^ro D H

. ..rJcrsoes highly diastereoselective -rir crvstallinityfor improving the iu:: rnolate or the titanium enolate,

NC^H^

.-'. r rth aldehydesto form syz-adducts r .:r:tallization. The observedfacial (supportedby r:r:rrcdiale(Z)-enolates alsoexhibits enolate r lithium l-hc :r-,:

a.rr-'Jl.-;r;,

-

:

R

c6Hs,.

o o H

. *"$" CHs

CHg

98-99:2-1

1 , T H F ,3 0 0

98%

H\...NC6H5

cuHu,. crHu (R),87%ee

NC(CH3)3

qH

1

cH3

Ha.NC(CHa)o

cuHu^cH. (R), 80oloee

I D. A. Evans, H. P. Ng, J. S. Clark, and D. L. Rieger, Tetrahedron,4g, 2127 (1gg2\. zD.A. Evans, J . S . C l a r k , R . M e t t e r n i c h ,V . J . N o v a c k , a n d G . S . S h e p p a r dA, m . 5 . c . , l l l ,

g66

( I eeO).

3 M. P. BonnerandE.R. Thornton, Am. Soc.,ll3, 1299(1991). 4 B. T. Cho and Y. S. Chun,Tetrahedron: Asymmetry,3,15U3(1992).

92:8 (matching R r-2-benzyloxypropanol chiral provides rl : :hc chiral auxiliary 1:-

Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide). (Vedejs reagent,MoOPH). (3R)' or (3s)-3-Hydroxyaspartates.t These amino acids can be prepared in high diastereoselectivityby hydroxylation of the enolate of N-(9-phenylfluorenyl)aspartates. Thus this derivative I of L-asparticacid on treatmentwith a basefollowed by reaction with MooPH provides the 3-hydroxy derivative, syn- and anti-2. The stereoselectivity of this hydroxylation is highly dependenton the base and the solvent. The highest syr-selectivity is obtained with LHMDS, LiN[si(cH1]12, as base in THF-DMpu or THF-HMPA. The highest anti-selectivity is obtained by treatment first with BuLi and then with LHMDS in THF.

Oxygen 1K. Kaneda. S. Haruna. T. Imanaka. \l l|r Letters, 33, 6827 (1992). 2 R. Ramasseul.M. Tavares.and J.-C. \lrctro

Pf=

Oxygen, singlet. Stereoselective photoorygenation of oxygen with allylic alcoholscan shou hr8 tivity. Thus the allylic alcohol (E)-l rer

1) base 2) MoOPH

-^\ -COzCHs CH.OTC- Y I NHPf

OH L-1

l- -cozcHs cH3o2c-Y

+

9H ;- -cozcHs

CHeOzC-

(2S,3R) - 2

(2S,35) - 2

LHMDS,HMPA

95"/"

BuLi, LHMDS,THF

7oo/"

I

NHPf

NHPI

Oxygen -Epoxi'dation.LTheepoxidationofalkenescanbeeffectedwithmolecularoxygen andanaldehyde.Isobutyraldehydeandpivaldehydearethemosteffective.Notethata metalcatalystisnotinvolved.Yieldsarehighestwhentheratioofalkenetoaldehyde is l:3.

+

I

H

o

Hoo' -'r 1o2, ccta Aar" l l - + cHr cH, cH. c ( SS t . i

(E)-1

1 1: 1 1 '.20

R.F. de Boer' and M'P' Alvarez'Tetrahedron rF.J. Sardina,M.M. Paz,E. Fernaridez-Megia, (1992). 463'7 Letters,33,

o6H13ACH2

o

)f

formed with 93 :7 diastereoselectivirI (82: 18) but onll' 31 :6E regioselectivity Photooxygenation of Gc-Gc bt or the azadigermiridine2 with tetraptn peroxides(3 and 4, respectivelv).

h v , 1 O 2 ,T P P ,

02 + (cHs)sccHo!gt#*'gg

Ar2Ge-GeAr2

coHo _ 61"/"

ArzG

1

c.",rX

(cH3)3CCO2H

*+:FaoO^"" O^"" Epoxidationofcholesterol.2Thisreactioncanbeeffectedwith02andisobuin CH2CI2 at room temperature'This tyraldehyde as reductant in quantitative yield I : I mixture. Addition of a (tetraphenylreaction provides the d_ and B-oxides as a porphrinato)nickel(ll)catalystdoesnotaffecttherate,butenhancesp-stereoselectivity

Qa:26).

Ar = C6H3(C2H5)2

H N vtes2ce/-beMes2

F

t\

+sz- Mes2Ge'

o-

Both 3 and 4 are reducedby tnphenll The 1,2-digermetene7 undergocr 1 (DCA) to form the I j dicyanoanthracene

Oxygen,singlet

251

1 K. Kaneda,S. Haruna,T. Imanaka,M. Hamamoto,Y. Nishiyama,and Y. Ishii, Tetrahedron Letters, 33, 682'7(1992). 2R. Ramasseul, M. Tavares,and J.-C. Marchon,J. Chem.Res.(S), 1O4(1992).

t-] ' ,f,

) / Oxygen, singlet. Stereoselectivephotoorygenation of allylic alcohols.t The ene reaction of singlet oxygen with allylic alcoholscan show high regioselectivityand also high diastereoselectivity. Thus the allylic alcohol (E)-1 reactsto form 2 and3 in the ratio 96:4,brtt2 is

9H LC

t,

+

.--- -COzCHs CHqOzC' Y I NHPI (2S' 3R) - 2

I

t'

cH. ro2,ccr4

l l cH.AcH,

-

I """Hoo- -j.f^.H,: f-"r' * a"r' Hoo-

cHs

cHz cHs

3

.rr lloer, and M P' Alvarez'Tetrahedron

oxygen n.. ..rrrbc effectedwith molecular that a Note effective' lc,-.Jc are the most aldehyde to alkene of g:.-' shcn the ratio

t L ^

cHz cHsfigoH

93:7

1:20 Ri

I

(s,R)-2

(s,s)-2

(E)-1

' 11 : 1

OH

OH

OH

OH

formed with 93:7 diastereoselectivity.In contrast, the acetateof (E)-1 shows high (82: 18) but only 32:68 diastereoselectivity. regioselectivity Photooxygenation of Ge-Ge bonds.2 Photooxygenation of the digermirane I or the azadigermiridine2 with tetraphenylporphine(TPP) as sensitizeraffords cyclic peroxides(3 and 4, respectively).

hv, lO2, TPP,

n

clcH2cH2cl,40oc 100%

Rr,celheRr,

.o

t Ar = C.11.16r'nu,,

+

(CHs)sCCOzH

coHo 61%

H N -M ,/\ Mes2ce-GeMes2 2 and isobu2.:. 'r can bc effected with Oz Thb temperature' ir! .: ll] CHrCl2 at room (tetraphenyla of I mixture. Addition -, c\' :'ri ratc. but enhancesB-stereoselectiviq

-9"Ar, Ar2Ge! b-d

t"='l-']"- Ar2Ge'. 'o,GeAr2 e5o/"

a

H (c6H5)3p -GeMes2 MeszGei tr o-o .N.

4

5 H N Mes2Ge( )cetvte",

o 6

Both 3 and 4 are reducedby triphenylphosphineto 5 and 6, respectively. The l,2-digermetene 7 undergoes photooxygenation in the presence of 9,108 in 80% yield. (DCA) to form the 1,2,3,6-dioxadigermine Jicyanoanthracene

oxygen, singl€t-Titanium(IV)

isopropoxide

si(cH3)

hv,1o2,DCA

zCaHs

l-l

/caHu

fu^' +

CHICN/CH2C|2

nrzcelenrz

o-o

Ar2Ge-GeAr2

'qn

(-\

n

\-,

e (3%)

I (80%) 7

si(cH3)3

tr-Aar. acids'3 Reaction of pyrrole-2of pyrrole-2-carboxylic water Oxidative decarboxylation in i-ProH or cH3cN and I and 2 with singlet oxygen as such acids carboxylic in high yield' (3: 1) results in 5-hydroxy-3-pyrrolin-2-ones

cHs

,cH.

/ \ \ CH3OOC--\*'^-cOon

1oz, (cH3)2cHoH/H20 ( 3 :1 ) ,

83"/"

cHs FH" /-\

cH3ooc*.,Ao H O T

I

r W. Adam and M. Richter,Tetrahedron l cttct

Ozone. Oxidation of RICH(OH)SiRJ to R'C( lanes are oxidized by ozone to the corrcrF attachedto silicon is an allyl group'

CHs

CHg

3

1

OH -,,\-si1cH.;rcH2cH:Cll2 csHtt-

CH30. CHsO.

'Oz'

H

/// \ \\\

cH3ooc--\*'^cooH

cH3cN/H20 ( 3 :1 ) .

92"/"

I

CHs

/-\

cH3ooc*.,Ao HO 'f CHs

o

-,\il -si(cH3)3 csH.r(

4 This reaction can be used to con\cn

1) BuqSnLi

6549 (1992)' I W. Adam and B' Nestler' Am' Soc'' f 14' cl\'.911m''

45't'4s8(1ee2)' ."0 *. o"J",l' i s 2M. Kako,r. Akasaka, (1ee1)' ' l' org, s6' 6e42 t ;.;.;;;"; "'tl c M' Baldino isopropoxide'15' 322' Oxygen,singlet-Titanium(IV) of vinvlsilanesin the presa"ntt', Vinylsilanes- sil)l ))""t ,t1t::::tt*ttion iigrt regio-anddiastereoselectivity' *ilvr epoxyalcohols*itr, p-silyl enceof Ti(o-i-pr)+ "tr-a. *ittt O' to providea first step an tnt '"u"'tn the as involves The conversion undergoesepoxidation' "Urtn """nt, which then

CHO

zi (ci.).sicN 3) BuLi

-------------.-79/o

-v

3-Atkoxy-1'alkenes - aatkort al in the presence of CH3OHNaOH' Prcs convertedinto a dimethyl acetal. rrhich reaction with ozone.

'U

si(cH3)3

v - |

t :

GeA12

o

a

,tcaHs

n12eelenr2

102, Ti(O-l-Pr)4

Ozone

7Oo/o

e (3%)

?.

si(cH3)3 Bu-.rZ\cHs

(cH3)3si, _o

-

"o)-!

59o/o

:'lic acids.3 Reactionof pyrrole-2water :cr rn i-PrOH or CHrCN and t h r r el d .

Bu I W. Adam and M. Richter,Tetrahedron Letters,33,3461 (1992).

cH3\-JcH3 t:l

""oo;o/Fo

Ozone. Oxidation of Rt CH@H)SiRj to Rl COOH.t a-Hydroxytrialkylsilanes and acylsilanesare oxidized by ozone to the correspondingcarboxylic acids,even when one group attachedto silicon is an allyl group.

CHg 3

OH |

crH'

--

1) os 2) s(cH3)2

c5H11co2H

81"/"-

si(cH3)2cH2cH:cH2

cH3O\---

{

"t'oor"o#o CHs

o crH,,,Asi(cHs)s

4

This reaction can be used to convert aldehydesto acids.

OH i ', t-:

-r57,458(1992)'

tr..

cHoll BuLi 3fr1,1'","3)

i

797o

pres".r *..otion of vinylsilanesin the diastereoselectivity' and n::. hrgh regioi ::.1!tronwith 02 to provide a B-silyl )c

os

nYsi(CH3)3 V

l

|

i

8oo/"

6\COOH l

|

\/

3-Alkory-1-alkenes - a-alkox! esters.2 This conversion can be effected by ozone in the presenceof CH3OH,I{aOH. Presumablyan intermediatea-alkoxy aldehyde is convertedinto a dimethyl acetal, which is convertedto the a-alkoxy ester by further reaction with ozone.

OBzl

c6^r")"'zcHz

U3

oBzr i,i:,jii ---.---------* cuH,,sAcHo

OBzl ,.. -o-Na* CoHrsI ocH3

za./" I o.

I

OBzl

I

c6H13^co2cH3

OBzl

Palladium(II) acetate. Cyclimtion of 4,6- and 5,74icnea 3) cyclize in the presenceof pd(OAcl: and indolizidinone 4, respectivell..in g

cH/"z\(cHr^col l,n=2

-SrlBi,?Ba-*coocH3 -

----rs%

(, 3.n-

cHsozc(cHz)6co2cH3 75o/o

I R.J. Linderman and K. Chen, Tetrahedron Letters, 33' 6'167 (1992)' 2J.A. Marshall, A.W. Garofalo, and R.C. Sedrani' Synlett, 643 (7992)'

Oxaspirocyclic addition to I J4icr, with p-benzoquinonein acetone-:rrtrc in a spirocyclic ether 2, formed bu an r addition of the oxygen function can tr which results in the spirocyclic erhcr J

.Y


(cHd3oH

1

1o1 ,aor"I eoton")r. ucl I

o1

A/ l

t

cl /\2

3 (>99% cis)

rc-

oBzl

{.--

I

,, ,.)-.--.O-ttta-

\.6n 13

|

OCH3 78YoI o"

I

OBzl

I

C5H13

Palladium(ID acetate. Cyclization of 4,6- and 5,7-dieneamides.l (ct., 16,261). These dieneamides(l and 3) cyclize in the presenceof Pd(OAc)2 and an oxidant (CuCl2/Or) to pyrrolizidinone2 and indolizidinone 4, respectively,in 85-90Vo yield.

CO2CH3

1-r'\ \-tf(

Pd(OAc)2,THF

OBzl

cHl'4(cH2)ncoNH,

**#g

1,n=2

2

O-coocH3 3, n=3

---------------85o/"

trl -*\,

F1.O2C(CH2)6CO2CH3

6 - ' - Ll ( ) 9 2 ) . -- ':1 (1992).

o

4

o

Oxaspirocyclic addition to l,3-dienes.2 Pd(II) catalyzed oxidation of the diene I with p-benzoquinonein acetone-aceticacid in the presenceof a base, Li2CO3, results in a spirocyclic ether 2, formed by an overall trans-addition to the diene. Overall cisaddition of the oxygen function can be effected by replacementof Li2COr by LiCl, which results in the spirocyclic ether 3.

(CH2)3OH

q-)

Pd(oAc)2, [o] HOAo,Li2CO3

^,.-/

860/o

AcO2 (>960/otrans) I

73"7.I I t

Pd(OAc)2, [Ol r-icr

o1 /\/

t

cl ,.'\/

l

3 (>99% cts)

Palladium(II)

ac€tate

Methyl enol ethers readily RCH2CHO - RCH:CHOCHj - RCH:CHCHO'3 prepared by reaction of aldehydes with (methyloxymethylene)triphenylphosphorane, and then with NaHCOT [(C6H5)3P:CHOCH3], when treatedwith Pd(OAc)z in CH:CN 'H2O (1 equiv.) are convertedinto a, B-unsaturatedaldehydes' and Cu(OAc)2

Pd(OAc)2,NaHCOg

tffittHo -srt C6Hs(CHs)aCH=CHOCHs c6Hs(cH3)4c

J CH.PTf "\K

z ,a d

t

)

+ H2c^cH2os I

-H

f'^Yott. cHz"''a

cHr

caHsN

ajt'^

c6H5(cH3)4cH=cHCHO

CaHsN Heck cyclization.a A short, efficient, and asymmetric synthesis of the anticancer (4) involvesN-alkylationof the optically activehydroxylactone alkaloid (S)-camptothecin 1 with the bromoquinoline2 to provide 3. This product undergoesHeck cyclization to the alkaloid 4 in 59% Yield.

Coupling of vinyl halides with oIIvinyl halides with allylic alcohols unJc mixture of products.Addition of silrer cr in a palladium-catalyzedcoupling of rrnr a y,6-enal, with retentionof confieur.ri

CHr:666"rO"

Et

Pd(ClAcll

&.rrt*rSO. KOC(CH3)3 DME

87"/"

rY*Y'' \,,'\Z\z

i

/-\ coHrs

I

Palladium-catalyzed coupling of a r rn presenceof silver acetateor carbonarcn configurationof the vinyl halide.

1 , c r 6+ 1 0 5 o

OH

cHtsAcrH,.,

A

CoHrs (S)-4,crp+42o

Heck-type coupling of allylic alcohols and enol triflates.5 This vinylation of allylic alcohols can be effectedby catalysiswith Pd(OAc)z and tri-o{olylphosphine (l:2) and triethylamine (excess) as base. The major products are conjugated dienols.

^tr

I

Arylation of allylic alcohok." ..\^t :rpe reactionto form p-aryl-a,p-unsarun P(CoHs): as catalysts and I equir'. of , :ompounds. Reaction of aryl iodides and allrlic r :ransferconditions(NaHCO:/BurNCl ) rcs

Palladium(II)

:H()

oTf

MethYl enol ethers readilY

rr r rr r t hvlene)triphenylphosphorane, r: ( I{.CN and then with NaHCO: r. r

Pd(OAc)2,Ar3P -t-\

+ H2C''

N(C2H5)3, DMF -CH2OH ---r"*-

Pd(OAc)2,NaHCO3 Cu(OAc)zHzO

= C H O C H g- -

,r%-

-r- cH"pH=cHcH2oH K cJr

-l

f

t

t a. 2 <-

. r l r \ a t u r a t e da l d e h Y d e s .

acetat€

)

aYott* "'z'uo' CHs

CaHsN

cHs

fr,

ar*oH__*a/Y' tu'to

caHsN r::rrtric synthesisof the anticancer rr ::r ()pticallyactivehydroxylactone il:il undergoesHeck cYclizationto

c.ru{

Coupling of vinyl hali.des with allyl alcohols.o Palladium-catalyzed coupling of vinyl halides with allylic alcohols under usual Heck conditions results in a complex mixture of products.Addition of silver carbonateand a phase-transfer catalystcan result in a palfadium-catalyzed coupling of vinyl halideswith a primary allylic alcohol to give a y,6-enal, with retentionof configurationof the vinyl halide.

CHr:6116tr.t +

Pd(OAc)2,Ag2C03 BuaNHSOa, CH3CN

coHrg cH2cH2cHo

CeHrs

I

Palladium-catalyzed coupling of a vinyl halide with a secondaryallylic alcohol in the presenceof silver acetateor carbonateresults in a conjugateddienol with retentionof configurationof the vinyl halide.

OH I

"tt =Acur,,

".rh, (S)-4,cp +42o

il rillates.s This vinylation of allylic c, .rnd tri-o{olylphosphine (1:2) and s .::f conjugateddienols.

Pd(OAc)2 AgOAc,DMF

CoHrg

75%

CsHrr

Arylation of allylic alcohols.E Aryl iodides and allylic alcohols undergo a Hecktvpe reactionto form B-aryl-a,B-unsaturatedalcoholsin the presenceof Pd(OAc)2 and P(C6H5)3as catalysts and 1 equiv. of AgOAc to prevent isomerizationto carbonyl compounds. Reaction of aryl iodides and allylic alcohols catalyzed by Pd(OAc)2 under phasetransferconditions(NaHCO3/BuaNCl)resultsin B-aryl aldehydesor ketones.

r

Psllrdiurlllr acetate

Palladium(Il)

Arl

/ -'oH

^,, Z-"t

+ unz

I R

Pd(OAc)2- P(C6H5)3 AoOAc,DMF

(5) in used for synthesisof 12-epi-PGF:" is corr which 4 provides (12,190) BINAL-H

Ar

60 - 90%

OH R (E)

Pd(OAc)2,NaHCO3

A. * cnrz\oH +i#-

?o*

O

nrcHzcuzAn

R

(s)-BINAL-H

exo-3

lithium catalysts with Pd(OAc)2' 2'altcynoatef and regioHydroacetoxylation of .^UnO:' high with to form (Z)-3-acetoxyalkenoates acetate adds to 2-alhynoites

7O"/"

g^g '

i

:

\'-rz

"l

: R3Si6

' stereosPeciflcitY

CH3-----.COzCoHs

+

LiOAc

"'tJ' 8fl:?b"Jfi --A* n"J

ta.r"u"u

effi[rer0 have reported an of alkenes' Larock and coupling (3) to Three-component an intermediate of three alkenesto form tntt"no't"liu''"()"Ott"' with cient one-step l' which couPles Ts the chiral cyclopentenol prostaglandins'fn" 'tuulnJrnti"n"t NaOAc' and NaI Pd(OAc)z' (2) in the p'"'"n""'of t-oc[n-3-one and ether ethyl vinyl this a t r o o m t e m p e r a t u r e t o a f f o r d t h e b i c y c l i c eseparated' n o n e 3 l n .AT 2number T o y i e ofanalogs l d a s a 2 . 3 .of .|m ixture "un be readily *t'itf' was exo-3 Pure of exo- and"'do-i'ot"'J' 1-alkenes' U' substitutionof Z Uy other bicyclic systemcan ot p"p^*a

HO_-

Pd(OAc)2' NaoAc'Nal

A

1 ) \

l

TBDMSO-

l

1

*

C2H5OCH:CH2 + CHz:CHCOC5H11 ,

oc2H5

72o/o

I P. G. Anderssonand J.-E. Biickvall' An '5
(reez).

nT. Jeffery, TetrahedronLeuers' 3l' 6611 tl' ' Idem, J.C'5. Chem. Comm, 324 (l99lt ( l()9l I ' ldem, TetrahedronLetters, 32, 2lll -fl! 'X. Lu, G. Zhu, and S. Ma, rbid', 33' ' C. Larock and N. H. Lee, Am' Srx l lJ' R.

"_-'^s O",,1'"u^" TBDMS6

O

3, cre-51o,2-3:1

Palladium(II) acetate 1'3-Bis(diphcryl a-Regioselectivearylation of cnol ea .light regioselectivity.However use of e t ravors a-regioselectivityin coupling of e

Palladium(Il)acetate-1,3-Bis(diphenylphosphino)pmpane 259

t-

used for synthesisof l2-epi-PGF2" (5) in 54% yield. Thus reduction of 3 with (S)BINAL-H (l2,l90) provides 4 which is convertedinto 5 by a Wittig reaction.

o,\

F

/-oH

R (E)

c

o tl eTCH2CH24R

(s)-BTNAL-H

exo-3 ,.1:.il\sts with Pd(OAc)2' lithium r\ l.icnoates with high regio- and

?""u o

tr

CHq i

43"

Aco

/

70%

: R3Si0

/

c[ .,nJ Leero have rePortedan effie 1.. l() form an intermediate(3) to :r.,'rcntenol 1, which couPleswith ii-.,! ,)i Pd(OAc)2,NaOAc, and NaI -)'h yield as a 2-3'.1 mixture 3 :. r,'.':rJ. A numberof analogsof this ! -\ ,'lhcr l-alkenes'Pureexo-3was

H::cHCoCsHrr

72o/"

, t.

-

Y

o I

\2

: oH :=\:.,.(cH2)3cooH \

""/"-"cutt''''

: 6H

: oH 5

'P.G. Anderssonand J.-E. Blckvall, Am. Soc., l14, 8696 (1992). 2 J.-8. Beckvall and P. G. Andersson,J. Org., 56, 2274 (1991). 3H. Takayama,T. Koike, N. Aimi, and S. Sakai,J. Org.,57,2173 (1992). a D. L. Comins, M. F. Baevsky, and H. Hong, Am. Soc., ll4, 10971 (1992). 5 E. Bernocchi, S. Cacchi, P. G. Ciattini, E. Morera, and G. Ortar, TetrahedronLetters, 33, 3073 (7992\. 6T. Jeffery, Tbtrahedron Letters, 31, 6641 (1990). 7 ldem, J.C.S. Chem. Comm., 324 (1991). " Idem, Tbtrahedron Letters, 32,2l2l (1991). eX. Lu, G. Zhu, and S. Ma, ibid, 33,'7205 (1992). r { ) R . C . L a r o c k a n d N . H . L e e ,A m . S o c . , 1 1 3 , 7 8 1 5 ( 1 9 9 1 ) .

-CsHtt

ll

J .

Pd(OAc)2' NaoAc'Nal

54o/"

",,/"'.cuH'''

\2

H

borcuHu

(C6Hs)3P(CH2)4COOHBr,-

DASE ....................................................................

a' ...................................._

Ho..

t::: L : - _ +

I

o

Palladium(Il) acetate-1p-Bis(diphenylphosphino)propane, Pd(OAc)2-dppp (l:l), f. a-Regioselective arylation of enol ethers.t This Heck reaction usually shows only slight regioselectivity.However use of a bidentatephosphine(a chelatingligand) greatly favors a-regioselectivityin coupling of aryl triflateswith butyl vinyl ether (2) in DMF.

Palladium(Il)

acetate-l-Octyl

isocyanide

I BUO O.CHz I

I l'Dl

z\-\

+ *tfoeu

q)

/l \ , \l

N(c2Hsl

ll

t

.t

l

.t

l

oY'cH3 I

l 1 "+ . o . l I

Qr|o/o

J "

(ilr)

"rrtyo

I +

cH3cH=cHoczHs

100" 85o/o

\).)

/cH"

-l\r'"\/

cH3 cH3

80"

+ ,u4oeu

90/"

\2

CHz{.

(rv) (cHd3si-Fl-/-tt,

oY"t'

oTf

t ^ , , fAftnt

cHz:1

(cH3)3Si-Fi-d/ cH3 cH3

r-\r'\/ "\-\

Intramolecular bis-silylation does not occ by chains of more than four atoms. TtEr undergo intermolecular addition of disilr the alkene bears an a- or B-group (egu:

[-]-"' \/

I W. Cabri,I. Candiani, A. Bideschi,andS. Penco,J. Org., 57,1481(1992). Palladium(II) acetate-t-Octyl isocyanide (1,1,3,3+etramethylbutylisocyanide). Bis-silylation of allqnes and alkenes.t Palladium(Il) acetate in combination with a large excessof a l-alkyl isocyanidecan effect bis-silylation of terminal alkynes by otherwiseunreactivedisilanes(equationl). Intramolecularbis-silylation of an alkyne is also possiblewith this catalyst (equationII).

This reaction can provide a stereos.L isopropoxydisilylethersof allylic or honx oxidized to triols.

0Hs / CHz4. ) r-PrO(CH3)25i-rsbd cH3 cH3 1) H2O2, KF, KHCO3 2) Ac2O, N(C2H5)3 9O/"

Ac(

Pd(OAc)2

(

(CH3)3S|-S|(CH3)3 l ) + C6H5-11

XXruc 82L

(CH3)3S;. CoHs

.S;(CH3)3 H

(ZlE = 96: 4l

cH3pH3 (cH3)3si-si-o (ll) (cHs)ssi----:-----J

CH3 ,CH3

t(cH3)3sil2c\.,si.o alvo

\_J

This intramolecularbis-silylationhas been extendedto terminal and 2,2-disubstituted alkenes.1,2-Disubstitutedalkenes do not undergo this reaction. The substrates,unsaturated disilanyl ethers, are preparedby silylation of allylic and homoallylic alcohols.

r-Pro(cH2)2si. -c6H5 ,0

Palladium(Il)

CHe

I Hso*

acetate-t-Octyl

isocyanide

261

Intramolecularbis-silylationdoes not occur if the disilane is tetheredto the double bond by chains of more than four atoms. Therefore, it is not surprising that alkenes do not undergo intermolecularaddition of disilanes.The bis-silylation is stereoselective when the alkene bears an a- or B-group (equationsIII and IV).z

l-

Pd(OAc)2

V*c

(ilr)

(cH3)3sicH2 _.cHs \ /-\ (cH3)2si\o2 (cisltrans= Z:93)

"rruy LI

15."

(lv)

,'-\,,'\ \

(cH3)3sicH2\ , \ (cH3)2si.oA"",

)

(cisltrans=96:4)

oY"t'

fttt'

\

C H_e 4 r_CHs (CH3)3si-rSr-5/ cH3 cH3

This reaction can provide a stereoselectivesynthesisof 1,2,4-triols.aThus use of isopropoxydisilylethersof allylic or homoallylic alcoholsresultsin adductsthat can be oxidized to triols.

\2

1481(1992). 'r{:r.tmethYlbutYl isocYanide). in h;nrtll) acetate combinationwith ,r:-'ilvlationof terminal alkynesby lc.Lrlarbis-silylationof an alkyne is

Cltz:1

cH3pH3 r-PrO-Si---r.-

/cH"

gH.

1) H2O2,KF, KHCO3 2) Ac2O,N(C2H5)3

-

AcO

coHs

OAc

si(cH3)3 H

(z/E = 96 :4)

'

@isltrans=5:95)

Aco/-yl

9O7o

cH3)3si\

--CHs

r-1 (cH3)2si\o2

r-PrO(CH3)2Si-rSFd cH3 cH3

r-PrO(CHdzSi:,.,

r-Pro(cHj2si,
(cH3)2si\o2-c6Hs

CH3 ,CH3 qi

CH3)3Sil2COz"''O

\J |cr.] lo tcrminal and 2,2-disubstituted ::rr rcaction.The substrates,unsat,.: .rllvlic and homoallylic alcohols.

oxidation 70%

(cH3)3si?--csHs AcO

l

)

OAc

l

coHu OAc

262

Palladium(Il)acetate-Tfiphenylarsine

f Y. Ito, M. Suginome, and M. Murakam|J. Org.,56, 1948(1991). 2M. Murakami, P.G.Andersson, M. Suginome, andY. Ito,Am.Soc.,1f3,3978(1991). Palladium(II) acetate-3,3/,3//-Phosphinetriyltribenzenesulfonate CIPPTS). Cross-coupling in homogeneous aqueous medium.l A catalyst I prepared from Pd(OAc)2 and TPPTS (5:1) is soluble in H2O-CH3CN or H2O-ethanol. It is highly effective in various reactions that have been effected with Pd(OAc)2. It is effective for inter- and intramolecularHeck reactions,for coupling of vinyl or aryl iodides with terminal alkynes, and for allylic substitution.

.,---.'...CH=6111

1 aoo

+cHe=cHCooczHs #

(,

4Y' r

i l r $..-CH2CH=CH2

i

l e7o/o

f--yr\.r\-COret

(,

or tosyl. The alkyne can bear a r.anq the caseof unsymmetricalalkvncs.r atom. The reaction shows 2:l regrc with silylalkynesfollowed bv desilr!

<'"Y---1"cHs | , J \Aru-

H

H CoHs + H c = c c A H R" +

\_.^\lz.\l

8O/"

Palladium(Il) acetate-Tripbergll Indole synthesis.t A ne* apg with internal alkynes catalvzed br (or BuaNCl) and 5 equiv. of K;(I

[-\-/\__-/

B icyclization-anion capturc.: tandemcyclization-anioncapturepro tormate, triethylamine,or KICO,

'J.P. Genet,E. Blart,and M. Savignac, Synleu,7l5 (1992). Palladium(ll) acetate-Triphenylarsine. ArBr - Ar-Ar.t Bromoarenescouple to biaryls in DMF at 140' in the presence of Pd(OAc), and triphenylarsineas catalystsand 1 equiv. of a trialkylamine.Iodoarenes couple under the same conditions but do not require triphenylarsine.

[aY''

(4,, c6H5so2-il) cH.

ocH3 Pd(OAc)2,(C6Hs)sAs D M F ,B u 3 N , 1 4 0 "

CnslzcHz g..\r-sozAr t l

cH"o2\-?

rY'

cH,

ra)Y ",O-'-

Pd(OAc)2 DMF, Bu3N, 140'

cn/v

CHs 'M. Brenda, A. Knebelkamp,A. Greiner, and W. Heitz, Synlett, 809 (1,997),

a-Allcylidene cyclic ethen.i ..1 rnvolves conversion of acetylenic el followed by Pd(Il)-catalyzed crosso

Palladium(Il)acetate-Tfiphenylphosphine

cr...)t)l). h r,': Soc..113'3978(1991)' lre nesulfonate (TPFIS)' A catalYst1 PreParedfrom Jtum. ( \ H2O-ethanol'It is highlY or ll Pd(OAc)2' It is effective \\ith N:-.: or aryl iodideswith vinyl of o-:,r:rs

263

Palladium(Il) acetate-Triphenylphosphine. Indole synthesis.r A new approachto indoles involves annelation of o-iodoanilines with internal alkynes catalyzedby Pd(OAc)r-(C6H5!P (1:1) with 1 equiv. of LiCl (or BuaNCl) and 5 equiv. of K2CO3 or Na2CO3(equationI). R1 can be H' CH:, Ac,

R2 NHRl

(t)

I

-lll

Pd(OAc)2,P(C6Hs)3 LiCl,Na2CO3 DMF,1OO" 60 - 90o/o

I

^'-.,,\.r\-co2Et I

R3

J

of tosyl. The alkyne can bear a variety of groups:alkyl, aryl, alkenyl, or trimethylsilyl. In the caseof unsymmetricalalkynes,the more bulky group is locatednealer the nitrogen atom. The reaction shows 2:1"regioselectivityeven with 2-pentyne.The facile reaction with silylalkynesfollowed by desilylation,providesa useful route to 3-substitutedindoles. Bicyclization-anion capture.2 Strained bicyclic systems can be prepared by a tandemcyclization-anioncaptureprocessusing a Pd catalystin combinationwith sodium

,CHS

t

.

'

-

//,r=--C6H5

formate, triethylamine,or K2COr

presence ;,'r tr itl DMF at 140" in the lodoarenes I -.:uir. of a trialkylamine'

Br

Pd(OAc)2, (C6H5)3P KOAC,80"

,.*",,

c6Hsso2''N)

c6Hsso;

lL::. lriPhenylarsine'

ocH3

cH.

cH,

cftycHz ,' \r-sozAr

untu

CHg rinlr'u, 809 (1991)'

5O/"

a-Altqli.dene cyclic ethers.3 A route to substituted tetrahydrofurans or -pyrans involves conversion of acetylenic alcohols such as I to the lithium alkoxide (BuLi) followed by Pd(Il)-catalyzedcross-couplingwith an alkyl or aryl halide.

Palladium(II)

acetate - Tfiphenylphosphine

1) BuLi 2) Pd(OAc)2(C6H5)3P 3) c6Hsl

OMOM cH3o-Y\Br l l |

C-O-cHc6Hs ro

60/"

+ c

\Z\oMoM I OMOM 1

oc=,,

/t\r-\ i l l \/'-ci

45o/"

,rcuHt 'eu

OMOM

(cHdsoH

cH3o

available Decarboxylation of allylic aryl carbonates.a These carbonates (1) are allylic an of by addition followed pyridine in triphosgene with by reactionof a phenol alcoho|(7|-govoyield).TheyundergodecarboxylationwithPd(oAc)2(5mol%)and (C6H5)3P(20 mol %)inTHF or CHzClz at25" to form allylic aryl ethers(2)'

Pd(OAc)2, (C6Hs)3P THF, 25"

cH Z-'''.oco2c6H5

87o/o

cH3o _ i

1

-\AoA"\;"),-l

63/"

Coz

cn;r'"""ocaHs 2

CHr l 74o/"

r-\-o#\ t t i t'?cr/V

l

o'l#3'"':,.ffi.,cHsq'

l

CHs

with 1,3-dienes Arytation of l,3-dienes.s Pd-catalyzed coupling of aryl iodides 1,3-diene. original the of geometry the of regardless resultsin (E,E)-4-aryl-1,3-dienes

Pd(OAc)2, (C6Hs)3P,

c6H5l + cn/vcoHrsAs911e!I'7L

Heck tetracyclization of dieryt P(C6Hs)3,K2CO1 (2 equiv.). and .\ product 2 (52% yield) togetheru'ith

c6HrA..\.-coHrs

coupling Alltylbenzoquinones via a Heck-type coupling.6 A palladium-catalyzed benzoquinones to route convenient a provides alkene a terminal with of bromobenzene coupling of bearing a long-chain alkyl group, such as masanin (5)' Thus Heck{ype Hydrogenationof the bromobenzeneI with 9-decene-1-olfurnishes 2 in 49Vo yield' undergoes wittig 2 followed by Swern oxidation furnishes an aldehyde (3), which oxidation (Ag2CO3) olefinationto (z)- .This productwas convertedby deprotectionand into the quinone 5.

Pd(O^ch K2Cq. Agx

CHz

tl

Br-

o

Palladium(II)

| 'nci

*

|cHcuHt

acetate - Ttiphenylphosphine

Pd(OAc)2 P(C6Hs)3

(cH2)7cH2oH

cnl\

49o/o

OMOM

2

OMOM 1 (cHa)noH

(cH2)ecHo

1) H2,Pd/C CH3O 2) DMSO,(COCD2 82o/o

h.r( iarbonates (1) are available f,,'r ,*cd by additionof an allYlic p- .r irh Pd(OAc)2(5 mol %) and rr

OMOM

OMOM

,llrlic arYl ethers(2).

OMOM

Coz

,",-otu"u

63/"

2

(z)-4 CHq

t -

-,'-.-ao>a\ t

i

"r'" /V tr: I :

f_i

l

l

arvl iodides with 1,3-dienes rr of the original 1,3-diene.

1 ) H B r( 9 3 % ) 2) Ag2COs(91%)

5 Heck tetracyclizption of dienynes.T Treatment of the dienyne I with Pd(OAc)2, P(C6H5)3,K2CO3 (2 equiv.), and AgNOr (1 equiv.) in CH:CN results in the tricyclic product 2 (527oyield) togetherwith the tetracyclicproduct 3 (llVo yield.)

-

c C6HuA"\-'CoHrs

'

couPling \ palladium-catalYzed benzoquinones to rinicnt route . 1 !, Thus Heck{YPe couPling of I ::: J9'/r yield. HYdrogenationof rhr.:- t3). which undergoesWittig Irn: ,:cctionand oxidation (AgzCOl)

Pd(OAc)2,P(C6H5)3 K2CO3,AgN03,CH3CN,

2 (527")

3 (10%)

Palladium(II)

acetate - T|iphenylphosphine

5 Treatmentof the related dienyne 4 under the same conditionsprovides tetracYcle ir TlVo yield (isolated).

Pd(OAc)2, P(C6H5)g A9NO3, CH3CN,

cH3ooc

coocH3 coocH3

Polycyclimtion of dienynes." Trce triphenylphosphineand a base(Heck corxlrt and trans-trienes2. At 130' and u'ith K:Cl Diels-Alder reaction to 3.

CHgOOC

71o/"

CHu l l Bt"^)

o

PdrOAc

4

5

*tctr

bromide Heck polycyclization of dienynes.s Treatment of dienyne I bearing a vinyl carbonate group with catalytic amountsof Pd(oAc)z and P(c6H5! and 2 equiv. of silver e 2 in 60Voyield. A similar reaction in CHrCN at 80" resultsin the tricyclic cyclohexadien ring (3 - 4, equationl)' a cyclohexane to group is attached dienyne the occurs if

CHr

i l Pd(OAc)4, P(C6H5)3 Ag2CO3, 80'

CHs CHs

cH3ooc a

cH3ooc

CHs CHe

cH3ooc

ocH3

QHs : 6,^--2CH3

I ocH3

I

Under the same conditions. the en d tricyclic 5 in >95Vo ee and in 67n rsrrlr Stille coupling of 2-carboxyahyl cs presenceof Pd(OAc)2/P(CoHsh(l:lf or Pd

couplewith vinyl-, allyl-, and alkvnrl(tntr

palladium(Il)ac€tate_Tfiphenylphosphine

i . :Jrti()nsprovidestetracycle5

coocHs

267

Polycyclization of dienynes.e Treatment of the enyne l with pd(oAc)2/ triphenylphosphineand a base(Heck conditions)resultsin cyclizationto a mixture of crsand trans-trienes2. At 130" and with KzCO-:, only trans-2 undergoesan intramolecular Diels-Alder reaction to 3.

coocH3

Pd(OAc)z/P(CoHs)s

5 dr- - r nc I bearinga vinyl bromide ). ,-.: I cquiv.of silvercarbonate 2 ..- ,,rt,, vield.A similarreaction nr 'r:t! (3 - 4, equationI).

CH3CN,Ag2CO3,80.

1, E = COOC2H5

x

K2CO3,

CHs

,coocH3

CHa

3ooc \

ocH. coocH3

--

-^ --l

"CHt X

.cHs QoHs

ocH3

9H' 6.^..*;CHs

I ocH3

67%

n1 ^-^Y

=Y -

ol ?c", "'"r" cHs

5 (>95%ee) Under the same conditions, the enantiomericallypure dienyne 4 cyclizes to the tricyclic 5 in >95Va ee and in 67Vo isolated yield. stille coupling of 2-carboxyethyl enor triflates with organostannanes.tu In the presenceof Pd(OAc)2/p(CuHs):(l:2) or pd[p(C6H5)j]4, the enol triflatesof p_keto esters couple with vinyl-, ailyl-, and alkynyl(tributyr)stannanes, but not with phenyltributyrtin.

Palladium(II)

acetate/Tiiph€nylphosphine - Hexaalkylditin

pd(oAc)2 -

+ cH2:cHSnBut -r19oH:b*cHr=cHY

rro^/

COOCzHs

COOC2Hs

o tl

o

r)

Tfo

rY.' \A*'

()

,:t

o

o

( )-)-t

o

+ CH2:CHSnBu3 6O"/o

)--)

'R. Grigg,A. Teasdale, and V. Sndhe

1R.C. l,arock and E.K. Yum' Am. Soc., 113' 6689 (1991)' 2 R. G.igg, V. Sridharan,and S. Sukirthalingam,TetrahedronLetters,32, 3855 (199r). 3 F.-T. Luo, I. Scheyder,and R.-T. Wang, J' Org', 57,2213 (1992)' a R. C. Larock and N. H. I'ee, Tetrahedron Letters' 32' 6315 (1991)' 5 T . J e f f e r y ,i b i d . , 3 3 , 1 9 8 9 ( 1 9 9 2 ) . 6J.S. Yadav, V. Upender, and A.V. Rama Rao, J' Org',57,3242(1'992)' 7F.E. Meyer, P.J. Parsons,and A. de Meijere, ibid'' 56' 6487 (1991)' 8 F. e. ueyer, J. Brandenburg, P. J. Parsons,and A' de Meijere, J ' C' S' Chem' Comm'' 39o (1992)' e F. E. Me er, H. Henniges, and A. de Mierjere, TetrahedronLetters' 33' 8039 (1992)'

Palladium(Il) acetylacetonate-Tri Hydrogenolysis of allylic lotr and Bu3Peffectshydrogenoll-sisof e to afford 1-alkenes.Allylic formatcs without use of ammonium formatc

RCH=CHCHzORI + Fl@

r0 I.N. Houpis, ibid., 32, 6675 (1991)-

Palladium(Il)

This hydrogenolysis can be uscd t systems.

acetate/TFiphenylphosphine-Hexaalkylditin'

Couplingofarylandbenzylichali.des.Grigglhasextendedtheinter-and catalyzed by 1'3-dienes to form bromides of vinyl coupling intramolecular halides benzylic and aryl of to coupling (13,8\ Pd(OAc)z-triphenylphosphine (1 equiv')' (Bu3Sn)2 or by the combination of a Pd(0) catalyst and [(CH3)3Sn]2

r-l ecto,3;l;(!Ji#')' r,s --ro%

('' 'Y) 60v"

ri\/\N"^\"''

\)

5o,"u"u

pSiR3 6g. a " , f,^\f_^ I | HCOr/?

(CHz)n

pdro !

n = 1 n=2

\).2

<\a-o \-\-J-

'sorcuHu

(l)' This coupling has been used for synthesis of the alkaloid hippadine

n=1 n--2 M. Kasad T. Mandai,T. Matsumoto,

acetylacetonate -Tributylphosphine

Palladium(II)

|: t.

al cHr=cH'l>"/ COOCzHs

A a -;** m+ O a ol1:f" ,$-\" ,$-\" qv,

.:(

.:(

I R. Grigg,A. Teasdale, andV. Sridharan, Tetrahedron Letters,32,3859(1991). I l r / , rrt'r.t,32' 3855 (1991). rt: [<

qqll q9l).

s- r:11(1992). *.- r1991). (1992)' :,:', ./ (. S.Chem.Comm.,39O t . . I . t t c ' r s , 3 38' 0 3 9( 1 9 9 2 ) .

lh\ lditin. itS has extended the inter- and , :,\rm 1,3-dienes catalYzed bY n! ,,t aryl and benzYlic halides Sr: {,r (Bu3Sn)2(l equiv.).

Palladium(II) acetylacetonate-Tlibutylphosphine, pd(acac)2-Burp (1: l). Hydrogenolysis of allylic formates.l The Pd(O) catalyst generatedfrom pd(OAc)2 and Bu3Peffectshydrogenolysisof allylic acetatesor carbonateswith ammoniumformate to afford 1-alkenes.Allylic formatesare also convertedto 1-alkenesbv this pd(0) catalvst without use of ammonium formate. to(o)

RCH=c11g11r9R1+ HCooN"o

'

RCH2CH=CH2+ co2

This hydrogenolysiscan be usedto control the ringjunction in hydrindaneand decalin systems.

6P" PS|R3 66" PS|R3 69" pSiR3 Pd(o),25" a.^--l-{ -.----------_ (cHdn + ll | | (CHdn | | | (cHdn \-'Y \-,iV HCO2/'#

/^-lX

/^-lX H

H

n=1 n--2 69.

pSiR3

82o/"

:

13o/"

600/"

:

38o/"

/^-F{ (cHdn ---------------_/^-{X (CHdn

| | HCO2""\Z\-'z v

'yN

'sorcuHu

(l). c ,lk.rloid hiPPadine

69. pSiR3

6g. PS|R3

I

I

v1-r

f

r

f

+ ll t.--f-J |

H

\

H

n=1

57o/o

|

38/"

n=2

85o/o

|

6o/o

lT. Mandai,T. Matsumoto, M. Kawada, and J. Tsuji, J. Org., 57,1326 (1992).

(CHz)n

270

PentacarbonYlimn

(R)-( - )-Pantolactone, 16,269-27 O' cyclopropanation of styrene can be Asymmetric cyclopropanation'r Asymmetric Rh2(OAc)a or rhodium(ll) octanoate as effected with chiral vinyl a-diazo esters with catalyst.Theproductscanbeconvertedintoopticallyactivecyclopropylaminoacids.of is the reagentof choice' severalchiral auxiliaries,(R)-(-)-pantolactone

o

cH".9H3

? h

CoHs..-Z#O."VO ll N

2

.?4-1. c6Hu""n

[l

O

I

22v"1 I

HCr.H2N"X'cooH be preparedin 15-957o de by (S)-a-Hato esters.z These a-halo esters (3) can (2)' reaction of a-haloketenes(1) with (R)-pantolactone

l - '

Br

o no1A6 121 -' \ _a

(oH3)2NC2H5 t-Bu. 5

THF -78"

l-\

'rl\

"\\

H'\ctt' 1

I B.E. Eaton,B. Rollman,andJ.A. Kadi

3113$1",-v#

+CoHsCH:CHI:;i-

(1 R,2R, 89o/ode)

? ll t-bu-.../,,^\nt

i

//" Cn"'t"'

--*F":o Br' 1

o

o

l r l l t_Bu_,\o_. o I \ - / Br

Pentafl uorophenyl diphenylphqf

Prepared by reaction of diphcnrl imidazole. Coupling of amino acids tritL t be effectedwith the phosphinate( I c Yields are generally )907o, and thc r be used for solid-phasepeptide slntl rS. Chenand J. Xu, Tetrahedron Lenat

Periodinane (l) of Dess-Martiq 12 Full details for preparationof thrs Since explosions have been rep
I D. B. DessandJ.C. Martin.An. Sa . I

3 (87"/"de)

Theproducts(3)canbeconvertedintoa-aminoacidsbyazidation(inversion,70% yield) and saponification('72Vaee)' Letters,32,6509(1991). l H. M. L. Daviesandw. R. cantrell,Jr.,Tetrahedron (1992)' 6799 2 T. Durst and K. Koh, Tetrahedron Leuers' 33'

PentacarbonYliron. [4+ 1]Cycload.dition; 2,5'd'iallqlcyclo-3-pentenones't

In the presenceof Fe(CO)5

orFe2(Co)g,diallenes(l)reactwithcarbonmonoxidetogive2,5-dialkylidene.3cyclopentenones2 in surprisingly good yield'

( - )-8-(4-Phenoxyphenyl)meotho|. Asymmetric synthesis ol dihtJr.t quently as a chiral auxiliary'. but tl auxiliary for enantioselectivereactlo reagents. Thus 2, prepared b1 rcrri the chloroformate of I reacls \rtlh I acidic deprotectionprovidesthe dihr< to a chloride [P(C6Hs)r and NCSI t

methanol cleaves the chiral aurilien sametime effectscyclization lo form

( - )-8-(4-Phenoxyphenyl)menthol

l--\ l, 1:,,panationof styrenecan be \i - ,'r rhodium(Il) octanoateas c::'. - crclopropylaminoacids.Of rii-nt of choice.

/f Cn""^",

"r\

+ co

H-\CH,

j#- "ua? ("" H

6

H

1 ' B. E. Eaton, B. Rollman, and J. A. Kaduk, Arz. Soc., ll4,

6245 (lgg2).

o n

C6Hut"

(1 R,2R, 89o/ode)

22%l V

HCT.HTN,K,COOH

n

.. preparedin 15-957a de bY

Pentafluorophenyl diphenylphosphinate,

S -OC6F5 tft. (caHs)z/' Prepared by reaction of diphenylphosphinicchloride and pentafluorophenolwith imidazole. coupling of amino aci.ds with a-amino esters.t This coupling to peptides can be effected with the phosphinate(l equiv.) and diisopropylethylaminein DMF at 25". Yields are generally )90Vo, and the reactionis racemizationfree. The reagentcan also be used for solid-phasepeptide synthesis. fS. ChenandJ. Xu, Tetrahedron Letters,32,671l(1991).

't,

o = a a

Hor.,z\6 \J

121

79"/"

o 't"

l

l

t

a

"Ao-. r \ Br

l

o l

Periodinane (l) of Dess-Martin, 12.378-379. Full details for preparationof this tetravalentiodine compound are now available.r Since explosions have been reported in the preparation, the directions should be followed with care. Moreover, the reagentis sensitive to moisture, which converts it into iodosylbenzoicacid, also reportedas explosive.The periodinaneoxidizes primary and secondaryalcohols rapidly and efficiently to carbonyl compoundswithout further oxidation to acids. Benzylic and allylic alcoholscan be selectivelyoxidized. It does not reactwith sulfidesor vinyl ethers.The iodine-containingby-productcan be removedby hydrolysis to 2-iodosylbenzoicacid. I D. B. DessandJ.C. Martin, Am. Soc.,ll3, 7277(1gg1).

3 (87"/.de) xr.i. by azidation(inversion,70%

', -r:. 6509(1991).

:

ln the presenceof Fe(CO)5 rd\. r.rr.jr' to give 2,5-dialkylidene-3-

( - )-8-(4-Phenoxyphenyl)menthol. Asymmetric synthesis of dihydropyridones.t g-phenylmenthol has been used frequently as a chiral auxiliary, but this derivative (l) is more effective as the chiral auxiliary for enantioselectivereactionsof N-acylpyridinium salts with organometallic reagents.Thus 2, preparedby reaction of 4-methoxy-3-(triisopropylsilyl)pyridine with the chloroformate of I reacts with the Grignard reagent3 to give an adduct that on acidic deprotectionprovidesthe dihydropyridone4 in94Vo de.Conversionof the alcohol to a chloride [P(C6H5L and NCS] followed by treatment with sodium merhoxide in methanol cleaves the chiral auxiliary as the methyl carbonate(94% yield) and at the sametime effectscyclization to form the chiral bicyclic dihydropyridones in g4vo yield.

( -)-8-(4-Phenoxyph€nyl)menthol

I D. L. Comins and H. Hong, Am. 9x

?c".sili-er1"

/-,n l t l

*

\N*'

?",ru--lillSl_,,. 65%-

erMglcHr).oActt,

CO2R* 2

(S)-Phenylalanine dimethylamilc.

3

o -\-s'1'-t4'

Ncs (89%) 1) P(C6H5)3. 2) NaOCH3,CH3OH(84olo)

..f,uj

o

il R*o ocH3 (s4"/.)

CO2R*

s

4 (94% de)

(+)asymmetric synthesis of the alkaloids This chiral product 5 was used for elaeokanineA(9)and(*).elaeokanineC(8).Thustheanionof5reactswithdimethylc a r b a m y l c h l o r i d e t o t o r m m a i n l y t h e t r a n s . a m i d e 6 ( 9 7 : 3 ) , D e s i l y l a t i o n ( o x agroup licacid, (967o) provides 7' The dimethylamide CH3OH, 96%) andcatalytic hydrogenation equiv') with PrMgCl catalyzedby cecl3- (2.5 is convertedto a propyl t<etoneuy ieaction in (+)-9 provides (+)-8 with NaOH in CHrOH to give (+)-8. Finally, treatmeni of

(R)- and (S)-a, a -Disubsr'rtuta acids of this type are known. ther A number of routes are knor*'n to this type, but the most practical rrr racemic N-acylated derivativesof rl (S)-phenylalanineresidues.Thc du by crystallizationor by flash chror acid (2) is converted to the l.-1(CDll as 1,l/-carbonyldiimidizole

amine 1 (DMF, 50) to form nao by crystallization or chromalosrapf cleaving the chiral amide, but thc n 80" (SchemeI).

Rl

3O7o yield.

o

o

o

(cH.),NYVsi(r-Pr)3 l]8f.,,*"o",, a2Yo

- cDl

*f,*taot3 2

..'\N/

6(97:3) 5

o o H

1) (HOOC)2,cH3oH (96%) 2) Hz, PtOz (96"/o)

-cooH

\l--t

(cH3)2N

PrMgCl,

s'

CeCl3

l

66"/"

)

[o cH4 l t t Rt>,..,J\N-\-,,

n'lf,r".fi. o (R)4

I t,^.r Jzrrto

7

s$'

o

o o H

Pr

(+)-8

NaOCH3,CH3OH

Pr

)-.-z\ t

l

D(+)-9

Rl .,cooH

fi|tt"ot' (R)-2

(S)-Phenylalanine dimethylamide

273

' D. L. Comins and H. Hong, Am. Soc., ll3, 6672 (1991). .

--F. -78'

-CaHs 65't

(S)-Phenylalanine dimethylamide, -HzN^,J,.,,r,"r.,,

(1)

y o

r.

* " ,

o .\.s'1i-e4. l l l

,t'-lt-

{.

\--J

5 .r rlhcsis of the alkaloids (+)c .:r'rrroof 5 reactswith dimethylr',- i). Desilylation(oxalic acid, rJ:' 7. The dimethYlamidegrouP I I ..,tulyzedby CeCl3(2'5 equiv.) )l{ rn CHIOH Provides(+)-9 in

(R)- and (S)-a,a-Disubstituted a-amino acids.t Although only a few a-amino acids of this type are known, they are present in some microbial peptide antibiotics. A number of routes are known to racemic or to one enantiomerof amino acids of this type, but the most practical route to both enantiomersappearsto be resolutionof racemic N-acylatedderivativesof these acids by a chiral amide containingone or two (S)-phenylalanineresidues.The diastereomersobtained in this way can be separated by crystallizationor by flash chromatographyon silica gel. Thus the racemic amino acid (2) is converted to the 1,3-oxazol-5(41{)-one(3) by an activating agent such as 1,l/-carbonyldiimidizole(cDI), which without isolation is coupled with the chiral amine I (DMF, 50) to form two diastereomericdipeptides (4) which are separated by crystallizationor chromatographyon silica gel. Several methods are available for cleaving the chiral amide, but the most useful is reactionwith cFrSo.H in cH.oH at 80' (SchemeI).

tl

o si(i-P03

I

o

cDl | -.---_

-coo'r

IRl--J

*ltt"ot3

)-o

\

I nr'trrr^n'

2

3

6(97:3) )H

t

PrMgCl, CeCl3

cH2c6Hs

?

O

tlA*\N(cH3)2

Rr' fiHcJil. o

Rrl NHcJl3 o

(R)-4

(s)-4

I 1)Ac,o.A I 2) H3O+ I

\ "-

:,

\ N-

I

CH2C6H5

t'>,""'(I\N(cH3)2

Rl .,cooH l|*t.o*3

I lir.cooH "'runcon'', .' i/

* 1

(R)-2

(s)-2 SchemeI

274

(1S,2R)-(+)-Phenylcyclohexanol

In some cases,better Iesultswere obtainedby use of l-phenylalanyl-l-phenylalanine dimethylamide in place of l. I D. Obrecht,c. Spiegler,p. Schonholger, K. Miiller, H. Heimgartner,and F. Stierli,Helv., 75, 1666 (1992). (1s,2R)-(+)-Phenylcyclohex anol (13,244; 14,128- 129, 16,113 114) (l)' use as chiral auxiliury. whitesellr has reviewed use of this chiral alcohol One particularly as comparedwith that of (-)-menthol and (1R)-(+)-8-phenylmenthol' of trans-2-phenylresolution by available I are of enantiomers both is that advantage 2-substituted cyclohexanol by means of enzymatic hydrolysis of the esters and that originally was used auxiliary this chiral Although available. readily are cyclohexanols of alkylation for asymmetric useful is also it glyoxylates, of reactions of ene for control enolates,and for control of various cycloaddition reactions' The reaction of a chiral vinyl ether (2) Asymmetric t4+2llt3+2lcycloailditions.2 adduct (a) and a nitroalkene (l) catalyzed by a Lewis acid results in an intermediate and (-)which undergoesan intramolecular [3+2]cycloaddition. Both (*)-camphor have been used as the chiral auxiliary. Thus the vinyl ether (2) trans-2-phenylhexanol Hydrogenation formed from the latter auxiliary reacts with I to give 3 in 737o yield. 4, in which lactam a-hydroxy tricyclic a provides and auxiliary chiral the cleaves

Noz

"r.\-JJ-coocH3

^ rt"-R* + l l CHz

Cl2Ti(O-l-P02 cHzcl2'-90"

:"""'l 2

730/o

cH3ooc

H2 RaneyNi I O-/o

H (1S)- 4' 98%ee

Clhasthe(S)-configuration.Ifthereactionofl.and2iscatalyzedbymethylaluminum MAPh, (1R)-4 is obtained in 797o ee' Surprisingly' use of bis(2,6-diphenylphenoxide), MAD' provides (1S)-a in 75% methylaluminum bis(2,6-di-r-butyl-4-methylphenoxide)' can also be ee. when (*)-camphor rs used as the chiral auxiliary, the enantioselectivity

controlled by the choice of lru is xr ee, and Cl2Ti(O-l-Pr)2provides ( ISF

the Lewis acid catalyst can be as effc Chiral a -methyle ne-y -but-vrfua y-butyrolactonessuch as 7 utilizcs tlx 1,l-dibromohexane andZn-TiCl,' T! reactswith dichloroketene to form thc 4 followed by oxidation with chromr (+)-5. Hydrogenationand oxidation p final stepinvolves introductionof a rn< a naturalantitumorantibiotic.

C6Hs,,../,^\

I c6Hsocory

l + Q H ' 2

( Z \ - 3 + C 't " C = C = .o! ^ 65-79a

1) H2,Pd/C 2) RuCl3,NalOa 3) cH2N2 _ 61oloOv€rdll

o

aP

Hooc"lr

( - )- 6

3 -H y dro xy -4 -phe ny l- p -lactans -' couplewith the N-(trimethylsilrl)im .tcreoselectivitydependsin part on c'stergroup. Use of either (+1- or r .ruxiliary results entirely in a as-p-l r -)-menthyl or of Oppolzer'so-i-.
(1S,2R)-( +)-Phenylcyclohexanol

c

l : -phenylalanyl-l-phenylalanine

l { . - r L f , r l n e r ,a n d F . S t i e r l i ,H e l v . , 7 5 '

l:.,l6.l13-rl4) :$i.r use of this chiral alcohol (1)' rnJ r I R)-(+)-8-phenylmenthol.One rl( ^\ resolutionof tans-2-phenyl)! :ir. csters and that 2-substituted cii:.'l auxiliarywas used originally r.ctul for asymmetricalkylation of

27S

controlled by the choice of Lewis acid, but in this case MAph provides (1R)-4 in 99va ee, and cl2Ti(o-l-Pr)2 provides (1S)-4 in 98vo ee.This result indicatesthat a changein the Lewis acid catalystcan be as effective as use of enantiomericchiral auxiliaries. chiral a-methylene-y-butyrolactones.3 An asymmetric synthesisof a-methylene7-butyrolactonessuch as 7 utilizes the benzoate(2) of (lR,2s)-1, which on reactionwith 1,l-dibromohexaneand zn-TiCla 'TMEDA forms the (z)-enolether 3. Thus this product reactswith dichloroketeneto form the cyclobutanone(-)-4. Baeyer-Villiger oxidationof 4 followed by oxidation with chromium(Il) perchlorateprovides the a-chlorobutenolide (+)-5. Hydrogenationand oxidation providesthe B-carboxy-y-butyrolactone(-) 6. The final stepinvolvesintroductionof a methylenegroup to provide (-)-7, methylenolactocin, a natural antitumor antibiotic.

ei.:l(\nS.

c :f.1ctionof a chiral vinyl ether (2) Frl:\ in an intermediateadduct (a) trir,,n Both (+)-camphor and (-)| .:uriliary.Thus the vinyl ether (2)

C6H5,,,.f1

I

c6H5oco/-Y

zn,rict4

-]ffi* I + c6H12Br2 -1o0"/"

i

znlcu (Z)-3 + clzc=c=o -79y" 65

buHu (z)-3

.'-*i. "=140li3l3ii:ii'"

'RO--H.

t3o/o

turu\rt,,

-

LJ

cuHJcrH,.,

C)-4

oR*

pC6H1rC6H5

F<.

2

1rrr -1 in 737a yield. Hydrogenation :lr. ri-hydroxy lactam 4, in which

Cl2Ti(O-iPr)2 cH2ct2,-90'

CsHrr

(+)_s

o

1) H2,PdlC 2) RuCl3,NalOa 3) CH,N,

tl

1 ) MgOCOOCH3 2\ HCHO,C6H5NHCH3

.tt'\^P

\__J

610/o ove'all

Hoocs' \aur', (-)-6

o-7

-xr-1

,v.1.7 r )

-

H

4 98o/o€€

N: : r\ catalyzedbY methYlaluminum u::.1 rn 197o ee. SurPrisinglY,use of rr.:r r. MAD, provides (IS)-4 in 15% can alsobe l:r. :hc cnantioselectivity

3'Hydroxy-4-phenyr-B-ractams.a The lithium enolate of (silyloxy)acetates (2) couple with the N-(trimethyrsilyr)imine3 to give 3-hydroxy-4-aryr-B-ractams (4). The stereoselectivitydependsin part on the size of the silyroxy group but mainry on the r'ster group. Use of either (+)- or (-)-trans-2-phenyl-1-cyclohexyl (l) as the chiral auxifiary results entirely in a cls-B-lactam (4) in g\vo yield and 96-9gvo ee. use of t-)-menthyf or of oppolzer's o-isobornyl auxiliary (l2,lo3- lo4) resultsin lower yields and enantioselectivity.The cyclocondensationwith the ester 2 from (_)-l results in t-3R'4S)-4in96vo ee. on desilylarionand acid hydrolysis,this lactam provides (2R,3s)-

(R)- and (S)-l-Phenylethylamine

R3S|OH-.,,,OSi(i-Pr)3

l Lio"'\oR"

l

*

ri'"utu TMS-N

-poHs

l H> l

Chiral tetronic aci.ds.' The kcl tetronic acids (4-hydroxybutenolideslI imine (2) derived from a dihl'drofun

)_NH

o'

ee) (3R,4S)-4 (96o/o

2 [R*=(-)1]

( "t';;{

o

: 6H

A I icHs -o

1

2 -l

s (2R,3S)1) CHz=CHCOOCHg 2) HOAo,H2O 3-phenylisoserine.TheN-benzoateofthisunnaturalaminoacidprovidesthesidechain potent antitumor activity ofthe taxol. ofth" dit.rpine taxol and is essential for the

78% overall

I J. K. whitesell , Chem. Rev., 92' 953 (1992)' 2 S . E . D e n m a r ka n d M . E . S c h n u t eJ, ' O r g ' ' 5 6 , 6 7 3 8 ( 1 9 9 1 ) ' 3M.B.M.deAzevedo,M.M.Murta'andAE'Greene'J'Org''57'4567(1992)' a l . o l i m a , I . H a b u s ,M . Z h a o , G ' I ' G e o r g ,a n d L ' R ' J a y a s i n g h eJ ' O r g ' ' 5 6 ' 1 6 8 1 ( 1 9 9 1 ) '

(1)' 14'257' (R)- and (S)-l'Phenylethylamine, CH3CH(C6H5)NH2 (via the tautomeric enamImines Asymmetric Michael reactions via enamines'r ines)undergoconjugateadditiontoelectrophiIicalkenes,butthefirstasymmetricreaction ofthistypewasaccomplishedinlg85usingchiraliminesderivedfrom(+)-or(_)-l (equationl).ofalargenumberofchiralaminesexaminedasthechiralauxiliary,the

C6H5 .€Hs

(t)

R + CHz=CHCN

HAr.r )"'t" "cH2cH2cN (r (>90%de)

group' Modern extensions of this most useful all possessan aryl group a to the amine in detail (77 references,1985-1991)' reactionincluding unpublishedre.ults are discussed

protectionof the carbonylgroup at C.. with ruthenium tetroxide (84% vieldt vertinolide(6) in 12 stepsin ll.5'i Asymmetric Diels-AWer rcottia eenerally require an acyl or tosrl r in the presenceof trifluoroacetic acid water (0.03 equiv.).4Under thesr crn benzylamineand an alkyl glvoxrlatc. pipecolic acid in high yield (equatto

(R)-and(S)-l-Phenylethylamine

R3SiO-- -CoHs I RS I T

277

Chiral tetronic acids.2 The key step in a synthesis of chiral 5,5-disubstituted tetronic acids (4-hydroxybutenolides)involves Michael addition to acrylatesof a chiral imine (2) derived from a dihydrofuran-3-oneand (R)-l-phenylethylamine (1). Aftet

zFNn o' (3R,4S)-4 (96"/"ee) CoH. " CHs,,1"

cH.,,;1cuHu H- 'N

o lt

lt It\d FcH.

1

CoHs

:

0n

H- 'NH

| )-cHs -\ci

|-o )-cHs

(2R,3S)s

2 'l)cH2=cHcoocH3 2) HOAo,H2O

ar:rn,r acid providesthe side chain l:-,::'unloractivity of the taxol.

1) 2,4-Pentanediol (75olo) 2) RuCls/NalOq (8a%)

78o/o overall

9: / /-.' 57. 456'7(1992). (1991)' r - i i r . . / . O r g . ,5 6 , 1 6 8 1

o.

\-

rl). 14,257. Inrrncs(via the tautomericenamn:.. but the first asymmetricreaction r:r::c: derivedfrom (+)- or (-)-1 r.::1oCd as the chiral auxiliary' the ll

,l

\\

o.rr)-oH l't a / _

cHe

s"veralsreps

**

OH

lrom 3

\^^^^,,

coocH3

"ttt->"H='HCH=cHCHs

o (S) - 6, co -25'

C6Hs sCH3

nArut l )-',,ta I l''curcH2cN \-/ (>90%de)

inr Lr,rup.Modern extensionsof this 1985-1991)' r: Jctail(77 references,

protectionof the carbonylgroup at Ca, the ketonegroup at C2 was introducedby oxidation with ruthenium tetroxide (84% yield\ to give 4. This compound can be convertedinto vertinolide (6) in 12 steps in Il.SVo yield. Asymmetric Diels-Alder reaction of imines. Diels-Alder reactions of imines generally require an acyl or tosyl activating group on nitrogen, but can be effected in the presenceof trifluoroaceticacid (1 equiv.) and a catalystsuch as BF3 etherateror water (0.03 equiv.).4Under theseconditions,the imine BzIN:CHCOOR, formed from benzylamineand an alkyl glyoxylate, reactswith simple dienes to form derivativesof pipecolic acid in high yield (equationI). This aza-Diels-Alder reactionhas been used

278

(S)-PhenylglYcine

?".

(t) \',

COOC2Hs

CHr H2o "t.-'.-A DMF,TFA,

"tt-n'\"", ll CHz

2

5

"

-

e4"/"

l

BrZn.._..\cHz

r-

I

Bzl

zcHcooR

adductisconvertedbyr'vo.g."",l."andremovalofthechiralauxiliarytoethyl(2S'4R)cyclopentadienegives (3)' Note that reactionof (R)-1 with and (2S,4S)-4-methylpicolate 897o de' the exo-adductin 827o yield with

?"'

fl"oo.,,,

(o"*, CHz

*-.CHCOOCzH5

c4tu)

cdtr)

"

I

"'"

csHs4c(

(>95\ ee)

I Y. A. Dembdl6, ard J C. Beland,P. Hitchcock.

(R)-(-)-2-Phenylglycinol (l)' 15.1-s6 Asymmetric synthesis of pynolidinet t amine (t) reactswith a 7-keto acid in reflu 2 in 75-987o yield. Treatmentof 2 '*'ith etc:

"

R OH

^r'_. Y*", ";_|

2 Fo% de)

1

9"'

CHq 1) H2,PVC,C2H5OAc 2) H2,Pd(oH)2

I '

\uAcoocrH,

t t \ltAcoocrHu

H -3 (2S,4R)

H (2S,4S)- 3

l t

,Q

cuHuAruA

(equationII)' synthesisof 4-methylpipecolicacid for an enantio- and diastereoselective and ethyl prepared from (R)-1-phenylethylamine Thus reaction of the imine (R)-1' de'This 7O7n prouidesthe adduct2 in 44Voyield and glyoxylate,with 2-methylbutudi*t

"'"

C5H5C=

l

\N^COOn

BzlN

(r)

+

l l

+

iuHu

o

(R)-1

AtH3 75 - 95"/"

Asymmetry'3' 459 (1992)' I J. d'Angelo, D. Desmadle,F' Dumas' and A' Guinganl'Tetrahedron: 2 D. Desiraele, Tetahedron' 48, 2925 (1992)' Letters"Sl' B' Tinant' and J'P' Declercq' Tetrahedron 3 L. Stella, H. Abraham, '' nt"l""-ntp"nt'

HO

R", " / >

\.,N-' a

0sHt 3 (>97\

cbl

2603(leeo).

aP.D.Bailey,R.D.wilson,andG,R.Brown,J.C.S.PerkinI,1337(1991). ;lcaves the C-O

(S)-PhenYlglYcine. The organozinc reagents deAsymmetric synthesisof a'methylene-y-lactams'r a-methylene-7-lactams' form react with imines to rived from 2_(bromomethyrju".yrut". provides theseproducts imine chiral auxiliary for the Use of (S)-1-phenylglycineas the in )95Vo ee.

bond and also redut-rr

:ransfer hydrogenolysis provides the l-suh

Reduction of 2 with triethvlsilanc catr bond to give 5 in >94% de. This pn

t'-O

t'nfortunately the chiral auxilian

is n<x n

(R)-(-)-2-Phenytglycinot (l)

cooc2H5 +

BrZn=_-\CHz

C6H5C=NH \ -.COOC2H5 rHF,20 30' go-esz I CoHs

//FHz

I

Bzl

cuHu4lrAo m. :hr lpipecolicacid (equationII). and ethyl lR ,-l-phcnylethylamine :; ) n 447oyield and TOVode.This h. . hiralauxiliaryto ethyl (2S,4R)gives t R r-l with cyclopentadiene

cuHu

+ c2H5oZnBr cooc2H5

(>95% ee)

'Y.A.

Demb6l6,c. Beland,P. Hitchcock, and J. vlrieras, Tetrahedron:Asymmetry,3,35r (rgg2).

(R)-(-)-2-Phenylglycinot (t), tS,2S6 Asymmetricsynthesisof pynolidines and pyrrolinones.t This chiral B-hydroxyamine(l) reactswith a 7-ketoacidin refluxingtolueneto form a chiralbicycliclactam 2 in 75-98% yield.Treatment of 2 with excessalane,generated fromAlcl.r andLiAlHa,

,,,.fl:oo""' 2 (7oo/ode)

9t'

OH ( \'-NHz -: CoHs

R

-

I

I

-NAcoocrHu

r ' ll37 (1991).

'l-he organozincreagentsdeLr. :".:' tirrm a-methylene-7-lactams. :..i imine providestheseproducts

75 - 9go/o

R, AtH3

i' I )eclercq,TetrahedronLetters,,31,

to.-, ll o

c6HscH3 A, -H2O

(R)-1

H (25,43)- 3

r-..,:,Jron: Asymmetry,3, 459 (1,992).

"^

75 - gso/"

HO

\.rru--z :

HCOONH4 Pd/c 60 - 7go/o

R1.,

HNJ

6uH, 3 (>97o/" de)

cleaves the c-o bond and also reducesthe carbonyl group to provide 3, which on transfer hydrogenolysisprovides the l-substitutedpyrrolidine 4. Reduction of 2 with triethylsilane catalyzedby Ticla effects only cleavageof the c-o bond to give 5 in )94o/o de. This product is reducedto the lactam 6 by Li/NHr. Unfortunatelythe chiral auxiliary is not recovered.

Phenyliodine(IIf

diacetate- Iodine

(CzHs)gSiH Ticl4 -t

a3 - 94"/"

>

*" Hq a\

R

w*{

Li/NHg CzHsOH 65 - 93%

CHr

,

oHil-

/--\

r*\/

.r^! l

l

t2 c6H5t(oAc)2. h v

l

tl

6uHuo

o

| ,^ l

-"-

l

cHs

t

6

5

|

1

r L. E. Burgessand A. I. Meyers,J' Org ' 57' 1656(1992)'

Phenyliodine(tll) diacetate, CcHsl(OAc)z' I with Oxidation of an N-protected tyrosine Oxidation of N-protecteil tyrosine't by treatment a spirolactone(2)' which is converted C6H5I(OAc)2in methanol p'ouid"' common to system bicyclic a 3' exo-hydroindole with NaHCO3 in CHrOH into the of can be converteddirectly into 3 by oxidation various Stemonaalkaloids.Actually 1 linthepresenceofsodiumbicarbonate.Theconversionoflto3evident|yinvolves intramolecular by a highly diastereoselective para-hydroxylationof u ph"nol followed

2 --^, "-"fI N"Hco.

l--\

HO-<

\:./

with BurSnH-AIBN under high dilutrrtnrc Iodoepoxides from allylic alcohds: c.t alcohol(l) with I equiv. eachof C"H.ltof results in the iodoepoxide 2. The prtrlrrr irradiation with (BurSn)z in refluxing t'cna

cH.on,zz'

)-curcHcooH :

OH

ttHn

Z>-V-\

1, R = Cbz or Boc 59o/"

rcoocH3

)-'-.F,("', l

t

v

H R 3

c6H5r(oAc)2 ,.N

a\CHt\

--1%

-

\--.

U]=-t-, OH

2 r

1

I

conjugate addition. Letters' 33' 54'7'7('1992)' I P. Wipf and Y. Kim' Tetrahedron

l

,:ncH.\ t

l

{

V't'/

OH

i 3 l

Phenyliodine(III) diacetate-Iodine' H y p o i o d i t e - t y p e r e a c t i o n . | T r e a t m e n t o f t h e a l l y l i c a l c o h o l l w i t h C o Hfollowed sl(oAc)z which undergoesB-scission to a and iodine generatesan alkyloxy radical' 2 can be ring system (2)' The CH2I group of by cyclization to a cis-hydroazulenone reducedtoamethylgroupbyacatalyticamountofBurSnH(6o7oyie|d).Treatmentof2

I C.W. Ellwood and G. Pattenden.Terrahcdm : V.H. Rawal and S. Iwasa, ibid., 33. {trl- t19

Phenyliodine(III)

- r'lHr

, -r;oH - H N . :: 93'/.

diacetate-Iodine

R /

\ )

Y

o frH,

C6H5l(OAc)2 , t2 nv

II

t

o

\--l--l cHs

6

l

o ll cu"t (/--V1t \

4oo/o

\,ry CHg

a

2 "n.r^| e'.snn --'"i ArBN

o 1' - ,'f an N-protectedtyrosine 1 with r '1,. shich is convertedby treatment ri, .. -1. a bicyclic system common to 6r-:ied dircctly into 3 by oxidationof L.:r:r'ion of I to 3 evidentlyinvolves

\ r \t---\

a

I

t )

L;fv

CHs 3

intramolecular rri^lr diastcreoselective

* o 2 r".r^ ' - ' " 1| ru"nco. c H 3 o H2,2 '

with Bu.rSnH-AIBN under high dilution results in ring expansionto 3. Iodoepoxides from alryric arcohors; cycropentanors.2 Reaction of a cyclic ailylic alcohol (1) with I equiv. each of c6HsI(oAc)2 and 12under irradiation with a sunramp resufts in the iodoepoxide2. The product undergoesan atom transfer cyclization on irradiation with (BurSn)2 in refluxing benzene.

OH r-::,

z\v-\ t t

rcoocH3

o)'-.,,-f{ H R

Y "'n

3

",",;1?lo, ---^%- f\5,,,all?,n' -*"t,) Ai-t' (-k?-=;q>/ (--p oH

oH

1 a:u^ zr=n"""\

(

t

2 ( 5 : 1)

I

l

vJ.---./ ---;OH

9Hs

,L$.-.

\--
40/"

( 3 . 5 : 1)

x .,llrlic alcohol I with C6H5I(OAc)2 t ..::JcrgoesB-scission to a followed r(:r (2). The CHzI group of 2 can be t.: Ilu,SnH (6OVoyield). Treatmentof 2

1C. W. Ellwood and G. pattenden, TetrahedronLerters, 32,1591 (1991). I V. H. Rawal and S. Iwasa, ibid., 33, 4687 (1gg2).

(2R,4S)-2-Phenyl-1,3,2-oxazaphospholidine

282

8-Phenylmenthol. The useful 1,2-dihydropyridines can chiral t-acyl-2-allqt-1,2-dihyilropyridines.t from be prepared by reaction of Grignard reagents with the chloroformate L derived bulky The reactionof (-)-8-phenylmenthol with 4-methoxy-3-(triisopropylsilyl)pyridine. in this reaction,and the ca-methoxy group at c3 is essentialfor high diastereoselectivity I group facilitates removal of the chiral auxiliary. Reactionof Grignard reagentswith

o ,\'s'1t-t4'

?.r. o)',,u.Si(i-Pr)s

p-CH3C6HaMgBr

t\N*'i l

2

1

oH

1) NaOCH3 2) (HOOC)2 88k from 1

CeCl3 1)NaBHa. 2 ) M s c lD , MAP _ 58"2.

I W.J. Richter, Ber., 117,2328(l9rr{r r J.M. Bruneli,O. Pardigon, B. Faurc.ad

N-(Phenylseleneno)phthalimide. Cyclizttion of hommUybc akol cyclization can be effected*ith alnrc with Nicolaou's reagentl. The prtrdr tetrahydrofurans.

l r l

P-CH3C6Ha\"'-TCO2R*

I

CO2R*

for reduction of ketonesby ditnranc Highest enantioselectivityobtains frtrr methyl ketone is reducedwith 9l-r c Use of 1 equiv. of 2 permits reducti<x ee. This oxazaphospholidineresembl

r rscr CHP"

CHa-.-..A.r_r,,,:-rra. I

H

bore=t

3

4

<-\ . . ( -lI- ) P-CH3C6Ha"' CO2Bzl 5, as -52-4

which can be convertedto enantiomericallypure provides2 in high diastereoselectivity, 5 as shown. lD.L. Comins,H. Hong,an
l : cH3 cH3

H

s

s

CoHre I

CHe

OH

.r./ncoHrs CHs

as,t

OH

cHrA;'\-cuHt' (2R,4S)-2-Phenyl-L,3,2'oxazaphospholidine(1)' Preparedfrom (S)-(+)-prolinol and bis(dimethylamino)phenylphosphine''

CHg OH .,J^-\..\.-c6H13 v,,r I

CHs

complex (2)' Enantioselectivereduction of ketones with a borane complex.z The .S(CH:)z catalysl effective .THF is an at 25", I with or BHr obtainedby reactionof BHr

In the last two exampleshigher rq :n CHTCN. But in any case the faro ScCoHs group and the adjacent nrth

N-(Phenylseleneno)phthalimi

I r; useful 1,2-dihydropyridinescan r:: :nc chloroformate I derived from The bulky 3-,:':r.opropylsilyl)pyridine. l\ :i :his reaction,and the Ca-methoxY R,.:,rrofl of Grignard reagentswith 1

o .

A

Y

-si1i-e4t

Cyclization of homoallylic alcohols to tetrasubstituted tetrahydrofurans.t This cyclization can be effectedwith almost complete stereocontrolby phenylselenenylation with Nicolaou's reagentl. The productsare reducedwith BurSnH/AIBN to trialkylated tetrahydrofurans.

'l

CO2R* 2

o ll

)3,-

r::CCl

rW.J. Richter,Ber., ll7,2328 (1984). 2J.M. Bruneli,O. Pardigon, B. Faure,andG. Buono,J.C.S. Chem.Conm.,287(7992).

N- (Phenylseleneno)phthalimide.

l\ ^ , /l l

.frj

for reduction of ketonesby diborane in toluene, but only at temperaturesabove -20". Highest enantioselectivityobtainsfrom reactionsat 110'. At that temperature,isopropyl methyl ketone is reducedwith 92Voee by BH3 .THF in the presenceof 2 mol % of 2. Use of 1 equiv. of 2 permits reductionof dialkyl and alkyl aryl ketonesat ll}' in >99% ee. This oxazaphospholidineresemblesCorey's chiral oxazaborolidine(16,254).

a\

I-fP-CH3C6Ha$"

l l CO2Bzl

oH

"tt)r'---'ocH.-!#*

1,rsoH

t-Pr"

CH3 CH3

4

CHs CoHrs CHs

n ^. !()nvcrted to enantiomerically pure

s6

-1,)7 (1991).

Y cHs

92"/"

/ .(

CHe.

-CoHre-

,SeC6H5

5- O -

'CHs

,SeC6H5

)---<

CH3'-

OH

r _\ CHs'

a

CHs

\

- O -.>, ' C o H t s

,SeC6H5

l__<

Bn** .{ ' o \ cHs'

_

.n

CHo

,SeC6H5

cuHrSt'8Hr-'\oz"coHre

OH I cH.-A-'.'--\.-coHrs

l. r- . :nrino)phenYlPhosPhine.l

a htrane complex.2 The complex (2)' "1 .r ith I at25", is an effectivecatalyst

CHs OH CHs. CHs. ,SeC6H5 I ,SeC6H5 cv " rH ^ . . ' \ ^ C o H t s , ' ' _ { * ' f - - . 8s% | { - O ' , \ . ' C o H5r s4 i 4 6 . t- O ' \ - C u H , . CHs CH3" CHg-' In the lasttwo examples higherregioselectivity canbe obtained by useof C6H5SeCl in CH:CN. But in any casethe favoredproducthas an anti-relationship betweenthe groupand the adjacentmethyl. SeC6H-5

(+)- or (-|-(\-Plaft

( + )- or ( - )-(N-Phenylsulfonyl-3,3-dichlorocamphoryl)oxaziridine

I E. D. Mihelich and G. A. Hite, Am. Soc.,ll4, '7318(1992).

.uruJ'i^".", (-)-2

Phenylsilane. Deorygenatiltn of alcohols.r This reaction can be effected by conversion of an alcohol to a derivative that undergoes radical reduction by a hydrogen atom donor (Barton-McCombie reaction).Xanthatesare usually employed as the intermediatebut the various thionocarbonatescan be used. TheY arereasily prepared by acylation of

ov

e C^Hol"-NH

I

csHs&coocH3

il

90 r(

(3s)-3

phenol alcohol by a phenoxythiocarbonylchloride, ArOCCl, preparedby reaction of a the most but reduction, for the was used R3SnH/AIBN originally with thiophosgene. dibenzoyl or AIBN an initiator, with in combination phenylsilane is reagent convenient peroxide.

73- ssv"l"t."oo*. ""ro', t NHz

I

coHs&coocH3 (3S)-4, >95% ee

S

p-rcoHooAct ROH

"ur,ur,r,. fr r#ffi*t RoAocunor-p

p-amino acid 4. Note that the enolate of a p-amino rrd

(1991)' rD.H.R. Barton,D.O. Jang,andJ.C. Jaszberenyi, Synleu,435

CHs\, (1)' 16'119- 120' (+)- or (-)-(N'Phenylsulfonyl-3,3-dichlorocamphoryl)oxaziridine acids't This to sulfinimines; sulfenimines B'amino Asymmetric oxidation of yield in 80-90% (-)-1 in CCI+ (+)(l equiv') or of by use oxidation can be effected and in 85-907o ee.

(-)-1

CHs

f,)\'"so,cuHu

Zr-s o ?ut' o4ttH: cuHufucoocH3

1) LDA 2 ) ( + )- s

o'

ry

(3R) - 6

cuHu-s-N CuHu #*

"uru1"i*^"u,u (-)-2 ' ( s0% ee )

TheproductsareusefulforpreparationofopticallyactiveB-aminoacids.Thus affords sulfinamides 3' addition of the enolate (LDA) of methyl acetate to (-)-(R')-2 by hydrolysis into the (S| separatedby flash chromatography. Pure (3S)-3 is converted

camphorylsulfonyl)oxaziridine(+)-5 to ttlc 19Vo yield with >93% ee.

F.A. Davis,R.T. Reddy,andR.E. Reddr..I (}l

nrlrndtDe

(+)- or (-)-(N-Phenylsulfonyl-3,3-dichlorncamphoryl)oxaziridine

o. j' cuHu-s-N4c6H,

'.

),

CHl'

oLi I

-OCH3

(-)-2

r ^"- ;tlccted by conversionof an c:: - .) a hydrogen atom donor c:':. ,rcd as the intermediatebut

oV

a:::.1rc'dbv reactionof a phenol d r - rhc reduction,but the most t ,- rniriaror,AIBN or dibenzoyl

-78"

Ei%-

oV a

c^H.-s-NH * t C6Hs"\--,-CoocH3

il.r ;';.por.6 by acylationof the

285

coHs/"-NH : coHs&coocH3 s0:10 (3R)-3

(3S)-3 7a- Bso/of cr.coo*, c".o"

t

NHz

t

c6H5-A-"-coocH3 (3S)_4,>95% ee .-'

a:r

c6HssiH3 cnHscoo), 8,- 10o.,"

RH

p-amino acid 4. Note that the enolate of a B-amino acid such as (3R)_6 is oxidized by the (10_

,r.)l).

CHr-._.-Ctta /\ _/,\__

r f ,rrraziridine(l), 16,119-lZO. irntnes; p-amino acids.t This ir.-r. r in CCIa in 8O-9OVoyield

/-t-Z

(^)N D c i O2 (+)-5

?u"u oAruH = coHs*coocH3 \^

(3R) - 6

t't4CuHu I

lr ,irirc p-amino acids. Thus r, i{. r-2 affords sulfinamides3, in-.r hv hydrolysisinto the (S)_

?ut' 1) LDA 2) (+)-5

OAtrtH :

-7 (sY") + (2s,3s) coHs-^)icooCH3 : OH ( 2 R , 3_S7) ( 4 9 V' o uu,,0

camphorylsulfonyl)oxaziridine(+)-5 to the syn-a-hyd roxy-B-benzoylaminoacid 7 in 49Vo yield with >93Vo ee. 'F.A. Davis, R.T. Reddy,andR.E. Reddy,J. Org., 57,6387(1,gg

.

286

(Phenylthio)methyl

azide

(1' azide, (azidomethylphenyl sulfide)' C6HsSCH2N3 l0'14)' (Phenytthio)methyl ' (+)-mitomycin A key step in a total synthesisof the alkaloid i-UrrnyUriri.dines.t K(7)istheintroductionoftheN-methylaziridinering,whichwaseffectedwiththis triazoline 3 in 9OVoyield' reagent. Thus 1 adds to the imide 2 at 80' to give the of the triazoline group After elimination of the carbonyl group to form 4, irradiation

cH39 o cH3o.--,\--4 PCH3,cHzscoHs

1.coHo,8o. ,

ll | >__,-_N: so"/. cr",'-yo-*l-_1._(,*

cH3o

r> \*At

I O'.,r,'CH2CH2CoH5

1, h\' cH2c,,2 -+0 L - 5 '

tl

2

I severat I steps

i D. H. R. Barton,J.C. Jaszberenli. arrJI

cHsQ t o

NCH3

RCOOH - EHNz.t Ac1'l &n 14,268) when photolyzed in the Prcv I to form the imine 3. These imirrs to primary amines (4).

o

{ 3

1) hv, C6H6(+8"/")CH3O 2) Raney Ni (70ol.)

3-Phenyl-3- (trifl uorometby! )dirrir

9CHs,CHzSCoHs - - N

//N N

cH3o

Phosphazenium fluoride (l). Preparation:

1) (Ctrt/ 3)'gj (ct3P=N+=PCt3)PCt6-

CH3O 5 (eoo/.) | ,1 1"*ry.r,"*2Li

(76"/.) As(r) l2) cH2si(cH3)3 CH30

,OH

PyHOTt lJn2Vt2

81%

CHg

I cH3o--.\'{

ll

cHc .ocHs

The value of this salt is that it i .hould be as useful as (CHr)rN-Frn THF at 25' in 93Va Yield.'

ll r='

CH.,,/Y'*N\,-DNCH3 o (r)-7

c6H55O2O (48Voyield),which is reducedby Raneynickel to resultsin a (phenylthio)methylaziridine conversionof the keto group at an N-methylaziridine(5). Remainingstepsto 7 involved precursorto (+)-mitomycin Ce to methyleneand oxidation to a quinone6, the immediate K (7). Angew.Chem.Int. Ed'' 31,915 (1992)' 1J.W. Benbow,G.K. Schulte,andS.J. Danishefsky,

2

R. Schwesinger,R. Link, G. Thick Chem. Int. Ed., 30, 13'72(1991\.

Phosphaz€niumfluoride (1).

\ - . : : . i c ) .C 6 H s S C H 2 N(31 ' 1 0 , 1 4 ) . sr :::rr.is of the alkaloid(+)-mitomycin h:- :rng. which was effected with this r' ir.i the triazoline3 in 907a yield' r: {. rrradiationof the triazoline group

CH3O

O

rc

PCHg ,CHzSCoHs N //- N N

l.

cH30

--\

,oCHerCHzSCoHs

//N

cH30

r\ i l

\trtAs

l

I O\y..CH2CH2C6H5

1, hv

cH2ct2

cF"

o-5" ' c6HscH2cH2N <

CoHs

tl

3

B(OH)3 c2H5oH, 91y"

c6H5cH2cH2NH2 4

I D. H. R. Barton,J.C. Jaszberenyi, andE.A. Theodorakis, Am. Soc.,ll4, 5gO4(lgg2).

V

N

h.

(1) c6H5,-\il RCOOH - EHNz.l Acyl derivatives (2) of N-hydroxy-2-thiopyridone (12,417; 14,268) when photolyzed in the presenceof this diazirine (l) transfer the alkyl group to 1 to form the imine 3. These imines are hydrolyzed by boric acid in refluxing ethanol to primary amines (4).

2

I severat sleps I

30

CF3 ><-N

o 3

CHgQ

3-Phenyl-3.(trifluoromethyl)diazirine, !t,rrlu,42","E,

287

Phosphazenium fluoride (l). Preparation:

N

1) (CH3)2NH, NaBF4 2) KF, CH3OH

(Cl3P=N*=P61.1P61u

CN.O

F[(CH3)2N]2P=N*=PlN(CHg)zle 1

The value of this salt is that it is anhydrousas obtained and is soluble in THF. It should be as useful as (cH3)aN+F- as a form of fluoride ion. Thus it converts 2 to 3 rn THF at 25" in 93Vo yield.l

CB.

\t\ -7

c6Hsso20 ic..:, * hich is reducedby Raneynickel to :- .,,lr cd conversionof the keto groupat hr ::rmcdiateprecursorto (+)-mitomycin | 1':J(,r. Chem.Int. Ed., 31, 915 (f 992)'

R. Schwesinger,R. Link, G. Thiele, H. Rotter, D. Honert, H.-H. Limbach, F. Mdnnle, Angew. Chem. Int. Ed., 30,1372 (1991).

288

Pinacolborane

Phosphoryl chloride. Preparation of cyanides.r An attractive route to cyanides involves as the first step dehydration of alkylformamides with phosgene-triethylamine (1,857) or phosphoryl chloride-diisopropylamine (13,249) to form isocyanides followed by isocyanide-cyanide rearrangement.This rearrangementtraditionally was conducted in the gas phase,but proceedsin almost quantitativeyield when carried out by flash pyrolysis at 600". This route to cyanidesis attractivebecauseallyl isocyanidesrearrange without allylic rearrangement. Moreover,optically activecarboxylicacidscan be obtained from optically active amines without racemization.

nr.:r-NHz

Ar.:r.NucHO

CHe

Hydroboration of alt catecholboranefor h1'droh chemistry and in toleranc

Hex:H

OctCH:CHe

CHs

nr':r.tlC

nr:r.cn

Hso*

nr:_r.cooH

90-110%

CHs

CHs

CHs

This scquencecan convert optically active amino acids to optically active B-acyloxy cyanides (equationI).

(r) Ry cooH NHz

R

cH2oH

R_Y CH2OCHO

Y

I C. E. Tucker,J. Davidson. a

Potassium t-butoxide. Furan synthesis.t R in (CH:).rCOH/IS-cro*n6 homopropargylicalkoxidc

Fat n-coHrs-_---!o

NHCHO

NHz

cH2oM

R

RYcHzocHo

CH2OCHO t

NC

70 -93%

CN

(cH3)3oH

rC. Riichardt, M. Meier,K. Haaf,J. Pakusch, E.K.A. Wolber,andB. Mitller,Angew. Chem.Int. Ed., 30,893 (1991).

n-C6H13 b

Pinacolborane (l). Preparation:

HO OH \ / cH"-7-tcH" cH3 cH3

MOMO(CH2)4C-------l BH3.S(CH3)2 cH2ct2,0" - 25' -H2

CH.

P-/-cl1s

HB. I btCHs

CHs

MOMO(CH2)4C--:

Potassium t-butoxide. r..:J

to cyanides involves as the | ::\)\qene-triethylamine(1,957) or ' t()rm isocyanides followed by r!-rr.nr traditionallywas conducted a::.. risld when carriedout by flash \ - -. causeallyl isocyanidesrearrange a. 'r i J carboxylicacidscan be obtained

289

Hydroboration of allqnes and alkenes.t This borane is more efficient than catecholboranefor hydroborationof alkynes and alkenesin terms of regio- and stereochemistry and in tolerancefor various functional groups. ,CHS

. cH2ct2,25' + 1 ------

Hex-H

Hex

/orL"t' 'o\cn. 98:1 CHs

t:

eHs OctCH:CHz

-B.P-4-cH3

cH3(cHz)s

+

+ I

70"/"

I b\cH.

99:1 CHs * l

ArI*-COOH Y I CHs

r, :-rdsto opticallyactiveB-acyloxy

R_*_-cH2ocHo

+

Y

I NHCHO

I C. E. Tucker, J. Davidson, and P. Knochel , J. Org., 57, 3482 (1992).

Potassiuml-butoxide. Furan synthesis.l Reactionof an alkynyloxiranesuch as I with Koc(cHr)3 in (cH3)3coH/l8-crown-6resultsin isomerization to a furan 2, via an a-methylene homopropargylic alkoxide.Underthesameconditions thea-methylene homoproparglyic

,cH'

n-coHrs------lo

KOC(CH3)3, (CH3)3COH 18-Crown-6

cH20MoM

, cH2ocHo ON

--1"'" 7Oo/" i-" ur,"-{.., \ " rro " o"

^.-. rnd B. Mi;Jller,Angew. Chem. Int.

2

Br MOMO(CH2)4C-H

+

cr2PdlP(c6Hs)312 H N ( C 2 H 5 ) 2C , ul

cn/cnron

CHo

P-/-cH3 HB, I b-tctt" " bH. 1

KOC(CH3)3, (CH3)3COH oH 18-Crown-6

MoMo(cH2)4 ""_-!"' cH2oH

/cH" /-\

MOMO(CHd4-''\(.1./

o

ZgO

Potassiumhydride-18'Crown'6

sa Potassium nitrosodisulfonate [Fremr's the.c to route A 4,7-Indoloquinones' azoles such as 1 to provide 2, which undctl un&t 7-hydroxyindoles(3)' These products 4-formyl-7-hvdrtrrr This 4. gel to provide

furan 4' alcohol 3 cYclizes to the (1992)' 1J.A. MarshallandW'J' DuBay'An' Soc''l l4' 1450

Potassium hYdride- 18-Crown-6' 1'5-dien-3The anionic rearrangementof Asymmetric o"y-Cop' "ouonget'ent} and cis-isomers of 3 are diast"ereoselectivity'The transof the ols (3) can proceed witn trigtr 1' followed by (E)- and (Z)-reduction preparedby [2,3]-Wittig "u?'un*"t"n'of

cH3\w1cH3 CHs.,CH=CHCH3

o*'-ctts

OCH2C=CCH3 1

anti - (E\ '4

94o/ode

l

t

-78' 88%ln-BuLi'

cns:rz1"cHe CHs

6s\ CHs

1

cHo 9Hs \

Ho'%cHs CHg

l

cH.o/\fir o-\

uu ,u*lKH'18-crown-6

I

t'r?g,g

r.\r2-cn.

N

anti - (E\ -3

OH

CH30H. sio2

7W

I

cH30"^

cocH3

CHs:r,1",.CHs

HO' CHe anti - (E\ '2

a2"/"

Ho'\:"'cH3 a n t -i ( Z \ - 3 xH,t a-"'o*n-o 65' 75Y"1 {

cft-,-z7.cus

rrcld salt to the indoloquinone5 in 95cr since 3 is inert to this oxidant' 'l lJ.M. Sae,C. Marti, andA Garcia-R:sr:'

OMCHg svn-(E\-4 88% de

anti-(E)-(Z)-3' Rearrangementof (E)-3 provides triple bond to provide anti-(E)-and de' reaffangesto syn-(E)-4 in 887o in 947ode, whereasanti-(Z)-3 5973(1991)' I S.-Y.Wei, K. Tomooka'andT' Nakai'J' Org'' 56'

Potassium triethylmethoxide, (C:H' x( reanangcxt Ratnberg-Biicklund nnt ( involves (4), A eremantholide Ramberg-Biicklund rearrangemenl TL ( base (1), 2.2 eqtiv., and HMPA l(r c{ Use of less hindered bases resuhs marn

Potassium triethylmethoxide

291

Potassium nitrosodisulfonate [Fremy's salt, (KSO3)2NO, l). 4,7-Indoloquinones. A route to these quinones (5) involves ozonolysis of benzoxazolessuch as I to provide 2, which undergoesready dehydrationto 1-acetyl-4-formyl7-hydroxyindoles(3). These products undergodeacylationon chromatographyon silica gel to provide 4. This 4-formyl-7-hydroxyindole(4) is oxidized by buffered Fremy's

):

of 1,5-dien-3i,:r, rcarrangement k :,,rr\- and cls-isomersof 3 are J ^i r[:)- and (Z)-reductionof the

c.t3,,,2?"-.,.,,.cH3

I

-

1 ) 0 3 ,C H 3 O H 2) S(CH3)2

ou'-cus ;^: - (E)-4

65/0

94o/"de

OH 1

CH: -zn-.CHo ' l

CHO

a n t l - ( E -) 3

riO-

CHsOH, Sioz _ 700/o

\ OH

.

9Hs 1 \

,-ro-,%cHs

CH3 --y,r\,.CH3

2

cocH3

1, NaH2PO4

9Hs

"-'-cH30 aqo/^

cH3o OH

1 r'-t-"'CHs

anti - (Z) -3 :1

xH, ta-"ro*n-o rgo/ol

I C/3,-v"\y.CH3

I oMcH.

salt to the indoloquinone5 in957a yield. This ready oxidation is unexpected,particularly since 3 is inert to this oxidant. rJ.M. Saa,C. Marti,andA. Garcia-Raso, J. Org., 57,58g('lgg2).

syn-(El-4 88o/ode

c:'.rr ()f (E)-3 providesanti-(E)-4 .l :r rSei dc.

Potassium triethylmethoxide, (C2H5)3COK (2,349). Ramberg-Biicklund reanangement.t The key step in a synthesis of (+)eremantholide A (4), involves ring contraction of the chloro sulfone 2 by the Ramberg-B?icklund rearrangement.Thus treatment of 2 with this highly hindered base (1), 2.2 eqtluiv., and HMPA (10 equiv.) in DME at 70" provides 3 in 82Vo yield. Use of less hinderedbasesresultsmainly in reductionof the chloro group.

2-Pyridinethiol

l-oxide

CH3(CH2)6CH25O2C6H5 1, HMPA DME,70"

a2v"

Aco-N' R

H

H

c*rG:

(cHr6cH3

HCI,THF 25"

(CHs)z

Note that samarium diiodide can .t radical process (16,297). I D. H. R. Barton,J.C. Jaszberenyi. andC'

N-(2-Pyridyl)trifl amide ( l) I N-('+cllr Preparedby reaction of the amrtrP CHzClz at 20". Vinyl triflates.r These triffatcs arc 1 with N-phenyltriflimide,(cFlso: ): \c-l are considerablymore reactive than \1

I R . K . B o e c k m a n J, r . , S . K . Y o o n , a n d D . K ' H e c k e n d o r n , A m S ' o c ' 'l f 3 ' 9 6 8 2 ( 1 9 9 1 ) '

II

a CHe 2-Pyridinethiol l-oxide, 12,417. involves deprotonationof an Julia alkene slnthesis.t The Julia alkene synthesis to form a B-hydroxy compound a carbonyl alkyl sulfone followed by reaction with amalgam.Although sodium with reduction on sulfone, which is convertedto an alkene can be low' An step second the in yields (11,474), this synthesishas proved useful alcohol, known secondary the of xanthate of the alternative method is a radical reduction toresultinanalkene(8,497-498).Tributyltinhydride/AlBNwasoriginallyusedas AIBN or B(c2H5)3 is the source of radicals, but (c6H5)2SiH2 in combination with of N-hydroxyderivaties acyl with obtain yields also effective. Generally the highest 2-thiopyridine,preparedbyacylationof2.pyridinethioll.oxide.Yieldsaregeneralll. is formed' around 85% for this radical process, and only the (E)-isomer

I D. L. Cominsand A. Dehghani.Tenalv&t

Pyridylzinc halides' PyZnX. These reagentscan be preparedbr ra Coupling wilh ArX or (AtOlrO. reagentscouple with aryl halidcs tx preparationof unsymmetricalbiplndm

Pyridylzinc halides

cH3(cH2)6cH25o2c6H5

lle"LI" Lio\

(CHd6CH3

R

r'\ t

CHs

t

R

\J

H

H

_,',f l Bi:,

l

n.o-N/

/so2c6H5

CH3S,

S c6H6,25" -85o/"

l-o,

,so2c6H5

S

R

(CH2)6CH3

(cH2)6cH3

H C I ,T H F 25"

CHg

cH(cH3)2 !','OH

o

a Note that samarium diiodide can also effect this reductive elimination, also by radical process (16,297). I D. H. R. Barton,J.C. Jaszberenyi, Letters,32,2703 (1991). and C. Tachdjian,Tetrahedron

H CHs

o (*)-4

(2)' N-(2-Pyridyl)triflamide (1); N-(5-chloro-2'pvridvl)triflimide and pyridine in anhydride triflic with aminopyridine of the Preparedby reaction CHzClz at 20". Vinyl triflates.r These triflates are generally preparedby reaction of lithium enolates with N-phenyltriflimide,(cF3s02)2NC6H5,12,395.Thesenew pyridine-basedtriflimides are considerablymore reactive than N-phenyltriflimide'

orf

I r J , q 6 8 2( 1 9 9 1 )

1)LDA 212,-78' +

88%

CHs of an \r. ln\olves deprotonation a form to rr,i--rn()und B-hYdroxY sr:r \odium amalgam.Although i!:- .ccond step can be low. An | : :hc secondarYalcohol,known dr \lUN was originallYused as s',- *rth AIBN or B(C2H5! is rh .,irl derivatiesof N-hYdroxYi . l-trride. Yields are generallY 'l\. :rcr is formed.

CHs CHs

CHs

I D. L. Cominsand A. Dehghani,Tetrahedron Letters,33, 6299(1992\'

Pyridyfzinc halides' PyZnX. These reagentscan be preparedby reaction of halopyridines with activated Zn in THF' In the presence of Pd[P(CoHsb]a these zinc Coupling with ArX or (ArtO)zO.r for reagents couple with aryl halides or aroyl anhydrides. It is particularly useful preparationof unsymmetricalbipyridines.

Pymn-2-ones

1 ) Z n * ,T H F

z\

rff \*2

2\l ll ,Pd(o) \-N^8,. 81o/"

I T. Sakamoto,y. Kondo, N. Murata, and H. Yamanaka,Tetrahedron Letters,33,53'/3 (1,992).

Pyran-2-ones. Diels-Alder reaction of pyran-2-ones, Diels-Alder reaction of 2-pyrones' if successful,can provide unusual cyclohexenecarboxylicacids, but thermally promoted cycloadditionswith theseelectron-deficientdienesusually result in decarboxylationand aromatizationof the adductsas a result of the requiredhigh temperatures(6,29I-292). SuccessfulDiels-Alder reactionsof 3-bromo-2-pyrone(l) with the electron-richdioxole 2 canbe effectedwith a catalyticamountof ethyldiisopropylamineat 90" (4 days)to give the major adduct(endo-3) in 63Voyield. The adduct is hydrolyzedby p{oluenesulfonic acid in methanolto 4 as the only diastereomer.The trisilyl ether of 4 was transformed to the a,B-unsaturated ester5 by radical debrominationand DBU isomerization.l

endo-3 t"o",

oo",^| --'-l cH3oH

coocH3;13;"'ih"'^" 3) DBU oao/^

R3SiO'

Br

(-f".oo"r.

Ho"-foH

osiR3

OH 4

/P CH2=CHOR* -

13kbar,25' ------:l5-/o

il.oo"

u-/LR. (88:12)

Diels-Alder reactionsof 2-pvrorrs r without decomposition by use of higlt 1 to effect cycloadditionof 3-acyloxl-3-pt adductsin good yield.2Use of chiral r.inr I The highest levels of induction are otxcn' vinr l cth 8-(3,5-dimethylphenyl)menthyl et d Posner [2+4]Cycloadditions. pyronesand 2-pyridonesin detail' *'ith sg

(*'

\-,o I G. H. Posner and T. D. Nelson, J. Orc . 32 V. Propansiri and E. R. Thorton' Tenalrlm 3 K. Afarinkia, V. Mnader, T. Thornton. D \<

PYran-2-ones 295

,!r(,n Letters, 33, 53'13(1992)'

l. \lJcr reaction of 2-PYrones,if rr..- .rcids,but thermallypromoted and !..- ')lr rcsultin decarboxylation -292)' (6,29I temperatures h rch .: rr, n-. , I t rr'ith the electron-richdioxole e 3- ,prlamineat 90' (4 days)to give I :- nrrlrolyzed by p{oluenesulfonic x -r.rlrl ctherof 4 was transformed n.:

.rntlDBU isomerization'r

o' y''"B'

'cHs

oryo9{"". endo-3

| ,ro", s8*fcH.on Br

(-f""oo"r. oH

no'l OH 4

/i

)..2'

25'

/( O | -OAc

rl*)

Hoa-

(88:12)

can also be effected Diels-Alder reactions of 2-pyrones with reactive dienophiles withoutdecompositionbyuseofhighpressure(8,254)'Thisversionhasbeenused at 25" to give bicyclic to effect cycloaddition of 3-acyloxy-2-pyroneswith vinyl ethers reactions' diastereoselective in result can ethers vinyl of chiral adductsin good yield.2 Use ether and vinyl 8-(B-naphthyl)menthyl with observed are The highestlevels of induction (88:12)' ether vinyl 8-(3,5-dimethylphenyl)menthyl Posner et al.3 have reviewed Diels-Alder reactions with 2[2+4]Cycloadditions. (213 references)' pyronesand 2-pyridonesin detail,with specialattentionto the selectivity

Z'''r'o l l \--o

Z''-r'O

l l \-NR

I c. H. PosnerandT. D. Nelson,J. Org., 56,4339(1991)' 2V. Propansiriand E. R. Thorton,Tetrahedron Leuers,32,3147 (1991)' 48,9|1,1(|992). ] K. Afarinkia'V. Vinader,T. Thornton,D. Nelson,andG. H. Posner,Tetrahedron,

hydrofurans.These products could be formcc And indeed the product in the fint ctaml (Z)-isomer of this alkene followed b} clclt R6{

c>rl Raney nickel. Reductive N-N cleavage of hydrazines. A diastereoselectivesynthesis of chiral a-amino aldehydes(4) from glyoxal involves an intermediatedimethylhydrazone(l), which reactswith an alkyllithium to provide an a-substitutedN/,N/-dimethylhydrazine (2). The mildest method for cleavage of hydrazinesto primary amines (3) involves hydrogenolysiscatalyzed by Raney nickel at 30-50'. This Raney nickel reductive cleavageis markedly improved by sonicationand proceedsat atmosphericpressureof

cH3"*oH

{

CHq

t cH.#oH

l

CHr

-

H2 at 20' in CHrOH in yields of 66-847o with no racemizationor debenyzlation.r 1) H2NN(CH3)2

coHj ,coHs t'""."rn*""*.

ocH-cHo

coHs\_\

FHs

1) RLi

2l Hzo

|\N' /-\ \N1cHr;t cuHuu" CHs

Oxidation of chiral ketals.: Thc chrnl ro 2-hydroxyketal 2 with high (>99:l t cn proceedvia a perrhenateesterof a l-hr.Jro cther3 is oxidizedto the 2-hvdroxr kctal . comparableyield.

cH3,.

,cHt

1

coHs\-\

,CHS

F

coHsl-r.i.

HzlNi

"^r^'.'frlNN(CH3)2

,CHS

CHs

bH.

I

/R

cuHr"'(r'ftH,

66 - 84%

o.t/o .-\ I \.,.

Re:G

I

1

1) (Boc)2O 2l HCl2o/"

O R \ \ /

a-\

H

NHBoc

4 I A. Alexakis,N. Lensen,and P. Mangeney, Leuers,32,1171(1991);idem,Synleu, Tetrahedron 625 (1991\.

Rhenium(Vll) oxide, Re2O7. Oxidative cyclization of S-hydroxy alkenes.t Reaction of these substrates with Re2O7and a base (preferably 2,6-lutidine) in cHzclz at 25'provides 2-hydroxytetra-

^" l Bi:,^ J cHt.

,cHt

o'ro" ReP-

/'\ (, 3 I R. M. Kennedy and S. Tang, Tetrohedrtn : S. Tang and R.M. Kennedy, Tetrahedm

I cttt ltor

Rhenium(VII)

oxide

hydrofurans.Theseproductscould be formed by dihydroxylationfollowed by cyclization. And indeed the product in the first example is also obtained by epoxidation of the (Z)-isomer of this alkene followed by cyclizatron.

rc:. '.clcctivesynthesisof chiral (1), rrr, Jratc dimethylhydrazone \: i : .r:cd Nt,N/-dimethylhydrazine t, :rimary amines (3) involves r' I his Raney nickel reductive :.!.r\ iit atmosPhericPressureof

9Hs

9Hs

.H A.,^\.A

ou

----azu*

Ho.

"f,|)o^"t. (trans/cis= 33: 1)

e - : r z . r r i oonr d e b e n y z l a t i o n . l

CH: t.

1) RLi 2\ l12O

--\

N

NN(CH3)2 CH:

oxidation of chiral ketals.2 The chiral ketal I is oxidizedby Re207and 2,6-lutidinc to 2-hydroxy ketal 2 with high (>99:1) enantioselectivity.This reaction is believed to proceedvia a perrhenateester of a 2-hydroxy enol ether, since the 2-hydroxyethylenol ether 3 is oxidized to the 2-hydroxy kctal 2 by Re2O7in similar enantioselectivityand comparableyield.

cHs,.

CHs

cHs

,cHt

1

FH' c-r' 1-Nr /R (*|a*r, C-H..

fl

,cHs

o-.r,'o

I

Re2O7, base

(, (S)-2 (>99:1)

1

t'crsi(cH3)3 ""'' I 2) Bu4NF I

cHr.

,cH, o.'l oH

lBoc

-12. I171 (7991); idem, SYnlett, .t\

a

-)

*",o,.0"""

84"/"

\_/ 3 lr.,.irrrn of these substrateswith - .': 15" provides 2-hYdroxYtetra-

I R. M. Kennedy and S. Tang, Tetrahedron Letters, 33, 3'729 (1992) 2 S. Tang and R. M. Kennedy, Tetrahedron Letters, 33,7823 (1992).

2g8

Rhoilium(ll) carboxylates

*"1#i;t1,.:"'1".:t"1il:'

osi(cH3)3

(1) with 1-T,::h"..y11:ltrimethvrof vinyrdiazomethanes.

'#':l: i"ffi i,ior*".*o-*,:."f ti;';f ;*::*:IT,"l::*::"ffi

silyloxy)butadiene(2)catury'eouy,,t'ooiu-1tt)acetateorrhodium(ll)pivalateresultsin

(3). Short exPosureor :

I 4-ocs" (r)

CHz .' N 2 <)

I \cH,

booclt

2

o /,.'--' osi(cH3)3

1cooczH5 Rhc(OAc)a, CHzClz \

("oca"

87"/"

CH,.

N21 'COOCzHs

\.*, 2

7

1

1or.l'sip$ooczHs ,

I

\

(

)

1

o

o

Hlo+,rHF $1"oo""' o

/

o

\

/

cooc'Hu

boocr"u

ketoncs ritL Reaction of a-diazo thc prc'
4

3

/ ooa/gzY' /

uo,o"r"r'\ cooc2Hs

CHr

e

CHr -

5

Clr3 611"e.CH3 40o/o

with can be effectedin one step The conversionof 3^to 5 tropone5 in high yield' Vo(oczHs)Cl2'2 o*"ni"r"onr"xyoxovanadium' (7) (equationI)' shortsynthesisof nezukone u'J'o'-u Ju' This troponetynttt"'i'

Rhodium(II)

carboxYlates

(cH3)3sixcH3 rr ::h 1-methoxY-1-(trimethYlr r:,'Jium(II) Pivalateresultsin tr.i;'.1t() form a cycloheptadiene rrr:.i.rlitrn(DDQ) Providesthe

(r)

osi(cH3)3 L -ocft *

( \cr,

cHz ) ur{ coocH3

Rh2(OPiv)4 Pentane

(

67"/"

2

) -aoo"". 6 I

I

2 CH3Li

I

(cH3)3sio Hgo*

:':Cl2

cHg

59"/" from 6

HO

CHs

OH -,-*rCOOCtttt / -aaooarru

Reactionofa.diazoketoneswithallqnes'lRcactionoftheacetylenica-diazo of Rh2(OAc)aat 25' resultsin an intermediate kctone I with an alkyne rn the presence a , f o r m e d b y a n i n t r a m o l e c u l a r a l k y n e i n s e r t i o n ' t h a t r e a c t s w i t hby t h Rh2(oAc)+a eexternalalkyne of the cyclopropenegrouP to form a cyclopropene(2). Rearrangement

4 -""

/

/92%

l-t.

CHs CHs

-l

Rhz(oAc)+

[-

,".fu:r: a

CHa CH3C=CH3 4Oo/"

with ..'r hc effected in one steP I)' r..1- rrf nezukone(7) (equation

CH3

CHe

Rh2(OAc)4 CoHs' 80'

-

Rhodium(Il)

carboxylates

CHs

CHs

CHs

-Ei%* cHs

CHs

CHs

CHg

Reaction of cyclic diazo-I)4icarfu of 2 mol % of Rh2(OAc)a,2-diazo-1.-1
N 2t . "r n, -o o 3. provides an intermediateb that cyclizes to form the dihydropentalenone (3).s synthesis (+)-griseofulvin in recent asymmetric The key step a Synthesis of I with rhodium(Il) diazo ketone of this antifungal reagentis the decompositionof the pivalate to provide 2 in 62% yield as the only isolable product.

COOCH3

cH30

80%

-2

CHe

/

cH3\,o>-cH3 \____/ CHs

i + al1

Rh2(piv)a "u"u, . 620/o cH3o

RhrrOr( FCil!

*n"ooo'(l

\-t'-d

cH)'%cH, 2, cre-60"

I

several steps

cH3o

proceedsin even higher yield to gir.c 3 Tricyclic dihydropyrrolizines.Thc lidines (l) with a catalytic amountof a rhu octanoateand a dipolarophile(DMADt. rcs major product.The expectedproduct 121rs intermediatecarbonyl ylide a reananecsro

Rhodium(Il)

CHs

carboxYlates

30f

In the presence Reaction of cyclic iliazo-1,3-dicarbonyls with aryl heterocycles.6 with dihydrofuran to (l) reacts of 2 mol 7a of Rhz(oAc) 0,,2-diazo-1,3-cyclohexanedione 2,5-dimethylfuran with I of reaction yield. The in 7O% form the dipolar cycloadduct 2

CHs

&:-,QHOffi 3. | .:1h\JroPentalenone synthesis asymmetric a recent rn rda rhodium(Il) with 1 ketone Jr.rzo h.

-o.,"r^ " ' - | cH3-7o'vcHs 12 \\ /

t

-

CHs

ahl! nroduct.

,Z>-x

1 + l

Rh2(oAc)4

l l )

\,,,^o

H 36/o

2, ce -€0' ul1.

proceedsin even higher yield to give 3' Tricyclic dihyilropyrrolizines.l The reaction of N-acyl-2-(1-diazoacetyl)-pyrroparticularlyrhodium(Il) lidines (1) with a catalytic amount of a rhodium(Il) carboxylate, 3 as the dihydropyrrolizine octanoateand a dipolarophile(DMAD), resultsin a tricyclic majorproduct.Theexpectedproduct(2)isformedonlyintraces(|07o),Apparentlythe azomethineylide b' intermediatecarbonyl ylide a rearrangesto the more stable

Rhodium(II)

carboxylates

Rh2(oAc4t Q#l :i

(vd

1"".\.J-l l"".-l|o.J l a I I DMAD V

b I I DMAD V

Rhodium(Il) pyroglutamates" A symm etric cyclop rop natioe. rhodium(Il) acetateand various amrdc catalystsfor enantioselectivecvcloprot promising to date are preparedfrom m tetrakis(methyl 2-pyrrolidone-,5-carbor

effect intramolecularcyclopropanalr propanated7-lactones3 in 65 > tNt is higher in cyclopropanarionof (Z)-i

CHs

0) "

cH3ooc 2 (1O%)

3 (877")

'r^o^

rR

Reaction with cyclopropenes.E Reaction of the cyclopropene I with Rh2(OAc)4 in C6H6 (80') results in two furans, 2 and 3, in 78Va and 3% yield, respectively.Thus the less substitutedbond is cleaved selectively.In contrast,treatmentof I with a Rh(I) catalyst in CH2CI2 at 25' gives only furan 3 in 867o yield.

H

(CHz)rCHg CHs ,n-C5H11 CHs ,H Rh2(oAc)4,80" )--{ ),-< / / \ \ + i l \ \

\7 cHlcoHu o

82o/"

(CHz)aCHs

\7 cHlcoHu o 1

\\

//

2 (7$o/o)

1 H

I

c6Hs-\o,^H

CHa 2s" lcrRh(co)212, 860/"

\\

n-CsHrr C6H5---\g 3 (37")

H

ll

I

Rz 2 R1,R2=H R1=H,R2=Cf R 1 = P r .R 2 = H

E nantio sele ctiv e cyclop ropc nab highly enantioselectivecyclopropcnr enantioselectivityincreases*'ith rlr , polarity of the alkyne substituenralstrel is observedwith d-menthyl diazorctr

HC=CR

*

NZC|(

l \

cuHu4o,^(cH2)4cH3 3

R=CH,OCH. R =C R=CHzOCH: R =d

I H. M. L. Davies, T. J. Clark, and G. F. Kimmer, J. Org., 56, 6440 (1991). 2 T . H i r a o , M . M o r i , a n d Y . O h s h i r o ,i b i d . , 5 5 , 3 5 8 ( 1 9 9 0 ) . 3 T . R . H o y e a n d C . J . D i n s m o r e ,T e t r a h e d r o n L e t t e r s , 3 2 , 3 7 5(51 9 9 1 ) . a P . M i i l l e r , N . P a u t e x ,M . P . D o y l e , a n d V . B a g h e r i ,H e l v . , 7 3 , 1 2 3 3 ( 1 9 9 0 ) . s M . C . P i r r u n g ,W . L . B r o w n , S . R e g e ,a n d P . L a u g h t o n , A m .S o c . ,1 1 3 , 8 5 6 1 ( 1 9 9 1 ) . 6 M. C. Pirrung, J. Zhang, and A. T. McPhail, J. Org., 56, 6269 (1991). 7A. Padwa, D.C. Dean, and L. Zhi, Am. Soc., ff4, 593 (1992). 8 A. Padwa, J. M. Kassir, and S. L. Xu, J. Org., 56, 6971 (1991).

R=Bu

R =r{

R=Bu

R -d

Yields and enantioselectivities arc I Asymmetric synthesis of lactonr.' ligand, dirhodium(Il) tetrakis[merhrI I

Rhodium(II) pyroglutamates

b I I DMAD I

o.\\

Rhodium(Il) pyroglutamates. Asymmetric cyclopropanation.r The ability to effect ligand exchange between rhodium(Il) acetateand various amideshas lead to a searchfor novel, chiral rhodium(Il) cyclopropanationwith diazo carbonylcompounds.The most catalystsfor enantioselective promisingto date are preparedfrom methyl (S)- or (R)-pyroglutamate(1), [dirhodium(ll) Thus thesecomplexes,Rh2[(S)-or (R)-1]a' tetrakis(methyl2-pyrrolidone-5-carboxylate)1. effect intramolecular cyclopropanation of allylic diazoacetates (2) to give the cyclopropanated7-lactones3 in 65 > 94% ee (equationI). In general,the enantioselectivity is higher in cyclopropanationof (Z)-alkenes.

/-\r-f \*11 -cHs \_/

coocH3 O C . l 3 cH3ooc' 3 (870/"1

o

ri'^o'\

(r) ._A_" -R2 lR'

t-C.H11

.

CHg \--1

,H

ll \\

C6H54g^n-CsHtr 3 (3"/")

,

J.l,

\--+'\ )-' 3

2

: .\.I()propene1 with Rh2(OAc)4 .,:.i .l'i yicld, respectively.Thus c::.:\1.trcatmentof I with a Rh(l) '.:,lJ.

.

H

R.

88o/oee

R1,R2=H

74o/o

fll=H, R2=C2H5

88"/"

> 94Y" ee

R 1 = P r ,R 2 = H

74%

75o/o9e

Enantioselective cyclopropenation.2 This chiral rhodium(Il) catalyst can effect highly enantioselectivecyclopropenationof l-alkynes with alkyl diazoacetates.The enantioselectivityincreaseswith the steric size of the ester group, and the size and The highestselectivity polarity of the alkyne substituentalso affectsthe enantioselectivity. is observedwith d-menthyl diazoacetatesas a result of double diastereoselection.

H l

H

ll :l'j::lli.'",QtY'-"'

HC=CR

+ N2CHCOOR'

_COOR'

1

nRH o

^(cttd+cHs

R = CHzOCHg R'= CzHs

73o/o

690/oe€

R = C H z O C H s R ' = d - M e n * 43o/o

98/o ee

3

5 $ , , r 1 ( l( 1 9 9 1 ) . t, . - r : 11 9 9 1 ) . -.1 l:33 (1990). , . { * \ ' r r . .1 1 3 , 8 5 6 1( 1 9 9 1 ) . .'i',rle9l). t

l

R=Bu

R'=f-Bu

R=Bu

R'=d-Men*

53o/oee 46o/o

860/o€€

are low in reactionswith disubstitutedalkynes. Yields and enantioselectivities Asymmetric synthesisof lactams.3 A rhodium catalyst with a chiral oxazolidinone ligand, dirhodium(Il) tetrakis[methyl2-oxazolidinone-4(S)-carboxylate](1), can effect

304

dioxide Ruthenium(IV)

cyclizationofN-2.alkoxyethyl-N-(t-butyl)diazoacetamide(2)toN-(l-buty|)-4-ethoxy.2pyrrolidone 3 in 78% ee and 977o yield'

czHso(cHz)z-''-c(cHs)s I

Ao lt

a\

D

c2H5o.^,yz'\N-c(cH3)3

c^H 'Ic t ' ' I -;;-

\

X

N2

t

'o

3'78o/oee

2 In the presence Enantioselective cyclopropanation of homoallytic diazoacetates.a

Salicyl alcohol (2-hydroxybenzyl elcotof I IJnsymmetrical biphenyls.t This ako of unsymmetricalbiphenyls with suhsrrtr Ullmann coupling.The two esterbondi of !i by NaOCH3 or a PrimarY amide.

ofthischiralcatalyst,homoal|ylicdiazoacetatesundergoasymmetricintramo|ecular in ll-9oVo ee' cyclopropanationto form oxabicyclo[4'1'O]heptanes

Nr lt-

"t'\-oV cHz

o

.'\foH

i l H

1, cH2cl2 760/o

o

\A*

?^Y> VCHs

+

791" ee Am' Soc"ll3' I M.p. Doyle,R.J. Pieters, S.F. Martin,R.E. Austin,C'J. Oalmann'andP' Miiller' 1 4 2 3( 1 e e 1 ) . (1992)' 2 M. N. Protopopova, M. P. Doyle,P Miiller,andD' Ene'ibid" ll4' 2'755 Letters,33, and K.L. Danidr,Tetrahedron 3M.P. Doyle,u.N. r,otopopouu, w.n. Winchester, 7819 (1e92\. aS.F. Martin,C.J. Oalmann, andS' Liras,ibid,33' 672'7(1992)'

Ruthenium(IV) dioxide, RuOz' (2 equiv') in a TFA/TFAA medium is Oxidative phenolic coupling.t RuOz'2HzO I to afford the lignan prostegoneA (2) an excellentreagent fo, po,o-po'o coupling of in80%yield.SubstitutionofRuo2byTl2olalsoconvertslinto2,buttheyieldis45To.

RuO22H2O BFgO(CzHs)z cH2cl2

.\o

T1IFryq* 80/o

I M. Takahashi,Y. Moritani, T. Ogiku. H ()htr

33, s103(lee2).

rJ.-P. Robin and Y. Landais, Tetrahedron,4S'819 (1992)

Samarium/Methylene iodide (ll.l-5 t. Cyclopropanation of viny lorgand tion of allylic alcohols substitutedhr srlr selectivity particularly when carried oul r

,sg- rl1 to N-(l-butyl)-4-ethoxy-2-

a't

D h:O -Kz'\N-C(CH3)3

\ --\ /

Salicyl alcohol (2-hydroxybenzyl alcohol). Unsymmetrical biphenyls.t This alcohol can be used as a template for synthesis of unsymmetricalbiphenyls with substituentsat ortho-positionsby an intramolecular Ullmann coupling.The two esterbondsof the coupling productcan be cleavedselectively

'o

3.78"/oE@ c duJtacetates.a In the Presence h--::\, asvmmetric intramolecular n

by NaOCH3 or a primary amide.

"tr? cH3ol.,o]

\rll' h eC.

+

6'\"\0H

\A*

*

/\ i l l *or/t(tcoct

f\cocr

7s%-

I

o ): '- ,nn. and P. Miiller, Am. Soc.' ll3, | : l l { . 2 7 5 5( 1 9 9 2 ) . h i Daniel, Tetrahedron Letters, 33' r .,1r

r.Yoffiocn" \z\o

,r.,,,,.$ocH,

o

UU DMF. A

9O"/o

Noz

860lo ruaocns

medium is c-.-r,. ) in a TF{TFAA ,:J thc lignan Prostegone A (2) i:: L r- : : . I i n t o 2 , b u t t h e Y i e l d i s 4 5 V o .

lr,O

|

ocH3

o .\o

r'\r'-\oH + 9o,

ocH3

H.O I M. Takahashi,Y. Moritani, T. Ogiku, H. Ohmizu, K. Kondo, and T. Iwasaki, TetrahedronLetters,

33, s103(lee2). Samarium/Methylene iodide (14,275). Cyclopropanation of vinylorganometallic compounds.r Molander cyclopropanation of allylic alcohols substitutedby silyl or stannyl groups can show high diastereoselectivity particularly when carried out with a large excessof the samarium reagent.

306

Samarium(O)/Samarium(Il)

iodide

The diastereoselectivityof an (E)-vinylsilane (1) depends on the steric bulk of the R group (equationI). Higher diastereoselectivityobtains in the cyclopropanationof a (Z)-vinylsilane (2), and is not affected by size of the R group (equation II). H I ( l ) ( C H s ) s S i)

-

uR

l

H

l

O

(cH3)3si. H

* *

H

81% 46:1 76o7o1:1O

H

t (cH3)3si oH

7

rA. Ogawa,N. Takami,M. Sekiguchi. I Rr1 (1992\.

1 a ,R = c - C o H r r lb, R = CHg

(ll)

9^Snt n+

(CHs)sSi'

H

,H"/'\rR , | ^

coHscoN(czHs)z

-

H-A-'n(cHs)ssi-*?R t l oH

H -n . . H ^

* 1cH.;rsi.--*-y't

OH

670/0 >1OOt<1 67% >100:<1

2a,R=Pr 2b, R = CHs

Samarium(Il) iodide. Coupling of lactones and kctor6. carbohydrate-derivedlactone such as I r followed bv a carbonvl addition reacrrm t

o

.Yo.r=o

Cyclopropanationof allylic alcohols substituted by a tin group gives a single diastereomerin good yield. These tin-substitutedcyclopropanescan undergo /ransmetalation (CH1Li, THF, 0').

\

/ * lor=,

1

,

-

\

cHrN

27o/o Bu3Sn

-t

cH3LiI Li

I ","

l-

H

ocH3

I M. Lautensand P.H. M. Delanghe, J. Org., 57, 798 (1992).

Samarium(0)/Samarium(Il) iodide. Deorygenative coupling of amiiles; vic-diamines.t This combination (1:2) can effect dcoxygenativecoupling of amides to form vic-diaminoalkenes.

Reduction of ATCOOH and dcritti to ATCH2OH by Sml2 (excess) in thc p actd (85%). In contrast pyridinecartxxrl methyfpyridine in 43-48Vo yield. Bcna reducedto benzyl alcohol, but in loscr r' conditionsto benzylaminein 99% rrcld. f Unexpectedly,SmI2 reduction of amd yield. Aryl radical cyclization.t Sml; cen I bromides with double or triple bonds. Th to heterocycles.

Samarium(II) iodide

sm/sml2 CeHs " -H 4 C6H5CON(C2H5)2 72/" (c2H5)2N'

dci(-nds on the steric bulk of the y-::r\ in the cyclopropanationof a c R rroup (equationII).

.N(c2Hs)2 'buH,

EIZ = 38:62

H

{

(cH.).si. n .H R +' -'H-+-<./.R OH

OH

rA. Ogawa, N. Takami, M. Sekiguchi, I. Ryu, N. Kambe, and N. Sonoda,Am. Soc., 114, 8729

(1.ee2).

8 1 o / o4 6 : 1 76/0 1:10

Samarium(Il) iodide. Coupling of lactones and ketones.t Sml2 in THF/HMPA effects coupling of a carbohydrate-derivedlactone such as I and a ketone that involves oxygenation of I followed by a carbonyl addition reactionwith high diastereoselectivity.

+ (cH3)3si O

B

I

6-.^ >100:<1 6-.- >100:<1 c ^\ a tin group gives a single (.,.1,'propanescan undergo trans-

B=to-\o17o {o' 1

,

.

t

H l

BzlO

^ - O

l

o ,,tCHo

(cH3)2cH

OH

( 3 5: 1 )

ocH3

('-:

cHsN

I

-"\rt'

td\

-

o sml, ll -\,,,cr1cHr;, - rHr]l'fipn 44|t Il

I-his combination(1:2) can rri noalkenes.

Reduction of ATCOOH and derivatives.2 Aryl carboxylic acids can be reduced to ATCHzOH by SmI2 (excess) in the presenceof an acid, particularly phosphoric acid (85Vo). In contrast pyridinecarboxylic acids are reduced to the corresponding methylpyridine tn 43-48Vo yield. Benzoic anhydride and benzoyl chloride are also reducedto benzyl alcohol, but in lower yield. Benzonitrile is reducedunder the same conditionsto benzylaminein 99% yield. This behavior is characteristicfor aryl nitriles. Unexpectedly,SmI2 reduction of amides provides aldehydesin almost quantitative yield. Aryl radical cyclization.3 Sml2 can promote an intramolecular cyclization of aryl bromides with double or triple bonds. This electron-transferreaction is a useful route to heterocycles.

Samarium(Il) iodide

,.\,,.8t

sml2

zCHz

/CHs

cH2ct2,2s"c

\r[--J

70%

(CHs)sCCOCl+ CHgCHzCHO

/,\1-{'

\z\r, H

('\

i

A

Ad.dition of CICH2OCH2CaHI to ( chloromethyl ether adds to carbonvl compu adducts on hydrogenolysisprovide l.l-Jxrl

FH"

*-''lll rrffi

\."^-o

\.Aol

o

Barbierlaldol

reactions of enones,a The iodo enone I on tfeatment with Smlz

(2equiv.)inTHFcontainingDMPU(l0equiv.)undergoesreductivecyclizationto (2) in 7O7oyield. Such reductivecyclizationshave been the bicyclo[3.3.0]octane-3-one is that it proceeds effected with a tin hydride. The advantageof the SmI2 reaction

q'.

I

I

gt,

os''"lep-o.,.I +*-F" ":' L "'. a

.i

zo%ln.sio(cn')'cno V

-,\tl-CHs CoHts-

crcHrolHrcuH,

o tl

-

L

cH3 cHoH (cH2)3osiR3 3

with an aldehyde' through a samariumenolate(a), which can undergoan aldol reaction dicyclopentadienylsamarium or of SmI2 equiv. 2 of presence In the i-Krtotrj (SmCp,),acidchloridescoupletoa-keto|sviaanacylsamariumintermediate.Inthe of ready air oxidation caseof benzoyl chloride, benzil is obtainedin high yield because a mixture of Rcocl of by addition formed also are a-Ketols of the intermediateenediol. (2 equiv')' of SmI2 solution (1:1) to a and RCHO or RCOR

C>l-a -r+ O 71

(=(-t"' \/

o

I

\-zf--,2 l

84cb

This Barbier-typereaction *ith ('ll-l cyclopropanols. Highest yields of xrlt CHzIzlSmIz-- 1:3:2.

CHs

,/--n, ( l F o

THF 25

ra*a

CHzEt

O -

\/

a-'(o t l

1 L } 2l Cxr: Sr. 55'a

Cyclization of allqnyl halidcs: retlll Bu3SnHfor cyclizationof 6-halo-l-rrrr g with DMPU as a cosolvent with THF

Samarium(II)

-\r1

/cH"

t l-N

(CH3)3CCOCl+ CHgCHzCHO

o It

2 Sml2

(cH3)3c-

64o/"

/

iodide

-cHzcHt Y OH

H

/

CHlr

-

r-\

In the presence of Sml2, benzyl Addition of CICHzOCHzC6H5 to )C:O.o chloromethyl ether adds to carbonyl compoundsto effect benzyloxymethylation'These adductson hydrogenolysisprovide l,2-diols.

,.\o

o .r 'nc I on treatmentwith Sml2 u:.lJrgocs reductive cyclization to :h :rJuctive cYclizationshave been

c6H13

cH3

Ho..

rHF.25. rcHs ---u*----* cur" t!o-"'"c6H5 crcHrolnrcu'u

rcaction is that it Proceeds

\lrl

This Barbier-type reaction with cHzlz can be used to obtain iodohydrins and cyclopropanols. Highest yields of iodohydrins obtain when the ratio of kctone/ CHzIzlSmIz: 1:3:2. "

H.

7oo'o

?

f^a^ F - : F I O

smt2, cH2t2,

tot/ttt

,

-cHs---7E-U rHFo" ' 25'

U

?

smt2, cH2t2,

?t

fff.H,e,.-fffa=av v \ 2 )s R3

r,"tl,l,?t',,/-\-oH a'-'
56%- L-A

Cyclization of allcynyl halides; methylenecyclopentanes'1 SmI2 is as effective as Bu3SnHfor cyclizationof 6-halo-1-ynes'particularlywhen used in excess(3 equiv.) and with DMPU as a cosolvent with THF.

iodide

Samarium(II)

R

R

*t]at

I

-lll r' '1,('"*'''Jll'"''oA (,

(,

83"/o 817o 67o/o

R = CoHs R=Bu R = Si(CHs)s

(cHr)"

1 ) S m l 2T, H F , 0 " 2) Ac2O,DMAP

OAc

)-coocnt

2(1:1)

69"/" 75V" 82o/"

Reductivecyclizationofunsaturatedketones.gTreatmentofunsaturatedketones w i t h S m l z ( 2 e q u i v . ) / H M f A l a " q u i u ' ; c a n l e a d t o 5 - a n d 6 - m e m b e r e d c a r b o cprovide ycles'The can be trappedwith variouselectrophilesto intermediateorganosamariun-l.,p""i", diastereoselective' elaboratecarbocycles.Both processesare highly S m 1 2H, M P A THF. I-BUOH

cH.A-t--'AcH,

(cHd30s

coocH3

I

o

o

(60%)

(CHz)"I

Br'

n=6 =9 = 13

1

2o/o 8o/o

IntramolecularReformatslcyreaction.sMedium-tolarge-sizedringscanbeobester (1) with SmI2 in THF followed by tained by reaction of an a-bromo-@-oxo 1'r'r-diols or cycloalkanones' acetylation.The precursorsof 1 can be

cHo

a-Go,J#i,,u,l /"r7 l:

HO.

86"/"

'.* l3$e,[YiA"" f

/CH3

er-"t' (>150:1)

(2 equiv') can effect cyclization of the Vinylogous Barbier reaction'a SmI2 DMPU (or HMPA) to give a bicYclic unsaturatediodo ketone I in THF containing by an aldol reaction' samarium enolate (a) that can be trapped

Reduction of fiJN02.to Priman' \'\1r duced by SmIz with CH3OH as thc Jrtrtn amines depending on the amount of Sml; in THF/CH:OH (2:1) for less than hrc mra 60-93Vo. Reactionswith 6 equir" of Sml; fo

in 50-tl{X? rrld the 4-phenylbenzamides, Review of SmI2 reduction of luliJct r reviewsvariousproposedmechanismsftx thc may involve organosamarium(lll)intcrrr'$

lE.J. EnholmandS. Jiang,Tetrahednn Ictut 2 Y. KamochiandT. Kudo,Tetrahednn4 lJ 3J. Inanaga, o. Ujikawa,andM' YamagrrtrrIa aD.P. CurranandR.L. Wolin,S.rn/erl. -:l- r19 s J. Collin,J.-L.Namy,F. Dallmer.and l{ B li 6T. Imamoto,T. Hatajima,N. Takilama'T Tt Perkin I, 3127 (1991) 7 S.M. Bennettand D. Larouche. S}n/r'r' {f I 8 J. lnanaga, Y. Handa'and \l l. Y. Yokoyama' e G.A. MolanderandJ.A. McKie.J ()rs 5: r0A. S. KendeandJ.S. Mendoza,Tetrahedna l' ll D. P. Curran,T. L. Fevig,C. P. Jaspcrscrn: \

Samarium(Il) iodide-Lithium emilc. Stl Reduction of esters, anhydrides. u col by SmI2 in combinationwith a ba*- (Lr\H; : source)in THF at 25' to alcohols

Samarium(Il)iodide-Lithiumamide

Sml2

,^-t.-.-^1

( ,) ,

|

rHvoueu

!g

CHS

l- ?".

I

g"

CH,

_l

cH.

3lt

r'"* lc]1-o'l tuYo fi^;o \'t-l I Y---/ | L

a

2

2%

l.rr,o1"rr1.cro

8o/o

+ r- :,, large-sizedrings can be obu::h Sml2 in THF followed by :r.l,,.rlkanones.

9H,

,l--L-r

( l F o v-t-/ t

)

tj|F-t.ri3osiR3

OAc

/AYlr

+ (

9H'

| F o \--1-< cH. \__16HrgOSiRs

I

{ u n 2 1 n1

(60%)

(5-20o/o)

coocHs 2 ( 1: 1 )

T:J.irmentof unsaturated ketones n.: r)-memberedcarbocycles.The ll: r .rriouselectrophilesto provide rtL \\clcctive.

qQ

zcH,

l'' A-cH" T

_

>150:1)

) ..:n cffect cyclization of the ' ': HMPA) to give a bicyclic f(i.:l()n.

Reduction of RNo2.t(. primary, secondary,or tertiary nitroalkanescan be reduced by sml2 with cHroH as the proton source to either alkyr hydroxylamines or amines dependingon the amount of Smr2. Reactionswith 4 equiv. of Smr2 at 25" in THF/cH:oH (2:l) for less than five minutes provides hydroxylamines in yields of 60-93%. Reactionswith 6 equiv. of Sml2 for eight hours provides amines, identifiedas the 4-phenylbenzamides, in 5o-80o/o yield. Review of sml2 reduction of halides and radicals. This report (69 references) reviewsvariousproposedmechanismsfor thesereactions,and suggeststhat both reactions may involve organosamarium(IlI)intermediates.rr I E.J. Enholmand S. Jiang, Tetrahedron Leuers,33, 6069(lgg2). 'Y. Kamochiand T. Kudo,Tetrahedron, 49, 43Ol(1992\. 3J. Inanaga,O. Ujikawa, and M. yamaguchi, Tetrahedron Letters,32, 1737(l9gl). a D. P. Curranand R.L. Wolin,Synleu,317 (1991). 5J. Collin,J.-L.Namy, F. Dallmer. andH.B. Kagan,J.Org., 56,3ll8 (1991). 6T' Imamoto'T. Hatajima, y. Kamiya,and r. yoshizawa, N. Takiyama, T. Takeyama, J.c'.S. PerkinI, 3127 ('19911. 7S.M. Bennettand D. Larouch e, Synlett,U05( 199| ). "J' fnanaga, Y. Yokoyama, Y. Handa,and M. yamaguchi, Tetrahedron Letters,32,637r(1991). " G.A. Molander andJ.A. McKie,J. Org., 57, 3132(lgg2). r0A. S. Kendeand J.S. Mendoza,Tetrahedron Leuers,12, 1699(1991). rr D. P. Curran,T. L. Fevig, p. C. Jasperse, and M. J. Totleben, Synteu,943(1992). Samarium(Il) iodide-Lithium amide, SmI2_LiNH2. Reduction ofesterc, anhydrides, or carbonyl groups, These groups can be reduced by SmI2 in combinarionwirh a base(LiNHr, LiOCHj, or KOH) and methanol(hydrogen source) in THF at 25" to alcohols.r

3r2

Selenium dioxide

Sml2,LiNH2' C H g O HT, H F ,

c6HscoocH3

Cyclic diacetylenescan also be obtatt as s-cyclodecynone7. In this caseonlr

C6H5CH20H

64o/" F

C6H5CH2NH2 8"/o

CoHsCHzOH 81"/"

C6H5CONH2

C6H5CH2NH2 + 45o/"

C6H5CH=NOH

c6HscH20H 3/o

wo

80+

7

t - \ \-r---/

Letters'32' 3511(1991)' rY. KamochiandT. Kudo,Tetrahedron Selenium dioxide' SeOz' of a to cyclic diacetylenes involves reaction Cyclic diaceEtenes' A useful routc c y c l i c d i k e t o n e s u c h a S l w i t h s c m i c a r b a z i d e a c e t a t e i n e t h a n o l t oaffords a f f o r dcyclic 2.Reaction (3 and 4)' which on thermolysis of 2 with SeO2 tbrms selenadiazoles diacetylcnes5 and 6'

c- 2q

*o*-5" 9

I R. Gleiter,D. Kratz,W. Schafcr'ir: \

H2NCONHNH2'HOAc c2H50H 94o/o

H2NOCHN

Selenium dioxide-Trimethl lsilll I Aromatimtion of cYclohcxctct t fected in refluxing CCl.r br trcatnral 11,427; 12,543). Note that a crckrttt

2

gi#=

__1t"il

\'{]!X*

*'iu-J.-,^--(,i\ ;,

?"'

..,S"*--r--/-\-rl

.)

Y

CHCHd z

3

-'*"

I "*'"'''""0'

I

rJ.G. l-ee and K.C. Kim. Tetrahe'lnqL

I

5 (4olo)

6 (27%)

Silver trifluoroacetate, CF.COO"\ga-Allqlation of ketoncs" Srlr (but not bromides)activatedbr stlra generallymoderate.this reaclion ts I

Silver trifl uoroacetate

313

Cyclic diacetylenescan alsobe obtainedby a similar strategyfrom a cyclic ynone such as s-cvclodecvnone7. In this caseonlv one selenadiazoleintermediate(9) was formed.r

20t

:o*

----

C6H5CH2NH2 B% \

i:NN: I

C6H5CH20H 3o/"

.1--,

2

1 Bovo

o 7

\

SeO2

',li'-NHcoNH2 a

, , rI )

\-?v l;i.

,.ct\'lenesinvolvesreactionof a rn cthanol to afford 2. Reaction . r ()n thermolysis affords cYclic

Cu,200'

*or-5" 9

1R. Gleiter,D. Kratz,W. Schiifer, Soc.,113,9258(1991). andV. Schehlmann,Am.

H2NOCHN

Selenium dioxide-Tbimethylsilyl polyphosphate (PPSE). Aromatizption of cyclohexenes and clclohexadienes.t This reaction can be effected in refluxing CCla by treatmentwith SeOz (1 eq.) and PPSE (10 cquiv.; 10,437; 11,427; 12,543).Note that a cyclohexanefused to an aromatic ring is not affected.

2 CHe

I '

-

Y

'"3a,::" ?r. ,i.\ -l*"\2

cHcH3)2

I

cHCH3)2

-* J2.Cu(o) ' 80'

I J. G. lre and K. C. Kim, Tetrahedron Letters,33, 6363(1992).

t

6 (27o/o)

Silver trifluoroacetate, CF3COOAg. 14,331; 16,30l -302. a-AllElation of ketones.l Silyl enol ethers can be alkylated by n-alkyl iodides (but not bromides)activatedby silver trifluoroacetate(1 equiv.). Although the yields are generally moderate,this reaction is a useful route to a-alkyl ketones.

314

Sodium borchydride-Cerium(III)

chloride (Luche reagent)

OSI(CH3)3

cF3cooAs cHeclz ,

+ RGH2[

Sodium bor*rl

cH2R

Ff(

a

qr-Apz

83Yo 56Vo 50/"

R=H R = CHsCHz R = CzHsOeC

_o [-K.-cns \l-(\cHe \ o

R"/

l a , R l , R 2= C H g

NaBH4,CfuOH, -78" rc.w.

Jefford, A.w.

Letters,33' 1855 Sledeski,P. Lelandais,and J. Boukouvalas,Tetrahedron

CH3OH NaBHa , -78' , CeCl2,

(1ee2).

Silver trifluoromethanesulfonate' AgOTf' (3 equiv') markedly promotes Iod.ocyclization of carbamates'l Silver triflate iodocyclizationwithlr4/,s-Stereoselectivityofcarbamates(1)derivedfromaminoacids,

o 1 2 c, c l 4

cooczHs -+#-

\o

"*\- |

,lcooc2Hs

f"''

t3 r) \-J

(20:1)

including NaBHa, results in highlr r<'lct-r give the endo-alcohol(2). Reaction srth \ provide exo- and endo-2 in ths 131i6q6 i I (85/15) even when only 0.1 cquir. of ('c The order of admixture of the reascnts hl

all is observed if the ketone is addcd t.' tl this case may be the unreactivesuJium tct reactionof NaBHa with the solvent is suppt with CeClr is comparableto NaBH. Cc{-I,. borohydrideshow only moderateslerc'osclcc stereoselectivereduction obtains in thc ab* However, the endo-methylgroup at C^ of lt

is reducedto a l:1-mixture of alcohols anti-Selective reduction of epox-t Laa cpoxy alcoholswith high anti-selectivitr un

H

?,t oY* o

cooc2H5

ttl,,,

cooc2H5

i-Fr "[;' (18:1)

Letters,33, 425'7(1992)' r y. Guindon,A. Slassi,E. Ghiro,G. Bantle,andG. Jung,Tetrahecrron

chloride (Luche reagent)' Sodium borohydride-Cerium(Ill) selective The Luche reagent is useful for Stereoselective reduction of ketones'. enones of reduction selective for of aldehydes,and reductionof ketonesin the preslnce of reduction hydride of selectivity can also invert the and enals to alcohols. rrr" ,'eug"nt hydrides' of la with a metal boron and aluminum cyclic ketonessuch as la' ReJuction

COCH,T -

-i')'

CHo 1.."9

)i

4-"t. oAcn.

NaBHr. C4Cb cH3oH 94$

,o 827."

HO-

Sodium bomhydride-Cerium(III)

a Ragcnll

('(" $cHrR E3'.

HO

.,O

1CslAs

/T-9cH"

ti{cn. \ o

\

l

nrARz

l a , R 1 , R 2= Q f l 3

rrtl.,:e (3 equiv.) markedly promotes r.::I.itcs (l) derived from amino acids.

tr

\

fo

HN

cooczHs

(20:1)

t

o \o **.- | ,acooczHs i F' "[.'' (18:1)

.O

u

endo-2

exo-2

7:93 96:4

NaBH4, CeCl2,CH3OH, -78'

including NaBHa, results in highly selective attack from the least hindered face to give the endo-alcohol(2). Reaction with NaBH+-CeCl3 (1:1) results in reduction to provide exo- and endo-2 in the ratio 96:4. Reduction to the exo-alcoholpredominates (85/15) even when only 0.1 equiv. of CeCh is present, but the reaction is slow. The order of admixture of the reagentshas no cffcct at -78', but no rcduction at all is observed if the ketone is added to the reductant at 20'. The actual reagent in this case may be the unreactivesodium tctramethylboronate.Apparently at -78' thc reactionof NaBHa with the solvent is suppresscd.Lithium borohydridein combination with CeCl.r is comparableto NaBH+/CeCl3,but chlorocerium borohydride and ccrium borohydrideshow only moderatestereoselectivity with la (exolendo: 65:35).The same stereoselectivereduction obtains in the absenceof the additional keto group of la. However, the endo-methylgroup at C6 of la is essential.When it is absentthc ketone is reducedto a l:l-mixture of alcohols. anti-Selective reduction of epoxy ketones.2 a,B-Epoxy ketones are reduced to cpoxy alcohols with high anll.-selectivityunder Luche conditions.

cocH"

liAe

l - - Itrruhedron Letters, 33, 425'7(1992)

l-uche reagent). x I .rchc reagentis useful for selective c.. ,nJ for selectivereductionof enones rr: ::r: sclectivity of hydride reductionof t : rctal boron and aluminum hydrides

315

RrARe

NaBH4, CH3OH,-78' !' -. :rrafas, TetrahedronLetters,33, 1855

H

_O

n\4.-cn" n\K-cn, * fifcr." (J5""." H \ o

RrARz

s',

chloride (Luche reagent)

CHo

"""''-"r, f;?5il 94"/o

/;

A.-"r,+

-f

{-""

o

82/"

cH.

Ho-

\cH,

syn-isomer e1'e

3f6

SodiumPhenYlselenide

1A. Krief and D. Surleraux,Synlett'273 (1991)' 2K.Li,L.G.Hamann,andM.Koreeda,TetrahedronLetters'33'6569(1992)'

Sodium borohydride-Iodine, NaBHa-I2 (12:5)' Reductionofamides,nitriles,esters,andacids;hydroboration.lThissystem (12:5)inTHFreducesamidesornitrilestothecorrespondingaminesinTo_757ayie|d. in 6o-907a yield. The actual reagent carboxylic acids or estersare reducedto alcohols of alkenes' is diborane,and indeed NaBH+-Iz can effect hydroboration

1lll Zt Ce gr ft

CHs 1

g tl

SeC5H5 1 ) 1 2 ,N a B H 4 ' T H F

Y#*c6H5cH2cH2oH c6H5cH=cH, l A. S.B. Prasad,J.V. B' Kanth,and M. Periasamy,Tetrahedron'48, 4623 (1992).

(\a""y; CHs 2

Sodium hyPochlorite. Ca(oCl)2 as oxidants during the Review.| Use of NaoCl and, to a lesserextent, NaOCI is readily available;yields period 1980-1992 has beenreviewed(104 references). amountsof Ruclr '3H2O (1 mol vo) can be improved somewhatby addition of catalytic orRuoz,2Hzo.oxidationcanbeconductedinatwo-phasesystembyuseofaphase. One significant developmentis that transfer catalyst, usually BuaNB(Cl), 5 mol 7o' presenceof primary-secondary diols primary hydroxy groups can be oxidized in the using NaOCI (1'3 equiv') and catalytic to give hydroxy aldehydes inlO-98% yield by (TEMPO) and of BuaNCl' This system' amountsof 2,2,6,6-retramethylpiperidine-1-oxyl butwith2.5equiv.ofNaoCl,canalsooxidizeprimaryalcoho|stocarboxylicacids, RcH2oH_RCooH,inSo-987oyie|d;Ca(oCl)2ispreferredoverNaoClforoxidative cleavageofvjc-diols'Thcreactioniseffectedinaqueousacetonitri|eandaceticacidat 20". rJ. Skarzewski Org Prep'Proc'Int'' 24' 623 (1992)' andR. Siedlecka,

Sodium PhenYl selenide,C6H5SeNa' of the 14-memberedcyclopeptide Enamides. one of ih. lu., steps in a synthesis alkaloidnummularineF(4)invo|vesdehydrationofthealcoholsltoformtheenamide groupof3.Thestandardroutethroughtheselenoxidefails,butthemesylatesoflare convertedbyreactionwrthC6HsSeNaintothecorrespondingphenylselenide.s(2)'which of thesedecomposesat 25" to 3; the other' are oxidized (HzOz) to the selenoxides'One whenheatedinbenzeneat60..Thelaststepsinthesynthesisof4involveremovalof (DCC' 59% yield)' the Boc group and coupling with N,N-dimethylglycine

I R.J. Heffner,J. Jiang,and M. \l J.'trl

N-Sulfi nyloxazolidinones, chirel Two of these reagents. I and !norephedrine(HXn1),the othcr (2t rs

O

C

lt

I

czHrzs''"/

r

CHr

(R)-t

N-Sulfi nyloxazolidinones, chiral

3J. 6s6e(19e2).

1)Mscl Lurru

q)-;t;

)

l This system I o<'ids: hydroboration 6. ".'prrnding aminesin 7O-75Vayield. )i- - hll-90% yield. The actual reagent \.:' il,ration of alkenes.

2) C6HsSeNaJ 3) HrO, (80%)

bo" l-'. cHs 1

ot l

/-\

F

o.H5CH2CH20H

1

..o1w ,)-{ )

.SeC6H5

1

C6H6, 600

\u\ooXil ,:. Jnm. 48, 4623 (1992).

53o/o

bo" I-', H

.r_CzHs / CHs 2 17o/o

:.:rr. (la(Ocl)2 as oxidantsduring the -, - r NaOCIis readilyavailable;yields of RuClr '3H2O (1 mol Vo) \ : - 1nr()unts '.\(,-phasc systemby use of a phaseI ( )nc significant developmentis that k !-:-.dnce of primary-secondary diols ..;:rr NaOCI (1.3 equiv.)and catalytic I I i \lPO) and of BuaNCl.This sYstem. z. :'rnrarv alcohols to carboxylic acids. '. prcferredover NaOCI for oxidative acetonitrileand acetic acid at :...ri()r.lS c\

l t. t,l.r ( 1992).

cyclopeptide r!--.:. r)f thc 14-membered the enamide form I to rhc alcohols : o: of 1 are mesylates the but rrJc fails, lc(2)' which selenides phenyl r':'-.nr)nding ':'--r dccomposes at 25" to 3; the other. r: :ri \\'nthesisof 4 involve removal of i l . . , r n c ( D C C , 5 9 %Y i e l d ) .

1) TFA, 50 (28olo) 2) (CH2)2NCH2COOH, DCC

e:

e

317

// \\ O-< )-l. : ) 1 1

\u\oo>-il N\-^

(cH3)2NcHl"^

"5"rr,

4 rR.J. Heffner,J. Jiang,andM.M.

Joulli6,Am.Soc.,ll4, 10181(1992).

N-Sulfinyloxazolidinones, chiral. Two of these reagents,I and 2, have bcen studied. One is derived from (4R,5S! norephedrine(HXp), the other (2) is derived from (4S)-phenylalanine(HXo).

o

o

l l l czHrzS'.rAo

\'J

cnlcuHs (R)-1

o

o

i r i i crHru"S'-"Ao

L/-

Bzt-" (s)-2

318

(*)-Sparteine

Asymmetricsynthesisof sulfoxides,sulrtnatus,and sulfonamides. Thesesulfinywith inversionat sulfur.l reactwith a wide rangeof nucleophiles latingreagents

s - B u L i .1 . O(CzHr)r. -78,'-

(l) \ru/ I

Boc 2

(S)-2 + CH3MgBr

THF, .78" 90%

NaOH

o

Hs\^,2',uc(cuHs)z rr ',H

e C7H77"-CH3

3, 99.3%ee

or l

zn

Ed

czHrzs-"r2cooc(cH3)3 > 987oee

Tt{tr

(S)-2 + (C2H5)2NMgBr

Enantioselective deprotonation of catt carbamatesof a sterically demandingorazolrri deprotonationwith sec-Buli/(-)-sparteine Tl t: sequentialreaction with CHTSOTH/Ba(OH

ot l

-7Ro

91o/o

9G

Ao" o

99%ee

(s)-2 + BTCH2COOC 'nils (C"'

r-8

a c7H77"-N1c2H5;2

1) s-ButJI 2) cH3l -

RO---^.--OR

> 98o/o€€

&3\ CHe l -

9H.-Jl

R= ('-n.-N _ O /

/

,

i

\

O Cri.

'Ctt.

I D. A. Evans,M. M. Faul, L. Colombo, J. J Bisaha,J. Clardy, and D. Cherry, Am. Soc., ll4,5977

(tee2).

RO--.( )z-.OR

(-)-Sparteine,

1) s-BuLr t O 2) s-AuU t O

( )-1

Asymmetric deprotonationr Treatmentof Boc-pyrrolidine(2) with a slight excess of a mixture of (-)-1 and.sec-Bul-i(1:1) in etherat -78" for severalhoursprovidesa chiral 2-lithio-Boc-pyrrolidine(a), which reacts with various electrophilesto provide 2-substitutedBoc-pyrrolidines in 88-96% ee. A typical synthesis is illustrated in equation(I).

f S . T . K e r r i c k a n d P . B e a k ,A m . i r r c . . l l 3 . e - r r \ | 2M. Paetow, H. Ahrens, and D. Hoppe. Tetralvdm

(-)-Sparteine

?\. dnd sufunamides. These sulfinYp : . . \ \ i t h i n v e r s i o na t s u l f u r . l

/

(l) \ru/

\

a

s - B u l i ,1 , -78o. O(CzHs)e,

I

Boc 2

(r)

1

i . J

a

""6t"utu"

NaOH,

%b#L

(*2.,,,616usu,, H

O

H

3,99.3%ee

te:

o q

6 -.r-/"-CH2cOoC(CH3)3 > 98o/o€€

-i-t-7

-eu{-

Ao" oH

^f.l^ v i

319

Enantioselective d.eprotonation of carbamates.2 1,3- or l,4-Diols protected as carbamatesof a stericallydemandingoxazolidinegroup undergohighly enantioselective deprotonationwith sec-Buli/(-)-sparteine. The protecting group can be removed by sequentialreaction with CH:SOrH/Ba(OH)2.

--

N (CzHs)2 '98%ee

RO.._-.--.---OR

1 ) s - B u L i , 1 RO_.._.,-Y-OR 2) cH3l 83"/" CHs

CH. t -

9H.-]-t

q = (-..,'_-N_ ,O

/ ) t O c4'CH3

HO-.....^-.*..O

H

I

CHs >97o/oaQ

RO..-.( )2,,-,OR

1:CHgt Ro_.r.( 1) s_BuLi, )z,r.oR 2) s-BuLi'1;cH3l > T T CH3 CH3

I

I

HO _ Oz-u.OH

l

f lt '.-pvrrolidine (2) with a slight excess il' ,r -78' for severalhours provides a r. .( rrh various electrophilesto provide : \ tvpical synthesis is illustrated in

l

CH3 CH3 (S,S/R,S)= 98:2

rS.T. KerrickandP. Beak,Am.Soc.,1f3,9708(1991). I M. Paetow,H. Ahrens,andD. Hoppe,Tetrahedron (1992). Letters,33,5323,5327

N-sulfonyloxaziridines

N-sulfonyloxaziridines. Asymmetric hydroxylation of enolntes'

Davis and Chenr have reviewed this

reactionusinginparticular(R,R)-and(S,S)-2-phenylsulfonyl)-3-phenyloxaziridene(1) (2)' Of thesereagents'I and (+)- and (-)-2' derived and (camphorylsulfonyl)oxaziridine from(1R).10-camphorsulfonicacid,providehighestenantiose|ectivityandinadditionare easytoprepare.l.heyareeffectiveforhydroxylatationofketones,esters,B-ketoesters, amides, lactones,and lactams.

6H.{ O .A.nCoHs

c6H5s9r/N-" (R,R)-1

^_-N-7"

.nCoHs

c6H5so" V (s's)-l

0Hs \>/\ /

4-\>y \s7v

Thntalum(V) chloride/Zinc. 15. -r Reaction of Th-allcyne co;21 fuom TaClsf Zn with unsYmmc'trica regioisomericallylic alcohols * rth

(both steric and electroniceffeost r group. The complexes from acr'tr

at the position a to the esler ertxt mainly at the position B to thc an

OrO (+)-2 rF.A. Davis and B.-C. Chen, Chem' Rev', 92' 919 (1992)'

=CCOzCzlt C1eH21C

c-C6H11C=CCON(CN

I Y. Kataoka,J. Miyai, M. Tezula. l'

R,R-Tartaric acid, 16, 3ll-ili Asymmetric allY ltitanatioa d from the chiral diol R,R-l derircd of aldehydesin )9OVo ee.

::.i C'henl have reviewed this (1) l.,i:,'nvl)-3-phenyloxaziridene n:. I .rnd(+)- and (-)-2' derived rr:: ,'\clcctivityand in additionare 1 : \ctones, esters,B-keto esters'

6H.{ C.H.

,CHg

/ \>--.' \ /

4\* \s{

Tantalum(V) chloride/Zinc, L6, 312. The Ta complexes formed Reaction of Th-allcyne complexes v,ith RlFPC:O.I compoundsto form two with carbonyl fromTaCl5fZn with unsymmetricalalkynesreact substituents on the alkyne on the regioisomericallylic alcohols with a ratio depending in the carbonyl of the substituents (both steric and electroniceffects)as well as the size mainly compounds with carbonyl group. The complexes from acetylenic esters react react acetylenic amides from at the position a to the ester group, whcreas complcxes mainly at the position B to the amide.

OrO (+)-2

1) TaCls/Zn

CloHgr

2)PrcHo' C1eH21C=CCOeCzHs 760/o

H

fOzC2Hs

lPr HO (95:5)

1) TaCls/Zn

"i#* c-C6H1 1C=CCON(CH3)2

c-coH1r /coN(cH3)2 H Pr-1 OH (90:10)

I Y. Kataoka, J. Miyai, M. Tezuka, K. Takai, and K. Utimoto,J. Org', 57,6796 (1992)

R,R-Thrtaric acid, 16, 312-315. Asymmetric allyltitanation of RCHO.I A complex, (R,R)-3, prepared in two steps from the chiral diol R,R-L derivedfrom l-tartaric acid(14,232;16,314),effectsallylation of aldehydesin )90% ee.

o o a

322

R,R-Thrtaric acid

CoHsrOHHOr rC6Hs C.Hut\-'"\C^ 9E:9!9I41 (R,R)-3 -tt * cpr,"r, NI94dr 1n,ny-z / \

oxo

cilt

'cH'

Acyloxyborane catalyzed allylatioa.' t c by reactionof borane' THF with (2R.-1RF'.( the reactionof allylsilaneswith aldehvdest< ee. The geometry of the silane has no cilcr l-PrO

(R,R)-1

Zr>/t t

1) (R,R)-3

c.HscHo

O

r

l

COOH

|

O.'\-,.COOH

i

l

BH:-X

:

ot

\Ao-,-p,

oH

-74: 2) NH4F'

i

(2R,3R)

"urrL"r, ( S ) , 9 5 %e e

-OH

OH

c6H5ycHo (*,*)-r, c.rr--TA.,scH" * cuHrQf^.r, w'12 dH. 6r? Ar? 48o/o,9oo/"de

487o,98.8"/"de

fcr a new asymmetric Asymmetric synthesis of B-lactams'2 The key reagent acid. Reaction (2S,3S)-tartaric from synthesisof B-lactamsis the chiral imine 1, prepared of which configuration the 3' of I with an ester enolate (2) provides a B-lactam

NAn

"ofo"t. "

An=c6H4ocH3-p

JL >(,o-l-oct. |

t-t-

Ho)'',,,,.oCHs

cH;\o) ",,.ocH"

CHs | - C " H . C H O +' ^ , , CH1.2',.,,.Sr(C}rr) E / Z= 5 1 3 9 I A. Hafner. R. O. Duthaler, R. Manr. (i

Rrir

rr4,232r (19e2).

2T. Fu.lisawa, Y. Ukaji,T. Noro.K. Datc r:: I I K. Furuta,M. Mouri, and H. Yamanxr.,-\.lir

a, u, at , at-Tetraaryl-1p-dioxoh*{-<{ Reviews. Seebachel a/.r pror r& I 1r has coined the abbreviationTADDOI- {: t of type 1 (C2-symmetrical)and ll of :rp analogouscompoundswith heteroan l. dla group of I and 2. All are preparcdt'r rrr

1

Ar.

c{s n

r + (cH3)2c{

OM /

'78o-

oc2Hs

cH,X")t cHs-ff

bcH.+ (n)-e 6J. ''-ocHe

hU,o^

2

1

(s)-3 M = Li, DME M = ZnClz,THF M = Ti(O-l-Pr)g

960/o 84"/" 96%

S:R = 99:1 S : R= 8 5 : t 5 S : R= 1 1 : 8 9

enolatereacts to form mainly (S)-3' dependson the metal of the enolate.The lithium enolate' *h"r"u. (R)-3 is the major product from the titanium

Ar

\/ "Fr\ 1 P-/-OH | ',,,aoH R'\o) ,/\ Ar' Ar

A

"Frr> 1 O-z R2' oA

2

Grignard reagents.The paper discusscsrr' least 25 titanates(3) derived from I and 2 h some in which Rr : R2 and X : \'- \lrtco

When used to catalyze the addttrtro bearing phenyl groups but diffenng 9ru.1

a. a, a' , a' :Lbtraaryl-1,3-dioxolane-4'5'dimethanols

Acyloxyborane catalyzed allylation'3 (cf' 16'314)'

p 2 91=9!9!4 (R,R)-3

323

The acyloxyborane 1' obtained

byreactionofborane.THFwith(2R,3R)-2,6-diisopropoxybenzoyltartaricacid,catalyzes thereactionofalIylsilaneswithaldehydestoaffordsyn-homoallylicalcoholswith>80% syn-selectivity' ee. The geometry of the silane has no effect on the

iPro

cooH

?

*"1\_.cooH

tr

li

tl

Vo-l-Pr'

-c

:H

BH3THF> 1*

(2R,3R)

OH R I

, -l coHs-!.t*cn, : S

CHs c6H5cHo * cH.-*zl.--.si(cH3)3 EIZ= 61139

11 -78", CzHsCN. 640/o

9tt C6Hs,,,/)',?rCH2 I

I

oH cHs (90o/'ee)

'

CHs 48o/o,9Oo/ode

c\ :-.rgcnt fcr a new asYmmetric Reaction t' r:r t 1S,3S)-tartaricacid' which of a:' -1. thc configuration

^

An = C6H4OCH3-P

OCH,

ocH3

Az Sac'' I A. Hafner, R. O. Duthaler, R. Marti, G. Rihs, P. Rothe-Strcit,and F' Schwarzenbach'

(1e92).

rr4,2321 48'5629(1992)' 2T. Fulisawa, Y. Ukaji,T. Noro,K' Date'andM' Shimizu'Tetrahedron' (1991)' Synleu'561 3 K. Furuta,M. Mouri, and H. Yamamoto, (TADDOLS)' a, a, a',c/'Tetraaryl-1,3-dioxolane-4,5-dimethanols of these reagents'for which he review general a ptovide et al.t Seebach Reviews. hascoinedtheabbreviationTADDoL.Atthepresenttimethereare26knownreagents (C1-symmetrical)'ln addition there are of type I (C2-slmmetrrcal)and 12 of type 2 analogouscompoundswithheteroaryl'alkenyl,andalky|substituentsinplaceofthearyl (R'R){artrate ester acetalswith aryl group of I and2. All are preparedby reaction of

Arr

Ot\rOt

Ot\rO'

n-7o1xoH n,-.-,P1xoH "Vo/-

6''t, O

'l

o).-tocH3

+ (R)-3

t-ocH"

N

rAr

n\-J... u

-oH u

nrl\'

?:r^ 'Y ,,.,,ott sz"\o) ",,ao' szAn) K \ J K n n,./ \'

Ar' hr

An S)-3

S:R = 99:'l S : R= 8 5 : 1 5 S . R= 1 j : 8 9

(S)-3' .:: ,l.ttc reactsto form mainly Ir-:'::ntllate.

convert I and 2 into cyclic titanates;at Grignard reagents.The paper discussesways to isolatedand characterized,including been least25 titanates(3) derivedfrom 1 and 2 have exist' Rr * R2' two diastereomers : and X#Y Y' When somein which Rr : R2 and X Whenusedtocatalyzetheadditionofdiethylzinctoaldehydes,allcomplexes C2 of the dioxolane ring show similar bearing phenyl groups but differing groups at

fl uoride

Tetrabutylammonium

cH3\ PH3

selectivitythan that A complex with a B-naphthyl group showshigher enantioselectivity. withana-naphthy|group.Whenthegem.diary|groupof3isreplacedbygen-dimethyl obtains' or -benzyl groups only slight enantioselectivity AreviewsuggestsamechanismforTADDoL-cata|yzedadditionofR2Znaswell

o'si-H

P.lc

\rz\""\oBzl CH3

asotherasymmetricreactionssuchas|2+2)and[4+2]cycloadditions,aldolreactions, allylic transfer,and others'2 AsyrnmetricadditionofRCH2MgBrtoketones.3Inthepresenceofl(1equiv.)' ketones in THF to form tertiary alcohols primary Grignard reagentsif equiv'; react with -99:5 1' in hish enantioselectivity,usually 95

CH3 1

BuaNF,DMF, 25"

OH (_,

oRo/^

cl

cols-oH cH3p-rAc6Hs X I '',,.-CaHs CH!'O/

l-on

This desilylation provides a ke1'step u joined by one carbon to a five-memtrrd deprotectionof a (H2,Pd/C) and Swem ori provide the unsaturatedamide 4 in 7(Fr cn to give essentiallyone product (5). Aftc

CoHs

I

1

o ll csHsAcH3

rHr,1roo" c2H5,roH * 3 CcH5MgBr--6%* 62"/o CoHsACHs (R)99:1

(teez). 'i021 (1992)' 2 K. Mikami an
TetrabutYlammonium fluoride' obtained by hydrosilylation of a Desilylation of siloxanes't The siloxane a' on treatmentwith BuaNF (3 equiv') substratesuch as 1, can undergoprotiodesilylation occurs if the hydroxyl group is not in DMF at 25" to give an ulcohol (2). No reaction protected as an ether.

1,o-f*+r

2 +

|) L"tt

--"

cFt3 3

o-.

o

,o-rffr. Helv" 75' 2l'71 I D. Seebach,D. A. Plattner,A. K. Beck, Y. M. Wang, D. Hunziker, and W' Petter'

cn"

\r---.\,\N-cH, ffi, CHg

r

cHs 4

l

ocH3

Tetrabutylammoniumffuorid€

cH3\ pH3

s rrchcr selectivitythanthat s :rplaced bY gem-dimethYl

H2 R catalyst

o'si-H

V\-"\oB/

d .,Jtlition of R2Zn as well l,,.,JJitions,aldol reactions,

CHs

cH3 cH3

a

1

h. rrcsenceof 1 (1 equiv.), l{F ro form tertiarYalcohols

6".

OH B u + N FD , MF,25" 95o/"

\r-\r^os'r cH3 cH3 2

This desilylationprovides a key step in an asymmetricosmylation of a double bond joined by one carbon to a five-memberd siloxane. Thus the aldehyde3, obtained by deprotectionof a (H2,Pd/C) and Swern oxidation,undergoesa Wittig-Horner reactionto provide the unsaturatedamide 4 in707o overallyield. This productundergoesosmylation to give essentiallyone product (5). After protection of the two hydroxy groups, the

Ir-eih. I

o o

lCrnuO;ri\A*.cH.

2+

CrHt.roH c6H5

BuLi

OCH3

| \--r--r.""o;

CH3

l"il.

(R)9s:1

cHs I 3

CHe

(,o-si-ci. l " r ol , elv.,75' 2171 : : : : r J W . P e t t e rH

H-,,,-\-t\^,-CH' r

cHs

'

.

'

i

ocH3

cHs

Tr pyr*BF4NaH.CHal

n -CHs--e"2.* CHs CH3 OH ocH3 I

5(94:6)

4

:

cHo 'g cHs-j; / \

n-.: hv hYdrosilYlationof a a::r.nt with BuaNF (3 equiv.) s r! rhc hydroxYl grouP is not

OsOa NMO 80% HO

,,.o-

?

cH3 cH3 oH 6

oH i

r'o^[{)i#.' T-"r.ffi ocH3 BuaNF

o I

Tetracarbonyl',''chlorodirhodium

326

group' Thus the siloxanering give 8' with a syn-1'3-dimethyl siloxanering is removedto double bond' of osmylation of an adjacent can be used to control the distereoselectivity (1992)' 1M.R. Hale andA'H' Hoveyda'J' Org'' 57' 1643

Tetrafluorosilane. 'f Selective cleavage of silyl ethcn'' CH2C!2or CH3CN at25" in ratesthat ar > The relative ratesare in the order: Et'Sr '-r' at in CHICI; SiFa to stable phenolsare

selective cleavage of primary or secondan (r)' lRh(Co)'Cll' Tetracarbonyl'p'dichlorodirhodium' (2) forms a rhodium vinyl "y"top'op"ne u with 1 of Phenol synthesis't ntuttion an oxepine 4 and a phenol u terminal alkyne (3) to fo'rn carbenoid (a) that "u"o *Un quantitativeyield' to the phenol 5 in practically O "u"un"' 5. On treatmentwith HCl

coc6H5

I

4,' 2

r,

I t,'. I FRnLn

PTCH2C=CH(3)

l>"

62"/"

cHrcla I I

Lcutt

Pr * s (av.)

I cn,m I E.J. Coreyand K.Y. \i, Tetrahedrm

Tetrakis(triphenylphosphine )pdbdir' CouPlin g of 2 -b romonaP ht hquin none I undergoesStille coupling rrth t

in good yield under catalysis*'ith Pd[Pt( ('uB ferrocene[Pdclr(dppf)]. Addition of rdr prtn 2 stannanc coupling of 1 with the { (ll rn I into the antibiotic WS 5995C

CH2Pr 4

oo' rooz.f"-,

a

4-\a'' l r l

cHre'

cuur/\ 1 45"/o

4Y> l i l

OH 5

o (\\''.

\ff HO

CH30.--,'r

(CH3)3Sn^

o

c

t

cur,utV

(CHd4C-CH 6

OH 7

o

ll o, C^H^"n'd 1co l i l 2 + (CHs)sSiC'=CHG;-

rot\'

si(cH3)3 I

7' The reactionof 2 with to obtain an annelatedphenol This reactioncan also be used rhodacycle' provides the phenol 8 via a I under a CO atmosphere (1992)' 1A. Padwaand S'L' Xu,Am Soc''ll4' 5881

Addition of (ArS)2 and (ArSct: b I catalystfor addition of diaryl disulfrlcr (Z\-1,2-adducts in high yield lequanxr I

Tetrakis(triphenylphosphine)palladium

--:'.:rncthvlgroup.Thus the siloxanering )l .-r\ lation of an adjacentdouble bond. t . ':

rl). ), t r'.,r,propcne (2) forms a rhodium vinyl c .1, i,r form an oxepine 4 and a phenol ,"-- I 5 in practically quantitativeyield.

JZ7

Tetrafluorosilane. selective cleavage of silyl ethers.t This gaseousreagentcan cleave silyl ethers in cHzcl2 or cH3cN at 25' in rates that are strongly dependenton the substituents at Si. The relative ratesare in the order: Et3si > r-BuMe2Si > r-Bu(c6H5)2si. Silyl ethersof phenols are stable to SiFa in cHzcl2 at 23" for 24 hours. SiFa is an excellent reagent fbr selectivecleavageof primary or secondarysilyl ethersin the presenceof tertiary ones. 1E.J. Corey and K. Y. Yi, Tetrahedron (IggZ\. Letters, 33, ZZgg

Tetrakis(triphenylphosphine)palladium.

{ - C= C H ( 3 )

Pr * 5 (Bolo)

€2'.

CH2Pr 4

coupling of 2-bromonaphthoquinones with stannanes.r The 2-bromonaphthoquinone I undergoesStille coupling with tetraalkyl-, alkenyl-, and aryltrialkylstannanes in good yield under catalysiswith pd[p(c6Hs):]+ or cr2pd(1,1/-bisdiphenylphosphino)ferrocene[Pdclr(dppf)]. Addition of cuBr usually improves the rate and/or yield. Thus coupling of l with the stannane2 provides 3 tng2To yield. This product was converted into the antibiotic WS 5995C (4) in 2 steps.

too.z"Jn-, +0.

(Y,, cH2Pr

curri a

I

\

?'

o

z-")"'..8'

w + HO

o

CHsOt -1r-CHs i l t (CH.I^Sn/'{

I coNHc(cH3)3

Pd(o),CuBr 82/o

2

OH 7

Y,,

1) t-BuOOH 2) HC|O4

-

98o/"

si(cH3)3 8

r.:.l.rtcd phenol7. The reactionof 2 with t ,r.r a rhodacycle.

):

Addition of (Ars)2 and (Arse)2 to l-ailcynes.2 pd[p(c6Hs)3]4 is rhe mosr effective catalystfor addition of diaryl disulfidesand diselenidesto terminal alkynes to provide (z)-L'2-adductsin high yield (equationI). Note that phoroinitiated addition of (c6HsSe)2

Tetrakis(triphenylphosphine)paltadium

(l) CH3(CH2).-C=CH

+ (C6H5Y)2

Pd(o), 80'

CH.(CHO)" H t'' /

/:'. c6HsY

YC6H5

Y=S

91V"

Z, 1000/o

Y=Se

82/"

Z, 1000/"

HzN../rCH

oTf l

r

(cH3)3c'\cH2

HO" I

(ll) R-C=CH + (C6H5Se)2

R.

\

hv

o ao^ (cH3)3c ..nA ) .,,.",."u, *

/,SeC6H5

C6H5Se'

H

btt, H

(E),95 : 5 to 1-alkynesresultsmainly in the (E)-1,2-adducts (E/Z:95:5), equation(II). Carbonylativeadditionof diaryl disulfidesand diselenidescan alsobe effectedwith the Pd(0) catalystto form (Z)-1,3-bis(arylthio)-2-alkene-1-ones and (Z)-1,3-bis(arylseleno)2-alkene-1-ones,respectively(equationIII).

(lll)CH3(CH2)u-C=CH+(C6HsY)2

co, pd(o) CH3(CHds \>/1,.ycuHu 60" | tl

c6H5Y

O

Y = S

860/o

z, 1000/o

Y = Se

8oo/o

Z, looo/o

r"\r'

l l

r"OTf

|

|

+ 1 . c !

Somewhatmore efficient catalr*r r Cyclization of triynes to Dr,n:crr, alkyne 2 both cyclize to the hcnzcrx r (3 mol %) and a base or acid rn rcflu

Coupling of acid chlorides with (E)-BqSnCH:CHSnBuj; 1,4-diketones.3 The Pd-catalyzedStille coupling can be extendcdto coupling of acid chloridcswith (E)-1,2bis(tributylstannyl)ethene. Uncxpectedly,a 1,4-dioneis formed,evidently by reductionof an intermediateenediketoneby BurSnCl. Reactionof an a, p-unsaturatedacid chloride also leads to a 1,4-diketone,as does the reaction of an acid chloride with a B-stannyl enone.

\

SnBu3

(cH3)2c=cHcoct '

o

H 1, E = COOCzHs

#

"u"ul*.ur, o

z

A-,q

Or

?r. ? a6; ora-\-\z^-",1coHs

ll

CH.

6

o

Bu3Sn, C6H5COCI+

eto D.

o

2

CH=CHSnBu3

Chiral oxazolines; Stille carbonylative coupling.a Pd-catalyzedcarbonylative coupling of triflatesof ketonesand phenolswith chiral amino alcoholsprovides B-hydroxy amides,which cyclize to chiral oxazolineswhen treatedwith thionyl chloride.

A partially intermolecularverivrn rs 1 4 and 3-hexyne cyclize to 5 under rhc se However, cocyclization of (E)-p-hrrrm derivative 7 (equationII).

Tetmkis(triphenylphosphine)palladium

CHe(CHe)c H

t'* /

a:

YC6H5 c6H5Y z, 1000/o

H2Ny,CH(CH3)z

OTf

+ (cH3)3c-\

cHr*

Pd(o),Licl THF.55. > B3o/"

co

Ho)

z, 1000/" R .Qo t v v

o

ao,

l( (cHd3c ^J,,'"rr"rd, #tcH')fi1,,.r,.r,,, Y H 6u"

D eC6H5

H

E, 95:5 , / - 95:5), equation(II). lc:rJcscanalsobe effectedwith the I -"lcs and (Z)-1,3-bis(arylselcno)-

CHr(CHz)s ,,\Z>1YC6H1 t l l c6H5Y O z, lco%

"'cH(cHs)e

. 1+ + co=5%* co-- ^^iJ

f)--o'' \2-\2

ry-)

Somewhatmore efficient catalystsarc pd(dba)2/p(C6H.5) and pd(OAc)/dppp. cyclization of triynes to benzenes.s The triyne I and the bromoalkenylalkyncalkyne 2 both cyclize to thc benzcnedcrivativc 3 when treated with this pd complcx (3 mol Va) and a base or acid in refluxing CH3CN.

z, 1000/o =('HSnBus; 1,4-diketones.3 The lrrr of acid chlorideswith (E)-1,2Ir :,,rmcd,evidentlyby reductionof [ .::] .r, B-unsaturatedacid chloride .r:r.rcidchloridewith a B-stannyl

o

tl

o

I'd-catalyzedcarbonylativecourrrr,, alcoholsprovides B-hydroxy n,.: *ith thionyl chloride.

\

r

-

i

:rcfy 'YcH. -o

z

c H-3 tol

'

l C H " H \. l,E=cooc2H.

o tl

tu-u),_"utu

.&cuHt

'l'

Pd(o),HOAC cH3cN,

-;-\

)

il

Pd(o),N(c2H5)3 cH3cN,

,/

*.Br \\ I CHzCHs 2

A partially intermolecularverison is possible,but lessefficient.Thus thc bromoenyne 4 and 3-hexynecyclizeto 5 under the sameconditionsin 4ova isolatedyield (equationI). However, cocyclization of (E)-B-bromostyreneand the diyne 6 results in a fulvene derivative 7 (equationII).

Tetrakis(triphenylphosphine)palladium

si(cH3)3 Et (t)

ll

si(cH3)3 Pd(o)N(czHs)s e_ ;-..,74;CrH, ---

4o%-

-1AA.,ru

oANet,

Et

e

(il) :x E'

f-_4CH \^,

/CaHs

*

.CH,

ll

Pd(0).N(c2Hs)3 tr 52o/o

Br2'

6

E'

poHs

/y^:, V--\,/ 7

Coupling of aryl iodides and arylboronic acids.6 This Suzuki cross coupling can be effectedwith this Pd(0) complex as catalystand Na2COr as base.It provides a rapid accessto rn- or p-tcraryls.

o-+

grF

ffil arF

Pd(0),NaCO3,DME

(HO)28- \ /

cH3 (HO)2BC6Hs

l"

r-

.'(t,

r N . T a m a y o ,A . M . E c h a r e 2 H. Kuniyasu, A. Ogaua. !

(1ee1 ).

3 M. Per6z,A. M. Casran '. a A. I. Meyers,A. J. Rd'lr-h 5 E. Negishi,L. S. Hanrng 6C.M. Unrau,M.G. Carn Tetramethylammoniur

Reduction of a-hy/ I in HOAc/CHTCN ( | I product, whereas (E)-l Bzl I

o-N Ho l l l r-Pr,Mr(4-2

H3

HO N-O l , l l-PrY,(E)-2 This coupling can be extended to a synthesisof rn-quinquearylsby using a 1,3dihalobenzenesubstitutedat C, bv a directing metalation group: CON(C2H5)2,CN OMOM. or NH,.

Bzl I

Ho

o'N

l r l

r-pr,,,Yi-l cHs

Tetramethylammonium

si(cH3)3 '

'

tr - x/--'z\','CzHs i l | E'vcrHu

tr ->1/----,2'x tr F

/

\

| |

\:/

n

r>

\v\..1aB(oH)2

,t'(t, o

triacetoxybomhydride

331

Pd(o),DME,

\)

ttEt,

PoHs

/

\_---v 7

I'rr. Suzukicrosscouplingcan r.( ( ) ;1sbase.It provides a rapid

lN. Thmayo,A.M. Echavarren, and M.C. paredes, J. Org., 56,64gg(1991). 2 H. Kuniyasu,A. Ogawa,S.-1.Miyazaki,I. Ryu,N. Kambe,andN. Sonoda, Am. Soc.,ll3, 9796 (1eel). 3,M.Perez,A. M. Castano, andA. M. Echavarren, J. Org., 57, 5047(1gg2). a A' I' Meyers, A. J. Robichaud, and M. J. McKennon,Titrahedron Leuers,33,1rg1 (1992). z. owczarczyk, M. M. Mohamud,and M. Azy,ibitt., t3,32s3 (1ss2). ::L. vr. ).i,,r],:..t _t, lu:". unrau.M. U. Campbell,and V. Snieckus, ibid., 31,2j73 ,lgg2\. Tetramethylammonium triacetoxyborohydride (1, t4, 2gg_3OO; 16, 324). Reduction of a-hydroxy oximino ethers (2).t This reduction can be eff.ectedby I in HOAc/cHrcN (1:1), -35'. Thus reducrionof (z)-2 providesmainry the l,3-anti product, whercas (E)-2 provides mainry the r,3-syn product. Note that an additionar

Pd(0),NaCO3,DME

Bzl j

o-N

Ho

l r l

r-pr--*-p. (z)-2

100%

Ho ,*-oBzl l : ,-pr-^*i-p, anti-3

+ sYn-3

67 : 33

CHs

Ho

*-oBzl

Ho ,*-oBzl l l

t t l

r-Pr--\*i-pr (E)-2 rz-uuinquearyls by using a L,3L:r,'n Broup: CON(C2H5)2,CN

+

,-pr-^*i-p, syn-3

anti '3

91:9

Bzl I

Ho

o-N

HO "-oBzl

l r l

l-Pr-*l-Pr CHs

94o/o

t iprl^*i-pr

l

+ 1 , 3 - a n t-i3

cHg 1,3- syn-3

96

332

2,2,6,6-Tetramethylpiperidinyl-1-oxyl

chiral center at C2 can overcomethe influenceof the oxime geometry (last example). I D. R. Williams and M.H. Osterhout,Am. Soc.,ll4, 8750(1992).

Tetramethylguanidine. Michael/aldol reaction,t The key step in a synthesis of the alkaloid huperzine (3) involves a Michael/aldol reaction of the B-keto ester I with methacrolein to A provide the bridged ketol 2. The usual Michael reaction catalysts(NaOCHr, BuaNF, ZnCl) arc ineffective, but the desired reaction can be effected in 93Vo yield with tetramethylguanidineas catalyst. DBU can also catalyze this reaction. Conversion of 2 to 3 is effected by dehydration of the ketol (45vo yield), wittig reaction of the ketone

H. 1 Tetraphenyldistibene, (C6Hs)3SbSHCRCH2I - RCHzOH. Irradiation of I reactswith RCHzI to form (c6H.)rSh('H:n

irradiation of a mixture of the iodidc 2 arrJ This product is stable to O1. but is oridrz contrast, the same reaction of I rr ith 5 p

CHa .O

,

cH.{ts-^ O-\--T.-\

r

1-------------. 80-85a

o l

"r.*o aY*Yott' ?'/'2

*

?" A"ro "

CHg

HN=crN(cHg)zrz -,s%*

2 (R1CH2t)

11

coocH3

9cHs

t"t tr1

1

oxo

+

1

40-6G

CHS CHS several steps

5 (R2CH2t)

2

which is oxidized in air to the alcohol 7 Tl convertedto a stibenethat is oxidizc'dhr r

(73Voyield), Curtius rearrangementof the ester to with ethylidenetriphenylphosporane of the o-methyl ether to a pyridone (iodotrimethylsilane). cleavage group, and an amine I A. P. Kozikowski,Y. Xia, E.R. Reddy,W. Tiickmantel, I. Hanin,and X C' Tang,J' Org'' 56' (1991). 4636

(rll) ca/#t

8

2,2,6,6-Tetramethylpiperidinyl- 1-oxyl (TEM PO), l. ortdation of a-amino or a-alkory alcohols.t (ct., 14,302). This oxidation of optically active a-amino or a-alkoxy alcoholswith sodium hypochlorite(slight excess) catalyzed by TEMPO and NaBr can provide the correspondingaldehyde with no racemization.Highest yields are obtained with toluene/ethyl acetate/H2Oas solvent with 1-2 mol Vo of TEMPO and 1 equiv. of NaBr. Overoxidationto the acid can be minimized by rapid stirring. Carbamoyl groups (Boc or Cbz) are preferred for protecting groups of the amine. Yields are generally 80-9OVoand the 7a ee is >95%' I M. R. Iranna, T. J. Sowin,and H. E. Morton,Tetrahedron Letters,33, 5029(1992)'

I A. G. M. Barrettand L. M. Melche r. .{n .!e

Tin.

Allylation of -CHO (l3.let't) ' Th. moted by tin in an aqueous/organicwrlrcnl proceeds with threo-selectivit\'({-6 -i I I

333

in-.. rcometry (last examPle)' FJ

1q.1. rrl the alkaloid huPerzine ir r-icr I with methacroleinto o: ..rtalvsts(NaOCH3,BuaNF, i.( .ttccted in 93% Yield with u, :hi\ reaction. Conversion of d, \\ ittig reactionof the ketone

(l)' Tetraphenyldistibene, (C6Hs)2SbSb(CoHs)z (C6Hs)2Sb" which RCH2I - RCHzOH. Irradiation of 1 produces the radical to RCH2OH' Thus oxidized be can which reactswith RCH2I to torm (C6H5)zSbCH2R, in 80-86% yield' 3 stibene in the I results irradiation of a mixture of the iodide 2 and Thisproductisstableto02,butisoxidizedto4inhighyieldbyalkalineH2o2'ln and in low yield to give 6' contrast, the same reaction of 1 with 5 proceedsslowly

.,:\r"K: o\_1S

+

1

"r.+5

+

RlCH2Sb(C6H')2

80-86%

H2O2,-OH ---^.RlCH2OH 84"/o

3

4

CHs HN=clN(CH3)212 )HO

2 (R1cH2l)

93"/"

11

9cH. (") +

1

#:,.

hv "''

Oz

-

R2CH2Sb(C6Hs)z

40-60%

;""

lff,:ii

7

5 (R2CH2|)

3 whichisoxidizedinairtothealcoholT.TheacycliciodideSunderthescconditionsis overall yield' convcrtedto a stibenethat is oxidized by air to 9 in 59o/o tL. :Jitrrangementof the ester to ) i :\ ridonc (iodotrimethylsilane)'

1) hv

i i , - r n . a n d X . C . T a n g ,J ' O r g ' , 5 6 '

*

(lll) Cul#t

1

2) oz 59/o

8 ,.r . l;1.302). This oxidation of Nr.rnr hvpochlorite(slight excess) !.,"r\ponding aldehYdewith no cr.r -rhvl ^cetatefKzo as solvent (t,.,r,rridationto the acid can be ): ( \/) are preferredfor Protecting ni :hc 'i ee is >95Vo' i

:.'.. -13,5029(1992)'

O.

CHzOH

9

f A.G.M. BarrettandL.M. Melcher, Am' Soc',l13' 8177(1991)'

Tin. Allylationof-CHO(13,2g8)'tTheadditionofallylbromidetoaldehydespromotedbytininanaqueous/organicsolventhasbecnextendedtoaldoses.Thereaction can be converted to higher proceeds with threo-selectivity(4-6.5:1)' The products

Tin(II)

chloride-Triphenylphospine

o Sn, CzHsOH/HzO

OH OH OH

TsN.C

(((((

* "r/u''

cunr\.'ncoHs

o AcH, I

a^cH,

D - glucose

Ho-l l-oH

Snlz/P(Ph)3.25:

+

BuSnl2/ P(Ph)-i{

rot

+

Ho-]

+

6.5:1

HO-l

l-oH

loH

| FOH

l-o'

r-oH

lot I

L_OH

I I. Shibata, A I]3hL N. Yoshimura.

Tin(IV) chloride. [4 + 2] Cy cloaddition ol nita in thermal reactions with drcrr reactionswith dienesto form rr r(equationI). Nitronatesare als. <

decreasesas the chain length decreases aldosesby ozonolysis.The diastereoselectivity gloup at cz. No reaction is and is low in the case of an aldose lacking a hydroxyl observedwith aldoseswith an N-acetyl group at C2'

(equationII). But in thc lattcr also undergoSncll-catal\zcd rrt adducts (equationIll).

rW. SchmidandG.M. Whitesides, Am' Soc',l13' 6674(1991)' NOr

t -

Tin(II) chloride-Tf iphenylphospine' chloride and an a, p-epoxy Cleavageof epoxy ketones.| The reactionof benzoyl additionof SnCl2complexed ketoneproceedsin low yield and regioselectivity.However, of Bu2SnClz/P(CoHs)ras use In contrast, regioselectivity. high in with (CoHs)rP results catalyst results i't cleavageat the opposite site'

o

il

^,,

_,4-

CoHs- V

c"H"cocr "'TnY".

z\t113

cl | c6Hs-.*,\,cH3

i

o

o

l

i

*

ococ6H5

/i\ -,4-\) \'/ CHrl

C6Ha-p-OCH3

'o_ CHsp-CH3OC€

ococ6Hs | coHs-...'a\,.cHs

l

|

o 1 cl NOe

+

SnClz/PPhg

+

Bu2Sncl2/PPh3

30% 93%

3 :97 7 9: 2 1

(")"r.At -

-

l

CoHs ketoneswith The correspondingtin iodides can also control the reactionsof epoxy to form 2-oxazolidones. TsN:C:O

Tin(IV)

o

l

o

cuHr-\

c^H",\-...'coHs \\ //

o

l

t

..GoHscuHu-\

TsN=C=O

T s N --.|i' , O

o

AcH"

t

chloride

.rCoHs

oY*t'

+

tl

o

o

+

Snlz/P(Ph)3,25o

55%

1:99

+

BuSnl2/ P(Ph)3,40o

88%

84:16

fo'

+

ro--l|-ot

6.5:1

I I. Shibata, N. Yoshimura, A. Baba,andH. Matsuda,Tetrahedron Letters,33,7149(1992).

|-ot |-ot r-oH

Tin(IV) chloride.

a.,. :i\ thc chain length decreases r'r,. I group at C2. No reactionis

[4+2]Cycloaddition of nitroalkenes.t Although nitrostyrene reacts as a dienophile in thermal reactions with dienes, it and other nitroalkenes undergo SnCla-catalyzed reactionswith dienesto form syn- and anti-ring-fused nitronateswith some syn preference (equationI). Nitronatesare also obtainedby SnCla-catalyzedreactionwith cycloalkenes (equationII). But in the latter reaction only anti-addtcts are formed. Nitroalkenes also undergoSnCla-catalyzedintramolecular14+2lcycloadditionto form syn ring-fused adducts (equationIII).

NOr (i) :c,',rlchlorida e n da n a , B - e p o x y of SnClzcomplexed , r. addition r'. as of Bu2SnCl2/P(CoHs)r r:.r. LrSC

t -

CH..\ -

SnCla

+

l

53o/"

C6Ha-p-OCH3

-o.il-o

-o-fi-o

CHs

ococ6Hs

.C1t

*'

I CoHu._r,r'\-c".

coc6H5

i

l

o

CHa

p-cH3oc6H4 \

p-CH3OC6H4

syn

|

H

H

80:20

anti

cl SnCla,

NOn 3 :97 79:21

(tl)

cir.i

t -

cH2cl2,78o +

93/" CoHs

rctions of epoxy ketoneswith

anti,10Oo/"

Tin0V) chloride

,o N +

tl

o H o o f t l -(

,CHS CHg H

iPr'l-N; CHs : l-Bu

SnCl4

68o/"

anfi -2

oI CHs H

CHs 'HCHs

SnCl4, -78o

68"/"

+ SnOlq(1 equiv.)

5r\

(1 equiv.) + (C2H5)2AlCl

s'a

+ TiCla(1 equiv.)

7t\

trans/ cis = 79 :21 Theintramolccular[4+2]cycloadditionformulatedinequation(IV)resultsinboth anti.andsyrr-adducts'withsomepreferencefottheanti-and'rans.isomer.Notethatin rctained' all casesthe geometry of the dienophile is The boron enolate of the (II'37g-381)'2 reaction Asymmetric Evans aldol Evansimidcliswidelyusedforpreparationofchiralsyn.aldols2.However,ifthe -7U" and then treatedwith the aldehydesprecomplexed boron enolatc is generatedat

^

o

Y cHt---Aru

ll

o

euzeort BcHo -

possible to prepare the chelation-t-rrrrn{l Asymmetric ene reaction ol .\''ll,fi promote ene reactions(ll.4l-1.{lJ. lt_f the SnCla-promotedreaction of chrnl \' thermally unstableadducts(2) rn hi-91 (L3,244) or 8-phenylmenthol as lh€ i{rltc

o H o ?

-AA*Ao n l \ J CHs i f-Bd

_l

-Bu'

syn-2

o 9 ct,..-A*Ao j

f-Bu1

Bu2BOTf (cH3)2cHcHo

o H o ? f l l A 'P l-Pr"'\r'^\' r

\__J

CHs : t-Bd s v n- 2

with a Lewis acid at -78'. entir!'l\ Jrflcrt Both SnCl+ and diethylaluminum chLrrd anti-isomer of the Evans sr.n-aldrl ln cn the chelation-controlledsln-aldol- Th,tt tt

+

induction in generation of the ncs r-artrr is applicableto both (E)- and lZ>al\ctrr adductscan be transformedinto tr{x-ellr conversionto an aryl allylic sulforrdc r!rof a thiophile (piperidine)to {. srth rctcr

ene reaction. The overall proces-scffct:r with retention of the original ptxrtx'o o{

Tin(lV)

o H o ? , l l J -Pl

o H o I f i l l \ i-er/'{{ P

9Hs CHs H CHr

chloride

i-pr/'{\-

: \ CHs .'t-Busyn-3

CHs --:t-BJ anti - 2

l

syn syn-2 CHs H

CHs HCHe

anti-2

+ SnCla(1 equiv.)

51o/"

0

9

(1 equiv.) + (C2H5)2AlCl

86o/o

0

86

+ TiCla(1 equiv.)

71o/"

0

17

syn-3 5

s 14

trans/ cis = 79 :21 :i ::r cquation(lV) results in both rr:; .rnd /rar.s-isomer.Note that in Thg boron enolatc of the \ \ n - a l d o l s2 . H o w c v e r ,i f t h e n:,1 .r::h thc aldehydesprecomPlexed r-

-

n

o H o ? r l l A -o

p'^\7^N' l \ _ _

.

CHe -:t-BLl sYn-2

o H o ? r'---,^ru' l l ) -O \ Y' I \_J_ CHs : f-BJ

syn-2

/

with a Lewis acid at -78', entirely different resultsobtain,dependingon thc Lewis acid. Both SnCla and diethylaluminum chloride are highly anti-selective,giving rise to the anti-isomerof the Evans syn-aldol. In contrastTiCla is syn-selective,but gives rise to the chelation-controlledsyn-aldol.Thus by choice of the Lewis acid and conditions,it is possibleto preparethe chelation-controlledryn- or anti-aldols. Asymmetric ene reaction of N-sulfi.nylcarbamates.3 The ability of kwis acids to promote ene reactions(11,413,414:'12,389) is useful for asymmetric reactions.Thus the SnCla-promotedreaction of chiral N-sulfinylcarbamates(l) with alkenesresults in thermalfy unstable adducts (2) in 65-91Vo yield. Use of trans-2-phenylcyclohexanol (13,244) or S-phenylmentholas the sourceof chirality resultsin high diastereoselective induction in generationof the new carbon to sulfur bond (usually >95:5). This reaction is applicableto both (E)- and (Z)-alkenes,but the former react more readily. These ene adductscan be transformedinto optically active allylic alcohols(4) by N-alkylation and in the presence conversionto an aryl allylic sulfoxide (3), which undergoesrearrangement of a thiophile (piperidine)to 4, with retentionof configurationat carbon imparted in the ene reaction.The overall processeffects enantioselectiveallylic oxidation of an alkene with retention of the original position of the double bond.

chloride

Tin0V)

GH3,..VR TFA 1) NaO6N, ? p*g;1 2) Soclz , p*6ArrS-'"

n

SnCl4, + CH,Cl2,

-78'

O... /' *ROOC-*-S--,rL.R

65 - 91%

H

1

z

eH.

2 (>95 : 5)

(c2Hso)38F4

o.\ ./. .ROOC_J>L.x-R

R*OOCNHC2H5

coHsMsBr

O.r .2'

t : C2H5 CH3

a radical coupling. Otela et a/.{ present e electron oxidation of the silyl ketenerd Coupling of the two radicals then regcrrr Rearrangment of allylic aceuk n J substituted tetrahydrofurans is based on t condensationof allylic diols with a c-art Lewis acid to a tetrahydrofuran. Of rarrrt allylic diols are available by reaction of

a-hydroxy ketones.Of particularintercsrThus the acetal 1, a mixture of four stcrcc obtainsrn tbt Even higher stereoselectivity

CoHu-S:-'=-* = CHs 3

I

4O-640/ol

Piperidine

overall I i

cH3oH

*H,

"t.-Lo,.

1

cH3,, /-cH3

9H

cHs.._Le

H3C.,,.,l$R

| )-ctxt cHs/-ci

4 (84 - 100o/"ee) Mukaiyama-Michael reactions.a This reaction involves addition of silyl ketene acetalsto enonesin the presenceof a Lewis acid to form 1,5-ketoesters(13,306-307; 15,15). Surprisingly, a B,B-disubstituted enone (1) in the presenceof various lrwis acid catalystsreactsmore rapidly with the disubstitutedsilyl keteneacetal2a than with the unhinderedsilyl keteneacetal 2b, to form the hinderedadduct 3 with two adjacent quaternarycarbon atoms.Similar resultsobtain with BuzSn(OTf)2and TiCla. The result is hardly consistentwith a nucleophilic reaction,but suggeststhat the reactioninvolves

? ? " cuHuMcH. 1

+ (CH3)2C:{

/OS|(C2H5)3 OC2H5

2a

SnCl4

"i4! j' 93/o

* CHzl

/OSi(C2Hs)3

oc2Hs 2b

? cH.FH'? "urul#oc2Hs cH3 cH3 3

a,

| )-cHs CHs'/-Ci

3 for synthesis of (*)-muscarinc t6t fi (equationI).

CHzs \

(,)

cHt+oH I

* c6H5co2cH

cH3l'-oH (s)-5

o 1)SnCl4 oH3NO2CH3 2) KOH _ 35o/o

cHd

ta

cH?oH

Tin(IV) chloride

o...,2'

€ - *ROOC-*)S.,.-.,1-P b H e H . 2 (>95 : 5)

R*OOCNHC2H5 F. \r:Br

o- ,r'

onea radical coupling. oten et c/.a presentevidencethat the reactionis initiated by a enone' to the transfer by electron followed electron oxidation of the silyl ketene acetal Coupling of the two radicals then regeneratesthe lrwis acid for further coupling. Rearrangment of allytic acetals to 3-acyltetrahydrofurans's A new synthesis of by substituted tetrahydrofurans is based on the fact that the acetals (or ketals) formed a with treatment on fearfange compound carbonyl a condensationof allylic diols with The efficient' most is the SnCla acids, lrwis various Of Lewis acid to a tetrahydrofuran. with allylic diols are availableby reaction of a vinyllithium or vinyl Grignard reagent stereoselectivity' high shows synthesis new this particular interest, a-hydroxy ketones.of Iearrangesto the all-cis-3-acylfuran2' Thus the acetal1, a mixture of four stereoisomers' of 3 to 4. The reactionwas used rearrangement in the obtains Even higher stereoselectivity

c6H5is\a-\,'R : CHs

3

CHs

o

CHs

o

SnCla, c{2cl2, -23"

)-CH" 4O - 64"/o overall

Piperidine cH3oH

cHs{_e

f cH*rcnsf

CoHs

| )-ctHu cH3''^O

4 (84 - 100%ee)

- CHal ,oSi(c2H5)3 oCzHs zo

CHs

77o/o

Cft-!'-CH3

H,C'\^n

Ir:.:e rcd adduct 3 with two adjacent r lt:r Sn(OTf)2 and TiCla. The result r! .uggcststhat the reactioninvolves

CH"

1

QH

n: rnrolvesadditionof silyl ketene r :'rnr 1.5-ketoesters(f3'306-307; Ir :i: the presenceof various Lewis u:r.t silvl keteneacetal2a than with

4

3 for synthesisof ( + )-muscarine(6) from (equationl).

(S)-5, available

from

ethyl

3

(*)-lactate

aHr\ fl)

cHtj-oH

t

* c6H5co2cH2cHo

"

cH3l'-oH (s)-5

o 1) SnCla C H 3 N O 2C H 3 2) KOH 35o/"

several steps

cH20H

Hq,. '/-\ / \ c H2N+(c H3)3-ors c H./\ g

cuHr-^ffoc2H5 cH3 cH3

339

(+)-6 (90% ee)

Tin(lV)chloride-Silverperchlorate

340

1S.8. Denmark, B.S. Kesler, and Y.-C. Moon, J. Org., 57,4912 (1992). 2M.A. walker and C.H. Heathcock,J. Org., 56, 5147 (1991). 3 J. K. Whitesell, J. F. Carpenter,H. K. Yaser,and T. Machajewski,Am. Soc., 112,7653 (1990). aT. Sato, Y. Wakahara,J. Otera, H. Nozaki, and S. Fukuzumi,Am. Soc.,1f3' 4028 (1991). 5 M . H . H o p k i n s ,L . E . O v e r m a n ,a n d G . M . R i s h t o n ,A m . S o c , 1 1 3 , 5 3 5 4 ( 1 9 9 1 ) ; L . E O v e r m a n and G. M. Rishton, Org. Syn., 71, 63 (1'993)'

Tinfl9

acid.

chloride-Tiifluonoacetic

Intramolecular 15,156; 16,190-101)

Tin(II) trifluoromethanesulfoortc- ! Addition of l-allqnes ro cafu this addition, but their strong basr- ; substrates.1-Alkynes can add dirctth Sn(OTf)2 and a base(1:1). In rcacrhrr but 1,8-bis(dimethylamino)naphtha Silvlationof l-alkvneswith R,Sr(l c

ene reactions.t

use of Lewis

Fech,

acid catalysts (particularly

has greatly extended the usefulness of intramolecular ene cy-

clization. Thus a new diastereoselective route to corynanthe-type alkaloids involves (2), a precursof to methyl the ene cyclization of I to tans-indolof2,3-a]-quinolizidine corynantheate (3) by demethoxycarbonylation.

+

Ar-C=CH

RCHO

Sncla (1 equiv.) is the only common

Lewis acid that is useful for this particular ene cyclization, and even so, it also requires the presence of trifluoroacetic acid (1.5 equiv.).

2 -A mino-2 -deoxy -B -o-glucqn tetra-O-acetyl-2-deoxy-( 2.!.1-tnt*rkrr actswith alkyl trimethylsilvl c'thcrstrr >90Va yield. This procedurcis al..' r1

1 ) T F A ,C H 2 C | 2 , 2 0 o 2) SnCl4,20o 42o/o

H

(cHJ3so

CHsOzC

aOAc

oi?;S{.-oo.

2, R = COzCHs 3,R=H

NHTroc f L.F. TietzeandJ. Wichmann, Angew.Chem.Int. Ed.,3l, 1079(1992)-

1

Tin(IV) chloride-Silver perchlorate. a-Glycosylation.t This combinationproducesa speciessuchas Sncli CIO; , which is an effective catalyst for reaction of a protccted l-O-acetylglucosewith a silyl ether

TinOI) trifl uoromethanesulfour-( Asymmetric aldol reaaioa d d. as promoter of aldol condcnsatr.n o in 1973 (6,590-591), has :*'cn rrd

to form a-glycosides.

BzlO

BzlO SnCl3+ClOa

OAc + OBzl = a:1) (cr/p

ROSi(CHs)s-

I M. Yamaguchi, A. Hayashr. an.JT Vc 2T. Mukaiyamaand K. Matsuharr. ( .n

OR 86 - 95% OBzl (a/9= 90-95:10-5)

I T. Mukaivama. T. Takashima,M. Katsurada,and H. Aizawa, Chem.Letters,533 (1991)'

the Lewis acid is required arxi thr aldehydesor chiral silyl enol c'tlrn a weak kwis acid, neither cffcctrrc in catalytic (5-10 mol %) amtxrnt-r coordinatedwith a chiral diaminc .-en (f3,302) and Michael reactions( l-(-ll aldol condensation.Eventuallr tlr ,

Tin(Iltrifluommethanesulfonate-Chiraldiamine

. :.:l (1992). ,< n 'rr. ..{m.Soc.,112,7653 (1990). n - 1 n r . S o c .1, 1 3 , 4 0 2 8 ( 1 9 9 1 ) . l l - 1 . 5 3 5 4 ( 1 9 9 1 ) ;L . E . O v e r m a n ;"

341

Tin(II) trifluoromethanesulfonate, Sn(OTf )r. Addition of l-allqnes to carbonyls.t Alkali metal acetylides are usually used for this addition, but their strong basic propertiescan cause problems with base-sensitive substrates.l-Alkynes can add directly if the reactionis carried out in combinationwith Sn(OTf)2 and a base(1:1). In reactionswith aromaticalkynes,DBU is the preferredbase, but 1,8-bis(dimethylamino)naphthalne is preferred for reactionswith aliphatic alkynes. Silylation of 1-alkyneswith RrSiCl can also be promoted by Sn(OTf)2 and an amine.

iirJ catalysts(particularly FeCl3, fulrc:s tlf intramolecularene cyr':' r.rnthe-typealkaloidsinvolves lr,':.jrnc(2), a precursorto methyl

+ RcHo

Ar-c=cH

DBU, Sn(OTfl2, cHzclz . 66 - 87o/o

l. I cquiv.) is the onlY common tr:r. t. ilnd even so. it also requires

CHr N H

ll-

g

Ar'

2-Amino-2-deoxy-B-o-glucopyranosides.2 In the presence of Sn(OTf)2, 1,3,4,6(l) retetra-O-acetyl-2-deoxy-(2,2,2-trichloroethoxycarbonylamino)-B-o-glucopyranose 2 in actswith alkyl trimethylsilyl ethersto form the correspondingB-o-glucopyranosides >90Vo yield. This procedureis also applicableto preparationof B-o-galactopyranosides.

H

H CHsOzC

R

(cH3)3sio .-oAc

2, R = COzCHs 3,R=H -.)(

T z,zAon

oi?o*Voo" NHTroc

Sn(OTf)2

. -\(--,

cH2ct2,2oo

aOAc ^i?&Vo-r-\

97o/"

NHrroc (, 2

1992). rM. Yamaguchi, A. Hayashi, andT. Minami,J. Org.,56,4091(1991). 2T. Mukaiyamaand K. Matsubara, Chem.Letters,1755(1992).

| .r.!ics suchas SncliClOa , which -{ )'.rectylglucosc with a silyl ether

e'

(
Tin(II) trifluoromethanesulfonate-Chiral diamine. The use of TiCl+ Asymmetric aldol reaction of silyl enol ethers. (16,221-222).' as promoter of aldol condensationof silyl enol ethers with aldehydcs,first reported in 1973 (6,590-591), has seen wide use, but has the drawbacks that 1 equiv. of the Lewis acid is required and that an asymmetric version requires use of chiral aldehydesor chiral silyl enol ethers. More recently, the combination of a salt and a weak lrwis acid, neither effective catalyststhemselves,was found to be effective in catalytic (5-10 mol %) amounts.Further researchshowed that tin(Il) triflate when coordinatedwith a chiral diamine can effect catalytic asymmetricallylation of aldehydcs (f3,302) and Michael reactions(f5,313-314), even though this complex cannotpromote aldol condensation.Eventually the combination of tin(Il) triflate, a chiral diamine,

342

Tin(II)trifl uommethanesulfonate - Chiral diamine

and a tin(IV) salt such as tributyltin fluoride was found to effect catalytic aldol reactions of the silyl enol ether of S-ethyl ethanethioatein good yield and high enantioselectivity(equationI). A number of chiral diamines are effective, but all are substitutedderiviates of (S)-1-alkyl-2-methylpyrrolidine.The most effective is (S)-1(1), as shown in Figure A. methyl-2-[(N-1-naphthylamino)methylpyrrolidine

"r!*fN-NaPhthYl rfo-ln-o.

CH3-....,.CHO * cHz{ : 6sitvte2-t-Bu

(A)

os

SC

(R)-2

R3Sri--

tll?lla ..,t:' 3--/osi(cH3) I

(l) (CH3)3CCHO + CH2{ tscrHu

CHa- -CHO

,-------* czHss 9,./o

c(cH3)3 >987" ee

H \ (ll) RcHo + F\ CHg

Sn(OTf)2,Bu25n(OAc)2 1, '78", CH2CI2

/9S|(CH3)3 SC2H5

85-96%

(z)

o H o t l t scrH" R/-:/ I - CHe (synlanti= 100:0, >98o/oee)

This chiral catalyst was then found to effect aldol reactionsof aldehydeswith the silyl enol ether of S-ethyl propanethioate(equationII). In this casedibutyltin diacetateis somewhat superior to tributyltin fluoride as the cocatalyst.With this chiral promotor, chemical yields are high, and only the syn-aldol is formed tn >987a ee. This high stereoselectivityobtainswith aliphatic and aromatic aldehydesand a, B-enals. The actual catalyst is believed to be a complex (A) of the three componentssince it is soluble in CHzClz even though none of the componentsis. The amine-coordinated tin(Il) triflate acts as a lrwis acid to activate the aldehyde,and the tin(IV) fluoride or acetateinteractswith the silyl enol ether. 2 The asymmetric aldol reaction of aldehydes Double asymmetric aldol reaction with silyl enol ethers catalyzedby tin(Il) triflate and a chiral diamine such as (S)-1, (16,221-222), has been extendedto 1-methyl-2-[(N-naphthylamino)methyl]pyrrolidine, aldol reactionsof a silyl cnol ether with chiral aldehydes.

+

I

3

OSiMe2-t-Bu (s)-2

The chiral aldehyde.(R)-2. rcrt give anti-4 with excellentselectrrrtr rl h the samereactionto provide na{ the (S)-configuration,an indicatxn d amine, and not by the chiralitr of rb catalyzed by (R)-l and Sn(OTft: Fr the (R)-configuration.Thus hr a suru

cH3\.-cHo

+ 3

osin. (R)-2

cH3\Y.-cHo I osiR3 (s)-2

+

culfonate-Chiral

TinOI)trifluommethane

q)--*Q

aldol rr.JnJ to effect catalytic high i.'.,1c in good Yield and are all tr.rr.\ are effective, but (S)-1: I hc most effective is

cHs

diamine

(s)-1

\-/

.r,r\\n in FigureA.

CH3-.-,.CHO : 0SiMe2{-Bu

(s)-1 /OSi(CH3)3 Sn(or0z + CHz{. 'scrHu 84o/"

OH t

cnr-_?4vcosc2Hs : 6siR,

1A)

(S,R)-antl-4(94:6)

(R)-2

r -.--'

qH

Il l

5

:

c2H5s'^$c(cH3)3 >98% ee r :Ac)2

OH

O

l-:

I

ll

1

n

l CHs $Ynlanti= 100:0' >98o/" €e)

(s)-1 CH3--.",.CHO

I

+

3

Sn(OT02 860/o

OH I

CHs\*.\..cOSczHs

l "

osiR3

OSiMe2t-Bu

(s)-2

(S,S)-sYn-4(96:4)

Thechiralaldehyde,(R)-2,reactswithl-ethylthio-l.trimethylsilyloxyethene(3)to aldehyde,(S)-2' undergoes give anti-4with excellentselectivity(94:6).The enantiomeric thesamereactiontoprovidesyn.4.|nbothreactionsthenew|yformedchiralcenterhas the(S)-configuration,anindicationthatthestereochemistryiscontrol|edbythechiral Indeed' the same two reactionswhen amine, and not by the chirality of the aldehyde' in which the new chiral center has catalyzedby (R)-1 and Sn(OTf12provide aldols the(R)-configuration.-I.husbya,suitablecombinationofachiralaldehydeandachiral

with the r'i rr.rctionsof aldehydes is diacetate I i:' thrscasedibutyltin promotor' '.r:.,1\\t.With this chiral This high i. :,,rmcd in >987o ee' , l . t : h r d c sa n d a . B - e n a l s r \ r of the three comPonentsslnce n3'ncnts is. The amine-coordinated or l.rr:rdc. and the tin(lV) fluoride ,nrr.tric aldol reaction of aldehydes as (S)-1' rn.: .r chiral diamine such to extended been 116.::l-222), has s^rJcs.

CH3.\-,.CHO

+

3

(R)-1 Sn(OT02 85"/"

6sin.

t osiR3 (s)-2

6sin. (96:a) (R,R)-sYn-a

(R)-2

CH3\\.,CHO

9H cH..\h/cosc2Hs

+

3

(R)-1 Sn(OT02, 85%

QH CHg\9.AyCOSC2H5

I osiR3 (R,S)-sYn- (94:6)

344

Titanium(IV)

chloride

catalyst,the four possible diastereomerscan be obtained. propargylic alcohols.3 The highly enantioselective aldol reaction of Mukaiyama can also be used to obtain optically active propargylicalcoholsby reactionof acetylenic aldehydeswith a silyl enol ether. The most effective chiral catalyst is obtained by a combinationof tin(Il) triflate with a diamine derived from (S)-proline, (S)-1-methyl-2an acetylenicaldehyde lN-naphthylamino)methyl]pyrrolidine(1). Thus the reaction of

9l l o

a

o

1rr(:.c

il

2\c/+d

ru-\.--.CHa Bzl 1

1 ) H 2 O 2O , H 2) cH2N2

93"6

Q-...il

This techniquecan also cffcrr hr3 in this case i-PrOTiCl, is \uttrr: (equationI).

CHs

?

R--------cHo

+ Ets

-

?si(cH3)3Sn(OT02,1

Bzl

CHs

7o) provides the trimethylsilyl

/

\-,.

73-82/" (synlanti-95:5)

with (Z)-1-ethylthio-1-trimethylsiloxypropene

cooct

o

ll tl (f) o'-t\\ \-1 / l

in the prescnce of sn(oTf)2

Reaction of RNt r'ilh Lctanr reaction of alkyl azides *.ith .rclr reaction can also occur but can hc azide. Highest yields arc obtatrr.J r be obtained in 2O-25Vc vic-ld frrvn

o

and I (20 mol

a\ t

ethcrs of propargylic alcohols in 92-97o/o ee.

rS. Kobayashi,H. Uchiro, Y. Fujishita,I. Shiina, and T. Mukaiyama,Am. Soc., l13' 4247 (1991)' 2 S. Kobayashi,A. Ohtsubo, and T. Mukaiyarna,Chem. Letrer.s,831 (1991). 3 T . M u k a i y a m a ,M . F u r u y a ,A . O h t s u b o ,a n d S . K o b a y a s h i i,b i d . , 9 t t 9 ( 1 9 9 1 ) .

c

l

+

RN3

R = n-l-ler R= Bt

o

/-''a"'" l l Titanium0V) chloride. Chlorotitanium enolates (16,332-334).r The titanium enolate of the N-propionyloxazolidone1, preparedwith TiCl+ and CzHsN-i-Pr2,undergoeshighly diastereoselective Michael reactionswith ethyl vinyl ketone, methyl acrylate,and acrylonitrile.

n-HexN3

5-1*

In some cases the ring crparx intermediate(equationI).

6i i\: N

.. ",Oot reaction of MukaiYama ,l.rrholsby reactionof acetylenic ;hiral catalYstis obtaincd bY a ::,'m (S)-proline,(S)-1-methyl-2.,.rion of an acetylenicaldehyde

?

o

H,,

o

o

qAN\.-A",,.', I \_-\ /

88"/o

CHS

Bzl 2 ( > 1 0 0 1: )

1

o

o

1 ) H 2 O 2O , H 2) cH2N2

't8 1

chloride

9

1)TiCl4,C2H5N(l-Pr)2 2) C2HsCOCH=CH2

oAr{',cH.

Titanium(IV)

cH,o\(\,Ac,H,

93o/"

CHs

This techniquecan also effect highly asymmetricintramolecularMichael addition,but in this case iPrOTiCl: is superior to TiCl+ and N(C2H5)r is the preferred base (cquationI).

?

?

(l) OAN\ \ l

l

arr,

\-2

l

2

coocH3 r-proricr3, Ol l N(c2H5)3,-78'

o

e

e

7

r.\

Y n f coocH3 r.r-\-{

q , u

"

Bzl (93 : 7)

(synlanti-95:5)

c ::. \cncc of Sn(OTf)2 and I (20 mol c .'.-,rhols in 92-97o/o ee.

Reaction of RNt with ketones.2 Ticl4 (2.5 equiv.) can effect a Schmidt type reaction of alkyl azides with cyclic ketoncs to afford N-alkyllactams.An aldol-typc reaction can also occur but can be supprcssedby use of excess(2 cquiv.) of thc alkyl azide. Highest yields are obtainedwith cyclohexanes,but ring expansionproducts can be obtained in 2O-25% yield from cyclopentanoneand cyclobutanoncs'

o

o

a\ t

\1 .,..ir\ama,Am. Srtc-,113,4247 (1991)' / : : ., ' . t t 3 l ( 1 9 9 1 ) . r r , r 1 19. t. t 9 ( 1 9 9 1 ) . r\'

.Ticl4, CH2C|2,0 - 20"

l

+

+

Nz

(_) R = n-Hex R = Bzl

80"/o a8%

o

o CHs

n-HexN3

5-19% t :::.rniumcnolateof the N-propionylr . :rndcrgoeshighly diastereoselective : - - r l . r t c .a n d a c r Y l o n i t r i l e .

An,,*

RN3

.A*'n-H"* / \

\ _fcH'

CHe. A /n-Hex Y - N +

|

\

+ N 2

1.7..1 \J

In some cases the ring expansion involves the rearrangementof an azidohydrin intermediate(equationI).

Titanium(IV) chloride

346

t

-

-

' -"l1A\.-. zo "' - lT - . t l = - ( / ^ o " o R"N \ -, , * ^ \ _ - / l r . r J l p:o

6 (r

l

Bicyclic enediYnes.o Ttx \t catalyzed Sakurai reaction of a o 3 as a single Product. This PruJu

l

(cH3)3si-...-

of TiCla' the (E)-vinylsilane (1a) reacts o-Hydroxy p,y-enoates.3 In the presence (E)-2a' in high yield' In with methyl glyoxylate to form an a-hydroxy-B'y-enoate' under the same conditions to give a 1:1 contrast,(Z)-la reactswith methyl glyoxylate The ene product' 3a is the exclusiveproduct mixture of (Z)-2aand the ene product (3a)'

n Y

r'\..Si(CHs)g ".r v " r |

*

quant'

coocH.

H

CHs

-

lt

Ticl4, cH2cl2,-78"

?"

o

(z\-1a

OH

I

cH.

(-coocH3 CHo (E\-2a

(E)-1a

\.,si(cH3)3 I CHs

H

+

llUl4'

cH2cl2

,A.oo"r. ?H. ?H \fcoocH. cHs

(cH3)3sit ?t - cHrl'Y'\coocH3 1:1

CHs

(z\-2a P d [ P ( C 6 H 5 ) r 1 4 ,C u l , a n d B u \ H '

catalyzedby SnCla' of reaction of (Z)-la with methyl glyoxylate S-phenylmenthylglyoxylate provides a with (Z)-vinylsilanes The reactionof (h,)- or single (2S)-alcohol (equationI)'

?u"u SI(CH3)3* \,.

(z)

t D.A. Evans, M.T. Bilodeau-T ('

(1ee1 ).

2J. Aub6,G.L. Milligan.and(- J 3 K. Mikami,H. Wakabavashr. enj a D. Schinzerand J. Kabbara.Srr

o

ll HACOOR*

o (>99o/" ee)

Titanium(IV) isoProPoxidcPnm 3-Amino-(,2-diokr to presenceof Ti(O-l-Pr)1 form

Titanium(IY)isoPmPoxide 347

c"o

Bicyclic enediynes.4 The key step in a synthesis of these enediynes is a Ticl+catalyzed Sakurai reaction of a conjugated allylsilane (1) with the enone 2 to provide 3 as a single product. This product, after conversion to the ketal, was cyclized to 4 by

f.fn

-N2

o (la) reacts l-. :hc (E)-vinylsilane high (E)-2a, in :n,,.,tc. Yield. In a L:1 ..rme give to conditions k N:.it. 3a is the exclusiveProduct

* (cHe)ssi--K--r. Ticl4 -74"

h

68/o

--\"

1

\

CHz

OH

-:

CH',.>.'\COOCH3 CHs

r) o..,,o (84%\ I ocH3 2\Pd(Ol, (24o/") Cul, BuNH2

(E)-2a

I

C H"" ) " S- |

I

t O Hl

cH/'fcoocH3 I CHs

4

3a

u -r SnCl,r. rnrlnrcnthylglyoxylateprovidesa

Pd[P(C6Hs)3]4,CuI, and BuNHz. This bicyclic enediyneis stable at 25"' I D.A. E ans,M.T. Bilodeau, J. Clardy,D. Cherry,andY. Kato,J' OrS'' 56'5750 T.C. Somers, (1991). 2J. Aub6,G.L. Milligan,andC.J. Mossman, J. Org.,57'1635(1992). 3 K. Mikami,H. Wakabayashi, andT. Nakai,ibld., 56, 4337(1991). a D. Schinzerand J. Kabbara,Synlett,766 (1992).

oR* 89'. (>99o/oee)

Titanium(IV) isopropoxide. 3-Amino-1,2-diols.t Primary amines react with chiral 2,3-epoxy alcohols in the presenceof Ti(O-i-Pr)+ to form 3-amino-1,2-diolswith high regioselectivity'

trifl ate

l-Toluenesulfonyl-3-methylimidazoliurn

n$/\on

9H

N H C"^ H -r r

C6H13NH2

I

Ti(o-iP04

* n---r/\oH I

nt^\/\OH : 6H

1,R =CoHs = cHs = Pr

NHC6H13

1J.F.O'ConnellandH. Rapopon. -/ rr't 100:0 93:7 92:8

83% 96% 51"/"

lM.Canas,M.Poch,X.Vcrdaquner,A'Moyano,M'APericas'andA'Riera'TetrahedronLetters' 32.693r (199r). (l)' N-(p-Toluenesulfonyl)iminophenyliodinane,CoHsI:NTs' Preparation.l this nitrene precursor ,qiiridination,2 Aziridination of alkenes can be effected with and cu(cH3cN)acloa particularly catalysts, cu(II) when catalyzedby various cu(I) and Cu(acac)2inyieldsof55_g5To.Notethataziridinationofasi|ylenoletherprovidesan

-

1 , C u c a t . ,C H 3 C N

---_--_.75 - Blo/"

\r

chromatography.

o

ll TotS:"AO l +

-EWG i CHz

1

N.

../ CHg"

3-(p-Tolylthio)-2-pyrone ( I ). Diels-Alder reactions.l l-Prnrr generally requiressuch high temlrrrr pressurecycloadditionshave alsrr trcr In contrast,this 3-substitutedd€n\ iln with electrophilicdienophilcsat l't - 9

l l \/

Ts u-3--Z\CoHs

p-Toluenesulfonamides and'stUt ondary amines into the arylsulfonam alcohols or phenols provides ar,rlsulfo scavengerimproves the yield.

EWG

-CoHs

NO:

C6Hs--l,CHz I osi(cH3)3

r'l

t .

CN cl-to COOClrr

o +

1,"';,t#1 -\

71o/o

CoHs-

v

-NHTs

N-substituteda-amino ketone (secondexample)'

* cH21

o tl o \__J

s 744

I Y. Yamada, and M' Okawara,Chem'Leuers'361 (1915)' T. Yamamoto' 2 D. A. Evans,M. M. Faul,and M. T. Bilodeau, J' Org'' 56' 6'144(1991)' (1)' preparedby reactionof l-Toluenesulfonyl-3'methylimidazolium triffate methyl triflate with p-toluenesulfonylimidazolein THF:

TfocH3

"r.O

(l -'

SOz

I

1\.

CHs

This Diels-Alder reaction can hc

even an unsaturatedspirolactonc.rrtl product of reaction of a-plrone rtrcl of COz.

(l) 3-(p-Tolylthio)-2-pyrone

p-Tbluenesulfonamides and -sulfonates' The reagent converts primary and secondary amines into the arylsulfonamidesin 7O-8OVoyields. A similar reaction with alcohols or phenols provides arylsulfonates.Addition of l-methylimidazole as an acid scavengerimproves the yield.

9H * n.^yloH

\J-

349

I NHC6H13

I J.F. O'Connelland H. Rapoport, J. Org., 57,47'15(1'992). 100:0 93:7 92:8 i' - ,- .rndA. Riera,TetrahedronLetlers,

|

3-(p-Tolylthio)-2-pyrone (l). Diels-Alder reactions.t 2-Pyrone can undergo thermal Diels-Alder reactions but generally requiressuch high temperatures(100-200') that the adductslose CO2. Highpressurecycloadditionshave also been effected,but the products are usually unstable. In contrast,this 3-substitutedderivative I can undergo thermal Diels-Alder reactions with electrophilicdienophiles at24-90" to give mainly endo-adductsthat are stable to chromatography.

\ I\. (l).

c .:rf ctcd with this nitreneprccursor and Cu(CH3CN)+ClOa s. I 'r-ticularly rr .:' ,'t a silyl enol ctherprovidesan

o to't\Ag \

(=*o 25.85">or4wc )

d-[

cH,

+

2 ( endolexo )

1 EWG NO,cN CHO

o

71o/o

CoHs-

coocH3

tl -\ v -NHTS 1

+

CH21,

o tl \_J

i: s6

98:2 2 : 1 98:2 3 : 1

82o/o 53"/o 44o/o 65"/o

6

,o',

2,Srot O o>(LA

74o/o

d-)-/

fJO

NaocHg86"/o

98:2

rr)l (1975). --+1(1991).

COOCH.

1l r. prcparedby reactionof

1 ) T B D M S O T f( 8 1 7 " ) 2) Bu.SnH.DBU (68%)

lllt:

o ,-V t t / / t - ,r\

R3S|O'

s9,

il

N+ I

CHs

-'

:\v ,O

4 This Diels-Alder reaction can be used to obtain functionalizedbicycloadductsand even an unsaturatedspirolactonesuch as 4 (equationI), which correspondsto the formal product of reaction of a-pyrone itself with a-methylene-y-butyrolactonewithout loss of CO2.

TFibutvl tin carbamate

The related 3-(tolylthio)-1-tosyl-2-pyridones(5) also undergo thermal Diels-Alder reactionswithout loss of an isocyanategroup (equationII).

o

ll o^. 2 9Tol e( TolS--ra-\ 'NSo2Tol O>(-!'--?,'CHO H-.*,.CHO c"rc', ( l l ) l l | + i l - - ; T o t s o z N { 42

\r'

bH"

This reaction can be extendedto r 7-halo ketonesby use of the stannrl r (2), prepared from Bu3SnOCH. arrl r stable trans-productspredominarc

ot l

-^ cHs- -(cH2)3ct - c€H

5 1G.H.Posner, J Org.,57,a083(1992);G.H. Posner, C.M. Kinter,andN. Johnson, T.D. Nelson, and K. Afarinkia,ibid.,57,4088(1992). V. Vinader, TFibutyl tin carbamate (1).

o tl

C"H^ l - -

- N --COOCH3 Bu35n-

Bu3SnOCH3+ C2H5N=C=O

DarZens-typereaction.t The Darzensreaction2of a-halocarbonylcompoundswith an aldehyderequiresa base, which can promote side reactions.Darzensreactionscan proceed under neutral conditions when effected with this neutral reagent (1 equiv.). Presumably,the reaction proceedsvia an organotin(IV) enolate. When the reaction is conductedin THF, the trans-epoxideis generally favored, but addition of HMPA can favor cis-selectivity.ci.s-Selectivityis also favored in reactionsof aliphatic aldehydes. The Darzens-typereaction can also be extended to a-halo esters,particularly in the presenceof BuaNF or LiBr.

o cH.AcHre,.

+

1 THF, 60' --.:,15o/o

C n H c C H e' C H O

o A CHs. V

3cH2c6H5

o

4Oo/o

c2H5o

= 61:39

o

o cH2Br

C6H5CHO

HMPA,60"

+

1 ,T H F

15o/o

+ BuaNF,-78"

8'|"/"

+ LiBr,25'

78o/o

il -A-

czHso-v

- cdq

'1. Shibata,H. Yamasaki. A. Baha.'r. H 2 M. S. Newmanand B. Magerlcrn. / >r' & Tlibutyltin

hydride. 3,4-Disubstituted tetrt,hfivtfr'l (CH3)3SnCl,NaBH3CN. and ..\,lB\ rl as I with carbocyclizationto 2 Orrft ammonium nitrate provides rtr etdd product isomerizeson treatmcnrrnt is convertedin several steps ro rlr lg

?"r. cH3olYocH3

cisltrans=4:96 + HMPA

cuHr^lcHr;ot

Dr,

^,, nuel-lc

o

cisltrans=60:40 = 58:42 =8:92

\s'rE

Y )

\o/

("^'

T[ibutyltinhydride 1.., Lrndergothermal Diels-Alder n : I li .

ro,SOzNN '

This reaction can be extended to a synthesis of disubstituted tetrahydrofurans from 7-halo ketonesby use of the stannyl iminocarbamateBu3SnN(C6H5)C(OCH3):NC6H5 (2), preparedfrom Bu3SnOCH3and C6H5N:C:]rIC6H5. In these reactionsthe more stable trans-products predominate.

) SIo, .\ // l/ ->l-*-r' _CHO

,

".

351

o

2,rHF,

cH.AlcHz)scr + c'HscHo +

"utt "la,,o)

.r.#-J o

5 7 , 4 0 8 3 ( 1 9 9 2 ) ;G . H . P o s n e r ,

cisltrans=38:62

'

C"H^ t - " - N ,- C O O C H 3 Bu3Sn-

,i ,'halocarbonylcompoundswith | :-.r!li()ns.Darzensreactionscan h :i:r. ncutral reagent(l equiv.). \ enolate. When the reaction is , :..i. hut additionof HMPA can '-.:.rions of aliphaticaldehydes. a,:.rl() cstcrs,particularlyin the

o ^r'CH2CoHs \ /

o

"'Yo)

o ll cuHu^lcHr;ot

+ c6H5CHo -*;

fro

coHs

cisltrans = 21 :79 rl. Shibata,H. Yamasaki, A. Baba, and H. Matsuda,J. Org., 57,6909 (1gg}). 2 M. S. Newman and B. Magerlein, Org. Reacr.,Vol. V, 413 (1949).

Tributyltin

hydride. 3,4-Disubstituted tetrahydrofurans,t Trimethyltin radicals generated from (CH3)3SnCl,NaBH3CN, and AIBN (14,313-314) add to allyl cinnamyl ethers such as I with carbocyclizationto 2. oxidative cleavageof the (cHr):sn group with ceric ammonium nitrate provides the aldehyde 3 without attack on the aryl group. This product isomerizeson treatmentwith DBU to the rrans-isomer(>23:l). This trans-3 is convertedin severalsteps to the lignan burseran4.

:lsltrans=4:96 = 61:39

ocH3 (CH3)3SnCl, NaCNBH3, AIBN

o

CH25n(CH3)3

-\ .''r_-f "C"H^ C,H"O\ /

o

("'"

o"

cisltrans=60:40 = 58:42 --Bi92

1) CAN (58o/") 2)DBU (82%)

Ttibutyltin hydride

""o"{o""

cH3o\

",.oQ-'.a-Qr "r.d

Y.cHo

'o2

(o)

Radical ring expansion of lt of an a;-bromoalkylchlorok!'renc r chain. Treatmentof this adduerr to a ring annelatedproduct RLlru reactioncan be used to appcnd -.

qj 3 +

Tetrahydrofurans.2 A new route to tetrahydrofurans involves cyclization of an alkoxymethyl radical derived from a homoallylic alcohol. Thc precursoris obtainedby conversionof the alcohol (1) to the (tributyltin)methylether (9,475), followed by Sn-Li exchange,and quenchingwith (C6HsS)2to form an a-phenylselenenylmethylether 2. Treatment of 2 with BurSnH (AIBN) generatesan alkoxymethyl radical that cyclizes

OH i

O |

H

//r-/-

4)(c6H5se)2>

S - -E- "C ^ H ."

\-/\ H

c6Hs"/----..\cH2

o

744

2

1

B u 3 S n HA, I B N c6H6,80"

o

\

1)KH 2) BU3SNCH2I 3)BuLi

coHs*cHz

Cl\,-(CH, tl C

,CHs

,,CH"

11 cuHr4o2

cuHr4o2 2.6:1

Radical ring expansion of qtr. by alkylation of a spirrxrcltfrrr'o BurSnH/AIBN in refluxins hcnra thc reduction product 4.

trans-s

cls-3

to the tetrahydrofuranwith cis-selectivity.Only traces of the product of reduction are observed. This cyclization can bc extendedto bicyclic tetrahydrofuransand to tctrahydropyrans.

H

a--.-l--.,

asecoHs \-"^\-.o

l t vT-/

p

o

A (-l

1) LDA 2) BrC}i:CF,C

83a

1

H

a' O

SeCuHs

caHs&cHz

'-*cuHu!

O---f"t.

O1-'"t.

*

auru-L.--,J

3 r{ 8.2:1

Ttibutyltinhydride

353

Radical ring expansion offused cyclobutanones.3 This reaction involves reaction of an ar-bromoalkylchloroketene with an alkeneto form a cyclobutanonewith an exo side chain. Treatmentof this adduct with Bu3SnH (AIBN) generatesa radical that cyclizes to a ring annelatedproduct becauseof relief of strain in the four-memberedring. This reactioncan be used to append7-, 8-, or higher-memberedrings to appropriatealkenes.

cH30

3

+

r:.-:.rn\ involves cyclizationof an r,: I fhc precursoris obtainedbY | .:hcr (9,475),followedbY Sn-Li ether2. .,,phcnylsclenenylmethyl

Cl.-.}r-(CH2)3Br tl

|

(CHz)sBr

IY'-cr

s" ,ofl

c

o

:lr,rrmethyl radicalthat cYclizes

-,,\-SeC6H5 9I c,H5MCH2

Bu3SnH AIBN

o 'l8o/o

2 ,CHg

11 \

cuHr4o/

Radical ring expansion of propenylcyclobutanes.a The substrates(2) are obtained Treatmentof 2 with by alkylation of a spirocyclobutanoneI with 1,3-dibromopropene. BurSnH/AIBN in refluxing benzeneprovides the tricyclic spiro ketone3 togcther with the reduction oroduct 4.

trans - 3 tc. ,'l thc product of reduction are

turansandto tetrahydropyrans. H

-'^.-f--\ '--.Fvt

p

'

+

5 a\ l l \-.-

o

1)LDA

l-r:cu*

2) BTCHzCH=CHBr a\ 8 3 o / o l \-"-

l

:CHZ

o1.'cHt )

CeHsN 3 ( 4oo/o)

8.2:1

Bu3SnH AIBN

l

o

H

r cHs

o

4 (457o)

Tfibutyltin hYdride

CHr tl

CHBr Bu3SnH, A I B N ,h v -

a!l/t"'

at\

+

q\"

er-,W@ cl

41"/"

5O/o

Reaction of BursnH/ cyclization and expansion of dichlorocyclobutanones.s AIBNwiththeadduct(l)ofthereactionofendo.6-vinylbicyclo[2.2.1]heptene-2with dichloroketeneresultsinfreeradicaladditiontothefreedoublebondandreduction 2 with ISi(cH3)r/ZnI2 results in of the remaining chloride to provide 2. Reaction of which is convertedto enone ketone, cyclic a-iodo transformationto a seven-membered 3 by DBU.

Bu3SnH AIBN

ether, souno

+ C|2C=C=O

90o/o

cb ButSnH insertion into aliPbr with aliphatic chromium carttrrs I I t t diastereoselectivity(4-13:I ).

9cH' (co)scr^Yc6Hs

hex^nE 66'

691

cH3

1

Znl2 1) lSi(CH3)3, 2) DBU > 92%

&asr*t 91

OCH.CnH" O

r - t - - l l

rCo)^CrZf*I

CHs \-.,,

/

71/o

/i

as 1' prepared as shown trom Spiroannelation.6 A spirocyclobutan-2-one such AIBN (2 equiv'' slow addition) and when treatedwith Bu3SnH methylenecyclopentene, (2)' und"rgoe. radical ring expansionto a spirocycloheptanone

I

< 8l\

Radical ring exPansion of cvcb to medium-size ring systems. Thus t cyclohexenone,on treatmenl u.ith Bu, in 787o yield.

Tributyltin hYdride

--/

o

?r,

.CHa

a\

+

b*,.,,

1) N(c2H5)3,cH2cl2

*

2)Nal B'/--'-YCO

-

CI

41"/o B u 3 s n HA , IBN ceHo'

95o/"

bn,tnes.5 Reactionof Bu3SnH/ with -r r: r lhicyclo[2.2.1]heptene-2 reduction and bond double I i:;r I .rirh lSi(CH3\fZnl2 resultsin c: ,1r. \\'hich is convertedto enone

"{)

b 2

Bu3SnH AIBN

58"/"

\

,Cl

o

r

BujSnHinsertionintoaliphaticchromiumcarbenes.lBussnHandpyridinereact compoundswith marked with aliphatic chromium carbenes(1) to form a-alkoxytin diastereoselectivity(4-13:1).

y'X 'cl

gcH, Bu3SnH, PYr'

QCH3 |

^,,

(co)su/Yvor15 1

cH3

hexane'65' -"t**

aursnlcuHu CHs

+ syn-2 77 123

anti - 2

9cH.?uH'? ?cH'?u"'? + sYnisomer Buss"'\lli rcoluc../ff 81"/" cHs \,

-

)

iL.i .r: l. PreParedas shown from ::'.: \lBN (2 equiv., slow addition) p : , r ,' n c ( 2 ) .

cHs \--J

9 3: 7

Radicatringexpansionofcyclohexanones,sThisreactionisausefulroute 1' prepared in two steps from to medium-size ring systems. Thus the precursor cyc|ohexenone'ontreatmentwithBurSnHandAIBNfurnishesthecyclodecenone2 in 78Vo Yield.

Tfibutyltin hydride

o tl

o A. l( -

1) LiSnBu3 HMPA 2) l(CH2)3CH(Br)CH3,

.l

75"/"

trans-Decalins.to traru-Dcc sutrstttutc methylenecyclohexanes ester group.

^\-.---.,,,.cHe l l \ B r

-v'

-SnBu3 1

cooczn /-]"'\ cHeooc--< ' \ A|

o

'' cLu

ll 9Hs

B u 3 S n HA, I B N CoHs,

a'^\3-.\ t

78%

l

\-.\-,'

1

2

This ring expansionis applicableto cyclopentenonesand cycloheptenones,but the yields are usually somewhatlower. It is not applicableto a,B-unsaturated lactones. Stereoselectiveradical reactions. Giese e/ al.e have found that radicals can show comparableto ionic reactions,and that the selectivity can be high 1,2-stereoinduction from cyclic to acyclic radicals. Thus the Bu3SnH radical proceeding reversedwhen providesthe only one isomer (2) with /rans-selectivity.The 1 dioxanone addition to the acyclic system (3) shows cls-selectivity. a corresponding with same radical

Radical cyclization of ocq estersI with BurSnH/AlB\ rn (E)-2, as the major prcJucr silyl)silane/AlBN providtr a mrr A different stereoselectirrtr.ttl initiated by triethylborarr O; .{ result of isomerizationoI tZ>2 In any case, this isomenzatxn cyclizations.

coocH3 OH O'

Bul,Bu3SnH hv,2o'

-\ - O

t

l

o2'{,CH" i l CHz

I

97"/o -

K2co3

oAo I

78v"

oM'cH^ t eu2

-

toot>A"r. I

osiR3

cHsooc-..,fcHs

(trans)

CHe

,

l

1 Bu3SnH/AIBN c6H6,80' oMS)3SiH/AIBN Bu3SnH/(C2H5)38

1 ) B u l ,B u 3 S n H hv, 20" 2) HgO+

t

Bu/

2 (trans/cis= >50 : 1)

1

lll ';-"t.

cH3ooc

fl-MS)3SiH/(C2H5)3P CHg

68o/"

Bu 4 (cis/trans= 42:1)

Radical reaction ol c*rJ o-iodoanilide such as I is ablc Thus on treatmentwith Bu.SnH

TiibutYltinhYdride

357

trans-Decalins.lo lrans-Decalins can be obtained by a radical cyclization of substitutedby an adjacent alkenyl bromide and a carboxylic methylenecyclohexanes ester group.

..---/CH" I Br 5nUU3

cooc2Hs

f__.1,., cH3ooc< I tgr h"- )

o

ll 9Hs

84"/o

t \-,,\.,'

l

rY)

CH3OOC/Y

CHe

a/\7\

cooc2H5

B u 3 S n HA, I B N C6H5CH3'

1

2

but the s .,rJ cyclohePtenones, p-unsaturated lactones. r' ,,. ,r :,,undthat radicalscan show ::.i that the selectivitYcan be -fhus the Bu3SnH radical c-rr' 'r rlr rvith /rans-selectivity.The r',,r. t'is-selectivity.

Radical cyclization of acetylenic esters,tt cyclization of ro-iodo-a,B-alkynyl esters I with Bu:SnH/AIBN in refluxing benzeneresults in the (E)-exocyclic alkene, (E)-2, as the major product. ln contrast, cyclization of 1 with tris(trimethylsilyl)silane/AlBN provides a mixture of (E)- and (z)-2, with the latter predominating. A different stereoselectivityobtains from cyclization of 1 with Bu3snH or (TMS)rSiH initiated by triethylborane/o2.Actually the high (E)-selectivity in BurSnH/AIBN is a result of isomerizationot (Z)-2 to (E)-2, promoted by BurSnH at high temperatures' In any case, this isomerization is an unexpectedexample of regiocontrol in radical cyclizations.

coocH3

lll ';."t. OH HOOC\ -,\ Y

(:-' 'c-:

cH3ooc\

..,coocH3

&"'

(,

'CHs

tl

'

1-"zcnt (zl-2

(E)-2

1

\_J

Bu/ (trans)

)H3ooc

Bu3SnH/AIBN C6H6,80"

82/o

98:2

(TMS)3SiH/AIBN

86"/"

34:66

Bu3SnH/(C2H5)sB

84"/o

60:40

[rMS)3SiH/(C2Hs)3P

85o/"

11:89

CHo

Bu 4 (cis/trans= 42 11)

Radical reaction of o-iodoanili.des.t2 The radical formed by reaction of an o-iodoanilide such as I is able to translocateto a radical a to the carbonyl group' Thus on treatmentwith Bu3SnH (AIBN, 80"), I undergoescyclization to a disubstituted

Ttibutyltin

hydride

o

R1

\_^

Bu3SnH,

N-CH.

c.rrra$lff

+

o

R2

I

A|BN. 800

CoHs OC2H5 2 (2.1:1) CHa t -

Ri

o\-t-"or^ CHs

w

|

R2

FcH2cH3

t B-Hydroxy ketonesfrom o.p<pry with Bu3SnHor b1 a tlrnnrl by photolysis The former reactionis particularll uscfulf<

4 (8:1) cyclopentane2. This radical transfer reaction provides a route to bicyclic and even tricyclic products. It can also be used to initiate radical additions to o-iodoanilides (equationI). O OH t i l

Bu3snH,

+ cH2=cHcH2snBu3

r-eu,AAN-cH'

SO2C6H5 72 78%

R ' E

/--l--\

(

71"/"

CoHs

(l)

Bu3SnH AIBN

R l . F \l-l

A.BN' 80:

o tl

tw. ASSr*t

ryr

coHs^-\-7\ b

'CoHs

gI%

C6Hal

o H o t

t

l

.ru-\AN-cHt r

l

CH2=61'1611, CoHs

*

o tl

o H o t t l t-auA**-cHo l

86:14 CH2=gg6g,

l

CoHs

Fluoromethylenation.t3 Methods for fluoromethylenationof ketonesresult in mixtures of (E)- and (Z)-vinyl fluorides, which are difficult to separate.A selectiveroute involves reactionof the ketonewith the carbanionof 1-fluoro-1-(phenylsulfonyl)methanephosphonate,preparedfrom fluoromethyl phenyl sulfonesand diethyl chlorophosphate. The reaction provides mixtures of (E)- and (Z)-fluorovinyl sulfones, which can be separatedby flash chromatography.Those products cannot be reduced by Al(Hg), but on treatmentwith tributyltin hydride (AIBN), they are convertedinto (fluorovinyl)stannanes with retention.Destannylationto vinyl fluorides can be effectedwith sodium methoxide in methanol or with CsF in methanolic ammonia.ta

C}o

CH.-1"-,,'\ cH.

AIBN, Bu3Srr< 98" , C6lt

cHs

Radical macrocyclizttion to ta.rane ri I with Bu3SnH/AIBN provides tr*'o cpimcl ring system2 correspondsto that pres€ntro of yew trees.

359

Ttibutyltin hydride

'-.-

I

.urr.orxfr.3:1[: -

F o +

o =-A*-cH' , i

Rl

Li\,F

R1

o

R2

R;

.F So2c6H5

(Elz=1-411)

CoHs

o4ocrHu 2 (2.1:1)

R 1- F \l-l

CHe l

So2c6H5

R;

-

o',orN-coHu

?t#' "i,, ,'

Bu3SnH AIBN

*l =rt

72'78o/o

*i1sn'".

liii.o

"lro,,,

cH2cH3 The conversion can be effected B-Hydroxy ketones from a'F-epory ketones'ts (98") with Bu3SnH/AIBN in ceHo' reaction thermal by a by photolysiswith Bu3SnHor Theformerreactionisparticularlyusefulforaroyl-substitutedepoxyketones.

CoHs 4 (8:1) h. .1 r()uts to bicYclic and even cr. ,l additionsto o-iodoanilides

o Bu3SnH, )H - SnBu3

c'"u

"u'u\"uru

'

c6H5cocH2cH(oH)c6Hs

93o/"

AIBN'8oo-

O

ol H o l l ..o,,\AN-OH' l r C8-=CHCHz

hv, Bu3SnH

CoHs

A |

cH"-A_.{ -"bil. -

xir r rldd into (fluorovinyl)stannanes tr. rlfected with sodium methoxide

Bu3snH AIBN, |;o

bHr

8 " ' c o H o'

A

|

.a) il

)o

cHs-M^.. "u.,r.*,"t.

CH,,-A.t\

cH.

cHs

(30ol")

tr i-:.rtion of ketonesresultin mixr-i: :t' scparate.A selectiveroute -i -,:,'- l -(phenylsulfonyl)methane1,,:r. .rnd diethyl chlorophosphate' u,,:,'rrnvl sulfones,which can be rn:.,: hc rcduccdbY Al(Hg)' but on

o

O

the iodotrienone Radical macrocyclimtion to taxane ring system.r6 Treatment of system.The ring taxane of the 3) (2 and 1 with Bu3snH/AIBN provides two epimers in the bark found alkaloid natural the in taxol, ring system 2 correspondsto that present of yew trees.

tibutyltin

hydride

Bu3SnH AIBN

l"'4I

BuaNCl. BuaNF is particularlveffc'oirc_ I In contrast,the combinationof Bu,SnH en

A,!S/l

OCH(CHr)r I

ttt\A"^r. l

"^,'/m^) u*so. \

\

o

t

-

"

;

H

I

^Er,:.srt^

+

3:1

H O

Reduction of a-iodo-B-alkoxy esters.t1 Radical reduction of these estens(1) with BurSnH/AIBN shows high ar?ti-selectivity.In contrast, reduction in the presenceof MgBr2 .O(C2H5)2or MgI2 (0.25 equiv.) proceedswith high syn-selecrivitybecauseof chelation(equationI). AlCl3 is also.syn-selective, but only when I equiv. is present.However,the configurationofthe startingmaterialaffectsthc stercochemistry ofthe reduction.

(r)

9cHs

Bu3SnH

j5F ".",JXcoocH3 "ur,\-"oo"t'

*cuHu-^-y'coocH3 I

cH3 |

CHs

+ MgBr2'O(C2H5)2

?"".

cuHul)(coocH3 cH3 |

8'lo/o

CHs

1:>25

syn-2

1

(ll)

?.r.

9CHg

anti-2 >25:1

B u 3 S n HA, I B N Mglz

syn-2

+ anti-2

61% 1 : 4

3 Thus the ester3 in which the iodide is syr?to the alkoxy group is reducedby Bu3SnH and MgI2 with moderatesyn-selectivity. Diastereoselectivereduction of a-alkoxy ketones.ts Bu3SnH alone reduces these substratesin low yield. The reactivity is enhancedby additionof a basesuch as HMPA or

Radical deoxygenation of scc.
known phenoxy thiocarbonyl derivarircr IR. phenoxythiocarbonyl derivative is sliehrlr r p-fluorophenyl

derivative. The penraflurtrg

slowest of all known derivativcs.

lS. Hanessianand R. Ifger, S)'xlerr.!r: r!\r9 2 V. H. Rawal, S. P. Singh, C. Dufour. anJ (' t 3 P. Dowd and W. Zhang, Am. Soc.. ll.l. 9\-S a W. Zhang and P. Dowd, Tetrahedronl.atrt 5 P. Dowd and W. Zhang, Am. Soc.. ll{. lrfir 6 W. Zhang and P. Dowd, Tetrahed.ronl.atat 7 E. Nakamura, K. Tanaka,and S. Aokr. {a ! " J. E. Baldwin, R. M. Adlington, and R Srnti. e M. Bulliard, M. Zehnder, and B. Gicsc. t/r:t . l0 M. Kawaguchi, S. Satoh, M. Mori. and \l St rrT.B. I-owinger and L. Weiler, J. Ore.. 57. (fl 1 2 D . P . C u r r a n ,A . C . A b r a h a m , and H. hu, u\rl 13J. R. McCarthy, D. P. Matthews, D. M. Srcnrrx a n d P . S . S u n k a r aA , m . S o c . ,l l 3 , 7 { - 1 9r l q v t la J. R. McCarthy, D. P. Matthews, M. L. Erir urtr 31, 5449 (1990). 15E. Hasegawa,K. Ishiyama, T. Karo. T ll.rl3r 16S.A. Hitchcock and G. Pattenden.Tetrahc,lm l7 Y. Guindon, J.-F. Levall6e, M. Llinas-Brurrt (1991). r8 I. Shibata,T. Yoshida,T. Kawakami. A. B.t\ 19W. P. Neu-unn and J. Pedain. Tetrahedna Lc 20D. H. R. Barton, J. Dorchak. and J. C. Jarztrcr

Tlibutyltinhydride

361

BuaNCl. Bu+NF is particularlyeffective,and this systemcan show high syn-selectivity. In contrast,the combinationof Bu3SnH and Bu2SnClHreshows good ar?ti-selectivity.

ocH(cH3)2 Bu3SnH/Bu4NF,

"t.-aAa^r^ t OH

OCH(CHq)r I

"t')^"u"

-

syn/anti = 99:1

o

ocH(cH3)2 CH.r" 9oo/o

-/-

>a

-coHs

OH anti/syn= 75:25

3

Radical

deoxygenation

of sec.-alcohols,

d . - . ' r , , no f t h c s cc s t e n s( 1 ) w i t h :,.ruetion in thc presenceof hr: r .r'rr-selcctivity becauseof ''.-. n I cquiv.is prcscnt.How-

p-fluorophenyl

tr', ,ihcmistryof the rcduction.

slowest of all known derivatives.

)F -^

ocH3 I _coocH3

CoHs- Y . ,25 cHs anti- 2 .'25: 1

,s,^,2 + anti-2 1 : 4

| !: ,up is reducedby BurSnH IJL-,SnHalonereducesthese tr,'- ,t .r basesuchas HMPA or

Barton-McCombie

reaction,ztt

This rc-

action proceeds more rapidly with xanthates IRTCHOC(S)SCH:] than with any of the known phenoxy thiocarbonyl derivatives IRTCHOC(S)OCaHs]. Of these the unsubstituted phenoxythiocarbonyl derivative is slightly more reactive than the 2,4,6-trichloro- or the derivative. The pentafluorophenyl derivative, R2CHOC(S)OC6F5, is the

rS. Hanessianand R. L6ger, Synleu, 4O2(1992). ' V . H . R a w a l ,S . P . S i n g h ,C . D u f o u r , and C. Michoud,J. Org.,56,5245 (1991). 3 P. Dowd and W. Zhang, Am. Soc.,113, 937-5(1991). aW. Zhang and P. Dowd, Tetrahedron Letters, 33,':1307 (lgg2). 5 P. Dowd and W. Zhang, Am. Soc., fl4, 10084 (1992). 6W. Zhang and P. Dowd, Tetrahedron Letters, 33,3285 (1992). 7 E. Nakamura,K. Tanaka,and S. Aoki, Am. Soc., ll4, g7l5 (1gg2). d J. E. Baldwin, R. M. Adlington, and R. Singh, Tetrahedron, 48, 33tl,5(1992). e M . B u l l i a r d ,M . Z e h n d e r , a n d B . G i e s e ,H e l v . , 7 4 , 1 6 0 0 ( 1 9 9 1 ) . f 0 M. Kawaguchi, S. Satoh, M. Mori, and M. Shibaski,Chem. Letters, 395 (1992\. rrT.B. I-owinger and L. Weiler, J. Org., 57, 6099 (lgg2). 1 2 D . P . C u r r a n ,A . C . A b r a h a m ,a n d H . Liu, ibid.,56,4335 (t991). l3 J. R. McCarthy, D. P. Matthews, D. M. Stemerick,E. W. Huber, P. Bey, B. J. Lippert, R. D. Snyder, '7439(1991\. and P. S. Sunkara,Am. Soc., ll3, f a J. R. Mccarthy, D. P. Matthews,M. L. Edwards, D. M. Stemerick,E. T. larvi, TetrahedronLetters, 3r, 5449 (1990). 15E. Hasegawa,K. Ishiyama,T. Kato, T. Horaguchi, and T. Shimizu,J. Org., 57,5352 (1gg2). 16S. A. Hitchcock and G. Pattenden, Tetrahedron Letters, 33, 4843 (1992). l7 Y. Guindon, J.-F. I-evall6e,M. Llinas-Brunet, Horner, G. and J. Rancourt,Am. Soc.,113, 9701 (leel). r8 I. Shibata,T. Yoshida,T. Kawakami, A. Baba, and H. Matsuda,J. Org., 57,4O4g (1gg2). reW.P. Neumann and J. Pedain, Tetrahedron Letters. 2461 (1964J. 20D. H. R. Barton, J. Dorchak, and J. C. Jaszberenyi, Tetrahedron, 45, 7435 (lgg2).

362

TributyltinhYdride-OxYgen

TFibutyltin hydride-OxYgen' RX - ROH (reductive oxygenation),1 Reaction of an organic halide with Bu3SnH (2 equiv.) in the presenceof dry air in toluene at O-20' results in conversionto the correspondingalcohol in yields generally >70%.The reactionis particularly useful for conversion of allylic halides to allylic alcohols with retention. It is applicable even to tertiary or hindered halides. The transformationis believed to proceed through a

Tiibutyltin hydride - Tetrabul-r-lemrtReduction of ketones.t This r-rrrnt 25-60" without reduction of halo rutrrrr

selectively to the more stable trarrr-akrrh tc in the caseof a-methoxypropiophenr'ne react with an added electrophile(R\ ot R

hydroperoxide. OH

02 2 Bu3SnH,

c6HscH3 ' 0-20"

cuHuMBr

+ .-,-.,-)"-,zcHz \16n5

coHsMoH

14"/o

80o/o

?r.

CHq

o\ur, t l \,,

?rr.

/1oa

vI

81%

cH.AcH,

(r) "utul^ar. o

cH.AcH, 52.48

92tB

OH

Br 55"/o

euMcoocH3

/'-Z\ o

COHS

,uA7--coocH3

(ilr)

h'

a\ t

/ / \

l

OH

Bu3SnH G e H s C H s0'" , 84o/"

i * .

o

cyclization as shown in This conversionof RX to ROH can be extendedto radical equationsI and II.

(t)

Et

t

l

Tributyltin hydride activated br HIII ketones such as a-chloro ketones.

( 1: 1 )

I I. Shibata, T. Yoshida,A. Baba.and ll v.l

f-/-caHs

q

coocHs

(lr) e:'t-coocH3 l E. Nakamura' T. Inubushi, S. Aoki, and D. Machii, Am. Soc.,1r3' 8980 (1991).

TFibutyltin hydride-TiiethylbonrRa.dical cYclization to tmnrhfr erally cyclize to a five-membered nngcyclizeslo e tr't I [Bu.rSnH-B(C:Hs).tl of an ener presence The b. a and icals

TFibutyltinhydride-tiethylborane 363

'n ,,r an organichalidewith Bu3SnH ll lrr' results in conversionto the rc :r.tction is particularly useful for rr: :rtcntion. It is aPPlicableeven r. l.clieved to Proceedthrough a

halide. Tiibutyltin hydride-Tetrabutylammonium Reduction of ketones.t This combination (t1) can reduce ketones in THF at 25-60" without reduction of halo substituents./-Butylcyclohexanonecan be reduced selectivelyto the more stable trans-alcohol(equation I). The reduction is syr-selective in the caseof a-methoxypropiophenone(equationII). The intermediatetin alkoxide can react with an addedelectrophile(RX or ROCI) to form ethersor esters(equationIII).

OH

'oH *

cgtu)"'r'cH"

o rcna"cjJ

3=J=g

(cH3)3c'JA7--oH

14"/o

C'.

(79:21)

CHs

t

- --a .oH

?*.

(u) "utrl^"r. o

'\cH, JZ

?tr.

81o/"

cuHu-.,A"r.'.^ -"o I

OH (lOOVo sfn)

qO

o OH

o

.\Z\coocn, (ilr)

a\ l

oA"uru

OSnBus

l

a\ I I

c6H5cocl 93"/o

Tributyltin hydride activated by HMPA can reduce aldehydesand some activated ketones such as a-chloro ketones. rI. Shibata, A. Baba,and H. Matsuda,Chem.Letters'307 (1991). T. Yoshida,

coocH3

r r ' , , . .1 1 3 '8 9 8 0( 1 9 9 1 ) .

Tlibutyltin hydride-Tbiethylborane. Radical cyclization to trans-hydrindanes.t Although 1,5-hexadienyl radicals generally cyclize to a five-memberedring, the radical formed from the vinyl bromide 1 [Bu3SnH-B(CzHs):l cyclizes to a trans-hydrindane2 selectively, possibly via radicals a and b. The presenceof an angular methyl group does not prevent a similar

Tfibutyltin

hydride -Tfiethylbomne

H , c H 2 o s i R 3

l H p H 2 o s i R 3

cH"ooc<-1-1_osiR3 dol I --"o Br |

cHz

d-J1-o".

I

\_f-/

lcr.ooc, .cr,

1

The report assumesthat thc' \cr s vinyl triflate to form a vinrlrrn rh

H pH2osiR3 ,t\t--(

H pH2osiR3 l .t"A |

ll crisooc#

|

) _ o H , l _ e?% ll cH.ooclf )

|

)_oH,

bromide.

lM. Mori,N. Kaneta, and\l Shrhs

(TFicarbonyl)chloroiridium.

2 (10O%trans)

lr(l Carbony lativ e hydrosilvbin. with terminal alkenesto form rhc cyano groups are nol affc'ctcd

6-endo cyclization of the bromo ester 3 to 4.

CzHso'.-a.\"r.,^ |

--z

+ H9rC2l

oc2Hs ,------CH3PS|R3

cHsooc< Y) Br CHz

87"/o

cH3ooc

H 4 (trans/cis= 95:5)

' S. Sato, M. Sodeoka,H. Sasai,and M. Shibasaki,J. Org., 56,227t1 (1991')

'N. Chatani, S. Ikeda.K. Oh<.Lr \

TFibutyl(trimethylsilyl) tin, BujSnSi(CH3)3,13, 21'l-21,2. Coupling of vinyl triflates with vinyl hali.des.t The Pd(0) coupling of vinyl triflates with organotins(12, 468-47O; 14, 295-296), first reportedby Stille, has wide use in organic synthesis.Stille coupling can be extendedto coupling of vinyl triflates with vinyl or aryl halides by addition of Bu:SnSi(CHr): (1.1 equiv.). Thus the vinyl triflate and the aryl bromide undergo intramolecularcoupling to form 3 in the presenceof (3 mol %), Bu3SnSi(CH3)3(l equiv.),Bu4NBr (3 equiv.), and LizCO: Pdclz[P(C6H5)3]2 (1 equiv.).

Tiichloromethylsilane - Diplcl;l Cystine peptides.t Conr crrrr effectedwith air or iodinc ()rrdarh{ oxidation of some amino aod. Tl silyl chloride and a sulfoxidc. a (r! of cysteine. lK. Rka.ii,T. Tatsumi,M. \(xhdr (1992\.

f

Ttichlommethylsilane

,cH2osiR3

-oHs

- Diphenyl sulfoxide

cooc2Hs

?t .,,\a'^.t-l-,^\

U*U

7Oo/o

The report assumesthat the key step involves an intermoleculartransmetalationof the vinyl triflate to form a vinyltin that undergoesintramolecularcyclization with the aryl bromide.

a-.-j--(tt2oSiR3 ll I F -oHr

o.Y

2 (10O%trans)

I M. Mori, N. Kaneta,andM. Shibasaki, J. Org.,56, 3486(1991).

(Tticarbonyl)chloroiridium, IrCl(CO)3, 1. Carbonylative hydrosilylation t IrCl(CO)3 [or Ira(CO)12] catalyzes this reaction with terminal alkenesto form the enol silyl ethers of acylsilanes'Acetal, epoxide, and cyano groups are not affected.

c 2 H 5 o - - - . 1 ^-"tr ,,

Y_

''"oj^.

&*#q: + HS;(C2H5),CH.

osiR3 A,rA czHso;.-\Z\sin.

OC2H5

OC2H5 EIZ=73127

CH3.PSiRs

'-Y'. 1. \-P H

4 (trans/cis= 95:5\

B5o/o

osiR3 EIZ -- 36164

i - - . rl 9 9 l ) .

I N. Chatani,S. Ikeda,K. Ohe,andS. Murai,Am. Soc.,114,9710(1992).

;,, ,r .()uplingof vinyl triflates t c . : ' . r S t i l l c ,h a s w i d e u s e i n xrlrng of vinyl triflateswith ce:rr.). Thus the vinyl triflate r{' | ,rnr 3 in the presenceof le. \ tlr (3 equiv.), and Li2CO3

Ttichloromethylsilane-Diphenyl sulfoxide, CHjSiClr-C6HsS(O)CoH.s. Cystinepeptides.t Conversionof a dicysteinepeptideto a cystinepeptideis usually effectedwith air or iodine oxidation.Air oxidation is slow, and iodine oxidationcan effect oxidation of some amino acids. The disulfidc bond can be formed efficiently with this silyl chloride and a sulfoxide, a systemthat can also cleavevarious S-protectinggroups of cysteine. rf. ekali, T. Tatsumi,M. Yoshida,T. Kimura,Y. Fujiwara,and Y' Kiso,Am. Soc.,ll4, 4137 (1992).

366

TfiethYlborane

chloride/Copper(Il) nitrate' Tiiethoxysilane-Rhodium(tll) can be effected by addition (D-alkenesi''t This reduction Reiluction o7 attqnesi ' and Cu (NO3)2in THF/H2O' oi the alkyne' RhCl3 3HzO' of (C2H5O)3SiHto a mlxture Hz is bubbled of (C'fftO)'sift' tut exogenous Moreover Hydrogen is generatedor'i'Orot"t8-20:1' is esareSo- 967aandtheZfErctio tiJt"" CbzN' throughthe mixture' vitro" ArNOz' RNOz' not affected: the following groups are alcohols under standardconditions -C propargylic and = CH' ttre oth-ertrand ArI' OH, ester, RBr, ArBr, t";;-O" are not stable to these conditions' 4':-86(1992)' J' P' Cooper'J Org'' 57' I J.M. Tour, S.L. Pendalwar'C M Kafka' and

Triethylborane [(CzHs):B];Triethylelor Ate complexes with ester enoldct"

TBDMSO

cHi

_\

H H,,.) |

T-1

COOCH3

1)NaNls.o

2)Clr3r -& ---"

)FN o ' H 1

't

isopropoxide' amount of TFiethoxysilane-Titanium(IV) of this silane and a catalytic *ttlnation ittt RCH';;'^ is isolated RCooR " 40-55''r The product tnil.":"j:d"tt,::::it in some and Ti(O-i-Pr)+generatesu t"'"t requires 4-22 hot'ts' NaOH (1$' The reduction by addition of THF and casesadditionofCoHsSiHrisrequiredforcompleteconuer,ion.Yieldstypicallyare "to-95%. (1992)' I S.C. Berk and S' L' Buchwald'J' org'' 57' 3'751

*'':1:##

or Reaction reaction:svn'I-!1vd.roxt:a."^:"^,1':::;". lti,e ,yn-otdot pres(1) with aldehydes in the

n' N-oit"tt'ylglycine ;;i the lithium enolate "; acid estersin >957o de in results equiv') (1 ence of B(CzHs)r .'sy":3-hylroxy-2-amino (equationl)'Thehighdiu'tt'"o*"lt"tivityisexplain"OUyttttexclusiveorpredominant

o H ? o *Aocr, ,y#Y*cuHu/Yl?"'"' (r)c6H5cHo I N(cH3)2 -.. . N(cH3)2

syn.2 98"/o

+ B(CzHs)

1) LDA' B(c2H5)3

0r)

.t

+anti-2 ,33,i3

OS|R3

il cisir"rd-l-e'' (cH3)2N-\o"rru (z)-3'100'/'

"t Thusthe of B(C2H5)3' of 1 in thepresence lltl:l:""t"t exclusively formationof the(Z)-enolate converted is unatn"n a trialtylctrtorosiiane' 1, whentreatedwith th" b;;;; 3' into the (Z)-silyl keteneacetal 32' 5521 (1991)' 1 G. I. Georg and E' Akgun' TetrahedronLetrers'

\_ -

-'f i LIA 7 C./\) 3O.y

! r provides the a-methyl derivatrrc tnlcrtu:( methyl derivative which is an (lrthrun- z Use of other metal enolates rctN'ts However, Merck chemists harc rs efficient cfrr B-methyl 2. The most o'r triethylborane.Thus reactionof tlx -75 V t'and then with (C2H5)3B at ocrl secondroute to B-CH3 (2) involrcr lr I results in formation of both ePrnrr l D. R. Bender,A. M DeMarco'D (; \Lr

(ree2).

Tiiethylsilane- Benzoyl peroxilc' Tl DeoxYgenation of alcohdl deorrecntcrJ are alcohols secondary (CzHs)rSiH and (CoH'CO):O:

I D. H. R. Barton,D. O' Jang'and.| ( ltrrt

(lU I clbil Ttiethylsilane-Titanium ol l*1a reduction Stereoselective c na stereo6el('ctl\ involves ethers cyclic \r on the reducing agent, the biclclx end cyclic ether3. Thus reductionof I anJ 5 3 ethers cyclic cis-disubstituted

(IV) chlorid€

Triethylsilane-Titanium

le. cjr bc effectedbY addition n,: ( u (NO:)z in THF/H2O' I :ro{cflouS Hz is bubbled '[ :.rtiois tt-20:1. Moreover c:,.r RNO2,ArNOz, CbzN, . ll. .,ndproPargylicalcohols

367

TFiethylborane [(CzHs):B]; Tiiethylaluminum [(C2H5)3AI]' o f l Atecomplexeswi|hesterenolates.lMethylationofthesodiumeno|ate

coocH3

TBDMSO THF, -78' l) NaNlsi(CH3)312, 2) CHgl,-80 - -50" , 6l-{., 84.30h

H H

coocHs N H cr-CH3(2)

E :- 1786(1992).

Ir)mn

6zy" | 2\ (c2H5)38

D( .:nrl a catalytic amount of The productis isolated :i: s. I J2 hours, and in some r.:\r{)n. Yiclds tYPicallYare

esters.t Reaction of lldehYdesin the Presn::: , .rciti csters in >957o de i:- -rclusivc or Predominant gntn| *::I

o H o ,

,^OC2H'

+ anti-2

I

1) LDA,THF, -76' 2) (c2H5)3Al 3) cH3l' -75"

I

sl nonc

V > cr - CH3 (2) +

p - cH3 (2)

(1O/.\

(35o/o)

providesthea-methy|derivative2inhighyield,theepimerofthedesiredplB-methylcarbapenems' methyl derivative which is an intermediateto the important Useofothermetalenolates(lithium,zinc)showednoselectivityforB-methylation. routes to the desired However, Merck chemists have reported two diastereoselective 2to of a-CH3 B-CH3 2 mediatedwith epimerization B-methyl 2. The most efficient is of LDA at -80" I equiv. with derivative triethylborane.Thus reactronof the a-methyl -':i5 to 70" provides B-methyl 2 in a purity of >99Vo' A and then with (CzHs):F at of (czHs):Al' which secondroute to B-CHr (2) involvesmethylationof I in the presence p-epimer favored' the with 3'5:1 ratio resultsin formation of both epimers in the J' Org'' 57' 2411 andI' Shinkai' rD.R. Bender, D.G. Melillo'S'M' Riseman' A.M. DeMarco, (1992).

N(cH3)2 sYn-2

70:30 >95 : <5

)s R3

-

ocrH,,

f., I hus the lithium enolateof rrl.':r. is convertedexclusivelY

TFiethylsilane-Benzoyl peroxide. Deorygenationofalcohols'|Thionocarbonatesorxanthatesofprimaryor secondaryalcoholsaredeoxygenatedin8g-l0o7oyie|dbyradicalreductionwith (CzHslSiH and (C6HsCO)2O2' lD.H'R.Barton,D.o.Jang,andJ.C.Jaszberenyi,TetrahedronLetters,32'7187(1991).

(1)' Tiiethylsilane-Titanium (IV) chloride, (C2H5)jSiH-TiCl4 to 6- and 8-membered route Stereoselectivereduction of bicyclic ketals't A new suchas 2' Depending ketals reductionofthe bicyclic cyclic ethersinvolvesstereoselectivc onthereducingagent'thebicyclicketa|2canbereducedtoeitherthecis-o|trans. and Ticlq at -78' yields the cyclic ether3. Thus reductionof 2 and 4 with triethylsilane of 2 and 4 cyclic ethers3 and 5 with high stereoselectivity.Reduction cJs-disubstituted

hydmtrioxide

Triethylsilyl

|

t-\9f,"

|

/-oBzt

cH2cr2> HoJ>Jt-o.k1^ori

s_3

2 +1 + DIBAH

a\ \

H-\o7-

/

trans-s

f-oBzt

99.93: 0'07 4 :96

100% 1O0o/o

/ \ 1 ) ----------> H - \ I'n Ho----\o/-4oart

+ trans-s

Lo

cls-5

4 +1 + DIBAH

9 1: 9 2:98

86"/" 887"

tothetrans-disubstitutedethersiseffectedwithalmostashighselectivitywithDIBAH. rH. Kotsuki,Synlett,9'7(1992).

This sequencew?S ux-d :o rcp particularly interestingas an an'irm"d

(l)' Ttiethylsilyl hydrotrioxide, (C2Hs)3SIOOOH -78' (13' 228)' Preparationby ozonizationof tricthylsilane'at reagent(1) can cleaveterminal and this Oxidative cleavageof alkenes't Although higher yields can be obtained much internar arkenes,the yields can be row. However, ifthesubstratebearsanalkoxyoranestergroupevenremotefromthedoublebond (equationsI and II).

CHe

I -

OZ---...^\-z^-,

-3

C 6H5 -,..-.O,,gz'-,r-,, 4 1)1 2\ tialH,

(l)

CH3(CH2hCH=CH(CHz)zR'tL'^"'4>

CH3(CH2)7cH2oH

42o/o R = CHg = COOCHg 83ol"

(ll) RCH3CH=CH2 pf = c6H5 = CoHsO

I G.H. posner,C. H. Oh. and\A X Vrh

RCHzCHzOH 54% 76/o

2 that can rearrange to the This oxidation can be used to Preparethe dioxetane 1.2.4-trioxane3, a Potent antimalarial agent.

Ttifl uoroacetic acid - Trhlkl- Sr. Intramolecular ionic hyew3ct A (4). from 5'nrt secopseudopterosin stituted double bond of l. Hrdn'.tct less hindered face to provide thc utd CF3COOH gives a 2:3 mixturc t'f J

Thifl uoroacetic acid -Ttialkylsilane

' ',-H -^oB.l

+

tans -3

1,CH2C|2

C

-78'>

o

3 99.93 : 0.07 4:96

n

2 5go/oIFBU(cH3)2siorJ, -78' | V

+ trans-s

,,H "-Aogtt 5

9l:9 2:98

r'.: .'. high sclectivitywith DIBAH. This sequencewas used to prepare other related 1,2,4-trioxanes,of which 5 is particufarlyinterestingas an antimalarialagainstcertain strainsof P. falciparun cloncs.

- - . ' r 1 3 .2 2 8 ) . , :..ilcnt (l) can cleaveterminaland rn...h highcr yields can be obtained c\ - ' rcmotc from the doublc bond

CHr| OZ---.-* |

|

4

1)1 2) t-Bu(CHg)zSiOTf _ QH3 8 / "

C6Hs,-.../.O--z/----2 OBzl l-'-

cur(cH2)7cH2oH I G. H. Posner, Letters,32, 4235(1991). C.H. Oh, andW. K. Milhous,Tetrahedron

f2oH

t \ - i . r n c 2 t h a t c a n rearrangeto the

Tlifl uoroacetic acid-Tiialkylsilane, 5, 695;6, 616. Intramolecular ionic hydrogenation' One step in a synthesis of a diterpene, secopseudopterosin A (4), from 5-methoxytetralonerequireshydrogenationof the trisubstituted double bond of 1. Hydrogenationcatalyzedby Pd/C resultsin attack from the less hinderedface to provide the undesired3. Ionic hydrogenationwith (C2Hs)rSiH and CFjCOOH gives a 2:3 mixture of 3 and the desired 2. Even higher stereoselectivity

370

Tfifl uoromethanesulfonic acid/Bomn(III)

trifl uoromethanesulfonate

.-CHs .H

--CHs .H

SnCla,but the higheststererxrLc to the correspondingl.-3{iols b rA.P. DavisandS.C. Heganr.{r

I

cH3o

CHs

(+)- (S,S,S)-TriisopnopenderThis amine (NLr) can hc p (-)-(S)-propylene oxide.

cH3YcH3

E nantio sele ctive additia ol 1, formulated as (LZrOHl;-r-Br followed by additionof H;C).rz

h-.cH. cH.-..-,,-x.,,{

i l t l

^otfi

RO

CHs

+

4

reaction of can be effected by an intramolecularversion of ionic hydrogenation.Thus which on 1, of ether I with t-Bu2siHCl and imidazole (DMF' 23) provides the silyl yield 65-757o 2 in gives slow addition to cF:cooH followed by desilylation(BuaNF) in >95% purity. Letters,32, 1s.w. Mccombie,B. Cox, S. Lin, A.K. Ganguly,and A.T. McPhail,Tetrahedron (1991). 2083 Tliffuoromethanesulfonic acid/Boron(Ill) trifluoromethanesulfonate, TfoH/B(orf)3. This combinationprovides the BronstedsuperacidTfOH2*B(OT04-' l' 2 are obStereoselectiveallylation of alkorysiladioxanes,t Alkoxysiladioxanes tainedbyhydrosilylationofB-hydroxyketoncs(16,S2),usuallyasal:lmixture (CHr)3SiI' and of translcisisomers.The allylation is also catalyzedby (CHr)3SiOTf,

o H o

(80 - 90%) 1) Cl(,-Pr)2SiH 2) Bu4NH,CH2C|2,0' (95 - 98%)

,uSo"r.

l-Pr, ,l-Pr

o'Si'o

,,AA*r. 2 , ( 1: 1 )

CHz=CHCHzSi(CHs)e 1, CH2C|2,-50'

o" Oo

o CH.- \

'o

rW.A. Nugent, Am.S<x..lla. :'t

2, 4, 6-TFiisopropylbcnrcraJ Ch i ra I a -azido aq ISI -vctu in the peptideunit. The ongrnel arylglycinesvia an intc'rnrdrlr group on addition of acetrc r.r promote decompositionto .n I

I D.A. Evans,D.A. Evrard.S D I Letters,33.lllrq r19 Tetrahedron

i-Pra ,r-Pr

o'Si-o

85o/"

,r"\-\-',\"r, 3. lpns/6js = 23 : 1

Ttiisopropylsilyl enol etberr r Reaction with azidotri*t (CH3)3SiN3and C6H.lO (l cqo The azido group of 2 is di+le

Tliisopropylsilyl

enol ethers of cyclohexanones

371

leoeulfonate

un3

,CHS

H

.H

obtainswith l. The products(3) can be desilylated SnCla,but the higheststereoselectivity to the correspondingl,3-diols by treatmentwith HF in CH3CN' 1A. P. Davis and S.C. Hegarty,Am. Soc., ll4' 2745 (1992).

oH cH3o

CH.

CHs

(+)-(S,S,S)-Tfiisopropanolamine, [C H : C HCH2l3N. with This amine (NLr) can be PreParedby reaction of (+)-(S)-1-amino-2-propanol (-)-(S)-propylene oxide. Enantioselective addition of RjSiNj to meso-epoxides. A chiral zirconium catalyst l, formulated as (LZTOH)z+-BuOH and prepared by reaction of L:N with Zr(o-r-Bu)+ cleavageof epoxidesby R3SiN3. followed by additionof HzO, can effect enantioselective

.CH .F

o"

cH3. pH3

O"

* "tt-rt''*,

* "tr-I-t'-*.

{. of rn:. hrdrogenation.Thus reaction on which 1, )\ r,:.\ the silYl ether of or , llurNF) gives 2 in 65-75Va Yield Letters'32' d r I VcPhail,Tetrahedron

(cH3)3si(ococF3) r,'-\..'osiR3 1'o' r 8O"/"

t

9N.

CHs

l

93o/"e€

cH3 pH3 CHs

"'osiR3

/)

E4%- H*, 83o/oe€

on)methanesulfonate' a. :.: I fOHz*B(OTf)4-' f' are obt rd\. AlkoxYsiladioxanes2 mixture l : 1 a a s u s u a l l Y f i 2 ) , ;,16. and r/,.1 h\ (CHr)jSiOTf, (CHrlSiI' \ e 95 rs'.)p

l-Prr ,l-Pr i O'"'-O

r

au

l

'4oct-t. 2' (1:1)

'a

l :

fl^

I W. A. Nugent,Am. Soc., ll4, 2768 (1992). 2, 4, 6-Tiiisopropylbenzenesulfonyl azide (trisyl azide, l), 14' 327' chiral a-azido arylglycines.l Several glycopeptide antibiotics contain arylglycines peptideunit. The original methodologyfor asymmetricazidation(14,327) to give the in arylglycinesvia an intermediateN-sulfonyltriazene,can fail to decomposeto an azide group on addition of acetic acid. In such cases,addition of NaI or KOAc at 25" can promote decompositionto an azide. rD.A. Evans,D.A. Evrard,S.D. Rychnovsky, and K.M. DeVries, T. Friih,W.G. Wittingham, Letters,33, 1189(1992). Tetrahedron

Tiiisopropylsilyl enol ethers of cyclohexanones. Reaction with azidotrimethylsilane.t The triisopropylsilyl enol ether I reacts with (cH3)3siN3 and coHslo (1 equiv.) to form the B-azido adduct2 as the major product. The azido group of 2 is displacedon reaction with a number of carbon nucleophiles

Tiimethylaluminum

inthepresenceofaLewisacid.Theoverallreactionrepfesentsaconjugateaddition to cyclohexnone.

Pr)s

?si(''

a\

osi(t-P03 (cH3)3siN3 CoHslO ,

LiAlHl 99%

1,^Ns

(, 1

osi(,-Pr)3

a\

oSi(r-Pr)3

",ft18?.i1,", o ,",T1.,,1'"*-)

\tu'u

'o*f "*'=tttH2snBu3

imine 2, which is reducedby LiAlH. to t acids (TiCla, ZnCl2) can effect this rcarranc added,but the isolatedyields of 3 arc rn th effect conversionof I to 3 in 99'Z ricl,J. h{ Moreover, this reagent is superior to t{hcr

includingvery sensitiveenaminc:. Methylntion of Y, t-ePory ocr-rbct'' 7,6-epoxy acrylatesuch as I resull' tn i n

--cH,

f P . M a g n u s a n d J . L a c o u r ,A m . S o c ' ,l l 4 ' 3 9 9 3 ( 1 9 9 2 ) '

Ttimethylaluminum. Si-transferfromoxygentocarbon.|Inthepresenceofatrialkylaluminum'par. at -78' to 20' to csters of trialkylticularly (CHj)iAl, silyl kctene acetalsrearrange of Si from oxygen to carbon is the reverseof silylacetic acid. This 1,3-rearrangement of Si from carbon to oxygen' But RrAl the well-known Brook thermal rearrangemcnt2 does not rearrangetrimethylsilyl enol ethers'

^,, Jo""^' cHzl osi(cH3)3

"I,!iilj?r",(cH3)3sicH2cooc2Hs 84o/o

This reaction has seen 3-Aza'Cope rearrangement of N'a@t'N-allylenamines'3 (200-250). A variety of reagents limited use becauseit requireselevatedtempelatures this type' 1' to the unsaturated of enamine an of can catalyze the rearrangement

o t'trrr"A--z--cozcH3

A cht heraru

However, the same reaction u ith c;rrr the e or f position results in a singlc ;rt Al(CHj)3 (8-10 equiv.) in CH;CI; an<Jr (E)-epoxy acrylate(2) is convened crclus is converted into syn-3 in 93'/ ricld

Trimethylaluminum

f:-\.nts

a conjugateaddition

Ar(cH3)3/^\y,,'\NZ'.-"'CH3 | | l-cHs

NAc(cH.)2

\'o"',

\-/

cHzs,,/ 2

a--a,,"--il.^..
cHz x-/ 3

OSi(t-Pr)3 f ,: l"J

r.

a\

\+cNl t

:.S-3-r

imine 2, which is reducedby LiAlHa to 3. Protic acids such as HCI and various Lewis acids (Ticl+, zncl2\ can effect this rearrangementat 111" even when only 0.03 equiv. is added,but the isolated yields of 3 are in the range 6O-857a. ln contrast,AI(CH:): can effect conversionof I to 3 in 99% yicld, but it must be used in stoichiometricamounts. Moreover, this reagent is superior to other reagentsfor a widc variety of substrates includingvery sensitivecnamines. Methylation of y,6-epoxy acrylates.a Thc reaction of Al(CHj)j with a simple 7,6-epoxy acrylatcsuch as I rcsultsin a mixturc of thrceproducts(equationI).

i:

co2cH3

80 CzHs

I

CHs

o

n.- ,t a trialkylaluminum'Parlr :,, 20' to estcrsof trialkylf,:' l() carbonis thc reverseof )n' ,.rrhon to oxygen. But RrAl

(ltrHr''A-"-z.-co2cH3

9H.

At(cH3)3, hexane,H20

18 crHu"\"\'cozcHs OH CHs I

2

F CH2COOC2H5

rrrne\.r This reaction has seen t r' 150'). A varietYof reagents hr- :rPc, 1, to the unsaturated

c,H.-\"\-co2cH3 ' " I OH

However, the same reaction with epoxy acrylatesbearing an alkoxy substituentin the e or f position results in a single product, especiallyin reactionsconductedwith -30--40'. Thus thc Al(CHr): (8-10 equiv.) in CHzClz and water (6-10 equiv.) at yield, whereas(Z)-2 tn 96Vo anti-3 into (E)-epoxy acrylate (2) is convertedexclusively is converted into syn-3 in 93Va yield.

Ttimethylaluminum

1,3,5-TFimethyl| J-(qfl

n BzlO-r,.{..L.CO2Et

-

H2O Ar(cH3)3, ctcH2cH2cl

co2Et

BzlO

96% I

CHs anti - 3

( E )- 2

Ar(cH3)3, H2o

R

azro..-.,.A--z-.-

co,rt

lT#4*

(tt)

"to

,o4"".

;

CHs

OH

cozEt

Bzt o._-,\,\,,.

R = Ts. Ac. Bzl

CHs

(z)-2

s y n- 3 reverse of that of simple diols (cquatr.rn lll

This reactionon extensionto 4 provides5 with five contiguouschiral centersin 95Vo yield.

MPMO

I K. Maruoka. H. Banno. and H. Yamarnri \rr 2 A. G. Brook, Acct. Chem. Res.. 7. 7- r l'r-l r 3 G. R. Cook, N. S. Barta, and J. R. Slillc. ., (r.r 4 M. Miyashita, M. Hoshino, and A. \'cxhr\.dr 5 D. H. R. Barton and J. Zhu. Tetrahedrca t tl

,q 95"/"

O H l

OH l

1,3,5-Tfimethyl-1,3,5-cyclohexrnctrirrt l

azto#cooc2H5 cH3 cH3 cH3

Supplier:Aldrich.This esteris comrncrcrd

5

CH3 @ Isopropylidine ketals.s The isopropylidine ketals of 1,2-diols on treatmentwith Al(CHr)3 (3 equiv.) in CHzClz at -78' are cleavedto hydroxy r-butyl etherswith high

"'ll?i1;",(o' * ,u) iV"", -cH3 R'\d R = CoHs,Bu, C2H5

cHs--1\-.1 ( cH3ooc

,ot-Bu

RAot-s,

*Ao',

86 - 74%

O - 1Oo/"

regioselectivity(equationI). This reactionprovides a simple method for monoprotection of primary-secondaryvic-diols. In the case of carbohydratesregioselectivitycan be the

by trimethylation of 1,3,5-cycloherarczrtr Chiral auxiliary for asymmctrie { bek et al.t have prepared the chiral u carboxylic acid groups to providc t - >!The rrtmr azabicyclo[3.3.1]nonan-2-one. carbamateto provide both (R)- or (SF2

13,5-Trimethyl-1,3,5-cyclohexanetricarboxylic

acid (Kemp's triacid)' I

f-BuO

OH

ezrO-.--,1-.rr,LCO2Et

HO

I

CHs anti- 3

(il)

',to

',to

81 - 98%

,o4-"r.

,o*-"r,

CHs

CHs

OH

Bzro--Aa\,/cO2Et

R = Ts, Ac, Bzl

CHs srn-3 reverse of that of simple diols (equation II).

e .,'ntiquouschiral centersin 95%

1 K. Maruoka, H. Banno, and H. Yamamoto, Synleu' 253 (1991)' 2A.G. Brook, Acct. Chem. Res.,7, 77 (1974). 3c.R. Cook, N.S. Barta, and J.R. Stille, J. Org', 57,461, (1992)' 4 M. Miyashita, M. Hoshino, and A' Yoshikoshi,ibid-, 56' 6483 (1991)' 5 D. H. R. Barton and J. Zhu, Tetrahedron, 48' 8337 (1992)'

9:'.

OH

OH

-,cooc2H5

-r {.

CH3 CH3

1,3,S-Ttimethyl-1,3,5-cyclohexanetricarboxylicacid (Kemp's triacid), l'

Supplier:Aldrich. This esteris commercially availablebut expensive.It can be prepared

5

t,;. ,,f l,2-diols on treatmentwith r., :rtlroxy t-butyl etherswith high

OH Ot-Bu

CHr\ ' COOCHa --\ |t |l -CH3 cH3--N.'{ COOCH3 CH3OOC

(1)

ao"' "Aon 0 - 1O"/o

a -rnrplc methodfor monoprotection ri:rJratcs regioselectivitycan be the

acid. by trimethylation of 1,3,5-cyclohexanecarboxylic curran, ReChiral auxiliary for asymmetric radical addition and allylation bek et al.t have prepared the chiral auxiliary 2 from I by manipulation of the carboxylic acid groups to provide 1+)-2, endo-l-(2-benzoxazolyl)-1,5'7-trimethyl-3The racemic auxiliary is then resolved via its menthyl azabicyclo[3.3.1]nonan-2-one. carbamateto provide both (R)- or (S)-2.

1.3.5-Trimethyl-1,3,5-cyclohexanetricarboxylic

acid (Kemp's triacid)' I

o (\,

{ll) CHa *

o/v 'Y/*'F,'i

cH3/coocH3

l

o

CHe

CH: (s),96 a

( x )- 2

o

:N

I J.G. Stack,D. P. Curran,S.V. Gcrh.J Rs.<

CHs

CHs CHs

CHs

(R) - 2, cre+7 4"

(S) - 2,
furegio- and B-stereoselectiveaddition to This chiral auxiliarY can provide high and rcgioboth control to auxiliary chiral marimides equation (l)' This is the first

o 1rlczHsol.\Axo

+

(CH.)qCl

c2HsO

TFimethyl orthoacetate, CH.C|(X}l t' Epoxidesfrom 1,2-diok.t .{ rvr'Sr conversion to an orthoester I br a.-r.J*:rt derivative is then treatedu'ith acctrI iil inversionat the halide centerforrncJ Be thc epoxidewith a secondinrcnxxl

Bu3Snh AIBN,c6H6' 80' 64%

3

o

cH.4

"tro.yr.

cHs-TFl-cHs

:N

*

^

I

4 steps

cH.--f{--cHt coocH3 cH3ooc

tu'--* l

'f-Bu i- o li

* c2H5o-\,,J---Ay* v* A r ^

6

o

ll ^u^ * czHso\a^t'". l

l

5 o r-Bu

9H

C|1€.Oc>1 Pe-s

,\ -CH" CeHs- Y : OH

5 4 : 5 : 6 = 7 8 : 1 9: 3

.o B-stereoselectivityinradicaladditions.Theoriginoftheregioselectivityisuncertainbut may result from inhibition of a-substitution' Thisauxiliarycanalsocontrolthediastereoselectivityofradicalallylation (equationII).

c6Hs''\i-cH3 ee 97'Yo

Tbimethyl orthoacetate I tn!( id r. I

o

(il)

A,V r ._rr"FJ

tl CHg\-A.*

*

l

^

I

AIBN C6H6,80"

c^ /t-aSnBu3

o "tr#x* -

flJ-cns CH:

l

34"/"

o cHrs-..\r^oH -lg9!* A l CHs (S),cro+10.5'

CHs ( S ) , 9 6: a

:)-2

z\

I i l "'\-/ " t - \H '-* Am. Soc.,ll4,7007 (1992). I J.G. Stack,D. p. curran,S.v. Geib,J. Rebek,Jr.,andP. Ballester,

-:.--^cH. J

2 . - - 7. 4 " p - - rcosclcctiveaddition to fuh.':. lrt control both regio- and

Tiimethyl orthoacetate, CHrC(OCHr)r. Epoxidesfrom 1,2-diols,l A one-potconversionof 1,2-diolsinto epoxidesinvolves This conversionto an orthoesterI by acid-catalyzedreactionwith trimethyl orthoacetate' with (cHr)rSicl and iodide or bromide, chloride, derivative is then treatedwith acetyl provides cyclization and hydrolysis Base-catalyzed inversionat the halide centerformed. thc epoxide with a second inversion.

u i _

F.

! -

;:

o

ceHso)f^y4". r. . O

cH3 pcH3

9H ^ -cH. CoHs- Y :

cH3c(ocH3)3 PPTS

OH

oXo \"r,

c.Hu

t-Bu

I I n"cr

| (cH3)3sicl

I

I

J

tl'- :rciosclcctivity is uncertainbut j..i,itivity

of radical allylation

..o CaHu"^-'-;"CHs 97o/o @a

cl K2CO3,CH30H

)'-.,r",, : 6nc

CoHs

Tlimethylsilylboron

OH I /,-_*.CHs

l

R3SiO

trifl ate

1)cH3c(ocH3)3 2) AcBr,(CH3)3SiCl

Qr CHs

,a"-,a"r" l l R3S|O OAc

+

l

OH

Addition of CHz:CHCHtSircHt b I a Lewis acid (1 equiv.), or a superrid lk catalyst, a "supersilylating" reagent I A. P. DavisandM. Jaspars, Anget.( lvr tt

8 5 : 15

I 83% K2CO3,CH3OH

l(lhimethylsilyl)ethynyll-9-BB\ Preparation:

| l r.

| i

/'r

y'Lcu" (CHg)sSi-Li

R3SiO

+ g11.g-g^

\-/

59o/oee 1H.C. Kolb and K.B. Sharpless, 10515(1992)' Tetrahedron,48' Tfimethylsilyl azide-Iodosylbenzene. (CH3)3SiN3- C6HsIO (1, 2: I )' -45" to form CaHsI(Nr)2,which decomposes The reagentsin the ratio 2'.7 reactat at 0' to CcHsI and 3Nz. triisopropylsilyl enol ether 2 with B-Azido triisopropylsilyl ethers.t Reaction of the L (2:l) at -45. gives two products,3 and 4, as a 1:1 mixture. Addition of 2,6-di+-butyl4-methylpyridine(BMP) to this reaction gives 3 and 4 in the ratio l:4. The product 3 can be obtainedin>95% yield by reactionof 2 with coHsI:o and then (cH3)rSiN3 at

OSi(iPr)3

osi(i-P03

a>

+

-45' 1, CH2CI2,

r.rrrir

\-/

N3 psi(iP03

rt-r*' t l

ftattll meta-Selective Diels-Adcr trimethylsilylvinyl-9-BBN, but it rcr-ts r quantitativeyield. The regiochemrstn r r preferentially over the para addtrls

(cH' - 'E + t | CHz RsSio R3 = (CH3)2-t-Bu 1)HOA. r73i 2) DDO r7.t

4

2

J

+ BMP

4'.1

25". This unusual B-azido functionalization of triisopropylsilyl ethers is a although the best conditions show some variation with the structure reaction, general ether. silyl of the enol I P. Magnusand J. l-acour,Am. Soc.,114' 76'7(1992)' -15. -

Ttimethytsilylboron triflate' (CH3)3SiB(OTf)4. The reagentis preparedby addition of (CH3)rSiOTf in CHzClz or CHCI: to freshly prepared B(OTf)3 (obtained from BBr3 and 3HOTf).

I D . A . S i n g l e t o na n d S . - W . I r u n g . . / t m

51

Tfimethylsilyl trifl uoromethencsrilrr* 1,2,4-Trioxan-S-ones.t -1.6.f'Trnnr paredby condensation of trimethrlsrlrla. ketones. These precursorsare obta.rrrri t't 1 acetals (2). The triflate I is an c'rscntrel

Tfinethylsilyl

Br = .CAl .,.",-.CHs + l l RsSiO OAc r

379

trifluommethanesulfonate

to RCHO.I This reaction requires fluoride ion, Addition of CH2:CHCH2Si(C& a l-ewis acid (1 equiv.), or a superacid.However, this reagentis a particularly effective "supersilylating" reagent. catalyst, a I A. P. Davis and M. Jaspars, Angew.Chem.Int. Ed., 31, 47O(1'992).

8 5 : 15

.:"" I xrco.,cH.oH

[(ftimethylsilyl)ethynyl] Preparation:

-9-BBN (r).

+

n

.1f,.cn,

BF3 O(C2H5)2

(CH3)3Si:-r-i

l : So

THF

+ CH'O-B)

,"r"rr",2'

59o/"€€

1 c:

,l{ lo (1.2:1). t lt.l(N:)2, which decomPoses enol ether2 with 1y1r.,'propylsilyl ir:::: .{ddition of 2'6-di-t-butYlI rr :hc ratio 1:4. The Product3 - l l l : O a n d t h e n( C H r ) r S i N :a t

N3 psi(i-P03

3-'

meta-Selective Diels-Alder reactions.t This alkynylborane is less reactive than trimethylsilylvinyl-9-BBN, but it reacts with 1,3-dienesat 100' to form adducts in quantitativeyield. The regiochemistryis unusual becausethe meta adductsare formed preferentially over the para adducts.

si(cH3)3-l

("r,+ 1 100", f R3sioAcH,

n

LR3sio"'-'-"\BBN

j

R3 = (CH3)2{-Bu 1) HOAC (73ol") 2\ DDO (74%\

f..,1si(cHor. R3SiOry

r ,: triisoproPYlsilYlethers is a j'1-.,srariation with the structure

[: :: ('t{-Cl2 or CHCIr to freshlY

I D.A. Singleton andS.-W.Leung,J. org.,57,4796(1992)'

TFimethylsilyl trifluoromethanesulfonate, (CHi)3SiOTf (l). 1,2,4-Trioxan-5-ones.t 3,6,6-Trisubstitfied 7,2,4-trioxan-5-ones(4) can be prepared by condensationof trimethylsilyl a-(trimethylsilylperoxy)carboxylicesters3 with ketones.Theseprecursorsare obtainedby photooxygenationof the correspondingketene acetals(2). The triflate I is an essentialcatalyst for this condensationand cannot be

Tf imethytsilyl trifl uoromethanesulfonate

r-n,,.VoSi(cH3)3 I osi(cH3)3

C6H5CHO + C6H5CH2OS

O-OSi(CHs)s

v2

, rr\osi(cH3)3

(cH3)3$ort

o

2

.\

1, (cH3)2c=o

92%

FH.

?."_f_"r.

This reaction can show signihr-ent d

,.ru\o

cHo *

o (t)

4

1c"1rso'

products,but is rep|acedby BuaNF. This ring system is rare|y encounteredin natural antimalarial' potent presentin artemisinine,a Acetat-8, p-diglucosides.2 In the presenceof trimethylsilyl triflate, trimethylsilyl-78" to form (1) reacts with aldehydesat 2,3,4,6-tetra-o-acetyl-B-o-glucopyranoside 2 in 3O-857o yield. At higher temperatures,mixtures of acetalacetal-B,B-diglucosides obtained'The yields arc dependenton the 9,9-, a,9-, and a,a-diglucosides are Ketonesdo not undergothis reaction. aldehyde. of the bulk reactivity and steric

( .OAc AcO-W

I

o

-^

,

(cH3)3siorf

/-'r.z^''I

I

This modified Sakurai reactxro hs I and -ketals by use of a bis-srlrlatc,j cd

(cH3)3siorf

-oSi(cH.)" + RCHo

nco-*or

(

-'?"

'

(CH3)2C(OCH3)2 +

30 - 85"/o

(cHd3s'o'/ t

OAc 1

l

l

(^-koc2H5 \r

TiCla-catalyzed Modified Sakurai reaction.3 The original reaction involved the and ketals to acetals the or ketones and aldehydes to allyltrimethylsilane addition of extended this form homoallylic alcohols or.ethers (7,3"10-37I). Mark6 et al. have of allylreactionto a synthesisof homoallylic ethersby a Lewis acid catalyzedreaction trimethylsilanewithacarbonylcompoundandatrimethylsily|ether.

+

1

(ch! lson

&a

OCzHs

Reaction of crotykilancs rrrl rri Noyori reactionof allylsilanessrth xt 440) to optically active (E)-crotrlsrl'rt (E)-hexenoates(1). These (EFcrtrr}ri rearrangement(6,276 - 277) of oprtxrllr

Ttimethylsilyl

trifl uommethanesulfonate

CoHsCHo+C6H5cH2osi(cH3)3+ cH1""-"si(cH3)3 O-OSi(CHa)o

ocH2c6H5

(cH3)3sioTl

,ur\osi(cH3)3

o .' . - C c HH: .

( ) a

c6H5,.,.,.$cH2 (equation I)' This reaction can show significant diastereoselectivity

c QHs

a'-y.CHO

( r ) l l \-/

cH Z"'.'si(cH3)3

T

(cH3)3sio'^c6H5

9t'

9t' but ls l-"'.:ctl in naturalproducts' rr:'- , :hr lsilyl triflatc,trimethylsilylat -78" to form 1. ..::h altlchYdes mixturesof acetall.' .:rtPcraturcs, ' dePendenton the are r iclds I ' reaction' ,i this un
(cH3)3siorf

o,

9^tu"u /''^#cH' l l

I

+ 2'.'t

\-,

cuHu

r'#cH, l l \,'-

ThismodifiedSakuraireactionhasbeenextendedtoasynthesisoftetrahydropyrans as l' and -ketals by use of a bis-silylatedether such

CHz

CHz (cH3)3siorf

(cH3)2c(ocH3)2 *

'::':

.c*: na -o- -o - _ Y ^ A ^

Jnu

:T+"-J

1"rr;r'o---/-si(cH3)3

|

R

2

r! :.' ,'n involvcd the TiCl4-catalyzed to \-' ,nc\ or the acetalsand ketals \l.rrkti er al. have extended this I .i:. ucid catalyzedreactionof allylt. t : : - :: : h r l s i l Y le t h e r '

ft'

,\

o

Ck:,,.,.'"#5}'H#d Panek and Yangr have extended the Reaction of crotylsilanes with aryl acetals'a Noyorireactionofallylsilaneswithacetalscata|yzedbytrimethylsi|y|triflate(10'439as a-methoxy-B-(dimethylphenyl-silyl)++O; to optically active (E)-crotylsilanes,such available by Ireland-claisen estet are (E)-crotylsilanes These (1). (E)ih"*.*^t., vinylsilanes(equationI and II)' ,"urrung"rn.n, (6,276- 277) of optically active

I I

I

I

Tiimethylsilyl

(t)

trifluommethanesulfonate

CHs-3..\--SiMe2C6H5 :

0- _..\-ocH3 )rt l

rMscr 1)LDA,

9"t.

i]!l?,."*..,,tcH.\Z-i+coocH3 8oo/"

siMe2c6H5

o

I o. _.,\-ocH3 Y o

o

o' Pr:._,..r

9"t'

cHe\z-9fcoocH3 ------------------_ 81"/"

BU

2

Sitrt"rcuH, quenchat 25'

73

quenchat -78'

rl

(2R,3R)- 1b

In the presenceof 1 equiv. or less of trimethylsilyl triflate these crotylsilanesreacl with aryl acetalsto form homoallylic etherswith high diastereo-and enantioselectivity. The new C-C bond (CsCo) is formed with high syn-selectivity(13-a0:l).

9cHg

concerned,but has only been reportcdfw g route to monoprotected1,2-diols.

[3+4]Cycloadditions.6 In rhe pc
coocH3

1a, (CH3)35iOTf

(t)

94o/o

o

il

cH3o

"r.? ?.r. [.aocH3

Y

cH3o

B.rp{! (cFrd3sorr

1

- 1a (2S,35)

CHg.-S..\.-SiMe2C6H5

flr)

o.

Pt--J.).-.-o-."r.FBu tl

CH..r^\-,.-\f-u113 " t

2 d , 9 5 o / oe E

l

R3S'o

C

+

cH?/-'-y'

o (il)

coocH3

1b, (cH3)3sioTl

^,,

o .

R

92o/o

l

cH3o

(ilr) Addition of R2CuLi to epox! esters.s Addition of Bu2CuLi/(CH3)3SiOTf (1:1) to the trans-epoxy ester I at -78' followed by quenching at 25' (thermodynamic control) resultsin a product (2) in which the estergroup has migrated to the secondary alcohol. The expectedproduct (3) can be obtained as the major product if the reaction is quenchedat -78". This unexpectedreactionis generalas far as the cupratereagentis

o

r-euA-''\ycHe o

+

2

Tlinelhylsilyl

trifl uommethanesulfonate

OCHe

I

-

-Z\ff-coocH3

Bu2CuLi tr.t-?->...--orrau(cH3)3sioTf

SiMe2C6H5

o

o tl

(2S,3S)- 1a

oAr-Bu er:-/\---'oH

9"t' 'z-''?G'coocH3

*

OH I P'-r-rA---o-..--f-Bu

t

t

B

I Bu 2

SiMe2c6Hs quenchat 25"

73o/o

quenchat -78"

1o/o

OCH.

t -"

O C H-I

|

i I x6coocH3 CHs

5o/o

concerned,but has only beenreportedfor pivaloylates.Even so, it providesa convenient route to monoprotected1,2-diols. In the presenceof a lrwis acid, particularly TMSorf, the [3+4]cycloadditions.6 bis(trimethylsilyl)enol ether (2) of methyl acetoacetate undergoesa [3+4]cycloaddirion with 1,4-dicarbonylcompounds(l) ro form 2-carbalkoxy-g-oxabicyclo[3.2.1]-octan-3ones (3) with high regioselectivity.This t*wis acid ordinarily does not promote reaction of silyl enol etherswith simple aldehydesor ketones,but it is more effective than Ticla

(t)

o

R3S|O

tl

2a 95o/oee

gcir, 9cH, 'F - \-G-coocH3 CHg

.H.../{.---^---CH3 " t

l

+

cHl\Z\ocHs

o (lt)

OS|R3

TMSOTf,-78" 560/"

2

3(1:1)O

o

o

,5.'

+

2

o

53 - 90%

2b 95% ee

F :.r. migratedto the secondary h, :r.rjor product if the reaction rl ,. fur as the cupratereagentis

rl\coocH3 "\ (200: 1)

\ O

o

(ilr) ,,: tlulCuLi/(CHrlSiOTf (1:1) rn,:rns at 25" (thermodynamic

O

3

( 2 R , 3 R- )1 b

::rll.ttcthesecrotylsilanesreact dr.,.:,'rco-and enantioselectivity. : l r . ' r ri t r ' ( 1 3 - 4 0 : 1 ) .

l

u

o

r-euA-,^ycHs

+

2 74"/o

o ( 2 8 :1 ) O

384

T[imethylsilyl

triffuorcmethanesulfonate

for this [3+4]cycloaddition. Unexpectedly,the reaction of 2 with a 1,4-keto aldehyde involves initial attack with the keto group (equationII). In the case of unsymmetrical diketones,the initial attack occurs with the more hindered ketone (equationIII). The reactionis also regioselectivein the caseof 4-keto aldehydesbearinga substituentat the interveningcarbonatoms.The report includesa possiblemechanismfor this cycloadition involving initial attackof the lrwis acid with the less hinderedcarbonyl group followed by participationof the more hinderedcarbonyl to form a cyclic oxonium ion that reacts with the terminal carbon of 2 to form an adduct that then cyclizes to 3. The [3+4]cyclization of 4-oxoheptanal(5) with 3-substitutedbis(trimethylsilyl)enol ethers of B-diketones (4a) and of B-keto esters(4b) is also regioselectivebut in the opposite sense (equationIV).

o

TMSO

o

OTMS

t l cHr4-\Z\R

73o/o

4b,R=OC2H5

76%

r

P'

is not a result of chelation.hur ,-f rr Thndem Sakurai- carb nvl -
l l \ CH3OOC ....(-/

3

ri

\

f

.coR

1

,-l\. /y'-..-\-ctr.

Pr'

o

8 -.rr.

o

o t\

,CHS

/y''\\-coR P

ocH3 ._ _-\ i-PrO' -Ol-Pr

chrr g

h

.Jlyoc(cH3)3

o

/-ln-

..'-'.,'.CH(C\12 l l c

TMSOTf

4a, R = CH3

I\

(l)

40:1

\

9H3 ^OC(CH3,:.

o

1:35

a-14

l H l cu",,,.M

+ i a

)

,

I H I H HO"'$CHz

Stereoselectivereactions with acetals.T Noyori e/ a/. (10,438) have used this Lewis acid to promote.an aldol-type reaction between enol silyl ethers and acetalsand have noted high .syn-selectivityin this process.Molander and Haar report that reaction of acetalswith cyanotrimethylsilane promotedby TMSOTf resultsin a-alkoxy cyanidesand that this reactioncan be diastereoselective when the acetalis substitutedat the 4-position by an alkoxy group. The diastereoselectivitydependson the nature of thc acetal and the 4-alkoxy group. Dimethoxy acetalsshow slight diastereoselectivity, but diisopropoxy and dibenzyl acetalscan show diastereoselectivityof 5-10:1. The diastereoselectivity also dependson the type of 4-substituent.Acetoxy and t-butyldimethylsilyloxygroups have no effect on the diastereoselectivity, but methoxy, benzyloxy, and allyloxy groups promote anti-selectivity.Since a metal templateis not involved, the diastereoselectivitl-

3a

CD t'-L

c2H5Arcr2 "- --o*cHr\-t-h

H

I H HOMCTi I

Ttimethylsilyl

rr 'r ()f 2 with a l,4-keto aldehyde I IIr. In the caseof unsYmmetrical rr:.icrcd ketone(equationIII). The dr 1\ dcs bearinga substituentat the il.i- nrcchanismfor this cycloadition .. :rn,lcrcd carbonyl group followed rr .r cvclic oxonium ion that reacts It ::r.n cyclizesto 3. enol i,.ubstitutedbis(trimethylsilyl) b

r. also regioselectivebut in the

trifl uommethanesulfonate

OPr-i (l) "

.-.^-.../.CH(CH3)2 I I OCH3 -\ -ol-Pr

i-PrO'

(cH3)3SicN'1' CH2CI2,_78" r^,r^-\.---CH(CH3)2 r v 92/o

(anti)

l

* (syn)

ocH3 1 5 :1

is not a result of chelation,but of neighboringgroup participation. Tandem sakurai-carbonyl-ene reaction; steroid synthesis.s The key step in a short synthesisof the BDC rings of steroids from the chiral aldehyde I involves a tandem Sakurai-carbonyl-ene reactionof 2 mediatedby trimethylsilyl triflate,which provides3a as the only cyclized product in 52Voyield. Amazingly, catalysiswith CzHsAlCl2 leads to two diastereomers,3b and 3c (3:l) in 4o% yield. Hydrogenationof 3a provides 4, which correspondsto the BCD ring of steroidswith an added methyl group in ring B.

ls

r[,rsorr ,oc(cH3)3 TMSOTf, cH2ct2

73o/" 760/o

:

o t\

CHs COR n

+

si(cH3)3

.coR

,-l^Y-

/-^-\\-cH3 Pr' \

4 0. 1

pc(cH3)3

o CHg,

1:35

H HO"'

r , : ,r1.(10,438)haveusedthis Lewis ll .rlrl cthersand acetalsand have c: .:nrl Haar rePort that reaction of l) I: rcsultsin a-alkoxy cyanidesand at the 4-position u..:.rl is substituted n.:. (\n the nature of the acetal and but diisopropoxy l.:.:!rcoselectivity, r r i l0:1. The diastcreoselectivity .,::J r-butyldimethylsilyloxygroups n, hcnzyloxy,and allyloxy groups n, ' rnrolved, the diastereoselectivity

9C(CH3)3 c2H5Alcl2 4Oo/"

386

Trimethylsilyltrifluommethanesulfonate-Silverperchlorate

Nazarov cyclizl.tion.s d,4/-Dienone esters 1, prepared by acylation/Knoevenagel in the presence of condensation of various esters, undergo Nazarov cyclization trimethylsilyl triflate to form cyclopentenone esters 2'

o ,#?i;r. "t.*cooc2Hs -.,\ -cocr --::-

+ CHe- Y CH3COOC2H5 iH.

CHa

Ho,,, ^^ l t

v

Ho---z t

'\

+

Ho/---AoH

ll

e1"/"

cH/

I c,u"cxo -ricr. |

1 K. Toshima,G. Matsuo.T. tshrzr\r /1992\.

V

o

oI I

tl

CHr-.-.r/.."-COOC2H5

\ t'cH2cH3

(cH3)3siorf

CHs\,,/r--,.cooCzH5

31o/"

CH"/

cH:-

l l l-crH, l 1

2

Trimethylsilyl triflate (5 equiv.) also converts3-ethoxycarbonyltetrahydro-7-pyrones cyclization' (3) into cyclopentenoneesters(4) by ring opening followed by Nazarov

ot l

cH.-\..\r.cooc2H5 tT".j:?Ji l

t

cH.

l

l oAcH.

55%

o cHs\<,Vcooc2Hs \

/

r( ll

air-sensitive,pyrophoric. The borane is obtainedhr rc.xt Ttrr Diels-Aderreactions. be effected at 25-85" *'ith m:rlcd r on oxidation (H2O2,NaOHI rfio.d TsOH at 55'afford l.4-crcktrctr

(c"

r 4s, 73\

t - - - - - - - - - - - - - -

cH.AcH,

c4r/

cHf-'cH.

1 C. W. Jefford, J. Currie, G. D. Richardson,J'-C' Rossier,Helv ' 74' 1239 (l99l)' 2 L . F . T i e t z e a n d M . B e l l e r ' A n g e w .C h e m 'I n t ' E d ' , 3 0 , 8 6 U ( 1 9 9 1 ) ' 3 A. Mekhalfia and l. E. Mark(t, TetrahedronLetters' 32, 4779' 4783 (1991) a J . S . P a n e ka n d M . Y a n g ,A m . S o c . , l l 3 ' 6 5 9 4 ( 1 9 9 1 ) ' 5 G . A . M o l a n d e ra n d K . L . B o b b i t t ,J - O r g . , 5 7 , 5 0 3 1 ( 1 9 9 2 ) ' 6 G. A. Molander and K. o. Cameron' ibid', 56, 261'1 (1991)' 7 c . A . M o l a n d e ra n d J . P . H a a r , J r . , A m - S o c ' , f n ' 3 6 0 8 ( 1 9 9 1 ) ' 8 L. F. Tietze and M. Rischer, Angew. Chem lnt' Ed', 3l' 1221 (1'992)' '7'131(1991)' q J. F. P. Andrews and A. C. Regan, Tetrahedron Letters, 32,

TMSOTf-Agcloa' TFimethylsilyl trifluoromethanesulfonate-silver perchlorate, of TMSOFf-AgClOl composed catalyst of a presence the In c-Arylglycosylation.t as protected' react well as unprotected glycosides' methyl (1:1), tree sugars or witha-naphtholtoformglycosidesinT2-92%yieldandwithhighp-se|ectivity

@lF : 1:15-ee).

2-Tiimethylsilylvinyl-9-BB\.

CI\'

I D. A. SingletonandJ.P. \lanrrrr. I

phcoy-l * [2+ 2]Cycloadditions.: T]c vinyl ketonesin the presenceof r quenchedwith HzO rather than u (Ilimethylsilyl)vinyl

i

(Tiimethylsilyl)vinyl

c n . :, J bv acylation/Knoevenagel c \ , rlrtion in the Presence of

o cr,- A ..cooc2+s

phenyl selenide (l)

'o"3;q '3; i"Y-ir-ffi * \-x--2-6 ,JJo, ,o$"Y OH

ctlP=1'7s

r

)

CHz'

rK. Toshima, G. Matsuo, T. Ishizuka, M. Nakata, and M. Kinoshita,J.C.S. Chem. Comm., 1641

I c,u.cno -ribr. | I

ot l

CH, -,-,,/---,-COOC2Hs

t:

CNr/

i l l-crHu l 1

r . ..rrhonyltetrahydro-7-pyrones

h

T .. ..1 hv NazarovcYclization.

o I

' /\ Y -COOCzH5

.J 4

F

(CH3)3SiCH:at-" 2-TFimethylsilylvinyl-9-BBN,

'-1. .ll -..r

Q,tl,

air-sensitive,pyrophoric. The borane is obtainedby reactionof trimethylsilylacetylenewith 9-BBN. Diels-Alder reactions.t This reagcntis a highly reactivedienophile.Reactionscan The adducts be effectedat25-85" with markedregioselectivityand high endo-selectivity. with which on treatment (HzOz, trimethylsilylcyclohexenols, NaOH) afford on oxidation yield. quantitative in TsOH at 55' afford 1,4-cyclohexadienes

(^''(o'
CHs

C F 1r

t,

(1ee2).

cH3Y'^Y'oH V"".,,.r.,, r*u

I t"o",uu'

I ll3e (1e91)

)rl1l

rr' h l o rate, TMSOTf -AgClOa. \: . nrn()sedof TMSOFf-AgClOr L.: '. xr'll as protected,react rrr .r .iod with high B-selectivitl

,"o", rr' CHe

I

(t991).

' leel)

|

V

i l tl I D.A. SingletonandJ.P. Martinez,Tetrahedron Letters,32,7365(1991).

(Ihimethylsilyl)vinyl phenyl selenide (1). The vinyl selenide I undergoes [2+2lcycloaddition with [2*2]Cycloadditions.l vinyl ketonesin the presenceof a l-ewis acid, usually SnCla or AlCl.. If the reactionis quenchedwith HzO rather than an amine, acylsilanesare obtainedin 37-5OVo yield.

chloride/AlBN

timethyltin

(cH3)3SiySeC6H5

^

1.1

CH
CHz

(cHdlg

1)SnCla c6H5Se, 2)N(c2Hs)3 > (cHd3si-E//cocH3

ft' i

66"/"

CHg

( E

o ,-"1]ilsulicHd3sio--qs"".t,l-"ffa 1+2--a

1"'..1'

(

Y

2

o

97%

E

E = COOCzHs,

coocH3

f'-(cH')'siA-'\AcH' I S. Hanessian and R.

[*ger. .{a .\"r ]

rS. Yamazaki, andH. Tamura,J. Org.,57,5610(1992). H. Fujitsuka,S. Yamabe,

Tlimethyltin chloride/AIBN/NaBH3 CN. Cyclization of dienes and trienes.t Reaction of a diene or triene with at least one terminal double bond with (CHr)rSnCl, AIBN, and NaBHTCN in r-BuOH results in addition of the (CHr)rSn radical to the terminal double bond followed by cyclization to the other double bond. The C-Sn bond of the carbocycleis oxidatively cleavedby CAN in methanol to the dimethyl acetal of an aldehyde.This two-step synthesisprovides a from useful route to tetrahydrofuransand pyrrolidines as well as 1,6-dioxatriquinanes

T[iphenylphosphine - Dierhl-l rarAry I 2 -deory -B -o- glycorilcr-_

selectivity by Mitsunobu couplrnl , phenyl)-a-o-pyranosnes2. prcperrd I (l). Reaction of 2 with a phcr{ r

allyl ethers.

-l

BzlO-

azo,,,1\o

cfrs.c

CG" -20.

-CoHs

Bzto* 1 BzlO-

*i \

o\_i-o

(CH3)3Sn

(^' /

) ,=roza\g

ezrogoA,

e

E

:

85"/"

SeC6H5 3(0/c=88-95:12.5r (cis/trans= 2: 1)

Tbiphenylphosphine - Diethyl azodicarboxylate

c6HsSe, ,.cocH3 ,CH")"S|-#

*

L_l

(cHr).sI E '

ft' i'

a

E E

o

o

)

+ ?

v

E

cH3o

87"/"

E

E = COOCzHs,

coocH3

)r-i..siA-"t--[-"".

'S. Hanessian and R. Leger,Am. Soc.,114,3115(1992). S - . 5 6 l t )( 1 9 9 2 ) .

r

dr;:rr or trienewith at leastone illlll,C'N in ,-BuOH resultsin h :.: tollowed by cyclization to c :. ,,rrdativelycleavedby CAN i . : r , ) - s t c P s y n t h e s i ps r o v i d e sa

Tiiphenylphosphine- Diethyl azodicarboxylate. Aryl 2-deory-B-o-glycosides.r These glycosides(4) can be preparedin high Bselectivity by Mitsunobu coupling of phenols with 2a-(thiophenyl)- or 2a-(selenophenyf)-a-o-pyranosnes 2,preparedby reactionof CoHsSClor CoH.sSeCl with o-glucals (l). Reaction of 2 with a phenol under Mitsunobu conditions provides mainly B-

from ,. 1.6-dioxatriquinanes

:l

Jll? cH30

-CoHs

BzlOC6H55eCl

cct4,-20'

BztON

edo)J :

1

2

-o H

7O - 85o/o

I

BzlO_ )

BzlO,,,.r)'.,O

"1lllllllllllllllisSSS3ft", Bzto,,,.r),,,o

Bao/*onr :

85-950/"

CH:

i

",oH

SeC6H5

BzlO-

{:.

ArOH (c6H5)3P,DEAD

B/O,.]o

SeC6H5 3(B/o=88-95:12-5)

I I gztol--'.^oRr

Tris(fr-cblomrlanln rr

Triphenylphosphine-Diethylazodicarboxylate

390

glycosides3. The thiophenyl or selenophenylresidueof 3 is removed by reactionwith Bu3SnH/AIBN. Mitsunobu reactions with o-nitrophenllacetonitrile.2 The Mitsunobu reaction can bonds. Thus o-nitrobonds as well as the usual C-O be used to form C-C phenylacetonitrile(f) reactswith various alcohols under Mitsunobu conditionsto form the alkylatedderivative2 in 45-70% yield. The productscan be convcrtedto indoles(3). CN

(c6H5)3P

CN

R

..

tt.o cH'o cfto,-,/.,.,./) o,?51?.. HdL + \z\X >o>A* l- tl ll ) |I illl |\..''--Nf -to, -, \_/.-

VNoz

Y2

1 R = CsHsCHz = cHs = HC=CCHz

i

H

oxidant to date is benzeneselenrnx in the presenceof l, converls.rr-r This radical epoxidation is su;r'rxv of 1,3-dienes,such as l-r'inrkrclrt bond is selectively epoxidizcd .{ l

(')a> atr)

54"/"

7O/o 45% 56%

Tiis(4-bromophenyl)aminium bcrrct Radical epoxidation.t In rhe g can effect epoxidation of stilbrne. ht of the catalyst. Selenium dioridc rS epoxidation, but suffers from hrr r

41o/o

rw. R. Roushand X.-F. Lin, J. Org.,56, 5740(1991). 2J.E. MacorandJ.M. Wehner,Tetrahedron Letters,32,7195(1991).

CH

\-.-

BSA 1 Ttiphenylphosphine - Diisopropyl azodicarboxylate. Mitsunobu reaction of B-hydroxy-a-amino acid peptides.t Reaction of the Cbzprolyl-threoninc N-methyl amide I with P(C6H5)r and DIAD provides the peptide aziridine 2 in 84Vo yield.

o

H \ .N=J/'-NHCH3

i

\ru\\

fH 60. b .FoH

o

clc6Hlco3f{

of 4-isopropenyl-1-vinylcyclohercrx r o

o

6He\

tt il P(c6H5)3.oDlAD /^>/-N_-'..n\*rCr.

--;;-

\-,{ 'coz v

6g,

1

(tt)

I

2

cn/\c++, In contrastallothreoninepeptidesare convertedby the rcactioninto oxazolinederivatives (64-83% yield) with no aziridine formation (equationI). Oxazolines are also

(t)

cH3rcHs N)
O HoAcHs

.,.:lfT6N., ',coocHs 73o/o

H

o1r.

obtainedby the Mitsunobu reactionwith serine-containingpeptides. rP. Wipf and C.P. Miller, Tetrahedron Letters,33, 6267 (1992).

I N. L. Bauldand G.A. Mirafzal..{a \.r.

Tiis(p -chloro)hexakis(tetrahy drolLrr 16,370-372.

Hydroxymethylation v.ilh po4 (16,371) is applicable to couplins r'f r a large excess of CH2O is neccs\.n I homocoupling to ethylene gllcol. Lndc obtained in yietds of >90%. Thc rcr-r diastereoselectivity.

Ttis(p-chlom)hexakis(tetrahydmfuran)divanadium

i. -:nrovedby reactionwith I -- \'litsunobureactioncan '- () bonds. Thus o-nitroll:..rn()buconditionsto form 1 ^, .'()nvertedto indoles(3).

hexachlomdizincate (l)

Tbis(4.bromophenyl)aminium hexachloroantimonate, (p-BrC6Ha[N+ SbCl6- (1). Radical eportdation.t In the presence of this radical cation, iodosylbenzene can effect epoxidation of stilbene, but only in low yield becauseof decomposition of the catalyst. Selenium dioxide (SeOr) is a suitable oxidant for this catalyzed epoxidation, but suffers from low solubility in CHzClz at 0". The most useful

tl

oxidant to date is benzeneseleninicanhydride, (C6H5S)2O (BSA). This oxidant, in the presence of l, converts cis-stilbene to rrcns-stilbene oxide in 85Vo yield. This radical epoxidation is superior to m-chloroperbenzoic for monoepoxidation of L,3-dienes, such as 1-vinylcyclohexene (equationI). Moreover the endocyclic bond is selectively epoxidized. A similiar selectivity is observed in epoxidation

:"b^,

(')a)

s

"t')

1'

{

I a\ (,

\-,-

/.

BSA,1 Rcactionof the Cbzidt,. l)l \l) pK)videsthe pePtide

760/o

55"/o

clc6H4co3H

21o/o

24o/o

of 4-isopropenyl-1-vinylcyclohexene (equationII).

c *'t

o

"t')

ll 'N.-7'"'-NHCH.

N

V Ccz 66, 2

(tt)

BSA,1 cH2ct2,o'

",x" .)

72"/"

H3

c.:.:i,\n into oxazolinederivar:: : l). Oxazolinesare also

CHs

'-<*).,'aooCH3 H

| :!:':ldcs.

o1r.

rN.L. BauldandG.A. Mirafzal, Am. Soc.,113,3613(1991).

Ttis(p-chloro)hexakis(tetrahydrofuran)divanadium hexachlorodizincate (l), 16,370-372. Hydroxymethylation with paraformaldehyde.t Petersen's pinacol coupling (16,371) is applicable to coupling of aldehydeswith paraformaldehyde.Even though a large excess of CH2O is necessaryfor satisfactoryyields, there is no evidence of homocoupling to ethylene glycol. Under optimum conditions,the desired 1,2-diols are obtained in yields of >90%. The reaction of chiral aldehydesshows modest to good diastereoselectivity.

Tris(p-chloro)hexakis(tetrahydrofuran)divanadium

Tris(pthlq

hexachlorcdizincate (l)

OH

1, cH2cl2

cH20

cuHu"----"CHo

c6H5'^\''\"oH

96%

?t'

it'

cH"-t),,,,,,^......",Moar - o 2

OH

c6H5YcHo

c6H5 --/,'\-..-,,oH I CHs

cH20 93%

CHs

"t.T,l-= OH 3 (81%t

= 3: 1) (anti/svn pinacol coupling with ketones' but by The reagent I is generally less effective for and 5 Zn' coupling between ketones use of a reagent(2) preparedfrom 2 VCI3(THF): and paraformaldehydeproceedsin yields of 8O-90%'

o

CH2O

cH3

c6H5

c.Hu

86"/o

C H q-

t

+

80a

cH.

HO, PHzOH

o ^.

o"

HO\/CH20H

2, c{2cl2

+

ll

cH:

?t'

/-Y"'"

cH20

l

J4 Asymmetric 1,44iani*J col homocoupling in thc trc!.tr-t ( diols (3) in good yield arxi hrgt d

(, (8:1)

Epoxides-olefins.2Thisreagent(1)canconvertepoxidestoalkenesin5o_987o of 1' and the cls-configurationof the yield. The reaction requires three equivalents substrateis not retained.

o

-\AH tl I NHCb

?

(s)-2 |

|

\ f Z l o

''cHs

1, CHzClz,0"

'

\

52o/"

CHs

| (cH3)3C"'-Y

|

\"'cH' CHs

R=l-Pr R=l-Bu R = CHeCrHs

o

//\A

.)

(Y"oocH3

-coocH3 92o/"

trr..v

In contrast reaction of the epoxide 2 with vcl3(THF! 3 as the main Product.

(3 equiv.) affords the halohydrin

I J. Park and S. F. Pedersen. fctrakt 2 T. Inokuchi, H. Kawafuchi. anJ S f 3A.W. Konradiand S.F. Pedcrrn..l

Tlis(p -chlorc)hexakis(tetrahydmfuran)divanadium

ril 'ndizincate (l)

cHe l -

OH

cHr C

l

H

z

cHs-l>..\-..,..*onc o'

c6Hs/-\-,\'-'-oH

hexachlomdizincate (l)

3 VCl3CrHfl3 l z

-C

2 OH

t l cH.-f\,..---Monc " c t I

C6H5 --r..\..--.,OH I CHg (anti/syn= 31

CI

HO\/CHzOH

93:7

3 (81ol")

o"

?'.

* cH.-f,)(*on"

OH

'l)

c. .,,upling with ketones,but bY ri ' 1n. coupling betweenketones

c.Hu

?'.

CHe

CHq

80%

cH.

HO\ PH2OH

/-Y"'"

Asymmetric 1,4-diamino-2,3-diols.3 (S)-N-Cbz-aminoaldehydcs2 undergo pinacol homocouplingin the presenceof 1 to afford (lS,2R,3R,4S)-1,4bis(Cbz-amino)-2,3diols (3) in good yield and high diastereoselectivity.

\-, (8:1) ,c" -n()\idesto alkenesin 5O-98Va . ,:'.i thc cis-configurationof the

-

.) \

.

\"'cH' CHg

o

tl R'-.,,\| " NHCb (s)-2

1 ) 1 , c H 2 c t 2 ,2 5 ' 2) H3O. 87"/"

l

CbzHN

l

N HCbz C

t

R

OH

-3 (2s,2R,3R,4s)

R=i-Pr

89o/"

R=l-Bu

61"/o

R = CHzCoHs

76"/"

(Y''coocH3

1ca.l3Cry lF , , i cquiv.) affordsthe halohydrin

OH

-h---A--A.t

1 J. Park and S. F. Pedersen, Tetrahedron, 48, 2069 (1992). 2 T. Inokuchi, H. Kawafuchi, and S. Torii, Synlett, 510 (7992). 3 A . W . K o n r a d i a n d S . F . P e d e r s e nJ,. O r g . , 5 7 , 2 8 ( 1 9 9 2 ) -

394

Ttis(phenYlthio)nethane

Tlis(dibenzylideneacetone)dipalladium, Pdzdbar' Allylic gem.-dincetates.l In the presenceof this Pd(0) catalyst, propargyl acetates I)' react with acetic acid to form (E)-allylic gem-diacetatesin 55-797o yield (equation prepared. be also can gen-dicarboxylates Mixed

HC(SC6H5)3+ 1

An intramolecularversion of this reactioncan result in macrolides(equationII)' nucleus 2 as a single cri. .urnhirsutene(3) by kno*n srcpl .

OAc

(dba)sPd2'CHClg CoHo, P(CoHs)s, . 52"/"

7

o ( 1 . 5: 1 )

I

I K. Ramig,M. A. Kuzemko.X r& or stille reaction The preferred catalyst for this coupling of unsaturated halides catalysts effective more Much Pd[P(C6Hs):]+. has been triflates with organostannanes a PdLn can be obtainedby treatmentof Pdzdbarwith 4 equiv. of various ligandsto form and (TFP)3 tri-2-furylphosphine are effective most catalyst.2Of a number of ligands,the triphenylarsine[As(C6H5)3]. I B. M. Trost,W. Brieden,and K. H. Baringhaus, Angew.Chem'Int' Ed'' 31, 1335(1992)' 2V. Farinaand B. Krishnan, (1991)' 9585 f13' Am. Soc., 3 D.w. Allen and B.F. Taylor,J.C.S. Dalton,51 (1982). Tiis(phenylthio)methane, HC(SC6H5)3(1). r This reagent can function as a dilithiomethane [2+1+2]Cyclopentannelation oxidized equivalent in consecutive conjugate additions to form a dienolate that is triquinane the obtain to used been has cyclopentannelation This to a cyclopentane.

TFis(trimethylsilyl)sibr rI r Review.t ChatgiliakStu I radical reducing reagenls ()n

the strength of the Si-H can t [(CHr)?Si]2SiCHrH slrcu's tlrh The silane I is useful for rcrjr.rcr in the presenceof onll smell r and purification of the prrrdtrt3 useful for radical reduoioo ud Selective hydrogcn otn . radicals such as 4 abstract hrdr observed by Cram for redrrtxn

Tris(trimethylsilyl)silane(l)

ru. tr.irrl) catalyst,propargyl acetates tr:.. rn 55-79Vo yield (equationI)'

9_,,-

oAc

*to-r-$oo.

fiz

1) BuLi 2) sec - BuLi

*{-"". HC(SC6Hs)3 1

r, :icr3

o

o

Lio

\ -lt oLi

l

\-"t.6!.rr.l Y""trl c6H5s sc6Hs

'""^?i 64"/"

f"t. \-./.cn.

CHe CHs

_l

r..-i: rn macrolides(equationII)' nucleus 2 as a single cis, anti, cjs-2. This triquinane 2 has been converted into (+)hirsutene(3) by known steps in l8o/o overall yield from l.

osiR3 CHs

o

CHe

( 1 . 5: 1 )

rK. Ramig,M.A. Kuzemko, J. Org.'57' 1968(1992). andT. Cohen, K. McNamara, halidesor rr- .,ruplingof unsaturated r, Much more effective catalysts {. , pn ,,l various ligandsto form a PdLa r. .,retri-2-furylphosphine(TFP)3and . , ,., ttt.Int.Ed-, 31, 1335(1992)'

): t_

:n: ..rn function as a dilithiomethane t., rLrrm a dienolate that is oxidized s ^Jcn used to obtain the triquinane

TFis(trimethylsilyl)silane (l). Review.t Chatgilialoglur has reviewed the use of organosilanes,particularly l, as radical reducing reagents.One advantageof organosilanesas rcducing agents is that the strength of the Si-H can be modulated by a choicc of substituentson Si. Thus donor, [(cH3)3si]2sicHrH shows only about lo%oof the reactivity of I as a hydrogen The silane I is useful for reductionof halo, NC, and SeC6H5groupsat room temperature in the presenceof only small amountsof radical initiators. For this reasonthe isolation and purification of the products is simplified. Tris(alkylthio)silanes,(RS)iSiH, are also useful for radical reduction and for hydrosilylationof alkenes. Selective hydrogen atom abstraction by radicals. Giese and Curran2 note that radicals such as 4 abstracthydrogen atoms in a ratio that is remarkably similar to that observedby Cram for reductionof ketonesby lithium aluminum hydride.

Tiis(trimethylsilyl)silane(l)

o tcHs)rcHlAcHs

OH I

(cH3)2cH )A"r.

CoHs 2

OH

-..1AcHs * {cHs)zcH

CH3-.."...CH3

,

A2'

CoHs

CoHs 13.3:1 syn-3

anti-3

I t, u"uo"=*or-tu

I

osilsi(cH3)313 I

HzsctzsH'

(CH3)2CH\,-\(_H^ -"r |

CoHs

syn-3 + '|2.6:1

f--r'cH' o h.r,

anti-3

63\

4

Hydrosilylation of alkenes and allqtnes.' This reaction can be effected with I and an initiator at 90'. Reactionwith monosubstitutedand gem-disubstitutedalkenesshows high anti-Markovnikov regioselectivity. cis- or ,rans-Disubstituted and trisubstituted alkenesare hydrosilylatedin high yield but require longer reaction times. RCOCI AIBN

RH.o

or tert-acid chlorides. C6H5CH=CH2

. A%I B - -1i 4 *N

(cH3)313 c6H5cH2cH2silsi tutuy^silsi(cHa)3r3

c6H5YcHz

CHs

CHs CHs

Ia

04oAo

a)

cHs

n

o4oAo

,silsi(cH3)313 cHs

.

x

,silsi(cH3)313

This rerrrn.r

in dodecane or toluerr Reducrin

.t rtr'

r

o{ prr

coproducts.

I C. Chatgilialoglu, Acc. Chem Rar l. i.tl 'B. Giese, W. Darnm, J. Dickhaur t nt{ 6097 (1991). 3 B. Kopping, C. Chargilialoglu.\l Zrbtu_ 'M. Ballestri and C. Chargiliak13lu \ (r (1e92).

16:1 o4oAo

- (L*si(cHo)st3."(> CHS --r-1"/" 51 : 4e SilSi(CH3)313 II (z) (E) H

Tirngsten carbene complexes. Aminocarbene Diels-AUcr n-i chromium carbenesto undergo Drcls-.1 acid catalyst (12,135- 136) has prnng.c aminocarbenecomplexes.Unfonunerch t alkoxy counterparts.But the (EFamrla c with Danishefsky'sdiene at 90' ro enc high exo-selectivity(>25:l). Houocr d

T[ngst€n carbene comPlexes

silsi(cH3)313

OH ctl --AcHs

cH3---,.cH3

4t2""

CoHs

82"/o

anti-3

CHs

,r--/CH'

o h.r,

/-l^tilsi(cH3)313 HcH.

:fl.;lcd with I and rtr.: .rlkcnesshows .i1.1 trisubstituted ln ..

RCOCI - RH.a This reaction can be effected with this silane in combination with AIBN in dodecaneor toluene at 80" in high yield, particularly in reactionsof secor tert-acid chlorides. Reduction of primary acid chlorides leads also to aldehydes as coproducts. rC. Chatgilialoglu,Acc. Chem. Res.,25, 188 (1992). 2 B. Giese, W. Damm, J. Dickhaut, F. Wetterich, S. Sun, and D. P. Curran, TetrahedronLetters, 6097 (1991). 3B. Kopping, C. Chatgilialoglu,M. Zehnder,and B. Giese,J.Org.,57,3994(1992)4 M. Ballestri and C. Chatgilialoglu, N. Cardi, and A. Sommazzi, Tetrahedron Leners, 33, 178'7

J

(

s [si(cH3)3]3

(1992t.

Ao

i, CHs)gls

T[ngsten carbene complexes. Aminocarbene Diels-Alder reactions.l The known ability of alkenyl alkoxychromium carbenesto undergo Diels-Alder reactionseven in the absenceof a l-ewis acid catalyst (12,135-136) has prompted an investigationof Diels-Alder reactionsof aminocarbenecomplexes.Unfortunately thesecomplexes are much less reactive than their alkoxy counterparts.But the (E)-amino complex I does undergoa Diels-Alder reaction with Danishefsky'sdiene at 90' to give 2 in 72Vo yield. Surprisingly,2 is formed with high exo-selectivity(>25:1). However the (Z)-isomer of I fails to undergothis reaction.

Tbngsten carb€ne complexes

NHCH3

ocH"

(co)swl/NHCH3 + = (E)-1

CH3

(co)5w 90"

)

(co)sw

I

AcH, R3SiO 2,(exo/endo=>25:1) CnH"

9{

n J - -

zcoHs

I

(co)4w1/NCH3

a

+ carbene comptex (22/")

: i^"."r0.=1

C H s R3S|O-

--CHz

3

4, 33o/o(exo/endo= 35:1)

Cycl& diphenyla

The chelated carbene3 is even more reactive than (E)-l and shows even higher exo-selectivity,but unfortunatelyis relatively unstable. Intramolecular bis-allqne annelations.2 A typical reaction of this type generally leads to a mixture of a phenol and a cyclohexadienone(equationI). However this annelation can be adapted to a construction of the steroid ring system by a

9Hs co (l)

(CO)5Cr

stable lsonx in the prcs.

cH3cN,70"

o ' CH3O

Diels-Alder reactionof the tungstencarbenecomplex I with Danishefsky'sdiene (1.5 equiv.) in acetonitrileunder CO to give the complex 2 in 62% yield.

) > CoHs

tion, but um. of a substitu

Tirngsten carbene complexes

OCHr

co)5w (co)5w

cH3O--

+

)

I

+

AcH, (cH3)3sio

cHccN.100" 62y"

2. @xo/endo= >- 25:1) CoHc / " -

RO 2

co)4w: + carbene complex (22o/o)

c H 3 O --

R3SiO 4 g3/" (exo/enle = 35:1)

i.:: tli)-l and shows even higher llr

ipri.il reactionof this type gener)( \.1(licnone(equationI). However .,1 rho steroid ring system bY a

lR=Hor(CHo)3Sil cycloheptadienones.3 The cyclopropylcarbene-tungsten complex 1 reacts with 2, which rearrangesto the more diphenylacetyleneat 100'to form a cycloheptadienone

l\---1 t/

.w(co)5 C 6 H 5 + C 6 H 5 \

dioxane.100"

ocH3

o rn'.-"urs

(

l l

Y"ur,

1

I

Y"coHs

ocH3

ocH3

2 (21o/o) 140"

|

I

* (

o r--\.-.c6+s

3 I I

stabfe isomer 3. Optimal yields of 3 (5570) are obtained in refluxing xylene (140') in the presence of triarylphosphines.Terminal alkynes do not undergo this reac-

.:

o

o

l3

o + CH3O

,,:"'X*(to)u -

bcH.

"u"u-"r. - (Y""" \,^-cH.

YcH.

majorproduct

minor product

ocH3

)lc\ I with Danishefsky'sdiene (L.5 :,. 2 in 62Vayield.

. (\"""' ocH3

tion, but unsymmetricalalkynes react with some selectivity (equationI). The complex of a substitutedcyclopropanereactswith high regioselectivity(equationII).

Thngstencarbenecomplexes

- i

C"Ho

(ll)

B-1 t,'

w(co), '\--lo \

CoHs coHs-----coHs -

ocH3

CoHs 'CoHs

Note that the cyclopropyl chromium carbene corresponding to I reacts with acetylenes to form cyclopentenones with loss of ethylene (f4,93). I B. A. Anderson,W. D. Wulff, T. S. Powers,S. Tribbitt, and A. L. Rheingold,Am. Soc., ll4, 10784 (1992). 2J. Bao, V. Dragisich,S. Wenglowsky, and W.D. Wulff, ibid., f f3,9873 (1991). 3 J . W . H e r n d o n ,G . C h a t t e r j e eP, . P . P a t e l ,J . J . M a t a s i ,S . U . T u m e r , J . J . H a r p s ,a n d M . D . R e i d ,

Urea-Hyd Pero4 merciallv a it can be p H2O2 coml

cl

ibid., tt3, 7808 (1991).

I R . B a l l i n r .l

'CoHs .

C6H5

ocH3 ' , \ : : i tJ c c t v l e n e s

Urea-Hydrogen peroxide complex, H2NCONH2' HzOz. Peroxytrifluoroacetic acid, CF3COOOH.\ This peracetic acid is no longer commercialfy availablesince9OVaH2O2is requiredfor the oxidationof CF3COOH.However, it can be preparedin the laboratory by oxidation of trifluoroaceticanhydride with the H2O2 complex with urea.

, , . : \ , I .D . R e i d ,

cH3(cHd4cH=NoH

6)

cF3coooH

r'roH 60%

CHg(CHz)qCHzNOz

c6HscH2N02

I R. Ballini, E. Marcantoni,and M. Petrini, TetrahedronLetters, 33, 4835 (1992).

9-Vinyl-9-borabicyclo[3.3.l]nonane (vinyl-9-BBN). This reagentis preparedby reactionof B-bromo-9-BBN with vinyltributyltin:

B,.-o

cH2^snBu,

cH2ct2

cHr?-B,.}'

Otheri4 trans- and cis< ately reactivcd Mnyldimerh.,been preparedI of thesevinvlh but shows lo*r and afford bcn regioselectiveo All the vinvlbo

74/"

1, b.p.28-30"/0.25 mm

CHr-

Diels-Alder reactions.t 9-vinyl-9-BBN is a more reactivedienophilethan methyl acrylate, and undergoesDiels-Alder reactionsat 25-55". Although the reaction with isoprenesshows the expected"para" selectivity, the reaction with lrans-piperylene shows an unusual"meta"-selectivity,possiblyas a result ofsteric factors.This reactionalso can show high endo-stereoselectivity (92:8).

,,"("" * , 7sv"

cHr^cH,

(""

cur"\J

+

1

25" 71"/"

CHs

rf^yto-

"t.)a)-tO

..--..--tO

l l l \ / z

Y

cHe

\-/

e3:7

+

92:8

(endo)

raY'o

lD.A. Singlerm 2 D. A. Singleroo

VinyldichloroD Diels-AI&t at 110"lo formi (equationl). Of

\.-

cHs (exo)

"t'Y" (r) cH.Act

a"^' + 1ss. _ ; ;f-..-ato

0

#

r---ato

**o#

CHr'-(Ct (il)

|

cH.Act

VinYldichloroborane 403 othervinylboranes.2onedisadvantageofvinyl-g.BBNistheconversion^t25"to trans-andcls-dimers.ThisreactioncanIimityieldsinDiels_Alderreactionswithmoder(2)' by use of 1-vinyl-3,6-dimethylborepane ately reactivedienes.This problem is solved (4) has best generatedin situ'Trivinylborane Vinyldimethylborane (3) is pyrophoric and is reactive most is the with BBr3. Trivinylborane beenpreparedby reactionoiulnyrtutyrtin ofthesevinylboranes.vinyldimethylborepane(2)isthemoststableofthevinylboranes' butshowslowerreactivitywithdienes;however'thereactionsaresignificantlycleaner of the absenceof dimerization' The most and afford better yields, probably because probably owing to steric hindrance' regioselectiveof theseboranes1-4 is vinyl-9-BBN, the highest selectivity shown by 2' All the vinylboranes are endo-selective'with

cH,-r/-lacH' |

s!:

("",

, i ' -

.i '

B(CH=CH2)3

CHz:C119,"".,, 3

\B/ lk:-.

4

2

! r . : -

I D.A. SingletonandJ.P. Martinez,Am' Soc''ll2' 7423(1990\' (1992). 2D'A. Singleton' J.V. watson'andG.M. Ndip,Terrahedron,48,5831 J.P.Martrrre.z,

t ,

Vinyldichloroborane. Diels-Alderreactions.|Mnyldichloroboranereactswithsimpledienesintoluene are isolatedas the boronic estersofpinacol at 110. to form adductsin good yield. These bond of the adduct can be replaced by (equationI). Of greater inlerest, the C-B

t1r"r. CH|'?,CH2 (l)

|

cH.

(-

BCt2 1 ) C 6 H 5 C H 3 , 1 1 0 '

+ CH"

cH,

CHs\r,-\.-B-d:

2) HOC(CH3)2c(cH3)20H

ca{v

?1<"" 'CH3

i l l

cH.ftNHcH2c6H5 cH s,,y',c*z,r.B C tz rl?.j,,i"",iil,tt" --;;"" cH."'\-'L-Bu c'r* Bu) "".A

Vinylsilanes

bond by reaction with benzyl azide at 25' to give the adduct of a secondary a c-N amine (equationII).

ao"

1N. Noiret,A. Youssofi, B. Carboni,andM' Vaultier,J'C'S' Chem'Comm',7lO5(1'992)' \

+

CHs Vinylsilanes. of RegioselectiveDiels-Atder reactions.l The intramolecular [4+2]cycloaddition an provides 1, alcohol diunsaturated with the a vinylsilane of 2, preparedby reaction 4 and 5 with adduct (3), which on oxidative desilylation provides the cyclohexenes 4. cls-1'3-diol for the marked preference

1b

80' 90%

ao' I * cnfsi(cH3)2cl

/ \

r-q

N(C2Hs)s '-'-;

:# ,,si(cHs)z

/ \ " '

CHs

CHe 1 ,-O

)(obitcH.r' ll l-H

Y

CHs

(o' BuaNF,H2O2 DMF 85v"

('(

OH i

Y

70:30

CHs 4

ao.oH i l l Y CHs 5

with (E)The advantageof a silicon tether is illustrated further by reaction of lb 8, (chlorodimethylsilyl)acrylate6 to provide 7. This cyclizes to a single, endo-adduct shown. l0 as and to 9 be converted which can

I G. Stork, T. Y. (

Vinylsilanes

b.'

*

f-o, / asi(cHs)z t l l

l

C2H5OOC,,y'\.

)i(cH3)2cl

)"6oc,r, CHs

7 D t i-

-O

l"-

80" 90y"

)(-bi1cH.v.

ll

l-H

t'coocrH,

BuaNF,H2O2 DMF

(o' A-ot

i\f"\cooc2Hs l l

CHe

I

,u*

|

I

","*,

cH20H

i-1^'coocrHs l l CHs 10 ' G. Stork, T. Y. Chan, and G.A. Breallt, Am. Soc., ll4,'7578 i1r992\.

l , i !\'X

CHs

c2Hso

Zinc. involves (1R,2R)-Diarylethllenediamines.| A novel route to these usefu| diamines N-deprotection by followed esterificationof an N-protectedvaline with 1,3-propanediol the diimine 2 by reaction to give the (R,R)-diaminesl. This product is converted to withccHscHo.Reductionof2withZnincH:oH/THFat0'resultsinintramolecular Hydrolysis of (R'R)-3 followed coupling to provide (R,R)-3 and (R,S)-3 in thc ratio 91:9' in 727o yield' R'R-4 by oxidation, Pb(OAc)+,and N-protection yields

?'.?-?

?'.? NHz

H,N \-{ 6He\

\

C6H5--rzNH

I

O,. b

\

,..-NH CoH" \

O" /

H.c-\

b

I

CHa (R,R)- 2

CHg ( R , R ) -1

I r. sho 2P. Erdr

Zine-C

cH./Y

cHr"\a\?

by vitarn when di

Cla of zinc rearTan allylic a the reac

CeHs'

?"?

cH.-'\y"-? Zn,O" CH3OH,THF

.utu,,,.(* \

.rtrA\t

P'

cr._\-\

1) NaOH 2) Pb(OAc)q 3) CbzCl, 727"

C6H5,,,.-NHCbz

I c.HuiNHcbz

^..( t L.A. s

(R,R)- 4

CHs e) ( R , R ) - 3 ( 9: 1 Notethatzincdustreductionofthephenyliminederivedfrom(S)-valinemethylester itselfprovidesamixtureof(R,R)-,(R,S)-,and(S,S)-diphenylethylenediaminesinthe ratio 63:30:7. Stereoselectiveadditionoft-BuBrtoa,B.enoates.2Reactionoft-BuBrwith results in syn-l and antidiethyl mesaconatewith reduction by zinc with ultrasound radical reactions promoted I in the ratio g5:15. Similar stereoselectivityobtains in

Zircooi Prep

q

cf

Zirconiun bisamides

""'i'+t1" c2HsoocrycooczHs : 87o/"

cooc2H5 (CHs)sC\.,^cFr^

+

-"r

|

CHs

anti-1

COOC2H5 85: 15 syn-1

involves .rnrines \ -deprotection . 2 by reaction s : : rntramolecular r l R.Rt-3followed NI:

obtains by vitamin B12or with t-BrHgCl, NaBH+ in CH2CI2.Even higher stereoselectivity when different amines are added. I T. Shono,N. Kise,H. Oike,M. Yoshimoto, (1992). Letters,33,5559 andE. Okazaki,Tetrahedron 2P. Erdmann, H.-G.Zeitz,andB. Giese,Helv.,75,638(1992). J. Schiifer,R. Springer,

{

o .^o h

\

II H

O

Zinc-Copper couple. Cleavage of 2,3-epoxy halides.t A zinc-copper couple, prepared by sonication of zinc powder and CuI in aqueousethanol, cleaves epoxy halides to a radical that rearrangesto an allylic alcohol. Since the epoxy halide is preparedby epoxidationof an allylic alcohol (n-chloroperbenzoicacid) followed by reactionwith P(C6Hs)rand CBra, the reaction effects 1,3-transpositionof the hydroxyl group.

m€lCeHaCosH ' ' 1l OH 2) P(C6H5)3, CBr4

b

f

C.Hu&

- z

Zn(Cul)

Br

"urr&

s7"/"

w\^

95o/"

^

92"/"

ti.

Brt"

_-NHCbz

,x.^NHcbz

-fi

I

c5t-tu/\r'CHz

cH;r

C H ql -

-l* r-F t t t

OH

))tr-

-

r-l}.-t* t t vf.--"

l

OH

r L. A. Sarandeses. A. Mourifro, and J.-L. Luche, J. C. S. Chem. Comm., 818 (1991)

R R )- 4

Zirconium bisamides, Cp2Z(NHR)2. Preparation: )-r .'lrncmethylester , 1 . : , J i a m i n e si n t h e

cp2zrcl2 + 2L|NHR

1 , , - r, ) t / - B u B r w i t h s - .rn-l and anti:. :.ti()ns Promoted

THF,25" - 2LiCl

CpzZr(NHR)z

c6H5cH3,140'

Cp2Zr(CHs)2+

H2NR

Cp2Zr(NHR)2

Zirtonium

408

bisamides

Hydroamination of allqnes.t Zirconium bisamides can react with internal alkynes which can dissociate to cp2Zr:NR and an at 85-120" to form azametallacyclobutenes, enamine (equationI).

(t)

I I

CpzZr(NHR)z

C6H5C=CC6H5

R N

--

cp2Zr:NR

H2NR

lco'z"tlcunu L

/NHR

CoHs

CoHs

cuHu

Of more practical value zirconium bisamidescan serve as catalystsfor reaction of primary amines with alkynes to form enamines.This reaction cannot be extended to alkenes,but allenesundergothis hydroaminationto form imines'

Cp2Zr(NHAr)2,80"

CHr=C=6gr +

N'At

H2NAr

cH.AcH, r P . J . W a l s h ,A . M . B a r a n g e ra, n d R . G . B e r g m a nA , m . S o c . '1 f 4 ' 1 7 0 8 ( 1 9 9 2 ) '

AUT]

Abdel-Mr Abe, R.. Abraharn Abraham. Adams. J Adam. \l Ader, U-. Adlingoo Afarinkie. Afarinkn Agami. C Agnel. G Ahmar. l Ahn, K. I Ahrens. l Aimi. \.. Aiza*'a. I Akai, S.. AkasalaAkg0n. E AkiyameAkutagab Alayrac. I Alexakir Allen. D Almstead Alonso. F Alper. H. Altmann. Amato, G ' Amberg. AnderschAnderson Andersoo Anderssa Ando. D.. Ando, \1.

AndrCs. C Andre*r Anjeh. T Ankianicc Anren. J.. Antes, 1.. Aoki, S.. Arai, K.. Arai, M.. Arai, S.. Arai, T..

\r

AUTHOR INDEX

N

lF.i

I r d{ ':

Abdel-Magid, A. F., 174 Abe, R., 198 Abraham, A. C., 361 Abraham, H., 278 Adams, J. P., 153 Adam, W., 252, 253 Ader, U., 134 Adlington, R. M., 27, 361 Afarinkia, K., 295, 350 Afarinkra, K., 53 Agami, C., 191 A g n e l ,G . , 1 1 1 Ahmar, M., 189 Ahn, K. H., 64 A h r e n s ,H . , 3 1 9 Aimi, N., 259 Aizawa, H., 340 Akai, S., 207 Akasaka, T., 252 Akgiin, E., 366 Akiyama, M., 118 Akutagawa, S., 38, 236 A l a y r a c ,C . , 2 1 8 Alexakis, 4., 134,218, 296 Allen, D. W., 394 A l m s t e a d ,N . G . , 1 3 Alonso, F., 9 Alper, H., 105 Altmann, 8., 3 Amato, G. S., ltt Amberg, W., 24O Andersch, P., 134 Anderson, B. A., 68, 400 Anderson, C. L., 2 Andersson,P. G., 259, 262 Ando, D., 40 Ando, W., 252 A n d r d s ,C . , 1 3 5 Andrews, J. F. P., 386 Anjeh, T. E. N., 53 Ankianiec, B. C., 34 Anren, J., 148 Antes, I., 86 Aoki, S., 31,, 361, 362 Arai, K., 113 Arai, M., 79 Arai, S., 161 Arai, T., 161

Arase, A., 173 Arienti, A., 139 Asao, N., 218 Ashimori,A., 38 Aub6, J., 81, 347 Aubert, C., 102 Auner, N., 79 Austin, R. E., 304 Ay, M., 331 B a b a ,A . , 3 3 5 , 3 5 1 , 3 6 1 , 3 6 3 Bach, T., 170 Biickvall, J.-8., 259 Baeckstrdm,P., 194 B a e v s k y ,M . F . , 2 5 9 Bagheri, V., 302 Bailey, M., 58 Bailey,P. D., 278 Bailey,W. F., 145 B a l a n d ,W . , 1 3 4 B a l d i n o ,C . M . , 2 5 2 B a l d w i n ,J . 8 . , 2 ' 7 , 3 6 1 Balicki, R., l4u Ballester, P., 377 Ballestri, M' 39'7 Ballini, R., 401 Bambridge, K., 164 Banno, H., 375 B a n t l e ,G . , 3 1 4 B a n w e f l ,M . G . , 1 2 7 Bao, J., 95, 400 Baranger,A. M., 40tl Baringhaus,K. H., 394 Barrett, A. G. M., 333 Barta, N. S., 375 Barth, L., 6tl B a r t o n ,D . H . R . , 1 3 2 , 2 8 4 , 2 8 7 , 2 9 3 , 3 6 1 , 3 6 7 , -t I) Barion, J. C., 70, 154 B a s h k i n ,J . K . , 1 6 Bauld,N. L., 391 Beak, P., 319 Beaudoin, S., 92 B e a u ,J . - M . , 8 6 Beck,A. K., 61,324 B e h r e n d t ,L . , 9 6 , 2 3 4 Beirich, C., 207 Belan, C., 279

410

frlr iii. ri

ffi ffi Tr

Author Index

Beller, M., 386 Belyk, K., 86 Benbow, J. W., 286 Bencheqroun,M., 162 Bender, D. M., 130 Bender, D. R., 367 Bennani, Y. L., 24O Bennett, S. M., 311 Bergdahl, M., 218 Bergman, R. G., 408 Bergu, M., 134 Berk, S. C., 366 Bernardinelli, G., 22 Bernocchi, E., 259 Bersani, M. T., 199 Bevan, C., 40 Bey, P., 361 Bezman, S. A., 8l Bezuidenhoudt,B. C. B., 218 Bideschi, A., 260 Bigi, F., 139 Bilodeau, M. T., 347, 348 B i s a h a ,J . J . , 3 1 8 Blart, 8., 262 Block, R., 189 Bloodworth, A. J., 146, 1'77 B o b b i t t ,K . L . , 1 0 1 , 3 8 6 Bocelli, G., 139 B o e c k m a n ,R . K . , J r . , 2 9 2 Boger, D. L. 252 Boisvert, G., 190 Boleslawski, M. P., 7 Bolm, C., 149 Bombrun, A., 94 B o n a t o ,M . , 2 1 8 Bonini, C., 175 Bonner, M. P., 249 B o u k o u v a l a sJ, . , 3 1 4 Bovicelli,P., 199 B r a i s h ,T . F . , 2 4 2 Brandenburg,J.,.268 Braun,M., 183 Braun,M. P., 153 Breault, G. A., 405 Breitmaier, 8., 9 Brenda, M, 262 Breton, G. W., 24 B r e y n a k ,J . D . , 2 Brieden, W., 394 Brook, A. G., 375 Brown, G. R., 278

B r o w n ,H . C . , 7 2 , 7 4 , 8 7 Brown, J. M., 40 Brown, K. V., 79 Brown, M. F., 195 Brown, S. M., 58 Brown, W. L., 302 Brunel, J. M., 283 Brunner, H., 43 Bruzik, K. S., 63 Bubnov, Y. N., 12 Buchwald, S. L., 71, 366 Buckman, B. O., 176 Budries, N., 223 Bulliard, M., 361 Buono, G., 283 Bureau, R., 187 Burgess, L. 8., 28O Burk, M. J., 46 Buschmann,H., 55 Buschmann,J., 85 Cabri, W., 260 Cacchi, S., 259 Cahiez, G., 226 C a i n e l l i ,G . , 2 1 8 Cameron, K. O., 386 C a m p b e l l ,M . G . , 3 3 1 Camps, F., 105 Canas, M., 348 C a n d i a n i ,I . , 2 6 0 Cantrell, W. R., Jr., 270 Capella, L., 217 Carboni, 8., 404 Cardi, N., 397 Carpenter,J. F., 340 Carreno, M. C., 49 C a r r y , J . - C . ,5 3 C a s n a t i ,G . , 1 3 9 Caspar, M. L., 176 Castaflo,A. M., 331 Castedo,L., 167 Cha, J. S., 173 Chandrasckhlar,S., 218 C h a n g ,M . , 1 3 9 Chan, T. H., 28, 152 Chan, T. Y., 405 C h a r e t t eA , . B., 116 Chatani, N., 365 Chatgilialoglu,C., 143, 397 Chatterjee,G., 400 Chavant, P.-Y., 226

Chen. B Chen, C Chen, C Cheng ) Chen. H Chen, K Chen, S Chen, Z Cherepa Cherry'. I ChesnuL Cho, B. Cho, D-Choi, S. Choi, W Chong. J Chou, C. Chun. Y. Churchill Ciatlini. CigancL Cimpri
Author

Chen, B.-C., 320 Chen, C.-S., 134 Chen, C.-T., 159 Cheng, X.-M., 179 Chen, H., 79 Chen, K., 254 Chen, S., 271 Chen, 2., 126 C h e r e p a n o vl,. 4 . , 2 2 Cherry, D., 3'1,8,34'7 Chesnut, R. W., 34 Cho, B. T., 249 Cho, D.-G., 218 Choi, S., 130 Choi, W.-B., 174 Chong, J. M., 125 Chou, C.-T., 100 Chun, Y. S., 249 Churchill, M. R., 81 C i a t t i n i ,P . G . , 2 5 9 Ciganek, E.,2O7 Cimprich, K. A., 179 Cirillo, P. F., 2 Clardy, J., 378, 34'7 Clark, A. B., 53 Clark, B. P., 164 Clark,J. D., 170 Clark, J. S., 249 Clark, T. J., 302 Coburn, C. A., 5l Coggins, P., 164 Cohen, T., 165, 395 Collin, J., 311 Collins, J. L., 170 Collum, D. 8., 172 Colobert, F., 49 C o l o m b o ,L . , 3 1 8 Colonna, S., 22 Comins, D. L., 259, 273, 282, 293 Conticello, V. P., 31 Cooke, R. J., 170 Cook, G. R., 375 Cooksey, C. J., 146 Cooper, J. P., 366 C o r e y ,E . J . , 7 , 2 6 , 4 3 , 1 2 5 , 1 3 O ,1 ' 7 9 , 2 4 7 , 3 2 7 Corley, E. G., 242 Cossio, F. P., 127 c6t6, B., 116 Couty, F., 191 Cox, B., 370 Cox, P. J., 118

Index

4ll

Cr6visy, C., 86 Crispino, G. A., 240 Crudden, C. M., 39 Csuk, R., 134 Curran,D. P., 144, 1.91,226, 311, 361',377, 397 Currie, J., 386 Cvetovich, R. J., 180 Cywin, C. L., 247 D a l l e m e r ,F . , 3 1 1 Damm, W., 397 D'Angelo, J., 278 Daniel, K. L., 304 Danishefsky,S. J., 286 D a n - o h ,N . , 1 5 0 Date, K' 323 Daus, K. A., 24 Davidson, J., 289 D a v i e s ,H . M . L . , 2 7 0 , 3 0 2 D a v i e s ,S . G . , 5 8 Davis, A. P., 371, 379 Davis, D. G., 176 Davis,F. A., 66, 285, 320 Davis, P., 242 D a w s o n ,B . T . , 2 l u Dean, D. C., 302 De Azevedo, M. B. M., 276 De Boer, J. L., 45 De Cian,A.,22 Decicco, C. P., 130 Declercq, J. P., 2'78 D e g l ' I n n o c e n t iA , ., 217 De Groot, A., 7 Dehghani, A., 293 Delanghe,P. H. M., 306 De Lombaert, S., 84 De Marco, A. M., 367 Demb6l6, Y. A., 279 De Meijere, A., 268 Deng, L., 99 Den Haan, K. H., 45 D e n m a r k ,S . C . , 1 5 9 Denmark, S. E., 13, 207, 276, 34O D e S h o n g ,P . , 1 3 9 , 2 2 6 Desma6le,D., 278 De Sousa,J. A. A., 58 Dess, D. B., 271 De Vries, K. M., 371 Dickhaut, J., 397 Dinsmore, C. J., 302 Diwu, Z'., 139

412

Author Index

Dokitchev, V. A., 100 Domrock, S. H., 217 Dorchak, J., 361 Dowd, P., 361 Doxsee, K. M., 69 D o y l e ,M . P . , 3 O 2 , 3 0 4 Dragisich, V., 400 Drysdale, N. 8., 172 Duan,J. J.-W., 153 Du Bay, W. J., 290 Dufour, C., 361 Dulcdre, J.-P., 15 Dumas, F., 278 Durst, T., 270 Dustman, J. A., 150 Duthaler, R. O., 323 Dzhemilev, U. M., 100 Eaton, B. E., 271 Ebina,Y., 14 Echavarren,A. M., 331 Ecker, J. R., 99 Eckert, H., 127 Edstrom, E. D., 120 Edwards, L. G., 33, 87 Edwards, M. L., 361 E g u c h i ,M . , 2 1 8 E i s c h ,J . 1 . , 1 2 5 , 1 7 9 Eisch, J. L., 7 Ejeri, S., 137 Ellsworth, E. L., 21'7 Ellwood, C. W., 281 El Marini, A., 218 E m o n d s ,M . V . M . , 2 1 8 Enders, D., 16 Ene, D., 304 Enholm,E. J., 311 Erdik, 8., 234 Erdmann, P., 407 Esser, P., 55 Euginome, U., ZOZ Evans, A., 157 Evans,D. A., 43, 68, 249, 318, 34'7,348, 3'71 Evans, W. J., 45 Evrard, D. A., 371 Ewald, M., 149 Fahrni, C., 23 F a l c k ,J . R . , 2 1 8 Fanwick, P. E., 34, 96 Farina, V., 394

Fau[, M. M., 318, 348 Faure, B., 283 Fegley, G. J., 123 Felder, M., 149 Felix, D., 96, 234 Feneau-Dupont,J., 278 Feringa, B. L., 30 Ferraboschi,P., 134 Ferreira, D., 218 Ferriera,J. T. B., 218 Fevig, T. L., 311 Fischer, J., 22 Fischer, R. W., 193 Fisher, G., 150 F i s h e r ,G . B . , 1 7 1 F i t z g e r a l d J, . J . , 1 7 2 Flessner,U. N., 193 Follet,M., 218 Forster, B., 127 Fortt, S. M., 105 Fox, D. E., 242 Fox, D. N. A., 170 F r a n z i n i ,L . , 1 1 8 Frescsel,C., 134 Friessen,R. W., 72 Fringuelli, F., 200 Friih, T., 371 Fu, G. C., 6tt, 197 F u j i e d a ,H . , 1 1 8 Fujii, H., 7, 204 Fuji, K., 47 Fujisawa, T., 323 Fujishita, Y., 344 Fujitsuka, H., 388 Fukase, K., 157 Fukumoto, K., 56 Fukuzumi, S., 190, 340 Fuller,D. J., 172 F u l l e r ,J . C . , 1 7 1 Funakoshi, K., 38 Fung, A. P., 146 Furata, T., 223 F u r l o n g ,M . T . , 2 2 2 Furuune, M., 88 Furuya, M., 344

Ganem, 8., 34 Ganguly, A. K., 370 Ganz, K.-T., 43 Garcia, E., 218

Garcia-Grea Garcia-Raso Garofalo. A Gasparski. (

Gavaskar. I Geib, S. \',. Genet, J. PGeorg, G. l. Germanas" J Germani. RGhiatou. \-. Ghiro, E.. -1 Giacominr. I G i a s s o n .R . Giese, B.. -1 Giguere. P Gilchrist. J. Gin, D. L.. Gin, D. 't'..

Glanzer. B. Gleiter. R.. . Godfrer'. A, Goesgens. U Goldman. A G6mez.B. G6mez-Bcla Gonzdlez. .A Gopalan. A. Goralski. C. Grabowskr.I Granberg. K Greene.A. I Green, J. \'.. GreenwoodGreeves. li . Greiner. A,. Grieco, P. A Griedel, B t Grigg, R.. 16 Grisenti. P.. Grisso, B. A Grivet, C.. l Grobe, J.. 19 Grubbs, R. H Guerrini. A-. G u e u g n o r .S . G u i n d o n .\ ' . Guingant. A-. Guitirin, E-. t Gurski, A.. " Gysel,U.. 6l

Author Index Garcia-Granda,S., 135 Garcia-Raso,A., 291 G a r o f a l o ,A . W . , 2 5 4 Gasparski,C. M., 67 Gavaskar,K., 145 Geib, S. V., 377 Genet, J. P., 262 Georg, G. 1., 276, 366 Germanas,J., 102 Germani, R., 200 Ghiatou, N., 125 Ghiro, 8., 314 G i a c o m i n i ,D . , 2 1 8 Giasson, R., 190 Giese, B., 361, 397, 407 Giguere, P. A., 148 Gilchrist, J. H' 172 Gin, D. L., 31 Gin, D. Y., 114 Glanzer, B. I., 134 G l e i t e r ,R . , 3 1 3 Godfrey, A. G., 34 Goesgens,U., 134 Goldman, A. S., 95 G6mez, 8., 167 G6mez-Beltri4n,F., 135 Gonz6lez,A., 135 G o p a l a n ,A . S . , 1 7 8 G o r a l s k i ,C . T . , l 7 l Grabowski, E. J. J., 242 Granberg,K. L., 91 Creene,A. E., 276 G r e e n ,J . V . , 5 3 Creenwood, R. J., 127 Greeves,N., 207 Greiner, A., 262 Grieco, P. A., 170 G r i e d e l ,B . D . , 2 l t l Grigg, R., 268, 269 G r i s e n t i ,P . , 1 3 4 Grisso, B. A., 32 Grivet, C., 22 Grobe, J., 79 Grubbs, R. H., 31, 1.9'7 Guerrini, A., 143 Gueugnot, S., 88 G u i n d o n ,Y . , 3 1 4 , 3 6 1 Guingant, A., 278 Guiti6n, E., 167 Gurski, A., 75 Gysel, U., 6l

Haaf, K., 288 Haaksma,A. 4., 7 Haar, J. P., Jr., 386 Habaue,S., 10, 26, 205 Habus, I., 276 Hafner, A., 323 Haiying, C., 148 Hakimelahi, G. H., 100 Hale, M. R., 326 Hall, P. L., 772 Halterman, R. L., 126 Hamamoto, M., 251 Hamann, L. G., 316 Hamashima,H., 40 Hamdouchi, C., 49 Hamon,L., 191 Hanaizi, J., 234 Hanaki, N., 204 Hanaoka, M., 22, 705 H a n d a ,Y . , 3 1 1 H a n e s s i a nS,. , 9 2 , 2 1 8 , 3 6 1 ,3 8 9 Haning, H., 226 Hanin, L, 332 Hansen,A., 207 Hansen, D., 43 Hanson, P., 99 H a n z a w a ,Y . l 1 l Harada, H., 188 H a r a d a ,T . , 1 7 , l 4 l Harmat, N., 142 Harms, A. 8., 7 Harms, K., 149 Harring, L. S., 331 Harrison, A. T., 172 H a r r i s o n ,J . , 1 7 1 Harrison, K. N., 45 Hartung, J., 240 H a r u n a ,S . , 2 5 1 H a r v e y ,D . F . , 8 4 , 1 9 5 Hasegawa,E., 361 Hasegawa,M., 96, 140 H a s h i m o t o ,Y . , 1 4 0 Hashiyama,T., 240 Hasuoka,A., 157 Hata, E., 41 H a t a j i m a ,T . , 3 1 1 Hatanaka,Y., 14 H a t t o r i ,K . , 1 1 9 Hayashi, A., 341 Hayashi, M' 125 H a y a s h i ,T . , 3 8 , 5 0 , 1 8 1

413

414

Author Index

Hayashi, Y., 22 Hayes, J. J., 400 Hazen, G. G., 180 Heathcock,C. H., 48, 340 Heckendorn,D. K., 292 Heckmann, B., 218 Heffner, R. J., 317 Hegarty, S. C., 371 Hegedus,L. S., 84 Heimgartner,H., 274 Heitz, W., 262 Helmchen, G., 43 H e n d r i x ,J . , 5 5 Hennigs, H., 268 Henry, K. J., 170 Henry, K. J., Jr., 170 Herdtweck, E., 193 Hermann, W. A., 193 H e r n a n d e zA, . 8 . , 2 1 8 Herndon, J. W., 400 Herrmann, W. A., 193 H e u m a n n ,A . , 1 9 4 Hibino, H., 26 H i g u c h i ,T . , 1 2 1 H i l e m a n ,F . D . , 1 6 Hill, D. K., 139 Hilvert, D., 134 Hinkley,W., 2lu Hirama, M., 122, 24O Hirao, T., 302 Hirata, K., 140 Hirobe,M., l2l Iiirose, Y., l3l Hisada, Y., 26 Hitchcock, P., 279 Hitchcock, S. A., 361 Hite, G. A., 2tJ4 H i y a m a ,T . , 1 4 Hoang, H., 69 Hoberg, J. O., 45 Hoffmann, H. M. R., 97 Honert, D., 2tl7 Hong, H., 259,273,282 Hoogsteen,K., 84 Hopkins, M. H., 340 H o p p e ,D . , 3 1 9 Ho, R., 90 Horaguchi, T., 361 Hori, Y., 38 Horner, G., 361 Hoshi, M., 173

Hoshino, M., 375 Hosokawa, T., 31 Hosoya, T., 106 Houpis, l. N., 268 Houri, A. F., 108 Hoveyda, A., 68 Hoveyda, A. H., 108, 326 Hoye, T. R., 302 Htang, Y.-2., 204 Huber, E. W., 361 Huffman,M. 4.,32 H0gel, H. M., l7O Hughes, E. W., l4tt Hunzlker, D., 324 Hwang, T. S., 26 Hwu, J. R., 100 I b a t aT , .,118 Ignatenko,A. V., 12 Ihara, M., 56 Ikebe,M., 167 Ikeda, S., 365 l k e m o t o ,N . , 1 3 9 Ikura, K., 115 l m a m o t o ,T . , 3 1 1 Imanaka, T., 251 I n a n a g a J, . , 3 1 1 Inoki, S., 41 Inokuchi, T., 393 Inubushi, T., 362 I s h i c h i ,Y . , 2 Ishihara, K., 43, 204 Ishii, Y., 147, 251 I s h i k a w a ,M . , 1 4 3 , 1 9 0 I s h i y a m a ,K . , 3 6 1 I s h i z a k i ,T . , 3 8 Ishizuka, T., 3ti7 lsoe, S., 2 Ito, H., I l1 Ito, K., 182 Ito, T., 62 Ito, Y., 9, 40, 188, 202,262 Iwasaki, T., 305 Iwasa, S., 281 Iwasawa, H., 156 Jacob, G. G., 34 Jacobsen,E. N., 99 Jagoe, C. T., 170 Jang, D. O., 732, 284, 36'7 J a n s e n ,B . J . M . 7

Janssen,A. I Jarvi, E. T,, Jaspars, M-. . Jasperse,C. I Jaszberenyi.t Jayasinghc. L Jefferies, 1.. I Jeffery, T.. & Jefford, C. W Jensen,M.. 7 Jeong, K_-S.. J i a n g ,J . , 3 r 7 Jiang, S., 3l r Jingfa, D.. l{ Job, K., 6l Johnson, C_ R Johnson, J. R* Johnson, N.. j Jona, H., 6l Jones, G. 8.. Joshi, K., 95 Joulli6, M. MJuaristi, 8.. { Jubert, C., tto Julia, M., l7l Julius, M.. {.1 Jung,G., 3t{

Kabbara,J.. ]l Kaczmarek. L, Kaduk, J. A.. l Kafta, C. M.. i Kagan, H. 8.. I Kagechika, K. Kahne, D., l5t Kakehi, T., l.ta Kako, M., lsl Kalinin, V. N.. Kamabe, N.. -13 Kamada, M.. l{ K a m b e ,N . . l t 5 , Kamijo, T., tr$ Kamiya,Y., ,lll Kamochi, Y.. 3l Kanai, M., 2ltt Kaneda, K., a
Author

Janssen,A. I. M., 134 Jarvi, E. T., 361 Jaspars, M., 379 Jasperse,C. P., 311 Jaszberenyi,J. C., 132, 284, 287, 293, 361, 367 Jayasinghe,L. R., 276 Jefferies,I., 172 Jeffery, T., 88, 259,268 Jefford, C. W., 314, 386 Jensen,M., 74 Jeong, K.-S., 240 Jiang, J., 317 J i a n g ,S . , 3 1 1 Jingfa, D., 148 Job, K., 61 Johnson,C. R., 153 Johnson,J. R., 32 Johnson,N., 350 Jona, H., 61 J o n e s ,G . B . , 1 2 5 Joshi, K., 95 Joulli6, M. M. 317 Juaristi, 8., 4 Jubert, C., 86 Julia, M., 172 Julius, M., 44 Jung,G., 314 Kabbara, J., 347 Kaczmarek, L., 148 Kaduk, J. A., 271 Kafka, C. M., 366 K a g a n ,H . 8 . , 1 3 6 , 1 6 0 , 3 1 1 Kagechika, K., 38 Kahne,D., 151 Kakehi, T., 144 Kako, M,252 Kalinin, V. N., 22 Kamabe, N., 331 Kamada, M., 143 K a m b e ,N . , 1 1 5 , 1 6 7 , 3 O l Kamijo, T., ltttt Kamiya, Y., 311 K a m o c h i ,Y . , 3 1 1 , 3 1 2 Kanai, M., 218 Kaneda, K., 251 Kaneta, N., 365 Kang, S. H., 26 Kang, S.-K., 218 K a n t a m ,M . L . , 2 2 8 Kanth,J. V. B., 316

Kassir, J. M, 3O2 Kataoka, O., 105 Kataoka, Y., 321 Kato, K., 41, 97, 21,8 Kato, T., 361 Kato, Y., 347 Katsuki, M., 6l Katsuki, T., 182 Katsurada,M., 340 Kattner, L., 85 '1.,2O7,227 Kauffmann, Kawachi, A., 9 Kawada, M, 269 Kawafuchi, H., 393 Kawaguchi, M., 361 Kawakami, T., 361 Kawakita, T., 49 Keil, R., 70, 218 Keinan, 8., 240 K e n d e ,A . S . , 3 l l Kennedy, R. M., 297 Kephart, S. E., 79 Kerrick,S. T., 319 Kesler, B. S., 340 Keumi, T., 146 Khanna, V. V., 87 Khanolkar, A. D., 145 Khasnis, D., 2 Khunder, A. J. H., 134 Kihara, N., 140 Kim, G., 7u Kim, J.-H., 207 Kim, J. M., 173 Kim, K. C., 313 Kimmer, G. F., 302 Kim, O. K., 139 K i m , S . - G . ,2 l u Kim, S.-H., l5l Kimura, Y., 1ti2 Kim, W. J., 26 Kim, Y., 2tt0 K i n o s h i t a ,1 . , 1 5 7 Kinoshita, M., 49, 3ti7 Kinter, C. M., 350 Kiprof, P., 193 Kise, N., 407 Kishi, N., 60 Kitagaki, S., 207 Kitamura, M., 38 Kita', Y., 2Oj Klaas, M. Riischgen,147

Index

415

416

Author Index

Knebelkamp,A., 262 Knight, K. S., 108 K n o c h e l ,P . , 8 6 , 1 5 5 , 2 2 2 , 2 2 3 , 2 3 4 , 2 3 5 ' 2 8 9 Knoess, H. P., 222 Kobayashi, K., 202 Kobayashi5 , .,2,26, 49, 89,93,'t41' 344 Kobayashi, Y., 188 Kocieriski, P., 234 Koga, K., 131,218 Koh, K., 270 Kohn, J., 95 Koike, T., 259 Kolb, H. C., 378 Komber, H., 193 Kondo, K., 305 Kondo, T., 93 Kondo, Y., 294 Konradi, A. W., 393 Kopping, B., 397 K o r e e d a ,M . , 3 1 6 Korkodilos, D., 146 Kornemann, D., {16 Kotsuki, H., 368 Kozikowski, A. P., 332 Kratz, D., 313 Krief, A., 316 Krishnan, 8., 394 Kropp, P. J., 24 Krotz, A., 43 Krysan, D. K., 75 Kubo, A., 3tt K u c h l e r ,J . G . , 1 9 3 Kudo, T., 311,312 Kulawiec, R. J., 73 Kulkarni,S. V., 87 Kumar, A., 66 Kumobayashi,H., 3tl, 236 Kiindig, E. P., 22 Kunieda, N., 49 K u n i y a s u ,H . , 3 3 1 Kuroki, Y., 3l K u s a n o ,K . , 1 3 , 3 u Kustitsyn, A. 8., 100 K u s u m o t o ,S . , 1 5 7 Kuzembo, M. A., 395 Kwak, K. H., 24 Kwong, H.-L., 240 Kwon, O. O., 173 LabaudiniEre,L., 234 Laboue, B., 226

Lacour, J., 157, 372, 378 Laine, R. M' 223 Lamatsch, B., 4 Lambert, J. N., 127 Lamb, G. W., 2 Landais, Y., 304 Larock, R. C., 259, 268 L a r o u c h e ,D . , 3 1 1 Larsen, R. D., 242 Laughton, P., 302 Lautens, M., 33, 39, u7' 306 Lauterbach,E. H., 57 L a v r i n o v i c h ,L . 1 . , 1 2 L e a n n a ,M . R . , 3 3 2 Lebrun, A., 160 lrcoq, J. C., 146 Lee, D. A., 130 Lee, D.-H., 130 lre, H. S., 173 Lce, J. C., 173 Lre, J. G., 24, 313 Lee, N. H., 99, 259, 26u Lee, S., 64 lre, S. 8., 173 Lee, S.-Y., lttl Leger,R., 361, 389 Lehmann, C., il5 Leite, M., 201 l e l a n d a i s ,P . , 3 1 4 Lensen, N., 296 Leuenbergcr,H. G., 134 I-eung, S.-W., 379 Leutenegger,U., 23 I - c v a l l 6 e ,J . - F . ,3 6 1 Li, c. J., 152 '75' 91' 94 Liebeskind, L. S., 32, Li, K., 316 Lim, A., 64 L i m b a c h ,H . - H . , 2 8 7 Lim, J. K., 26 L i n d e r m a n ,R . J . , 2 1 t t , 2 5 4 Link, I. O.,24'7 Link, R., 2U7 Lin, S., 370 Linstrumelle, G., 8fJ Lin, X.-F., 390 Liotta, D. C., 174, 218 Lippert, B. J., 361 L i p s h u t z ,B . H . , 7 0 , ' 1 5 4 ' 2 1 7 ' 2 1 ' 8 Liras, S., 304 Liu, H., 144, 361

Liu, Z.-R.. Livinghous, Llinas-Bru Loewe. M. Lohrav. B. I-oh, T.-P. l,o, L.-C.. Loo, R. l*'

Lorenz. Il. ' Lowinger. l-own. J. T Lubell. l'l'

Lucarini. V L u c h e .J . - L Lue, C.. l{ Luger. P.. t Lund. K. P Luo, F.-T.. L u p a t t e l l i .I Lu, X.. 59 Lyford. L.

McCanhy.. McCombr. McGranc. P Machajer:l M a c h i i .D . Mackar. V. McKennon. Mackenzic. McKie. J I McNamarr Macor. J. E McPhail. ,A Maeda. S.. M a e d a .T . . r Maeka*a. 1 Magerlein. I Maggi. R.Magnus. P.. Mahrwald. I Majid, T \ Makita, K-. M a n d a i .T . . M a n d v i l l e .(

Manfredi. A Mangenel. I Miinnle. F.. Manzocchr. , Marcantoni. Marchon. J.-

Author Index Liu, Z.-R., 7, 125, 179 Livinghouse, T., 74 Llinas-Brunet, M., 361 I-oewe, M. F., 180 Lohray, B. 8., 90, 24O Loh, T.-P., 247 h, L.-c., 139 Loo, R. W., 72 Lorenz, M., 734 l-owinger, T. 8., 361 Lown, J. W., 139 Lubell, W. D., 38 Lucarini, M., 143 Luche, J.-L., 407 Lue, C., 148 Luger, P., 85 Lund, K. P., 84, 195 Luo, F.-T., 268 L u p a t t e l l i ,P . , 1 9 9 Lu, X., 259 Lyford, L., 2O7 M c C a r t h y ,J . R . , 3 6 1 McCombie, S. W., 370 McGrane, P. L., 74 Machajewski, T., 340 Machii, D., 362 Mackay,M. F., 127 M c K e n n o n ,M . J . , 3 3 1 M a c k e n z i e ,P . 8 . , 3 2 M c K i e ,J . A . , 3 l l McNamara, K., 395 Macor, J. E., 390 M c P h a i l ,A . T . , 3 0 2 , 3 7 O Maeda, S., 143 Maeda, T., 60 Maekawa, T., 2 M a g e r l e i n ,B . , 3 5 1 Maggi, R., 139 M a g n u s ,P . , 6 8 , 1 0 5 , 1 5 7 , 3 7 2 37tl Mahrwald, R., 142 Majid, T. N., 234 Makita, K., 56 Mandai, T., 269 M a n d v i l l e ,G . , 1 8 9 Manfredi, A., 22 Mangeney, P., 296 Mfinnle, F., 287 Manzocchi, A., 134 Marcantoni, E., 401 Marchon, J.-C., 251

M a r c o u x ,J . - F . , 1 1 6 Marek, I., 218 Marino,J. P., 218 Mark6,f. E., 58, 172,228, 386 Marks, T. J., 45 Marshall, J. A., 13, 254, 29O Marth, C. F., 170 Marti, C., 291 Martinez, J. P., 387, 403 Martin, J. C., 271 Martin, R., l-5 Martin, S. F., 304 Marti, R., 323 Maruoka, K., 187, 188, 37-5 Maryanoff, C. A., 174, 218 Marz, D. W., 193 Ma, S., 2-59 Ma, X., 179 M a s a k i ,Y . , 6 2 Mascarenas,J. L., 192 M a s h i m a ,K . , 3 t l M a s u d a ,Y . , 1 7 3 M a t a s i ,J . J . , 4 0 0 M a t s u b a r aK , ., 341 M a t s u d a ,H . , 3 3 5 , 3 5 1 , 3 6 1 , 3 6 3 Matsuda, S., 207 Matsuda, S. P. T., 247 M a t s u i ,J . , 2 l t l M a t s u m o b , T . , 6 1 , 1 0 6 ,2 6 9 Matsumoto, Y., -50 Matsumura,Y., 3il Matsunaga,S., 2 Matsuo, G., 3tl7 M a t t a y ,J . , 2 0 1 M a t t h e w s ,D . P . , 3 6 1 Mcier, M., 2titl Mekhalfia, A., 3tl6 Melcher, L. M., 333 Melillo, D. G., 367 M e n d o z a ,J . S . , 3 l I Merlic, C. A., ll4 Metais, E., 226 Metternich, R., 249 Meyer, F. E., 2613 M e y e r s ,A . I . , 1 6 3 , 2 8 0 , 3 3 1 M e y e r - S t o r k ,M . , 5 5 Miao, G., 21lt Michoud,C., 36t Mihelich, E. D., 284 Mihna, A.,22 Mikami, K., 30, 60, 324,34'7

417

418

Author Index

Milhouse, W. K., 369 Miller, C. P., 390 Miller, D. B., 84 Miller, J. R., 84 Miller, M., 84 Miller, M. J., 67 Milligan, G. L., 347 M i n a m i ,T . , 2 2 , 3 4 7 Mincione, E., 199 Min, S. J., 173 Mioskowski, C., 218 Mirafzal, G. A., 391 Miranda, E. I., 2 Mitsudo, T., 93 Miura, M., 88 Miyai, J., 321 Miyakawa, M., 22 Miyake, R., 22 Miyake, T., 38 Miyamoto, H., 47 Miyano, S., 118 Miyashita, M., 375 M i y a z a k i ,S . - I . , 3 3 1 Moberg, C., 194 Modi, S., 2 M o h a m u d ,M . M . , 3 3 1 M o i s e e v ,S . K ' 2 2 M o l a n d e rG , . A . , 4 4 , 4 5 , 1 0 1 ,3 1 1 , 3 8 6 M
Mudryk, B., 165 Mueller, B., 178 Muka| C.,22, 1'05 Mukaiyama, T., 17, 26, 41,,89, 141, 247, 340, 341, 344 Mtiler, B., 288 Mtller, F., 201 Miiller, K., 274 Miiller, P., 3O2, 304 Mulzer, J., 85 Murahashi, S., 236 MurahashiS , . - I . ,3 1 , 1 5 7 , 1 5 8 Murai, S., 167,365 Murakarni, M., 262 Murata, N., 294 Murray, C. K., 101 Murta, M. M.,2'76 Mutter, M., 3 Mutti, S., 134 Myers, A. G.,'79, 114 N a k a d a ,M . , 2 Nakahashi,K., 198 N a k a h i r a ,H . , 1 6 7 Nakahira, T., 3l Nakai, T., 30, 60, 290,347 Nakamura, 8., 79, 137, 361, 362 Nakamura, S., 2 N a k a m u r a ,T . , l l l N a k a n i s h i ,K . , 1 3 9 N a k a t a n i ,K . , 1 1 3 N a k o t a ,M . , 3 U 7 Nam, W., 90 Namy, J.-L., 160,311 Nantka-Namirski,P., 148 Nantz,M. H., 130 Naota, T., 15'7,236 Narisawa, S., 30 N a s t a ,T . , 1 5 8 Ndejs, G. M., 403 Nebel, K., 3 Nefedov, O. M., 100 N e g i s h i ,E . , 9 6 , 1 0 8 , 1 1 1 , l 1 2 , 2 3 4 , 3 3 1 Neitcler, C., 227 Nelson, T. D., 295, 350 Nemoto, T., 79 Nestler, 8., 252 N e u m a n n ,W . P . , 3 6 1 Newbold, R. C., 130 N e w m a n ,M . S . , 3 5 1 Ng, H. P., 249

Ngu! Nilss Nishr Nishr Nish Nino Noin Nokr Nom Norn Nom Nor'r Norri Nolo Noze Nugc Num Nwc.

Oaln Obcn Obni Obrcr Ochu O'Co OdaOdm Ogar Ogitr Ogun Oh6l Ohaz

oh. (

Ohc. Ohlu Ohmi Ohnk Ohm. Ohm. Ohshi Ohr.t OhraOhtsrr Oikc. Oishi Ojiru Okam Okam Okaw Okuro Olalr.

Author Index Nguyen, M. T., 34 Nilsson, M., 218 Nishimura, H., 22 N i s h i m u r a ,T . , 1 4 1 Nishiyama, Y., 251 Nitto, Y., 108 Noiret, N., 404 Nokami, J., 49 Nomura, M., 88 Normant, J.-F., 134, 218, 234 Noro, T., 323 Novack, V. J., 249 Nowatny, S., 86 Noyori, R., 38 Nozaki, H., 68, 150, 340 Nugent, W. A., 371 Nunokawa, Y., 173 Nwe, K. T., 28 O a l m a n n ,C . J . , 3 0 4 Obermann, U., 43 O b o r a ,Y . , 1 0 1 Obrecht, D., 274 Ochiai,M., 62 O'Connell, J. F., 349 Oda, Y., 157, 158 Odriozola, J. M., 127 O g a w a ,A . , 1 3 , 3 0 7 , 3 3 1 Ogiku, T., 305 Oguni, N., 125 O h a s h i ,Y . , 7 9 Ohazaki, E., 407 oh, c. H., 53, 369 Ohe, K., 365 Ohkuma, T., 38 Ohmizu, H., 305 O h n i s h i ,M . , 5 6 Ohno, M., 2, 49, 93 Ohno, T., 141 Ohshiro, Y., 302 O h t a k e ,H . , 1 2 1 Ohta, T., 38 Ohtsubo, A., 344 Oike, H., 407 Oishi, T., 240 Ojima, I., 198, 276 O k a m u r a ,A . , 1 1 8 Okamura, H., 182 Okawara, M., 348 Okuro, K., 88 Olah, G. A., 146

Olah, J. A., 146 O l i v e i r a ,A . R . M . , 2 1 8 Ollis, W. D., 58 Olofson, R. A., 172 O l s s o n ,T . , 2 1 8 Ontoria, J. M., 127 Ooi, T. 187 Oppofzer,W., 65, 66, 234 Ortaggi, G., 199 Ortar, G., 259 Osborn, J. A., 81 Oshima, K., 7, 2O4 Osterhout,M. H., 332 Osterhout,M. Y., 18 Otera, J., 68, 150, 340 Otte, A. R., 97 Ovaska, T. V., 145 Overman, L. 8., 38, 340 Owczarczyk,2., 111, 331 Owczarczyk, Z. R., 234 Ozawa, F., 3tJ P a d w a ,A . , 3 O 2 , 3 2 6 P a e t o w ,M . , 3 1 9 Pakusch,J., 288 P a l o m o ,C . , 1 2 7 Palucki, M., 99 P a n e k ,J . S . , 2 , - 5 1 ,5 3 , 3 8 6 P a n u n z i o ,M . , 2 1 8 Pardigon, O., 2[33 Paredes,M. C., 331 P a r k e r ,K . A . , 5 l Park, J., 393 Parsons,P. J., 26u Patel, P. P., 400 Patil, V. D., U7 P a t t e n d e nG , ., 281, 361 Patterson,R. G., 2lti Pautex, N., 302 P e d a i n ,J . , 3 6 1 Pedersen,S. F., 393 Pedrosa,R., 135 Penco, S., 260 Pendalwar,S. L., 366 P e n g ,X . , 8 l P6rez-Encabo,A., 135 PErez,M., 331 Pericas,M. A., 348 P e r i s a m y ,M . , 3 1 6 Peters,D., 178 Petrini, M., 401

419

Author Index Petter, W., 324 Pfaltz, A., 23 Philipp, C., 207 Piers, E., 162 Pieters,R. J., 304 Pilcher, A. S., 139 Pimm, A.,234 Pine,S. H., 69 Pirrung, M. C., 302 Pitterna,T., 105 Pizzo, F., 200 Plattner, D. A., 324 Poch, M., 348 PosnerG , . H., 53, 184,295,35O,369 Powers, T. S., 400 P r a s a d ,A . S . 8 . , 3 1 6 Price, D. W., 40 Prieto, R., 178 P r i n c e ,8 . , 1 9 1 Propansiri,V., 295 Protopopova,M. N., 304 P u c h o t ,C . , 1 9 1 P u l l e y ,S . R . , 8 4 Qtazzotti, 5., 22 Q u e s n e l l eC , ., 201 Q u i n t a n a ,D . , 4 R a a b e ,G . , 1 6 Racherla,U. S., 87 R a d i n o v ,R . N . , 2 3 4 R a f f a e l l i ,A . , 1 1 8 R a g u s e ,B . , 1 7 0 Ramachandran,P. V., 72, 74 Rama Rao, A. V., 268 R a m a s s e u lR , ., 251 R a m c h a r i t a rS, . H . , 2 7 Ramig, K., 395 Rancourt,J., 361 Rangaishenvi,M. V., 74 Rao, C. J.,222 Rao, S. A., 222, 223 Rapoport, H., 349 Raslan, D. S., 201 R a w a l ,V . H . , 2 8 1 , 3 6 1 Rawson, D., 163 Razafindramboa,D., 218 Razuvaev,G. 4., 22 Reamer, R. 4' 242 R e b e k ,J . , J r . , 3 7 7 Rebidre,F., 136, l'72

Reddy, E. R., 332 Reddy, R. E., 285 Reddy, R. T., 285 R e e t z ,M . T . , 5 7 , 7 4 2 , 1 . 7 0 , 2 2 6 Regan, A. C., 386 Rege, S., 302 Reginato, G., 217 Reider, P. J., 242 Reid, M. D., 400 Reuter, D. C., 217 Rheingold, A. L., 400 Ricant, S., 105 Ricard, L., 136 Ricci, A., 217 Richardson,G. D., 386 Richter, M., 253 Richter, W. J., 283 Riecke, R. D., 42 Rieger, D. L., 249 Rieke,R. D., 218 Riera, A., 348 Righi, G., 175 Rihs, G., 323 Rischer, M., 386 R i s e m a n ,S . M . , 3 6 7 Rishton, G. M., 340 Rivera, 1., 2 Rizzo, C. J., 76 Robbe, S., 227 Roberge,J. Y., 162 Roberts, L. R., 234 Robichaud,A. J., 331 Robin, J.-P., 304 Robinson, L. A., 18 R o l l m a n ,8 . , 2 7 1 R o m a i n ,1 . , 1 8 9 Roohi,A. H., 130 Roper, T. D., 247 Rossier,J.-C., 386 Rossi, K., 145 R o s s i n i ,C . , 1 1 8 R o s s i t e r ,B . 8 . , 2 1 8 Rothe-Streit,P., 323 R o t h w e l l ,l . P . , 3 4 Rotter, H., 287 Roumestant,M. L., 218 Roush, W. R., 390 Rousset,C. J., 96, 108 R o z e m a ,M . J . , 8 6 , 2 2 2 , 2 3 4 Ruano, J.-L. Garcia,49 Riichardt, C., 288

Ruiz Rybcc Rychn Ryu. I

Sa:i. J Saburi Saigo. Saito. Saito. Sakai. Sakai. Sakam Sakan Sakate Salvad Salvad Salvad Samrrl Santan Santcl Santirr Sarand Sarsh:l Sanorl Sasai. I Satalc, Satoh. Sato. J Sato. 0 Sato. S Sato. T Satyanr Savelli Savignr Sawa. I Sawam Savo. I Schifcr. Schifer, Scharf. Schehln Schercr Schel'& Schinza Schling Schmi4 Schneil Schnutc Sch
Author Index Ruiz, P., 49 R y b c e z y n s k iP , . J.,226 Rychnovsky, S. D., 371 R y u .I . . 1 3 . l 1 5 . 1 6 7 . 3 0 7 . 3 3 1 Sa6, J. M., 291 Saburi, M., 96, 108 Saigo, K., 140 S a i t o ,S . , 1 8 8 Sairo, T., 236 Sakai, K., 38, 91 Sakai, S., 259 Sakamoto,T., 294 Sakata, S., 131 Sakata,Y., 147 Salvado, M. A., 135 S a l v a d o r i ,P . , 1 1 8 Salvador,I. M., 282 S a m u e l ,O . , 1 3 6 Santaniello,8., 134 S a n t e l l i ,M . , 1 5 Santinelli, F., 200 Sarandeses,L. A., 407 Sarshar,S., 179 Sartori, G., 139 Sasai, H., 161, 364 Satake,N., 93 S a t o h ,S . , 3 6 1 S a t o ,J . , 1 8 7 Sato,O., 122 Sato, S., 364 Sato, T., 68, 340 Satyanarayana, V., 139 S a v e l l i ,G . , 2 0 0 Savignac, M., 262 Sawa, E., 30 Sawamura,M., 40 Sayo,N., 38 Schifer, J., 407 Schiifer, W., 313 Scharf, H.-D., 55 S c h e h l m a n nV, . , 3 1 3 S c h e r e r ,H . J . , 1 6 Scheyder,I., 268 Schinzer, D., 347 Schlingloff, G., 149 Schmid, W., 334 Schneider,M., 134 Schnute, M. E., 2'76 Schonholger,P., 274 Schrock, R. R., 197

Schrtider, C., 85 Schulte, G. K., 286 Schultz, A. G., 182 Schwarzenbach,F., 323 Schwesinger,R., 287 Scott, M. J., 43 S e c o n i ,G . , 2 1 7 Sedrani, R. C., 254 Seebach,D., 4, 61, 96, 734, 234, 324 Seh, C. J., 134 Sekiguchi, M., 307 Seki, T., 108 Senanayaka,C. B. W., 153 Sengupta,S., 201 S e n n ,D . R . , 7 1 S e r v i n ,S . , 1 3 4 Sestrick, M. R., 84 Sharpless,K. 8., 240, 378 S h e a ,J . , 7 6 S h e n ,G . S . , 6 9 Sheppard,G. 5., 249 S h i b a s a kM i , . , 3 8 , 1 1 1 , 1 6 l , 3 6 1 , 3 6 4 ,3 6 5 S h i b a t a ,I . , 3 3 5 , 3 5 1 , 3 6 1 , 3 6 3 S h i b u y a ,S . , 1 5 6 S h i e h ,W . - C . , 2 6 S h i i n a ,I . , 3 4 4 Shimizu, M., 30, 323, 324 S h i m i z u ,S . , 1 3 4 S h i m i z u ,T . , 3 6 1 S h i m o y a m a ,L , 1 1 2 S h i m s h o c k ,S . J . , 1 3 9 S h i n d o ,M . , l 3 l S h i n k a i ,1 . , 2 4 2 , 3 6 7

shi,s., rltt Shono, T., 407 Shulman-RoskeE s ,. M . , 5 3 , 1 8 4 Sidduri, A., 155, 223, 234 SiedleckaR , ., 316 S i e d o ,N . , 3 8 S i e g m a n n ,K . , 2 1 8 Signer, M., 65 Silva, R. A., 170 S i m o n e l l i ,F . , 2 1 8 Simon, H., 134 S i m p k i n s ,N . S . , 1 6 4 S i n g a r a m ,B . , I 7 l Singh,M., 125 Singh, R., 361 Singh,S. P., 361 Singleton,D. A.,379, 387, 403 Sinha-Bagchi,A., 240

421

422

Author Index

Sinha, S. C., 240 sjd, P., 240 Skarzewski,J., 316 S l a s s i ,A . , 3 1 4 Sledeski,A. W., 314 Smeets,W. J. J., 45 Smith, A. B. 0ll), 76, 153 Smith, S. C., 48 Smitrovich, J. H., 70 Snider, B. B., 176 Snieckus,V., 118, 167, 201, 331 S n y d e r ,R . D . , 3 6 1 Soai,K., 131 Sodeoka,M., 7, 364 Soderquist,J. A., 2 Sojka, M., 147 Solladi6-Cavallo,A., 22, 162 Solladi6, G., 49, 125 Somers, T. C., 347 Sommazzi, A., 397 S o n o d aN , . , 1 3 , 1 1 5 ,1 , 6 7 , 3 O 7 , 3 3 1 Sotgiu, G., 175 Southern,J. M., 228 Sowin, T. J., 332 Spek, A. L., 45 Spiegler, C., 274 Sprenger,P. A., 153 Springer, R., 407 S r i d h a r a nV , .,268,269 Staab, A. J., 76 S t a c k ,D . E . , 2 1 8 Stack, J. G., 377 Stanchev,S., 226 Starkemann,C., 66 Steenkamp,J. A., 2lt Stella, L., 278 Stemerick, D. M., 361 Stengel, P. J., 21tt S t e r n ,K . , 2 1 8 Stern, M. K., 16 Stierli, F., 274 S t i l l e ,J . R . , 7 , 3 7 5 Stork, G., 78, 405 Strecker,A. R., 85 Street, S. D. A., 234 Strickland, J. B., 2 Sturino, C. F., 72 Suda, K., 2 S u d a ,S . , 2 6 , 1 4 1 Suemune,H., 91 S u g a ,H . , 1 1 8 Suginome, M., 262

Suh, H. S., 78 Su, J., 84 Sukirthalingam,S., 268 Sumayev, R., 134 Sumi, K., 218 Sundarababu,G., 65 Sunkara, P. S., 361 Sun, S., 397 S u r l e r a u x ,D . , 3 1 6 S u s l i c k ,K . S . , 1 5 0 Suzuki, H., 218 S u z u k i ,K . , 6 1 , 1 0 6 Suzuki, N., 96 S u z u k i ,T . , 3 8 , 1 6 1 Swaminathan,S., 72 Swanson, D. R., 234 S w i n g l e ,N . M . , 2 1 8 Swiss, K. A., 774, 218 Tachdjian, C., 293 T a g u c h i ,T . , 1 1 1 Taing, M., 11 Takahashi,H., 49 Takahashi,K., 41 Takahashi,M., 305 Takahashi,T., 96, 108 Takai, K., 321 Takai, T' 41, 241 Takami, N., 307 Takanami, T., 2 T a k a n o ,M . , 3 1 , 5 6 Takashima,T., 340 Takaya, H., 38 Takayama,H., 259 Takemoto, Y., 188 T a k e y a m aT , ., 311 T a k i y a m a ,N . , 3 l l Takusagawa,F., 8l Tallant, N. A., 177 Tamai,Y., lltt Tamao, K., 9, 202 Tamayo, N., 331 Tamooka, K., 290 Tamura, H., 388 Tamura, O., 65 Tam, W., 87 Tanaka,K., 47,218, 361 Tang, S., 297 Tang, X. C., 332 Tang, Y., 13 Taniguchi, M., 7, 2O4 Taniguchi, N., 56

Tava Tayk Taylo Teasa Tego Teng Teodt Terad Teras Te1as Teuh Tezul Thcq Thicl Thrcl Thod Thor! Tidrr Tierzc Tinal Tokei Tokul Tomil Tomio TorirTixhu Totlcb Tonrc Tour. Tribti Trost Tsai. I Tsuchi Tsuji. Tsuji. Tsuanl Tuclcr TUcln Turrr Tuncel Tuncel

Uchiro Uemur Uesalr Ujikar Ukaji. Ukolo UIiban Umbrir Unrau. Uozum

Author

Tavares, M., 251 Taylor, B. F., 394 Taylor, R. E., 182 Teasdale,A., 269 Tegenfeldt, J., 194 Teng, M., 67 Teodorovic,A. V., 72, 74 Terada, M., 30 Terashima,S., 188 Terashime,S., 113 Teuben, J. H., 45 Tezuka, M., 321 Theodorakis, E. 4., 287 Thiele, G., 287 Thiel, Y., 145 Thoma, G., 191 Thornton, E. R., 249, 295 Tidwell, l. H.,'71 Tietze, L. F., 340, 386 Tinant, 8., 278 Tokahashi,H., 93 Tokunaga, M., 38 Tomilov, Y. V., 100 T o m i o k a ,K . , 1 3 1 , 2 1 8 Torii, S., 393 Toshima, K., 387 Totleben, M. J., 226, 311 Tottie, L., 194 Tour, J. M., 366 Tribbiu, S., 400 Trost,B. M.,'73,394 Tsai, M.-D., 63 Tsuchiya, Y., 89 Tsuji, J., 269 Tsuji, Y., 7Ol, 144 Tsuzuki, Y., 207 Tucker, C. 8., 86, 234, 235, 289 Tiickmantel, W., 332 Tumer, S. U., 400 Tuncay, A., 150 Tuncay, C. I., 150 Uchiro, H., 344 Uemura, M., 22 U e s a k a ,N . , l 1 1 Ujikawa, O., 311 Ukaji, Y., 323 Ukokovid, M. R., 153 Ulibarri, T. A., 45 Umbricht, G., 23 Unrau,C. M., 331 Uozumi, Y., 38, 181

Upender, V., 268 u t i m o r o ,K . , 7 , 2 0 4 , 3 2 1 Uyehara, T., 218 Valentine,J. S., 90 Van der Meer, F. T., 30 Vander Roest, J. M., 170 Van Heerden,P. S., 218 Vaultier, M., 404 Verdagner,X., 348 Vernier, J.-M., 84 Verpeaux,J.-N., 172 Viallefont, P., 218 Villieras, J. 279 Vinader, V., 295, 350 Vifras, J. M., 105 Volkhardt, U., 193 Vollhardt, K. P. c., 102 Von Matt, P., 23 Wagner, W., 193 Wakabayashi,H., 347 Wakahara,Y., 340 Walah, P. J., 408 Waldmann, H., 183 Walker, M. A., 340 Waltermure,R. 8., 139 Wang,L.,240 Wang, M., 193 Wang, M. D., 105 Wang, R.-T., 268 Wang, S. L. 8., 84 Wang,W., 118, 167 , Wang, Y., 81 Wang,Y. M.,324 Wang, Z.-M.,24O Warwel, S., 147 Watanabe,A., 218 Watanabe,J., 2 Watanabe,Y., 93 Watson, J. V., 403 Waymouth, R. M., 108 Weber, 8., 324 Wehner, J. M., 390 Weichselbaumer,G., 193 Weiler, L., 361 Wei, S.-Y, 290 Wender, P. 4., 1.92 Wenger, E., 22 Wenglowsky, S., 400 Weng, X., 176 Wetterich, F., 397

lndex

423

424

S

Author Index

Whitesell, J. K., 276, 340 Whitesides,G. M., 334 Wiberg, K. B., 145 Wichmann, J., 340 W i d d o w s o n ,K . L . , 1 1 4 Wilde, A., 97 Williams,A. F.,22 Williams, D., 2 W i l l i a m s ,D . R . , 1 8 , 3 3 2 Williams, R. M., 55, 123 Wilson, R. D., 278 Winchester,W. R., 304 Wingbermiihle, D., 207 Wipl P., 70,28O, 39O Wittingham, W. G., 371 Woerpel, K. A., 43 Wolber, E. K. A., 288 Wolin, R. L., 311 Woolsey, N. F., 22 Wovkulich, P. M., 153 Wu, G., 112 Wulff, W. D., 84, 400 Wu, X.-M., 38 Xia, H., 1l Xia, Y., 332 Xinhua, X., 148 Xiong, H., 42 Xu, D., 84, 240 Xu, F., 51 Xu, J., 271 Xu, S. L., 11,3O2,326 Xu, 2., 108 , YAdav, J. S. 268 Yamabe, S., 388 Yamada, H., 134 Y a m a d a ,K . , 1 1 3 Yamada, M., 26 Y a m a d a ,S . , 2 1 8 Yamada,T., 41, 241 Yamada, Y., 348 Yamago, S., 137 Yamaguchi, K., 218 Y a m a g u c h iM , ., 311, 341 Yamamoto,H., 10, 26, l l9, 187, 188, 2O4,205 3IJ

Yamamoto, K., Yamamoto,T., Yamamoto, Y., Yamanaka,H.,

218 348 218, 223 294

Yamasaki,H., 351 Yamashita,M., 198 Yamato, T., 198 Yamazaki, H., 13 Yamazaki, S., 388 Yanagisawa, A., 70, 26, 2O5 Yang, D., 151 Yang, M., 53, 386 Yaser, H. K., 340 Yasue, K., 10 Yi, K. Y., 247, 321 Yokomatsu, T., 156 Yokomizo, Y., 26 Y o k o y a m a ,Y . , 3 1 1 Yoon, S. K., 292 Yorozu, K., 41 Yoshida, J., 2 Yoshida, T., 361, 363 Y o s h i d a ,Y . , 3 1 Yoshiga, T., 125 Yoshikoshi,A., 375 Y o s h i m o t o ,M ' 4 O 7 Yoshimura, N., 335 Yoshioka, M., 49, 93 Y o s h i z a w aT , ., 311 Youssofi, A., 404 Yu, J., 218 Yu, J. S., 34 Yum, E. K., 268 Yus, M., 9 Zadel, G., 9 Zahneisen, T' 172 Zandi, K. S., 76 Z a r a n t o n e l l oP , ., 218 Zehnder, M., 361,397 Zeitz, H.-G., 4Oj Zhang, C.-H., 39 Zhang, H., 2 Zhang, J., 91, 302 Zhang, S.-W., 93 Zhang, W., 99, 361 Zhang, X.-L., 24O '198, 2'76 Zhao, M., Zheng, G.-X.,779 zhi, L.,302 Zhu, G.,259 Zhu, J.,3'75 Zorctic, P. 4., 176 Zwanenburg,B., 134 Zykov, A. G., 72

At At At A( A( Ar A( A( l-,

{-,

A( l-r Ac Ac Ac -3AC l-t Ac Ac

:\Ac Ac NAc

p-

-1-/ N-/ Acl 3-l Aq Adl Adi Acr Ale

p-t (R

(s) ,en Atd Atd Atd

I

oi anti Ald Ath Alk l-At

SUBJECT INDEX Acenaphthene,34 Acetal cleavage,203 Acetaldehyde,157 Acetal-B, B -diglucosides, 380 Acetalization, 149, 2O4 Acetamidoacrylates,46 Acetonides, 139 Acetonitrile, 150 3-Acetoxyalkenoates,258 4-Acetoxy B -lactams, 235 Acetylacetic acid, 61 I -Acetyl-4-formyl-7-hydroxyindoles,29 l Acid chlorides, 397 Acrolein,210 Acrylonitrile, 32, 344 3-Acryloyloxazolidine-2-one,43 Actylenic ketones,74 I -Acyl-2-alkyl-1,2-dihydropyridines, 282 Acylation, l5 Acyl azides,24 N-Acyl-2-(l-diazoacetyl)-pyrrolidines,301 Acyldimethylphenylsilanes,I Acylfurans, 225 N-Acyliminium ion, 241 Acyfoxyboranes,13, 323 p-Acyloxy cyanides,288 3-Acyloxy-2-pyrones,295 N-Acylpyridinium salts, 271 Acyfsilanes, l-2, 253, 3tl7 3-Acyltetrahydrofurans,339 Acyl triflates, 259 A d a m a n t a n e l, 2 l Adipaldehyde, 148 Aerobic oxidations, 157 Alanine,2-3 B-Alanine,3-4 ( R ) - A I a n i n e ,8 0 (S)-Alanine, t3l /e,'/-Alcohols,52 Aldehyde olefination, 193 Aldehydes, 321 A f d o l r e a c t i o n s2, 0 , 5 0 , 7 8 , 1 0 3 , 1 6 3 , 1 6 9 , 1 8 9 , 223,243,248, 341,342, 366 of propynals, 104 anti- Aldol reactions,174, 247 Aldol-type reactions,384 Alkenyl alkyl ketones,50 Alkenylaluminum reagents,230 l-Alkenylborane, 229

Alkenylcopper reagents,155 Alkenylcopper/zincreagents,219 Alkenyltributylstannanes, 32 Alkenylzinc bromide, 230 Alkenylzinc rcagents, 232 a-Alkoxy esters,253 a-Alkoxy ketones,360 3-Alkoxy-l -alkenes,253 2-Alkoxy-1,3-diols, 5.1 N-4-Alkoxyethyl-N-(l-butyl)diazoacetamide, 304 7-Alkoxy enals, 79 a -Alkoxyorganocuprates,208 4-Alkoxy-2-oxazolines,118 Alkoxysiladioxanes,370 a-Alkoxysilanes2 , a - A l k o x y - p , 7 - u n s a t u r a t ee ds t e r s5 ,1 a - A l k y l a , B - e n o n e s ,9 9 a - A l k y l k c t o n e s ,3 1 3 2 - A l k y l - 3 - a l k o x y c y c l o b u t e n e d i o n9e0s , N - A l k y l - N - a l l y l c n a m i n e s3,7 2 A l k y l a l u m i n u mh a l i d e s ,4 - 7 a-Alkylation, 313 N-Alkylation, 256 Alkyl azides, 345 Alkylbenzoquinones,264 AIkyl l-butyl sulfoxides, 136 Alkyl cuprates,69 Alkylformamides, 28tl Alkyl hydroperoxidcs,145 a - A l k y l i d e n e c y c l i c e t h e r s ,2 6 3 Alkylidene-7-butyro-lactoncs,35 Alkylidenecyclopentanes, 22 I 2-Alkylidenecyclopentanes, 35 Alkyl isocyanate,24 N-Alkyllactams, 345 A l k y l l i t h i u m s ,7 - 9 Alkylmethoxycarbencs,8 I (S)-I -Alkyl-2-methylpyrrolidines,342 N - A l k y l m a l e i m i d e s2, 4 1 A l k y l p e r o x y m e r c u r i a t i o n1,4 5 t-Alkyl isocyanides,260 Alkyl trichloromethyl ketones,243 2 - A l k y l - 2 - t r i m e t h y l s i l y l - 1 , 3 - d i t h i a n1e s , 2-Alkynoates, 258 Alkynylcoppers, 220 4-Alkynyl-4-(propargyloxy)cyclobutenones, 10 Alkynyl (tributyl)stannanes, 267 Alkynylzinc halides, 234

425

426

Subject Index

Allenes, 83, 235 a-Allenic alcohols, 214 Allenic alcohols, 85 Allenylzirconium reagents,111 Allyl-allyl coupling, 25 Allylation, 12, 152, 321, 333 of aldehydes,341 Allylbarium chlorides, 204 Allylbarium reagents,9 -10, 25, 2O4 N-AIlyl-N-benzyl-2-bromoaniline,70 Allylboration, 1l (Allyl)chloropalladium dimer, 180 Allyl cinnamyl ethers,351 4-Allylcyclobutenones,10- 1I Allyl(diisopinocamphenyl)boran e, 7| - 12 Allylethylzinc, 229 Allylic alcohols,72, 1,69,321, 362 Allylic alkylation, 23 Allylic aryl ethers,264 Allylic bromides, 84 Allylic dimetalli c zinc reagents,229 Allylic organocopperreagents,209 Allylic oxidation, 337 AIlyl isocyanides,2138 1-Allyloxy-2-halobenzenes,189 A l l y l s i l a n e s ,3 2 3 A l l y l s i l y l e t h e r s ,1 1 4 Allylstannanes,13, 168 A l l y l t i t a n a t i o n3 , 21 A l l y l t r i b u t y l i n r e a g e n t sl,2 - 1 3 Allyltributylstannane,12 Allyltrifluorosilanes, 14 Allyltrimethylsilane, 12, 380 A l l y l v i n y l e t h e r s ,1 6 7 Alpine-Borane,71, 74 A l u m i n u m c h l o r i d e ,l 5 Aluminum tris(trimethylsilane),I Amide cuprates,209 Amides, 17,95, 162, 17O Amine oxide, 57 tert-Amir,es, 2O5 a-Amino acids, 243 a-Amino esters, 135 Amino alcohols, 198 antt p - Amino alcohols, 64 F-Amino acid esters, 130 B-Amino acids,37, 284 B-Amino alcohols, 212 B-Amino esters,2Ll F-Amino a-hydroxy esters,129 AminocarbeneDiels-Alder reactions,397 1-Aminocyclopropane- I -carboxylic acids, 122 2-Amino-2-deoxy-B-o-glucopyranosides, 341

3-Amino-1,2-diols,347 (1S,2R)-2-Amino-1,2-diphenylethanol, 82 7-Amino acids, 211 7-Amino enoates,56 3-Amino-2-hydroxybutyricacids, 188 (R)-7-Amino-B-hydroxybutyric acid, I 1 (R)-(-)y-Amino-B-hydroxybutyric acid, 11 (R)- 1-Arnino-2-methoxymethylpyrrolidine, 15-16 (S)-1-Amino-2-methoxymethylpyrrolidine, 15-16 (+)-(S)-I -Amino-2-propanol,371 (S)-B-Amino acids, 285 (Aminosilyl)lithiums, 9 Ammonium formate, 269 Ammonium triancetoxyborohydride,125 A n a b a s i n e ,1 1 9 Anaerobes,133 Aniline and nitrobenzene,16 Anodic oxidation, 1 Anomerization, 138 Anthracenes.34. 171 Antimony chloride, 204 Antimony(V) chloride-Silver hexafluoroantimonate, 17 (+)-Aphidicolin, 76 Arabinofuranosides,26 Arenes, 100 2-Arenesulfonyl-3-aryloxaziridines, 17- l8 Arene(tricarbonyl)chromiumcomplexes,18-22 Aromatization, 313 Artemesinine,380 Aryl allylic sulfoxides,337 Arylation, 257, 259, 264 of alkenes,36 Arylboronic acids, 72, 117 Aryl O-carbamates,201 Aryl carboxylic acids, 307 C-Aryl glucals, 72 C-Aryl glycosides,50 Aryl 2-deoxy- B-o-glycosides, 389 4-Aryl-1,3-dienes,264 3-Aryl-3,4-dihydroisoquinolines, 24 1 Aryl epoxides, 162 Arylglycines, 54, 82, 371 Aryl C-glycosides,105 c-Arylglycosylation,386 Aryl isocyanides,202 Aryllithium, 60 Arylmanganese piv alates, 224 Aryl methyl sulfoxides, 135 Aryl nitriles, 307 (Aryloxy)dimethylaluminum,203

Ar_vl Afylz Afvl,

Aryr Asyn

Aslrn Asyr Asyn A.lrm Asln Asvn Alc o

Az2< Azz-l Azdt Aztu Azz-a Azcrid Azkt a-Azi a-Azi a-Azi

P-Azt Azidoa Azidq

(s)-o Azi.Jd Aziri.I Aziril

Bacyer Bakcr: Bartrr Barbrr Barbaq Bariuo Bartoo BBN r Be.fE B€nz.l 1,2-l(B Benzct Benzca Benzcr B€nzil Benza Benzofi Benzox Benzm p-Benz Benztrr endo-11 az

Subject Index

n

l\\ I . l l f , :

1nc.

f( ,:rnt

R \ r ' :U ( ) r O a n t i -

..l:r...

lf.t

Aryl triflates, 36, 201 Arylzinc chloride, T2 Arylzinc reagents,232 Aryne cycloaddition, 166 Asymmetric amplification, 149 Asymmetric cyclopropanation, 303 Asymmetric Diels-Alder reactions,7iB, l9j Asymmetric dihydroxylation, 90 Asymmetric epoxidation,97, 98 Asymmetric oxidation of ArSr with H2O2, 98 Asymmetric reductions,163 Ate complexes,367 Aza-Cope rearrangement,372 Aza-Diels-Alder reactions,ll8 Azadigermiridine,251 Azametallacyclobutenes, 408 Aza-semicorrins,22- 23 Azetidines, l9T A z i d a t i o n ,2 4 . 6 6 . 3 7 1 a - Azido arylglycines, 371 a-Azido ketenes, 68 a-Azido ketones, 68 B-Azido triisopropylsilyl ethers,378 Azidohydrins, 345 Azidornethyl phenyl sulfide, 286 (S)-a-Azido acids,243 Azidotrimethylsilane,24, 37 | Aziridination, 348 Aziridines, T9, 1O2

ltl-22

Baeyer-Villigeroxidation, 40, 158, 2i5 B a k e r s ' y e a s t ,1 3 3 Barbier/aldolreactions,308 Barbier reactions,226 Barbier{ype reactions,309 Barium, activated,25 -26 Barton-McCombie reaction, 284, 361 BBN see Borabicyclo[3.3.1]nonane, Beckmann rearrangement,l7 Benzaldehyde,158 1,2-[(Benzenediolato)-O,O/ loxotitanium, 26 Benzeneselenenyl chloride, 26 Benzeneseleninicanhydride,391 Benzeneselenol,1I 3 Benzil, 308 Benzocyclobutenols,l7l Benzofurans,11 Benzoic anhydride,307 Benzonitrile, 307 p-Benzoquinone,7 Benzoxazoles, 291 endo -7 - (2-B enzoxazolyl) - 7,5,7-trimethyl-3 azabicyclo[3.3. 1]nonan-2-one,375

427

Benzoyl chloride, 307 Benzyl alcohol, 307 Benzylamine, 307 Benzylchlorobis(triphenylphosphine)palladium

(rr),27 Benzyl chloroformate, 2 Benzyl chloromethyl ether, 309 Benzyl copper, 216 N-(Benzyldimethylsilyl)methyl-2-(+)(methoxymethyl)py nolidine, 27 -28 Benzylic substitution,18 Benzylidine acetals,139 a-Benzyloxy aldehydes,52 B-Benzyloxy aldehydes,52 B c n z y l o x y k e t e n e s18 .8 Benzyloxymethylation,309 (R)-2-Benzyloxypropanol,248 N-Benzyl-2-vinylpiperidine,I l 9 N-Benzyl-2-vinylpyrrolidinc,120 Benzylviologen, 133 B e n z y n e s ,l 7 l BFr etherate,214,277 Biaryls,139 Biaryl synthesis,213 Bicyclic dihydropyridone,271 Bicyclic lactones,53 Bicyclization-anioncapture,263 Bicyclo[3.2.0lheptenones, 10 Bicyclo[3.3.0]octane-3-ones, 308 Bimetallic reagents,219 BINAL-H, I63

(s)-BTNAL-H, 2se | ,lt -Bi-2,2t -naphthol, 2tl - 30 Binaphthyls,130 BINAP see 2,2/-Bis(diphenylphosphino)-l,l/binaphthyl Bf NOL see 2,2t-Dihydroxy-1,I /-binaphthyl Biphenyls, 30-5 2,2t-Bipyridine, 148 Bipyridines, 293 Bis(acetonitrile)dichloropalladium(ll), 30- 3 1 Bis-alkyne annelations,39tl Bis[(allyl)trifluoroacetatolnickel(ll),3 1 I,3-Bis(arylseleno)-2-alkene-I-ones, 328 I ,3-Bis(arylthio)-2-alkenel -ones, 328 ( I S,2R,3R,4S)-1,4Bis(Cbo-amino)-2,3-diols, 393 Bischler-Napieralskireaction,241 1,2-Bis(chlorodimethylsilyl)ethane, 233 Bis(cyclooctadiene)nickel, 32 Bis(1,5-cyclooctadiene)nickel, 32 - 33, 202 Bis(cyclopentadienyl)chloro(hydrido)zirconium, 33-34

Subject Index

B-Bromo-9-borabicyclo[3.3. 1]nonane, 4O2 278 2-(Bromomethyl)acrylates, I -Bromonaphthalene,100 138 5-Bromo-1,2-naphthoquinone, 3-Bromo-2-pyrone,294 5-Bromo-2-pyrone,53 Bronsted superacids,370 Brook rearrangement,372 Burgess reagent,52 1,3-Butadiene,31 Butan-4-olides,117 34-35 /(5S,6R)-4-t-Butoxycarbonyl-5,6-diphenyl( R ) - 2 . 2 - B i s ( d i p h e n y l p h o s p h i nl ,o| ) 2,3,5,6{etrahydr o-4H - 7,4- oxazin-2-one, b i n a p h t h y l ,3 6 - 3 8 /54-55. 722 1 S ; 2 , 2 - B i s ( d i p h e n y l p h o s p h i nl .oI) Butylcopper, 215 binaphthyl, 36-38 [ 1,4-Bis(diphenylphosphino)butane]norbornadi-4-t-Butylcyclohexane,159 (1 R,25)-2-t-Butylcyclohexanol,55 enerhodium trifl uoromethanesulfonate, 4-t-Butylcyclohe xanone, 224 39-40 r-Butylcyclohexanone,363 1,1//2,2//-Bis[1-(diphenylphosphino)ethyl]r-Butyldimethylsilyl ethers,125, 139 biferrocene, 40 40 -4 I r-Butyldimethylsilyl trifl uoromethanesulfonate, Bis(dipivaloylmethanato)nickel(II), 5 5- 5 6 ansa-Bis(indenyl)titaniumdichloride, 125 r-Butyldiphenylsilylethers, 139 Bis-P-lactams, 198 304 N-(l-Butyl)-4-ethoxy-2-pyrrolidone, IN,N/-Bis(4-methoxysalicylidene)-oB u t y f l i t h i u m ,5 9 - 6 0 , 1 0 8 - 111 , 1 6 ' 7 ,l 7 O phenylenediaminelcobalt(II), 41 Butyllithium-Potassium r-butoxide,60-61 41 -42 1,2-Bis(methylene)cycloalkane, 1,3-dioxin-4-one, (2R)-2-r-Butyl-6-methyl-4H4l 1,2-Bis(methylene)cyclohexane, 61 Bis(oxazoline)ligands, 23 ' Bisdebenzylation,135 144 Bis(dibenzylideneacetone)palladium, 1,4-Bis(9-O-dihydroquinidinyl)phthalazine,237 36, 34 1 1,8-Bis(dimethylamino)naphthalene, Bis(dimethylamino)phenylphosphine, 282 Bis(2,6-diphenylphenoxide)tris(4methylbenzyl)niobium(V),34 1,4-Bis(diphenylphosphine)butane(norbornadiene)rhodium(l) tetrafluoroborate, 39 1,1'-binaphthyl, 2,2/-Bis(diphenylphosphino)-

t-Butyloxirane, 28 Bis(oxazolines),42-43 Bis(pentamethylcyclopentadienyl)[bis(trimethyl-2-t-Butylperhydropyrimidinone,3 l-(l-Butylperoxy)-1,2-benziodoxol-3(1Fl)-one, silyl)methyllyttrium,44 61.-62 Bis(pentamethylcyclopentadienyl)methylt-Butyl acrylate, 3 yttrium, 44-45 /-Butyl N-boc-aspartate,211 Bis(pentamethylcyclopentadienyl)samarium l-Butyl bromoacetate, 129 tetrahydrofuran, 45 r-Butyl hydroperoxide,56-58, 160 46 Bis(phospholanes), l-Butyl methyl fumarate, 187 Bispiperazines,46-47 FButyl thioproponoate,130 Bis-silylation, 260 I -vinylcyclohexane,126 meso-trans-4-ButylBissteroidal pyrazines, 47 - 48 I , l - B i s ( p - t o l y l s u l f i n y l ) - 1 , 3 - b u t a d i e4n9e , (S,S)-Bis-p-tolylsulfi nylmethane,48 - 49 242 Bis(trifluoroethyl)alkylboronates, ( I R,2R)-1,2-N,M-Bis(trifluoromethanesulfonyl amino)cyclohexane,49 23 N,O-Bis(trimethylsilyl)acetamide, cis-5,6-Bis(trimethylsilyloxy)-1,3cyclohexadiene,31 Boc-pyrrolidines,3 I 8 49-50 9-Borabicyclo[3.3.1]nonane, Borane-Dimethylsulfide, 50-51 Boron trifluoride etherate,52-53 Bromination, 100 crr-Bromoalkvlchloroketene.353

Butyrolactones,83 Calcium hypochlorite,316 ( + ) - C a m p h o r2 , 74,275 o-Camphor dimethyl acetal, 63 (l R)--Camphorquinone, 248 64 - 65 ( 1R)-10-Camphorsulfonamides, 64-65 (1S)-1O-Camphorsulfonamides, (1 R)- I 0-Camphorsulfonic acid, 32O Camphorsulfonic acid, 223 o-Camphorsulfonicacid. 155 10-Camphorsultam,65-66 320 (Camphorylsulfonyl)oxaziridine, 66, 285 (10-Camphorylsulfonyl)oxaziridine,

(+)Campd (S)-Campt 2-Carbdlcl 383 Carbamac: O-Carbanr Carbaperrr Carbomcthr Carbon nro Carbonvlrti Carbonrleri Carbonr l-cr Carboxamr p-Carborrt p-Carborl. Carboxr Lt (S)-Canc (S)-(+lcen

Catecholbd Cephalosu Ceric amru Cerium har Ceriun( lll I Cesium 0r Cetylpvrrdl Chalcooc. I Chiral autrl a-Chlom h p-Chlorotrr numF, Chlorobrlo (lvl. c Chlorobislo 70-11 B-Chlorob,c borar, Chlorobis{tr Chloroccnr Chloroc!'clo rulhcar Chloro(crcl 73-71 B-Chlorodir Chlorodiisq B-Chlorodii (E)-(Chloro. 4-Chloro.lJ 74-15 (Chloromal 1-Chloro l -r z-Chlorogcr Chloro(phcr 1-Chloro ll

Subject Index

2-[(p-Chlorophenyl)sulfonyl]-3-(p(+)Campothecin, 143 chlorophenyl)ox aziridine, 17 (S)-Camptothecin,256 78 1]-octan-3-ones, (3-Chloropropyl)dichloromethylsilane, 2-Carbalkoxy-8-oxabicyclo[3.2. N-(5-Chloro-2-pyridyl)triflimide, 293 383 Chlorotitanium enolates, 344 Carbamates, 30 Chlorotrialkylsilane,32 O-Carbamates,201 tetramer, Chloro(triphenylphosphine)copper Carbapenems,236

k_\ I

r l-',nc.

a..-.!(\naIC'

. _ - i l 3 "'i 6l - j-{)nc. I

i .l/ r-,rne,

91 Carbomethoxycyclopentanones, Carbon monoxide, 270 Carbonylation, 12, 38, 102, 111 Carbonylativehydrosilylation,365 Carbonyl-enereactions,29 Carboxamides,173 p-Carboxybenzenesulfonyl azide, 66- 67 B-Carboxy-7-butyrolactone,275 Carboxylation,9 (S)-Carvone,6 (S)-(+)-Carvone,6 Catecholborane,45, 49, 67 -68, 243, 244, 245 Cephalostatins,47, 48 Ceric ammonium nitrate, 68, 351 Cerium borohydride, 315 Cerium(lII) chloride, 2'72, 315 Cesium fluoride, 68 Cetylpyridinium chloride, 146 Chalcone, 216 Chiral auxiliary, 274 a-Chloro ketones.363 pr-Chlorobis(cyclopentadienyl)(dimethylaluminum)-p-methylene titanium, 69 Chlorobis(cyclopentadienyl)hydridozirconium

(rv), 6e-70 Chlorobis(cyclopentadienyl)methylzirconium, '70-11

l16

'',,.185

79-84 Cholesterol, 250 Chromium amino-carbenes,80 Chromium carbenes,355 Chromium(II) chloride, 84-85 Chromium(II) chloride-Lithium iodide, 8 5- 8 6 Chromium(lI) chloride-Nickel(lI) chloride,86 C h r o m i u m ( V I )o x i d e . 8 6 - 8 7 (+)-Cinchonine,89 Cinnamaldehyde,206 C i t r o n e l l e n e1 , 10 Claisen rearrangements,134 ClzPd(1,I /-bisdiphenylphosphino)ferrocene, 327 fl7 Cobalt(ll) acetylacetonate, C o l c h i c i n e ,1 2 6 Conjugateaddition,69, I 68, l'12, 214, 215, 216, 21"7 Copper, activated, 209 Copper(I) chloride, 30 Coppe(ll) acerate, 176 Copper(II) nitrate, 366 Copper(l) iodide, 87-88 Coppe(l) trifluoromethanesulfonate,43 Copper/zincreagents,155

Coupling, 330 B-Chlorobis(iso-2-ethylapinocamphenyl) of amino acids,27l borane,71.-72 of lactonesand ketones,307 72 Chlorobis(triphenylphosphine)palladium, CPzYH, 44, 45 Chlorocerium borohydride,315 Chlorocyclopentadienylbis(triphenylphosphine)-Cross-coupling, 262, 263 Crotyl chlorides, l5 ruthenium. 72-73 Crotyl propionate, 128 Chloro(cyclopentadienyl)dimethyltitanium, Crotylsilanes,3tl l 73-74 (E)-Crotylsilanes,52 74 B-Chlorodiisocamphenylborane, l8-Crown-6, 17, 289 2 Chlorodiisopinocamphenylborane, Curtius reaction, 183 7I B-Chlorodiisopinocamphenylborane, Curtius rearrangement,332 404 (E)-(Chlorodimethylsilyl)acrylate, 4-Chloro-2,3-disubstituted-2-cyclobutenones, Cyanides, 288 '74-75 a-Cyano carboxylates,40 Cyanohydrin trimethylsilyl ethers,89 (Chloromethyl)dimethylsilylchloride, 75-76 Cyano(methyl)ar gentates,226 78 1-Chloro-1-methylsilacyclobutane, Cyanomethylation,131 m-Chloroperbenzoic acid, 5'7, 76, 407 Cyanomethylzincbromide, 131 rlane,77 -7 8 Chloro(phenylethynyl)dimethyls '78-'79 Cyanosilylation,89 1-Chloro-1-phenylsilacyclobutane,

430

Subject Index

Cyanotrimethylsilane,89, 123 Cyclam, 89-90 Cyclic enediynes,103 Cyclic enones, 172 Cyclic a,B-enones, 149, 157 Cyclic sulfates, 90 Cyclic sulfites, 90, 136 Cyclization: of 1,5- and 1,6-dienes,44 of alkynyl halides, 309 [2+2]Cycloaddition,10, 73, 93, 188, 387 f2+2+2lCycloaddition, 102, 183 [2+4]Cycloaddition, 295 [3+2]Cycloaddition,118, 136, 274 of azirines, 201 [3+4]Cycloaddition,383 [4+l]Cycloaddition, 270 [4+2]Cycloaddition,335, 404 l4+2lll3+2lCy cloaddition, 274 [5+2]Cycloaddition, 191 Cycloalkane-1,2-diols, 148 Cycloalkenones,153 Cycloaromatization, 86 acids, 93 Cyclobutane-B-aminocarboxylic Cyclobutanones,353 Cyclobutene-I ,2 -diones, 222 Cyclobutenediones,90-91 ' Cyclobutenones,32 Cyclodecenones,355 5-Cyclodecynone,3 I 3 Cyclodehydration,180 Cycloenediynols,86 399 Cycloheptadienones, Cycloheptenones,356 86, 38? 1,4-Cyclohexadiene, acid, 375 1,3,5-Cyclohexanecarboxylic (lR,2R)-Cyclohexanediamine,231 ( R , R ) .1 , 2 - C y c l o h e x a n e d i ( 2 . 2 dimethylpropyl)amine,91-92 (S,S)-1.2-Cyclohexanedi(2'2' dimethylproPyl)amine,97 - 92 (1S,25)-Cyclohexanediol,9l tr ans- Cy clohex^ne-(1R,2R)-disulfonamides, 93

Di-r 1,2vic-l vic-l

12+7+2lCy clopentannelation,394 Cyclopentanols,281 Cyclopentanones,176 Cyclopentenols,258 Cyclopentenone esters, 386 Cyclopentenones,15, 356 (Cyclopentyl)methyllithiums,144 Cyclopropanation,23, 43, 81, 93, 100, 115' 116' 126, 194,270. 305. 306 Cyclopropanes, 233, 399 Cyclopropanols,309 Cyclopropenation,303 Cyclopropenes,326 a-Cyclopropyl esters,96 a-Cyperone, 6 Cystine peptides,365

(rR (tr

l.+l Dier Diar (lRt.&l l.&l

Dirz Di:z Di.z Dib. 7-D 7-D 2J-l 23{ Dibo Dibr L6.I Dibr Dic.

DABCO, 239 Danishefsky'sdiene, 182, 397, 398 Darzens reaction, 129 Darzens-typereaction, 350 Debenzylation,138 Debromination,53 Decalindiones,176 Decalins, 269 lrans-Decalins,357 Decarboxylation , 134, 252, 264, 294

Db Di-1 8e* Dkr Dkr Dkl

Dehydrogenase,133 Demercuration,145 Demethoxycarbonylation,340 Dengibsin, 166 Deoxygenation,5, 284, 367 DeoxygenativecouPling, 306 Deprotonation,164, 318, 319 Desilylation, 139, 272, 324 Destannylation,358 Desulfonylation, 17 gem-Diacetates, 394 Diacetylenes, cy clic, 372

Dkr Dicl Dkt Did

Dialdehydes,147 Dialkenylzinc reagents,230 Dialkoxyboranes,172 2,4-Dialkylanisoles,8

Did Did Dicf Dicf Dicl Dkl l.+l 2.Cl l-!l

96 Dialkylbis(cyclopentadienyl)zirconium, N,N/-Dialkyl bispiperazines,46 270 2,5-Dialkylcyclo-3-pentenones, 2,4-Dialkylphenols,7 Cyclooctatetraene,170 Dialkyl tartrate,57-58 Cyclopentadiene, 43 Dialkylthallium chlorides, 228 (Cyclopentadienone)(cyclopentadienyl)dicarbonDialkylthallium halides, 227 ylmolybdenum hexafluorophosphate,94 Dialkylzincs, 49, 96, 735, 228 Cyclopentadienyltantalum(V) carboxylates, 95

Cyclohexanol, I57 Cyclohexanone,157 93 (Cyclooctadiene)(cyclooctatriene)ruthenium,

Cyclopentanecarboxylates,15 Cyclopentannelation,110, 395

9,to Dict

Diallenes, 270 Diallylamines, 197

I

Subjmt Index Di-,o-allylpalladiumchloride, 96-97 1.,2-Diamines, 127 vtc-Diamines, 306 yic-Diaminoalkenes,306 (1 R,2R)+rans- 1,2-Diaminocyclohexane, 97 _ 99 (l S,2S)+rans-1,2-Diaminocyclohexane, 97 _ 99 1,4-Diamino-2,3-diols,393 Diaryl diselenides,328 Diaryl disulfides,327, 328 (1R,2R)-Diarylethylenediamines, 406 1,8-Diazabicyclo[5.4.0]undecene _7, gg _ IOO 1,8-Diazabicyclo[5.4.0]-7-undecene hydrobromide, 100 Diazaborolidines,128. 130 Diazirines, 287 Diazomethane,Kn, n3 Dibenzyl acetals,384 7-Dibenzylaminoenoates, 5cl 7-Dibenzylamino-B-ketoesters,56 2,3-DiO-benzyl-o-glyceraldehyde, 92 2,3- O -D ib enzy| - r.-gl y ceral dehyde, 92 D i b o r a n e ,1 0 1 , 2 8 3 , 3 1 6 Dibutylboron triflate, 103 2,6-Di-t-butyt-4-methylpyridine, tO4, 378 Dibutylrin diacetate, 342 Dicarbonylbis(triphenylphosphine)palladium, l0l Dicarbonylcyclopentadienylcobalt. 102 Di-p-carbonylhexacarbonyldicobalt, 102_ 105 gem-Dicarboxylates, 394 Dichloroalane,197 Dichloroaluminum phenolates,139 Dichlorobis(cyclopentadienyl)hafnium, 105-106 Dichlorobis(cyclopentadienyl)titanium, 6 Dichlorobis(cyclopentadienyl)zirconium, 106*108,108_1ll Dichlorobis(triphenylphosphine)palladium(II), 1 1 1_ 1 1 2 Dichlorobis(triphenylphosphine)palladium(II) _ C o p p e r ( t )i o d i d e , I I 2 - I l l Dichlorocyclobutanones, 354 Dichlorodiisopropoxytitanium,2g _ 30 Dichlorodimethylsilane,I l3- 1l4 Dichloro(ethylene)platinum dimer, 1l4_ I l5 Dichloroethyloxyoxovanadium,29g Dichloroketene,119-12O, 354 1,4-Dichlorophth alazine, 236 2,6-DichloropyridineN-oxide, 121 1,3-Dichloro-1,1,3,3-tetraisopropyldisiloxane, 63, 121-122 9, 10-Dicyanoanthracene,25 1 Dicyclohexylbor ane, 86, 229

431

Dicyclohexylchl oroborane, 247 (Dicyclooctadiene)nickel, 2O2 Dicyclopentadienylsamarium, 30g Dicysteine peptide, 365 Didehydro-4-piperidinones, l g2 Di-1,3-diphenyl-1,3-propanediam ine, 206 aza-Diels- Alder reactions, 277 Diels-Alder catalyst,6, 43 Diels-Alder cycloadditions,53 Diels-Alder reactions,75, 119, 134, 246, 267, 277, 294,295, 349, 379,387, 398, 402, 4O3, 4O4. see also Homo-Diels-Alder re_ actions 4,6-Dieneamides,255 5,7-Dieneamides,255 7,3-Dienes, 69, 237 1,3-Dienoates,209 3,5-Dienoic acids, 93 Dienol ditriflates, ll2 Dienols, 256, 257 D i e n y n e s ,1 9 5 , 2 0 2 Diethylaluminum fluoride, 203 (Diethylamino)(phenyl)oxosulfonium methylide, 122-123 Diethyl azodicarboxylate,389-390 Diethyl chlorophosphate,358 Diethyl mesoconate,406 Diethylzinc, 21, 49, 148, 149, l8l, 228, 323 Diethylzinc-Methylene iodide, I l6 Diethyl-Chloroiodomethane, I l5 2,3-Dihydrofuran,36 Dihydrofuran-3-one, 277 Dihydrofurans, 196 Dihydropyrans, 196 Dihydropyrazine, 127 Dihydropyrazoles,206 1,2-Dihydropyridines, 282 Dihydropyridones,271 Dihydropyrrolizines,301 Dihydroquinidine,236 Dihydroquinine, 236 Dihydroquinine phthalazine, 237 2,2t-Dihy dtoxy -l,l /-binaphthyl, t l6_ I l9 (S)---2,2/-Dihydroxy- l, 1/-(S)--binaphthyl, 160 2,2t -Dihy&oxy -l , I /-binaphthyl Trimethylaluminum, I l8 (S)-2,2/-Dihydroxy -4,5,6,4t,5t,6t -hexamethoxybiphenyl,162- 163 Dihydroxylation, 46, l2l, 147, 239. see also Asymmetric dihydroxylation Dihydroxyserrulaticacid, l8 Diisobutylaluminumhydride, 123- 125, ZO2

SutrjectIndex

432

Diisoprenoids,25 Diisopropoxy acetals,384 acid, (2R,3R)-2,6-Diisopropoxybenzoyltartaric JZJ

-Diisopropylcyclohexane1,4(1S,2R,4S,5R)-2,5 diol, 725-1.26 a-Diketones, 17 1,3-Diketones,40 1,4-Diketones,328 46 Dilithium bis(phosphido)ethane, Dimeric macrolides,27 Dimerization, 144 o f 1 , 3 - d i e n e s1, 4 4 Dimethyl acetals,253 - -3-exo-(Dimethylamino)isoborneol, 229 Dimethylcarbamyl chloride, 272 Dimethyldioxirane,224 D i m e t h y l e t h e r ,1 3 0 N , N - D i m e t h y l g l y c i n e3, l 6 Dimethyl malonate,23 Dimethyloxosulfoniummethylide, 123 m(lll), 227 Dimethyl(phenylacetenyl)thalliu vinyl ether,295 8-(3,5-Dimethylphenyl)menthyl 2,6-Dimethylpiperidinylketones,103 chloride, 43 2,2-Dimethylpropane-1,3-dioyl Dimethyl squarate,10 89 I , | /-Dimethylstannocene, Dimethyl sulfoxide, 127 Dimethylsulfoxoniummethylide, 126-127 2-Dimethyltetrahydrofuran,224 69 Dimethyltitanacyclobutene, Dimethylzinc, 229 ine, 122 N,N/-Dineohexyl-2,2/-bipyrrolid 1 , 2 - D i o l s ,1 7 4 , 3 0 9 , 3 9 1 1,3-Diols, ztl, 124, 319 I,4-Diols,319 1 , 5 - D i o l s ,1 6 5 t r a n s - I , 2 - D i o l s ,I 9 3 vic-Diols,3l6 1 , 2 , 3 , 6 - D i o x a d i g c r m i n2e5, 1 Dioxane acetals, l2 1 , 6 - D i o x a t r i q u i n a n e3s8, 8 Dioxetanes,368 1,3-Dioxolan-4-ones,2 I 8 Dipeptides, 80, 95 D i p h e n y l - 1 , 2 - d i a m i n o e t h a9 n7 e, 1 , 2 - D i p h e n y l - 1 , 2 - e t h a n e d i a m1i n2e7,- 1 3 O ( R , R ) - 1 , 2 - D i p h e n y l e t h a n e - 1 , 2 - d1i3o0l ,- 1 3 1 406 Diphenylethylenediamines, 242 (S)-2-(Diphenylhydroxymethyl)pyrrolidine, Diphenylmethanes,140 ( S ) - ( + ) - D i p h e n yIl -( m e t h y l - 2 pyrrolidinyl)methanol,13 1

(R)- - -Diphenyl(l -methyl-2pyrrolidinyl)methanol,l3l Diphenylsilane,132 Diphenylsilane/AIBN, 132 D i r e c t e do r t h o l i t h i a t i o n ,l l 6 Dirhodium(lI) tetrakisImethyl2-oxazolidinone4 (S)-carboxylatel,303 Dirhodium(II) tetrakis(methyl2-pyrrolidone-5carbonylate),303 Diselenides,327 Disilanes, 9, 260 Distannoxanes,149 a,a-Disubstituted a-amino acids,2'73 cis-2,5-Disubstitutedtetrahydrofurans,26 94 cis-4,5-Disubstituted-2-cyclopentenones, 1,2-Divinylcyclohexane,194 Diynes, 202 1 , 3 - D i y n e s2, 0 2 1 , 6 - D i y n e s2, 0 2 l,7-Diynes, 202 DMAP, 82 DMPU, 308, 309, 310 DMSO, 68 Dodecacarbonyl-tri-tr iangulo-ruthenium, 103 Double kinetic resolution,58 '104 Dynemicin, ElaeokanineA, 272 ElaeokanineC, 272 Eldanolide, 83 a,B-Enals, 32, 256 y,6-Enals,257 Enamides,3l6 (E)-Enamides,30 Enamines2 , 76,408 Enantiolselectiveaddition, 134 Ene cyclization, 28, 340 Enediynes,347 Ene reactions,92, 252, 337, 346 Enoates,33, 76 a,B-Enoates, 55 Enol triflates, 14, 256 Enones, 149, 354 a , B - E n o n e s ,1 4 6 B,y-Enones, 12, 41 Enynes, 202 1,3-Enynes,238 1,6-Enynes, 2O2 Enzymes, 733-734 Ephedrine, 134 '1,99, '76,89, 250 160, 192, Epoxidation, 41, 56, '1,46, 198, 37'7 170, Epoxides, 2,3-Epoxy alcohols, I 25

2.J a.l

Ep EP E4 t.l -J

6.7

r.l Ep (+

E Es Eli (5

-1Ed Ed Ed Eil

&r &i

&r

Eri (E Erl Erf Etl Erl E-r s-I S.T lzl l-E Eri Eri Eri Eri Fllr

(E (L

Fcr Flu Ru Flu l-F

Flu (Fh

Flu +F

Subject Index 2,3-Epoxy halides, 407 a,B-Epoxy silyl ethers, 184 Epoxy acrylates,373 Epoxydienes,5 Epoxy esters,382 7,6-Epoxy acrylates,373 2,3-Epoxygeraniol,200 6.7-Epoxygeraniol.200 1,2-Epoxyhexane,28 Epoxy ketones,315, 334 (+)-EremantholideA, 291 Ergot alkaloids, 166 Esterification,149 Ethers, 198 (2S,4R)-2-Ethoxycarbonyt-4-phenyl1,3oxazolidine, 135 3-Ethoxycarbonyltetrahydro7-pyrones,386 Ethyl (R)-a-aminocarboxylates,135 Ethyl diazoacetate,43 Ethyldimethylamine,247 Ethyl N,N-dimethylglycine,366 Ethylene glycol, 149 Ethylene oxide, 28 Ethyl glyoxylate, 27tl Ethylidenation,9 I (E)-Ethylidenecyclopropanone ketal, 136- 137 Ethylidenetriphenylphosphorane, 332 Ethyl (+)-lactate,339 E t h y l ( S ) - l a c t a t e1, 3 5 - 1 3 6 Ethylmagnesiation,107 Ethyl propiolate, 20lt S-Ethyl ethanethioate,341 S-Ethyl propanethioate, 342 (Z)-1-Ethylthio-1{rimethylsiloxypropene, 344 1 - E t h y l t h i o - l - t r i m e t h y l s i l y l o x y e t h e3n4e3, Ethyl vinyl ether, 258 Ethyl vinyl ketone, 344 Evans aldol reaction,336 Evans reagent, 125 Farnesylbariurn,26 (E,E)-Farnesylbromide, 26 (E,E)-Farnesylchloride, 25 Ferric chloride, 138 Fluoride ion,287 Fluoromethylenation,358 Fluoromethyl phenyl sulfones,358 1-Fluoro-1-(phenylsulfonyl)methanephosphonate,358 Fluorosilicic acid, 139 (Fluorovinyl)stannanes, 358 Fluorovinyl sulfones,358 4-Formyl-7-hydroxyindole,29 I

433

B-Formylpropionamides,4 Fremy's salt, 291 Friedel-Craftsacylation, 140 Friedel-Craftsreaction, 140 Fries carbamoyl transfer, 165 Fries iearrangement,15 Fumarimides,376 2,5-cls-Furans,52 Furan synthesis,289 Furanylglycine,54 Furanyl ketones,225 Furoyl chlorides, 22-5 Furylmanganesechloride, 225 GABOB see (R)-(-)-7-Amino-B-hydroxybutyric acid 34 1 B-o-Galactopyranosides, G a l l i u m ( l l ) c h l o r i d e ,1 4 0 G a l l i u m ( l l l )c h l o r i d e- S i l v e rp e r c h l o r a t eI,4 0 141 G e r a n i o l ,2 5 , 1 6 0 G e r a n y l b a r i u m2, 5 G i f i r o n s y s t e m ,1 5 7 Gilvocarcin, 105 o-Glucals, 3[i9 Glutamic acid, 211 Glutaraldehyde,148 Glycidic esters, 129 Clycosidation, 156 a - G l y c o s y l a t i o n3, 4 0 G l y c o s y l s u l f o x i d e ,l 5 l Glyoxal,190 Glyoxylate ene reaction,29 G r i g n a r dr e a g e n t s1, 0 ,7 5 , 9 4 , 9 6 , 1 0 6 ,l 1 7 , 1 3 6 , 141-142, 212, 216, 226, 227,271, 282, 323, 324, 339 (+)-Griseofulvin, 300 Halides, 143, 170 H a l o h y d r i n s ,1 7 9 , 3 9 2 6-Halo-1-ynes, 309 Heck cyclization, 256 Heck polycyclization, 266 Heck reaction,36, 37, 257, 259, 262, 267 Heck tetracyclizationof dienynes,265 Hecktype coupling, 256, 264 Hemiperoxyacetals,176 I, I , I,2,3,3,3-Heptamerhyltrisilane, I 43 Heptanal,157 1 , 6 - H e p t e n y n e s1,1 0 Heteroannelations, 73 Heterobimetallicreagents,218 Heterocycles,196, 197, 242, 3Ol, 307

434

Subject Index

Hexahydroazulenes,195 Hexalkylditin, 268 Hexamethylditin, 743- 744 5-Hexen-1-yllithiums, 144- 145 Hippadine, 268 (+)-Hirsutene,395 Hiyama reaction, 84 Homoallyl carbonates,152 Homoallylic aicohols,84, 154, 204,38O Homoallylic aldehydes,167 Homoallylic carbonates,153 Homoallylic ethers,382 syn-Homoallylic alcohols, 323 o-Homo-5a -androstanes,17t) [2+2+2]Homo-Diels-Alderreactions,32 Homo-Diels-Alder reactions,87 Homopropargylicalcohols,85, 220 Hydrazoic acid,24 Hydrazones, 206 Hydrindanes,269 rrazs-Hydrindanes,363 Hydroacetoxylation,258 Hydroamination,408 280 cis-Hydroazulenones, Hydroboration, 45, 6'1, 86, 172, 289, 316 1,4-Hydroboration,49 Hydrogenation,34, 45, 46 Hydrogen atom abstraction, 395 Hydrogenolysis,269 Hydrogen peroxide, 145-146

B-Hydroxy acrylates,57 B-Hydroxy aldehydes,184 B-Hydroxy amides, 329 a-Hydroxy-p-benzoylamino acid, 285 2-Hydroxybenzyl alcohol, 305 B-Hydroxy esters,34, 65 p-Hydroxy ketones,57, 359 B-Hydroxy sulfone, 292 (R)-3-Hydroxybutanoicacid, 61 4-Hydroxybuten olides, 277 (R)-3-Hydroxybutyric acid, 20tt (R,R)-6,6/-(I -Hydroxy-2,2-dimethylpropyl)2,2t -bipyridine, | 48 - 149 (S,S)-6,6/-(l -Hydroxy-2,2-dimethylpropyl)2,2t -bipy r idine, 748 - 1'49 a -Hydroxy-P,y-enoate, 346 7-Hydroxyenones,215 1-Hydroxy-3-isothiocyanatotetrabutyldistannoxane,149-150 Hydroxy-7-lactones,239 Hydroxylamines,31 I Hydroxylation, 249, 32O of naphthalene,145 Hydroxymercurials,145 Hydroxymethylation,391 N-Hydroxy P -lactam, 6'7

3-Hydroxy-4-phenyl-B-lactams,275 77 2-Hydroxyphenylselenoglucoside, 5-Hydroxy-3-pyrrolin-2-ones,252 296- 297 2-Hydroxytetrahydrofurans, 292 ridine, iopy N-Hydroxy-2{h Hydrogen peroxide/Urea-Phthalic anhydride, N-Hydroxy-2-thiopyridone,287 148 I 50 Hydrogen peroxide- Peroxotungstophosphates, IHydroxy(tosyloxy)iodo]benzene, a-Hydroxytrialkylsilanes,253 146-1.47 N-Hydroxyurethane,15 1 Hydrogen peroxide-Rhenium(VII) oxide, 147 Hydrozirconation,69, 70, 234 Hydrogen peroxide-Tungstic acid, 147 -148 Hypoiodite{ype reaction,280 exo-Hydroindole,280 Hydrolases, l33 Hydrolytic enzymes, 133 Hydrosilylation,42, 44, 96, 1,8O,202, 324, 341, 396 Hydrostannylation,27 a-Hydroxy aldehydes,123 Hydroxy acrylic esters,152 a-Hydroxy esters, 129 a-Hydroxy ketones,240 1-Hydroxy-2-alkanone,146 5-Hydroxyalkenes,296 Hydroxyamines,57 3-Hydroxy-2-amino esters,366 B -Hy droxy-a -amino acid peptides, 390 a-Hydroxy oximino ethers,331 3-Hydroxyaspartates, 249

lbuprofen, l4 lmidazoles, 201 202 Iminocyclopentadienes, Iminocyclopentenes,202 Indane,18 Indenyllithium, 126 Indium, 152 Indole synthesis,70, 263 23? (9-O-Indolinylcarbamoyl)dihydroquinidine, Indolizidines, 719, l2O Indolizidinones,255 Indolo[2,3-a]-quinolizidines,340 lndoloquinones,291 4,7-Indoloquinones,291

Subject Index ,rryo-Inositols, 63 a-Iodination, 153 Iodine monobromide, 152_ 153 Iodine/Pyridine, 153 Iodine-Silver trifluoroacetate,154 a-lodo-B-alkoxy esters,360 o-Iodoanilides,357 Iodocyclization,3 14 3 - l o d o - t . 2 - d i o l s ,I 7 4 B -Iodo-a, p -enones,2 I 9

Ketopinic ethyl esler, 63 Kinetic resolutions,66, 163 Knoevenagelcondensation,3g6

Lactams, 17, 120, 197,303 B - L a c r a m s ,1 0 2 , 1 6 3 , t 8 0 , 1 8 8 , 1 g 7 , 2 O g , 2 3 5 , 322 Lanthanide(lII) alkoxides, 160 Lanthanide(III) isopropoxides,160 Lanthanum(Ill) r-butoxide, 160_ l6l Iodoepoxides,281 Lead tetraacetate,406 Iodohydrins, 174,309 t-Leucinol, 43 4-Iodoindoles,70 Lipases, 133 a-lodoketones, 354 2-Lithio-Boc-pyrrolidine,3 I 8 Iodolactonization,155 4-Lithiobutoxide, 164 ( I o d o m e t h y t ) z i n c1, 1 5 2-Lithiodihydropyran,50 (Iodomethyl)zinciodide, 155, 220 4-Lithio- 1,3-dioxanes,20g Iodonium di-syn-collidineperchlorate,155_ 1-56 2 - L i t h i o - 1 , 3 - d i t h i a n el 9, Iodosylbenzene,90 L i t h i u m a c e t y l i d e s l,0 I o d o s y l b e n z e n e - T r i f l i ca n h y d r i d e ,1 5 6 _ 1 5 7 L i t h i u m a l u m i n u ma m i d e s ,1 6 2 Iodosylbenzene-Trimethylsilyl azide, 157 L i t h i u m a l u m i n u mh y d r i d e ,3 9 - 5 2-Iodosylbenzoicacid, 27 | L i t h i u m a l u m i n u mh y d r i d e - ( S ) _ 2 . 2_t D i _ Iodotrimethylsilane,332 hydroxy-4,-5,6,4/,5/,6/-hex amethoxybi_ | -Iodo-3,4,5-tri-o-(rriisopropytsilyl)-u-glucal, phenyl,162-163 72 L i t h i u m a m i d o c u p r a t e s2,l ( , Ionic hydrogenation,369 Lithium aminoborohydrides,170 Ireland-Claisenester rearrangement,3gl L i t h i u m / A m m o n i a ,l 6 l ' Ireland-Claisenrearrangement,128 Lithium biphenylide,25, 204 Iridomyrmecin, I l l L i t h i u m ( R , R ) - b i s ( l - p h e n y l e t h y l ) a m i d1e6,3 _ Iron(llI) acetylacetonate, 225 164 Iron(III) oxide, l5u L i t h i u m b o r o h y d r i d e3, 1 5 Iron powder, 157 Lithium bromide,134 Isobutyraldehyde,24O, 247, 25O L i t h i u m 4 , 4 / - d i - l - b u t y l b i p h e n y l i d1e6, 4 _1 6 5 Isocyanide-cyaniderearrangement,28g L i t h i u m d i b u t y l c u p r a t e1. 3 4 Isocyanides,143 L i t h i u m d i i s o p r o p y l a m i d e1, 6 5 ' 1 6 l Isomerases,133 L i t h i u m d i i s o p r o p y t a m i d e / B u t y l l i t h i u1m6,7 Isomerization,125 Lithium hexamethyldisilazane, 33 4-lsopropenyl-l-vinylcyclohexene,391 Lithium perchlorate, 167- l./(l Isopropoxydisilyl ethers,261 Lithium(phenylthio)-(trimethylstannyl)cuprate, Isopropylidine ketals, 374 l6l N-Isopropyl-(2S,6S)1,3,2-oxazaphosphorinane, Lithium pyrrolindoborohydride, I 70 1 5 8 _1 5 9 Lithium 2,2,6,6-tetramethylpiper idide, 1.7| _ t j2 Isovaleraldehyde,40 Lithium tetramethylthallate,I 72 Lithium triethytborohydride,t72 _ 173 Julia alkene synthesis,292 Lithium tris(diethylamino)aluminumhydride, Kemp's triacid, 375-317 173 Ketals, 198 Luche reagent,314 B-Keto acids, 133 2,6-Lutidine, 240 4-Keto-2-alkytborateesters,101 Lyases,133 p-Keto esters,33, 34, 133 B-Ketoimide,247 Macrolides, 394 a-Ketols, 146, 308 MAD see Merhylaluminumbis(2,6_di_l_butyl_4_ Ketones, 5 methylphenoxide)

436

Subject Index

Magnesium,4l-42 Magnesium(II) bromide etherate,174 Magnesium iodide, 174-175 Magnesium tetraphenylborate, 43 Makaiyama-aldolreaction,243 Maleamic acids, 241 Maleimides, 241 Mandelic acid, 218 Manganacycles, 223 Manganese(Ill) acetate, l7 5 - 176 Manganese(III) acetate-Copper(lI) acetate, 176 Manganese pivalate, 224 Mannich reaction, 182 Masanin, 264 Meerwein-Ponndorfreductions,160 Meerwein-Ponndorf-Verley reduction,203 Menthols, 55, 274 Menthyl carbamate,375 (S)-Menthyl p-toluenesulfinate,124 Menthyl sulfinate,48 Mercury(ll) acetate, 176 - 177 l-Mesityl-2,2,2-trifl uoroethanol, 178* 179 ortho-Metalation, 60, 2O1 Methanesulfonamide.237 Methanesulfonylchloride/Sodiumhydrogencarbonate, 180 . Methoxybis(trimethylsilyl)methyllithium, l I -Methoxy-1-(t-butyldimethylsilyloxy)ethylene, 168. 169 a -Methoxy-B-(dimethylphenylsilyl)-(E)hexenoates,38l (R)-2-Methoxy-2/-diphenylphosphino1,1/b i n a p h t h y l ,1 8 0 - t 8 l (S)-2-Methoxy-2/-diphenylphosphinol, I /b i n a p h t h y l ,1 8 0 - t 8 t (S)-2-(Methoxymethyl)pyrrolidine,182 2-Methoxynorbornadiene, 33 ( I S,2R)-2-(p-Methoxyphenylsulfonyl)aminoIphenylpropanol,l8l a -Methoxypropiophenone,363 5-Methoxytetralone,369 4-Methoxy-3-(triisopropylsilyl)pyridine,27 l, 282 I -Methoxy-3-trimethylsilyloxy-1,3-buradiene,

Methylaluminum bis(4-bromo-2,6-di-r-butylphenoxide), 184-187 Methylaluminum bis(2,6-di-/-butyl-4-methylphenoxide), 187-188, 274 Methylaluminum bis(2,6-diphenylphenoxide), 274 N-Methyl-a-amino esters,190 p-Methylanisole, 50 Methylasparticacid, 3 N-Methylaziridines,286 endo-2-Methylbicyclo[2.2.l)hept-5-enylethyl ketone,189 2-Methylbutadiene,278 2-Methylbutane,15 lB-Methylcarbapenems,367 Methyl corynantheate,340 Methyl crotonate,224 2-Methylcyclohexanone,41 4-Methylcyclohexanone,9l Methylcyclohexanones,91 Methyl cyclopentanecarboxylates, 183 10-Methyl-9,10-dihydroacridene/Sodium boroh y d r i d e ,1 8 9 - 1 9 0 Methylenation,69 a-Methylene homopropargylicalkoxide, 289 a-Methylene lactones,38 Methylenebenzofurans, ll a-Methylene-7-butyrolactones,155, 275, 349 2-Methylenecyclohexenones, 182 Methylenecyclopentanes, 309 Methylenecyclopentenes, 354 a-Methylene-7-lactams,278 Methylene 7-lactones, 152 Methyleneolactocin,275 Methylenetriphenylphosphorane, 69 2-Methylglutamic acid, 3 Methyl glyoxalate, 29 Methyl glyoxylate, 29, 346 1-Methylimidazole,349 Methyl ketones,30 Methyllithium, 60 M e t h y l m a n d e l a t e1, 8 8 , 2 1 8 Methyl methacrylate,224 N-Methylmorpholine N-oxide, 104 (S)-I -Methyl-2-[(N-naphthylamino)methyl]

244 lrans-1-Methoxy-3-trimethylsilyloxy-1,3butadiene1 , 82-183 a-Methyl aldehydes,189 a-Methyl a-amino acids, 2 M e t h y l a c r y l a t e ,1 8 3 - 1 8 4 , 2 2 3 , 3 4 4 Methyl p-(acylamino)acrylates,37 ( + )-3-Methylalerolactone,66

pyrrolidine, 344 (S)-1-Methyl-2-[(N-1-naphthylamino) methyllpyrrolidine, 342 (S)-1,I -Methyl-2-[(N-naphthylamino) rnethyllpyrrolidine,342 N-Methyl-N-nitrosourea,100 Methyl norbornadiene-2-carboxylate, 32 3-Methyl-1,6-octenyne,1l0

I

( (

: t I I

(

a l I (l

v v

U

v v v

M

v

M M M Mr

(-

Mi Mi Mi Mr M( M( M(

Mc Mo

Mo Mo Mo

Subject Index t. rl

Methyl orthoformate, 160 2-Methyl-3-oxo amides, 204 (Methyloxymethylene)triphenylphosphorane, 256 (R)-N-Methylphenylglycinol,190 (2R,3R,5R)-4-Methyl-5-phenyl-3-phenylthio-2morpholinol, 190 (S)-N-Methyl-l -phenyl-2-(I -piperidinyl)ethanamine.210 Methyl(phenylseleno)malononitrile, I 91 (2S,4R)-4-Methylpicolate,278 (2S,4S)-4-Methylpicolate, 278 4-Methylpipecolic acid, 278 2-Methylpropanal,157 Methylpyridines, 307 Methyl (R)-pyroglutamate,303 Methyl (S)-pyroglutamate,303 (2R,25,3S,4S)-3[( I -Methylpynolyl)methylamino]-1,7,7-trimethylbicyclo [2.2. 1l-he ptanol-2, 217 crs-B-Methylstyrene,98 a -Methylstyreneoxide, 226 2-Methyltetrahydrofuran,165, 213 Methylthioglucosides,156 (R)-Methyl-p-tolyl oxide, 48 Methyl (R)-p-tolyl sulfoxide, 48 Methyl trifluoromethanesulfonate, 191- lE2 Methyltrioxorhenium,I 92- 193 3-Methylundecane,106 Methyl vinyl ketone, 33 Methylvirologen, 133 M i c h a e l a d d i t i o n s 3, , 4 0 , 1 0 9 , 2 7 7 , 3 4 5 Michael-aldol cyclization, 55 Michael/aldol reaction, 332 Michael cyclization, 15, 182 Michael-Michael-Dieckmancyclization, ltl3 Michael reactions,276, 341.344 Microbial asymmetricreductions,133 (+)-Mitomycin K, 286 Mitsunobu esterification,27 Mitsunobu inversion, 185 Mitsunobu reactions,390 Molander cyclopropanation,305 Molecular sieves, 194 Molybdenum carbenecomplexes,81, 194- 195 Molybdenum imido alkylidine complexes,196197 Monochloroalane,197- 198 - Dimethylsullide, Monochloroborane 198-199 Monoclonal antibodies,134 Monodihydroxylationof 1,3-dienes,237 Monoperoxyphthalicacid, 199-2OO

Mukaiyama aldol reaction, 344 Mukaiyama-Michaelreactions,338 (+)-Muscarine,339 (R)-Muscone, 217 Naginata ketone,225 Naphthalene,100, 145 1,4-Naphthalenedicarbonitrile, 201 l-Naphthol, 145 2-Naphthol, 145 Naphthoquinones,90 l-Naphthyllithium, 130 8-(B-Naphthyl)menthylvinyl ether, 295 Nazarov cyclization, 386 Neocarzinostatinchromophore,112 Nephromopsinicacid, 85 Nezukone, 298 Nickel acetylacetonate, 202 Nickel(II) acetylacetonate, 201 Nicolaou's reagent,283 Nitrilases,133 Nitriles, 170, 205 Nitroaldol reaction, 160 Nitroalkanes,3l 1 Nitroalkenes,335 4 - N i t r o d i p h e n y l a m i n el 6, o-Nitrophenylacetonitrile,390 a-Nitroso reagents,64 4-Nitrosodiphenylamine,l 6 Nitrostyrene,335 Norbornadienes,32, 87 (1S,25,4R)-Norbornanol,180 Norbornene, l80 ezdo-5-Norbornene-2-ol,108 --Norephedrine, 64 (4R,5S)-Norcphedrine,3 I 7 Noyori reaction, 381 Noyori's reagent, 163 Nummularinc,3l6 N - O l i n k c d g l y c o s i d e s l, - 5 1

Octahydrophenanthrenc, 34 r-Octyl isocyanide, 260 -261 Olefination,9l Olefin metathesis,192, 196 Oppenaueroxidations, 160, 203 Oppolzer's auxiliary, 65 Oppolzer's o-isobornyl auxiliary, 275 Organoaluminumreagents,203-2O4 Organoantimonycompounds,204 Organobarium reagents, 204 -2O5 Organocerium reagents, 2O5-207 Organochromiumreagents,207

437

438

Subject Index

-27'7 OrganocoPPerreagents,2Oi 218 reagents' Orlanocopper/magnesium -222 Organocopper/zinc reagents, 218 Organolead comPounds, 223 reagents,223-226 Organomanganese Organosamarium(lII)reagents,226 Organosilver reagents' 226 22'7 -228 Organothallium reagents, 227 233 Organozinccarbenoids, -234 Organozinc reagents' 228 234 -235 reagents' Orlanozinc/zirconium Orthoesters,377 -236 Osmium(III) chloride, 235 Osmium tetroxide, 236-240

Palladium(II) acetate 1,3-Bis(diphenylphosphino)ProPane,259 -260 palladium(II) acetate-t-Octyl isocyanide' 260-261 262 Palladium(II) acetate-Triphenylarsine' -Triphenylphosphine' Palladium(II) acetate 263-268 Palladium(lI) acetylacetonate Tributylphos269 phine, (R)---Pantalactone, 2'7O 391 ParaformaldehYde, Pauson-Khandreaction, 1O5,2O2 -3-oxaPentacarbonyl[(R - | - aza-2,2-dimethyl

Osmium tetroxide-Bis(3-methyl-2,4-pentane-241 dionate)nickel(II), 240 325 4'7,236' Osmylation, 46, Oxabicyclo[4.I .0lhePtanes,304 -242 Oxalyl chloride' 241 s, 242-246, 283 Oxazaborolidine 283 OxazaPhosPholidines, Oxazinones,54, 63-64, 190 Oxaziridines,79 -249 Oxazolidinones,2, 247 334 2-Oxazolidones, Oxazolines,329 2 - O x a z o l i n e s1, 1 8 Oxepines, 326 Oxidation, 62 N-Oxidation' 14ti Oxidative cleavage,368 Oxidative cYclization, 175' 296

5-phenylcyclopentyl)(methyl)carbenel chromium, 80 27O-27 1' PentacarbonYliron, 223 Pentacarbonyl(trialkylsilyl)manganese' PentafluoroPhenol, 2O3' 2'l 1 27 1 Pentafluorophenyldiphenylphosphinate' Pentalenicacid, 109 144 Pentamethyldiethylenetriamine' 37 entamethylpiperidine' 1,2,2,6,6-P 4-Pentenals,37 Peptides,271 Peraceticacid,235 Perhydroindoles,108 Perilla ketone, 225 Periodinaneof Dess-Martin,271 acid' 401 PeroxYtrifluoroacetic Perylenequinone,138 Petersonelimination, 59

Oxidoreductases,133 (3S)-2,3-Oxidosqualene'244 Oximes, 170 Oxodiperoxymolybdenum(pyridine)(hexa-250 methylphosphorictriamide), 249 4-OxohePtanal,384 Oxy-CoPe rearrangement,290 O x y g e n ,s i n g l e t ,2 5 1 - 2 5 2 O*y!"n, singlet-Titanium(lV) 252-253 Oxygenation,30 Oxygen heterocYcles,196

isopropoxide'

Ozone,253-254 Ozonization, 368 OzonolYsis,291 -259 Palladium(II) acetate,255 acetate-3,3/'3l/-phosphinatriyltriPalladium(II) benzenesulfonate,262 Palladium(lI) acetate/Triphenylphosphine HexalkYlditin, 26A 269

l2epi-PGF2o,259 PhalazinesPacergrouP, 238 Phenols,74, 100 Phenol sYnthesis,32' 326 2'71- 2'72 - -8-(4-Phenoxyphenyl)menthol, Phenoxythiocarbonylchloride, 284 317 (4S)-PhenYlalanine, (S)jpt enytulaninedimethylamide' 2'73-2'74 dimethr--Phenylalanyl-r--phenylalanine ylanide, 274 PhenYl l-alkenYl ketones,49 31I 4-PhenYlbenzamides' 231 PhenYlbenzenethiosulfonate, 274 - 2'76 (1S,2R)-(+)-Phenylcyclohexanol' 337 55' -2-Phenylcvclohexanol' rrans (+\-tans-2-Phenyl-1-cyclohexyl,275 - - trans-2-Phenyl-1-cyclohexyl' 275 Phenylenes,31 160 1-PhenYl-2-ethanol, (R)-1-PhenYlethanol,42 (PhenylethYl)amide'241 (R)-1-Phenylethylamine,2'76 - 2'7I

Subject Index 276 - 27I (S)-1-Phenylethylamine, N-(9-Phenylfluorenyl)aspartates,249 (S)-Phenylglycine, 43, 278 - 279 (R)- - -2-Phenylglycinol,27I -28O tr ans -2-Phenylhexanol, 274 Phenyliodine(III)diacetate,280 Phenyliodine(lll) diacetate- Iodine, 28O-281 Phenyl isocyanide,143 276 (2R,3S)-3-Phenylisoserine, S-Phenylmenthol,55, 27 1, 274, 282, 337 8-PhenylmenthylglyoxYlate,346 (2R,4S)-2-Phenyl1,3,2-oxazaphospholidine' 282-283 2-Phenylpropanal, 223 4-PhenylpyridineN-oxide, 98 283 N-(Phenylseleneno)phthalimide, 283 Phenylselenenylation, a-Phenylselenenylmethylethers,352 P h e n y l s e l e n i d e s3, 1 6 Phenylselenylchloride, 154 Phenylsilane,284 (+)-(N-Phenylsulfonyl-3,3-dichlorocamphoryl)oxaziridine,284- 285 - -(N-Phenylsulfonyl-3,3-dichlorocamphoryl)oxaziridine,284- 285 (R,R)-2-Phenylsulfonyl-3-phenyloxaziridine, 320 (S,S)-2-Phenylsulfonyl-3-phenyloxaziridine, 320 232 a -(Phenylthio)alkenylstannane, a-(Phenylthio)alkenylzincreagents,231 Phenylthioalkynes,231 (Phenytthio)methyl azide, 286 286 (Phenylthio)methylaziridine, Phenyltributyltin,267 N-Phenyltriflimide, 293 3-Phenyl-3-(trifluoromethyl)diazirine,287 Phenyl vinyl sulfone, 33 Phoboids, 192 Phosgene, 288 Phosphazeniumfluoride, 287 159 Phosphonamidates, Phosphoryl chloride, 288 Photocatalysis,189 Photodemetalation,223 Photooxygenation,251 Phthalic anhydride, 148 Pig liver acetonepowder, 55 Pinacol, 403 Pinacolborane, 288 - 289 Pinacof coupling, 391',392 Pinacol homocoupling,393 Pinacol rearrangement,17

439

Pipecolic acids,277 Piperazines,l28 Piperidones,102 trans-Piperylene, 402 Pivaldehyde,250 PLAP see Pig liver acetone Powder PMDTA see Pentamethyldiethylenetriamine Polyamino alcohols, 198 Polyamino ethers, 198 Polycyclization, 267 Polyene cyclizations, 178 Poly(p-phenylene),3 1 Potassiumt-butoxide, 56, 289-29O Potassiumhydride-l8-Crow n-6, 290 Potassiumnitrosodisulfonate,291 Potassiumtriethylmethoxide, 29 | - 292 PPSE see Selenium dioxide-Trimethylsilyl polyphosphate Prelog-Cramrule, 133 P r e n y l h a l i d e s ,l 7 l r--Proline,216 (S)-Proline,344 (S)-(+)-Prolinol, 282 Propargyl acetates,394 Propargylamines,207 Propargylic alcohols, 344 Propargylic copper/zinc teagents, 220 Propargylic halides, 87 353 Propenylcyclobutanes, N-Propionyloxazolidinone,248 N-Propionyloxazolidone, 344 Propriolic acid,27 --(S)-Propylene oxide, 371 Prostaglandins,25[l Proteases,l33 Proton sponge, 36 Pyran-2-ones,294-295 Pyridinecarboxylicacids, 307 2-Pyridinethiol | -oxide, 292- 293 Pyridinium dichromate,U7 Pyridinium p-toluenesulfonamide,83 ll0 , ' 128 P y r i d i n i u mp - t o l u e n e s u l f o n a t e Pyridones,332 2-Pyridones,295 Pyridyloxazolines,42 N-(2-Pyridyl)triflamide,293 Pyridylzinc halides, 293 -294 Pyroglutamic acirJ,22 2-Pyrones,53, 294, 295, 349 Pyrrole-2-carboxylicacids, 252 Pyrrolidines, 102, 279, 388 Pyrrolines, 79, 197 Pyrrolinones,279

440

Subject Index

Pyrrolizidinones,255 Pyrylium salts, 191 Quinolizidines, 179, 12O Quinone ketals, 50 m-Quinquearyls,330 [4+l]Radical annelation,143 R a d i c a la d d i t i o n s ,1 9 1 , 3 7 5 , 3 7 6 Radical allylation, 376 Radicafcyclization,I 76, I 89, 307, 35'7,362, 363 Radical deoxygenation,361 Radical epoxidation,391 Radical macrocyclization,359 Radical reactions,356 Radical reduction, 743, 360, 367 Radical ring expansion,353, 355 Ramberg-Biicklundrearrangement,291 RAMP see (R)-l -Amino-2-methoxymethylpyrrolidine Raney nickel, 286,296 Reduction, 282,36-/ Reductivecleavageof hydrazines,296 R e d u c t i v ec y c l i z a t i o n ,3 1 0 Reductive lithiation, 164 Reductive oxygenation,362 Reformatsky reaction, 310 Reformatsky rcagents,228 Resolution,164 Retro-aldol reaction, 56 R h e n i u m ( V l l )o x i d e , 1 4 7 ,2 9 6 - 2 9 7 Rhodium(ll) carboxylates,29tl -302 Rhodium(ll) octanoate,2'70,3Ol Rhodiun(ll) pivalate, 300 Rhodium(ll) pyroglutamatcs,303-304 Ring expansion, 102 Ruthenium(lV) dioxide, 304 Ruthenium tetroxide, 27'7 reaction,385 Sakurai-carbonyl-ene Sakurai reaction,347, 380, 381 S a l i c y l a l c o h o l ,3 0 5 Samarium diiodide, 293 S a m a r i u m ( l l )i o d i d e - L i t h i u m a m i d e , 311 -312 Samarium iodide, 226 S a m a r i u m ( I l )i o d i d e ,3 0 7 - 3 1 I Samarium/Methyleneiodide, 305-306 iodide, 306-307 Samarium(O)/Samarium(II) SAMP hydrazones,15 SAMP see (S)-1-Amino-2-methoxymethylpyrrolidine SarohorneneB, 59

SarohorneneC, 59 Schmidt type reaction, 345 , 3, 69,212,234 S c h w a r t zr e a g e n t 3 A, 369 Secopseudopterosin Seebach'sspirotitanate,228 para-Selectivity, 4O2 Selenadiazoles,31.2,313 Selenides,143 S e l e n i u md i o x i d e ,3 1 2 - 3 1 3 Selenium dioxide-Trimethylsilyl polyphosphate,313 2 a - ( S e l e n o p h e n y l ) - a - o - p y r a n o n3e8s9, Selenoxides,316 S e m i c a r b a z i daec e l a l e ,3 | 2 Semicorrins,23 36 Sesquiterpenes, Sharplessasymmetricdihydroxylation,76 Sharplessasymmetricepoxidation,57, 58, 184, 185 Sharplessepoxidation, 194 Sharplesskinetic asymmetricepoxidation,110 [3.3]Sigmatropicrearrangement,195 Sifacyclopentadiene,202 Silica,156 S i l o x a n e s3 , 24,326 Silver perchlorate,105- 106 3 ,1 3 - 3 1 4 Silver trifluoroacetate 314 Silver trifluoromethanesulfonate, a - S i l y l k e t o n e s ,2 0 6 B - S i l y l a l l y l i c a l c o h o l ,2 5 2 B-Silyl-(E)-crotylsilanes,52 Silyl epoxy alcohols, 252 Silyl ketene acetals,33ll O-Silyl-N,O-keteneacetals,65 O-Silyl ketene acetals, 168 a - S i l y l o x y a l d e h y d e s1, 2 3 (Silyloxy)acetates,27-5 B - S i l y l o x y a l d e h y d e s1, 8 4 , 1 8 5 Silyloxycyclopropanes,l l4 1 , 4 - S i l y l s t a n n a t i oonf 1 , 3 - d i e n e sl ,0 l Simmons-Smithreagent,93, 115, 11.6,22O Skipped diynes, 87 Sodium amalgam, 292 Sodium azide, 68 hySodium bis(2-methoxyethoxy)aluminum dride,59 Sodium borohydride, 189 Sodium borohydride-Cerium(III) chloride, 314-315 Sodium borohydride-Iodine, 316 Sodium dichromate,87 Sodium hydrogen carbonate,180 Sodium hypochlorite,316, 332

s s s

s s s s s s

S (l f

s s s s

S

s s s s s c

S

s s

\ :{

S

s s T

s

S' S

s

S. S| St

T/

n

Tl

(n

Tt

Tr Tr

Tc

Subject Index Sodium phenyl selenide,316-317 Sodium tetramethylboronate, 315 Sonication, 150 - - S p a r t e i n e ,3 1 8 - 3 1 9 Spiroannelation,354 Spirocyclic ethers,255 Spirocycloheptanones, 354 S p i r o k e t a l s2, 2 3 , 2 2 4 Spirolactones,223, 280 Spirooxindoles,37 Squalene,25 (E)-Squalene,26 B-Stannyl ketones, 167 Stannylcupration,207 Stemodin, 102 Stemona alkaloids, 280 Steroidal alkaloids, 47 Steroids, 385 cls-Stilbene,90 Stille carbonylativecoupling, 329 Stifle coupfing, 232, 261, 327, 328, 364 Stilf e macrocyclization, 27 Stille reaction, 54, 364,394 Styrene, 226 C-Styryl glycosidation,77 Sulfenimines,284 Sulfinates,3l8 Sulfinimines, 2tl4 N-Sulfinylcarbamates,337 N-Sulfinyloxazolidinones,3 I 7-3 I 8 Sulfonamides,3 18 Sulfones, 148 N-Sulfonyloxaziridines,320 N-Sulfonyltriazene,371 S u l f o x i d e s ,1 3 5 , l 4 l J , 3 l t 3 Sultams, 155 Superacids,145 Supersilylation,379 S u z u k ic o u p l i n g , 1 1 7 Suzuki cross coupling, 330 Swern oxidation, 127, 244, 264, 325

TADDOLS see a,a,at,at -Tetraaryl-1,3dioxolane-4,5-dimethanols Tantalum-alkynecomplexes,321 Tantalum(V) chloridelZinc, 321 .(R,R)-Tartaric acid, 228, 321- 323 TASF see Tris(diethylamino)sulfonium difluorotrimethylsilicate Taxanes,359 Taxol, 276 Tebbe reagent, 69

441

TEMPO see 2,2,6,6-Tetramethylpiperidineloxyl p-Teraryls, 330 a,a,a',a | -Teftaaryl-1,3-dioxolane-4,5dimethanols,323-324 Tetraaryls, l39 1,4,8,11-Tetraazacyclotetradecane, 89 Tetrabutylammoniumacetate,36 Tetrabutylammoniumchloride, 87-88 Tetrabutylammoniumfl uoride, 324- 326 Tetracarbonyl-p,-dichlorodirhodium, 326 Tetracetyl acetals,139 Tetrafluorosilane,327 Tetrahydroazepines, 197 Tetrahydrofurans,52, 154, 164, 223, 263, 351, 352, 388 Tetrahydroindenones, 15 Tetrahydroindolizines,103 1,2,3,4-Tetrahydronaphthalenc, l13 Tetrahydropentalenones, l5 Tetrahydropyrans,165, 263, 3-52,381 Tetrahydropyridines,73, 197 Tetrakis(triphenylphosphine)palladium, JZI_JJI

Tetramethylammoniumtriacetoxyborohydride, JJ | - -t-rz

1,1,3,3-Tetramethylbutyl isocyanide,260 Tetramethylguanidine, 332 2,2,6,6-Tetramethylpiperidine1-oxyl, 3 16 2,2,6,6-Tetramethylpiperidinium bromide, 17 I 2,2,6,6-TetramethylpiperidinylI -oxyl, 332 Tetraphenyldistibene, 333 Tetraphenylporphine, 25 I (Tetraphenylporphrinato)n ickel(ll), 250 Tetrasubstituted tetrahydrofurans,2ii3 Tetronic acids,277 Thallium acetate,3tl Thexylborane,fl6 Thioglucoside, l-56 Thionocarbonatc s, 2t14,367 Thionoesters,I43 Thionyl chloride, 329 Thiophosgene,284 Three-componentcoupling, 210, 258 (S,S)-Threitol 1,4-dibenzyl ether, 239 Tigliane, 192 Tin,333-334 Tin(lI) chloride, 334-335 Tin(II) trifluoromethanesulfonate, 341 Tin(II) trifluoromethanesulfonate-Chiral dianine,347-344 Tin(lV) chloride, 335-339 Tin(IV) chloride-Silver perchlorate,340

Subjmt Index

Tin(IV) chloride-Trifl uoroacetic acid, 340 Titanacycles, 73 Titanium(IV) chtoride, 179, 223. 344_347 Titanium(IV) isopropoxide, 49, 57_58, 181. 252_253,347_348 (R)- - -Tolualdehyde(tricarbonyl)chromium complex, 20 p-Toluenesulfonamides, 349 p-Toluenesulfonic acid, 294 N-(p-Toluenesulfonyl)iminophenyliodinane,

Triethoxysilane -Titanium(IV) isopropoxide, 366 Triethylaluminum, 367 Triethylamine, 139 Triethylborane, 357, 366, 367 Triethylsilane-Benzoyl peroxide, 367 Triethylsilane-Titanium(IV) chloride, 367_ 368 Triethylsilyl hydrotrioxide,368-369 Triflic acid, 89 348 Trifluoroacetic acid, 277 I -Toluenesulfonyl-3-methylimidazolium trifl ate, Trifl uoroacetic acid -Trialkyls ilane, 369_ 37O 348-349 Trifluoroaceticanhydride, 13, 90, 401 3-(p-Tolylthio)-2-py rone, 349 Trifl uoromethanesulfonic acid, 24 3-(Tolylthio)-l -tosyl-2-pyridones,350 Trifl uoromethanesulfonic acid/Boron(lII) tri_ Tosylmethyl isocyanide, 20 fl uoromethanesulfonate,37O- 37 1 a-Tosyloxylation, 150 Tri-2-furylphosphine,394 N-Tosyl-(S)-tryp tophan, 246 Triisobutylaluminum,124 N-Tosyl-(S)-valine,246 (+)-(S,S,S)-Triisopropanolamine, 371 t TPPTS see Palladium(ll) acetate-3,3t St Triisopropyl azide,68 phosphinotriyltribenzenesulfonate 2,4,6-Triisopropylbenzenesulfonyl azide, 37 1 Transesterifi cation, 133 Triisopropyl enol ethers, 157 Transferases, 133 Triisopropylsilyl enol erhers,68, 371-372 TRAP see 2,2//-Bis[1-(diphenytphosphino)_ Triisopropylsilyl ethers, 184 //-biferrocene ethyll- 1,I Trimethylaluminum, 372 - 375 Trialkylsilylacetic acid, 372 1,3,5-Trimethyl-1,3,5-cyclohexanetricarboxylic Trialkylsilylketenes,206 acid, 375-377 Triazolines, 286 Trimethyleneamines,197 Tribenzyl-o-arabinofuranose, 26 Trimethyl orthoacetate,377 -3711 Tribromophenol, 100 Trimethylsilyl azide,'l 57 2,4,6-Tri- t-bltylphenol, 203 Trimethylsilyl azide- Iodosylbenzene,37g (Tributylstannyl)allylamines, 207 Trimethylsilylboron triflate, 378-379 -(Tributylstannyl)-1,3-dioxanes, 208 Trimethylsilylcyclohexenols,387 crs-2-Tributylstannylvinyl(cyano)cuprate, 2l I [(Trimethytsilyl)ethynyll-9-borabiTributyltin, 161 cyclo[3.3.I lnonane, 379 Tributyltin carbamate,350-351 N - ( T r i m e t h y l s i l y l ) i m i n e2,7 5 Tributyltin fluoride, 341, 342 Trimethylsilyl-2,3,4,6-tetra-O -acetyl- -oB Tributyltin hydride, 1,32, 143, 174, 2g2, 3Og, glucopyranoside,380 3 6 1 3 5I (Trimethylsilyl)triburylsrannane, l 01 Tributyltin hydride-Oxygen, 362 Trimethylsilyl triflate, 26 Tributyltin hydride-Tetrabutylammonium, 363 Trimethylsilyl trifluoromethanesulfonate, 379_ Tributyftin hydride-Triethylborane, 363- 364 386 (Tributyltin)methyl erher, 352 Trimethylsilyl trifl uoromethanesulfonate _ Tributyl(trimethylsityl)tin,364 -365 Silver perchlorate,3g6-3g7 (Tricarbonyl)chloroiridium,365 Trimethylsilyl a -(trimethylsilylperoxy) TricarbonylIo-(rrimerhylsilyl)benzaldehyde] carboxylic esters,379 chromium complex, 20 Trimethylsilylvinyl-9-borabicyclo[3.3. I lnonane, Trichloromethyl ketones,245 379 Trichloromethylsilane - Diphenyl sulfoxide, 2-Trimethylsilylvinyl-9-borabicyclo[3.3. 1| 365 nonane,387 Trienes, 59 (Trimethylsilyl)vinyl phenyl selenide,387_388 Triethoxysilane- Rhodium(III) chloride, Trimethyltin chloride/AlBN/NaBHrCN, 388_ 366 389

1 I I t T I

TI Tl

Tl

Tr Tr Tr Tn

Tn

Tn Tri

Tn Tn Tn Tn Trr Tn; a-l Tq Trr Tur I:.: Tue

uth Ultr a.p 9.t Urcz L-\h

(s> Vc* (2Sj Vcni

p-\r Vira

Subjmt Index Triols, 261 1,2,4-^lriols, 261 1,2,4-Trioxanes,176, 368, 369 1,2,4-Trioxan-5-ones, 379 Triphenylarsine, 262, 394 Triphenyl borate, 118- 119 Triphenylphosphine,88, 334-335 - Diethyl azodicarboxyTriphenylphosphine late, 389-390 - Diisopropyl azodicarbTriphenylphosphine oxylate, 390 Triphenylsilyl ethers, 184 Triphosgene,127,264 Triquinanes,109, 395 Tris(alkylthio)silanes,395 Tris(4-bromophenyl)aminiumhexachloroantimonate, 391 -chloro)hexakis(tetrahydrofuran)diTris(,r^c vanadium hexachlorodizincate, 391-393 Tris(dibenzylideneacetone)dipalladium, 37, 394 Tris(diethylamino)sulfonium difluorotrimethylsilicate, l4 Tris(phenylthio)methane, 394- 395 Tris(trimethylsilyl)silane,357, 395- 397 Trisyl azide,67,371 Tri-o{olylphosphine, 256 Trivinylborane, 403 Triynes, 329 a-Tropolone O-methyl ether, 126 Tropones, 298 Tungstencarbenecomplexes,397-400 Tungstic acid,147-748 l2-Tungstophosphoricacid, 146 Tunicaminyluracil, 113 Ullmann coupling, 305 Ultrasound.206.406 a,p-Unsaturated ketones,189 p,7-Unsaturated carboxylic acids, 9 Urea-Hydrogenperoxide complex, 401 t--Valine, 182 (S)-Valine methyl ester, 406 Vedejs reagent, 249 (25,3R)-- -Verrucarinolactone, 66 Yertinolide, 277 6-Vetivone, 184 Vineomycinone82 methyl ester, 60

443

endo-6-Yinylbicyclo[2.2. I ]heptene-2, 354 Vinyl-9-borabicyclo[3.3. I ]nonane,402 9-Vinyl-9-borabicyclo[3.3. I lnon ane, 4O2- 4O3 Vinyl chloroformate, 190 Vinyl cuprates,210 I -Vinylcyclohexene,39 I Vinylcyclopropanes,81, 171, 195 Vinyldichf oroborane, 4O3- 4O4 Mnyldimethylborane,403 I -Mnyl-3,6-dimethylborepane,403 Vinyl ethers, 295 Vinyl fluorides, 358 Vinyl halides, 364 Mnylic lithiocyanocuprates, 212 Vinyl ketones,40 Vinylogous Barbier reaction,310 Mnylsilanes, 252, 381, 404*405 (E)-Vinylsilanes,346 (Z)-Vinylstannanes,70 Vinyl sulfones,39 Vinyl sulfoxides, 39 2-Vinyltctrahydrofuran,165 Vinyf triflates, 293, 364 Viologen, 134 Vitamin 812, 407 Williams glycinate, 54 [2,3]Wittig rearrangement,59, 290 Wittig-Horner reaction, 159, 325 Wittig olefination, 264 Wittig reaction, 259, 332 Wittig reagent,69 Wittig-type reactions,204 Xanthanates,367 Xanthates,2{34 o-Xylene, l8 Ynediols, 238 Z e i s e ' sd i m e r , 1 1 4 Zinc, 406-4O7 Zinc chloride, 182 Zinc-Copper couple, 407 Zirconacycles,70, 108 Zirconium bisamides, 407 -408 Zirconium hydrochloride,69