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