Photochemical Key Steps in Organic Synthesis

Photochemical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck VCH Photochemical Key Step...

Author: Jochen Mattay | Axel Griesbeck

34 downloads 2094 Views 21MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!

Report copyright / DMCA form

DOWNLOAD PDF

Photochemical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck

VCH

Photochemical Key Steps in Organic Synthesis An Experimental Course Book Edited by Jochen Mattay and Axel G. Griesbeck in cooperation with Christian Stammel, Joachim Hirt and Thomas Rumbach

4b

VCH

Weinheim - New York Base1 - Cambridge - Tokyo

0 VCH Verlagsgesellschaft mbH, D-69451 Weinheim (Federal Republic of Germany), 1994 ~~

~

_______

Distribution: VCH, P.O. Box 101161, D-69451 Weinheim (Federal Republic of Germany)

Switzerland: VCH, P.0.Box, CH-4020 Basel (Switzerland)

United Kingdom and Ireland: VCH (UK) Ltd., 8 Wellington Court, Cambridge CB11HZ (England)

USA and Canada: VCH, 220 East 23rd Street, New York, NY 10010-4606 (USA)

Japan: VCH,Eikow Building, 10-9 Hongo 1-chome, Bunkyo-ku, Tokyo 113 (Japan) ISBN 3-527-29214-4

Synthetic organic photochemistry constitutes a research area with exceptional importance for the development of efficient and selective transformations for the preparation of natural products as well as unnatural and complicated molecules. However, a remarkably high level of resistance still exists towards integrating this type of reactions in experimental courses for students, and thus presenting this important area of chemistry at an early stage of the training of chemists. A reason for this resistance could be the lack of appropriate experimental procedures in textbooks and manuscripts for experimental courses. Another reason should be sought in the lack of the necessary photochemical equipment in many laboratories - basically trivial reasons having a great effect on the training of young chemists. Some time ago we developed the idea of combining a number of experimental procedures for multistep synthesis with one or two photochemical key steps. We tried to collect these procedures directly from the respective researchers. Who else could tell us more about all the tricks and requirements than the photochemist himself who developed the synthesis? Therefore we asked leading chemists active in the field of organic photochemistry to kindly support us with their "showpieces".The very positive response allows us now to present a collection of experimental procedures from nearly every area. An important task was to define the requirements for useful and widely applicable photochemical procedures. Nor only should the light induced reaction be efficient and show high chemo-, regio-, and (if possible) stereoselectivity but also be an integral ingredient of an interesting multistep synthesis. The starting materials, solvents, and reagents for these syntheses should be cheap and readily available, the necessary photochemical equipment available in most institutes, and the products well characterized and not synthesized for the sake of example. Additionally, we tried to include other modem techniques and reactions such as the preparation of organometallic compounds as well as catalytic or stoichiometric stereoselective transformations. This book should therefore give supervisors of lab courses the opportunity to take over new experiments and students to learn more about modem techniques and especially about the importance of photochemistry. We would like to express our thanks to all colleagues who have contributed experimental procedures of a high quality. The help of Christian Stammel, Joachim Hirt and at an early stage of Thomas Rumbach is gratefully acknowledged. Their effort was substantial as well as the help of Dr. Ute Anton and her coworkers at the VCH.

Jochen Mattay, Axel G. Griesbeck

Editors: Prof. Dr. A. Griesbeck Institut fur Organische Chemie der Universitgt GreinstraSe 4 D-50939 Koln Germany

Prof. Dr. J. Mattay Organisch-Chemisches Institut der Universitt CorrensstraBe 40 D-48149 Miinster Germany

This book was carefully produced. Nevertheless, editors and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Published jointly by VCH VerlagsgesellschaftmbH, Weinheim (Federal Republic of Germany) VCH Publishers Inc., New York, NY (USA) Production Manager: Dip1.-Wirt.-Ing. (FH) H.-J. Schmitt

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library Die Deutsche Bibliothek - CIP-Einheitsaufnahme: Photochemical key steps in organic synthesis : an experimental course book / ed. by Jochen Mattay and Axel G. Griesbeck. In cooperation with Christian Stammel .. -Weinheim ;New York ;Basel ;Cambridge ;Tokyo : VCH, 1994 ISBN 3-527-29214-4 NE: Mattay, Jochen [Hrsg.]

0 VCH VerlagsgesellschaftmbH, D-69451 Weinheim (Federal Republic of Germany), 1994

Printed on acid-free and chlorine-free paper All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form - by photoprinting, microfilm, or any other means - nor transmitted or translated into a machine language without written permission from the publisher. Registered names, trademarks, etc. used in this book, even when not specifically marked as such are not to be considered unprotected by law. Printing and Bookbinding: Druckhaus ,,Thomas Mtintzer" GmbH, D-99947 Bad h g e n s d z a Printed in the Federal Republic of Germany.

Contents List of Contributors How To Use This Book

1

General Features

1

1

Carbonyl Compounds

11

1.1 Aldehydes and Ketones

11

1.2 Enones and Dienones

70

2

Nitrogen-containing Chromophores

119

3

Aromatic Compounds

169

4

Alkenes, Arylalkenes and Cycloalkenes

201

5

Organometallic Compounds

261

6

Photooxygenation and Photoreduction

285

7

Photochemistry in Organized Media

299

8

Photochromic Compounds

307

Graphical Index

319

Index: Photochemical Key Steps

336

Subject Index

339

List of Contributors A. A. Abdel-Wahab, Department of Chemistry, University of Assiut, Assiut I Egypt Waldemar Adam, Institut fur Organische Chemie, Am Hubland, D-97074 Wiirzburg I Germany Angelo Albini, Dip. di Chimica Organica, Via Taramelli 10,1-27100 Pavia / Italy Diego Armesto, Departamento de Quimica Organica I, Facultad de Ciencias Quimicas, Universidad Complutense de Madrid, E-28040 Madrid / Spain Henri Bouas-Laurent, Photophysique et Photochimie MolCculaire CNRS U. A. 348, Laboratoire de Chimie Organique, UniversitC de Bordeaux 1, F-33405 Talence Cedex I France Janine Cossy, Ecole Superieure de Physique et Chimie Industrielles, Unit6 de Chimie Organique, 10 rue Vauquelin, F-75231 Paris Cedex 05 / France Denis De Keukeleire, Faculty of Pharmaceutical Sciences, University of Ghent, Harelbekestraat 72, B-9000 Ghent I Belgium Martin Demuth, Max-Planck-Institut fiir Strahlenchemie, Stiftstr. 34-36, D-454 13 Mulheim an der Ruhr I Germany Dietrich Dopp, Universitat-Gesamthohschule Duisburg, Organische Chemie, Lotharstr. 1, D-47048 Duisburg / Germany Heinz Durr, Fachbereich 11.2, Organische Chemie der Universitat des Saarlandes, D-66123 Saarbrucken / Germany Andrew Gilbert, Department of Chemistry, University of Reading, Whiteknights, PO Box 224, Reading, Berkshire, RG6 2AD / United Kingdom Rolf Gleiter, Organisch-Chemisches Insitut, Im Neuenheimer Feld 1, D-69 120 Heidelberg / Germany Axel G. Griesbeck, Institut fur Organische Chemie, Universitat Wiirzburg, Am Hubland, D-97074 Wiirzburg / Germany Eietsu Hasegawa, Department of Chemistry, Faculty of Science, Niigata University, Ikarashi, Niigata 950-21 /Japan Louis S. Hegedus, Department of Chemistry, Colorado State University, Fort Collins, CO 80523 / USA

Tsutomu Miyashi, Department of Chemistry, Faculty of Science, Tohoku University, Sendai 980 I Japan Kazuhiko Mizuno, Department of Applied Chemistry, College of Engineering, University of Osaka Prefecture, Sakai, Osaka 593 I Japan Reinhard Neier, Institut de Chimie, Avenue de Bellevaux 5 1, CH-2000 Newhatel/ Switzerland Albert Padwa, Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta, GA 30322 I USA Bipin Pandey, Division of Organic Chemistry, National Chemical Laboratory, Pune 41 1 008 I India Ganesh Pandey, Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 41 1 008 I India Jean-Pierre Pkte, Laboratoire des Rearrangements Thermiques et Photochimiques associe au C.N.R.S., Universitk de Reims Champagne-Ardenne, U.F.R. Sciences, F-5 1062 Reims Cedex I France Horst Prinzbach, Chemisches Laboratorium der Universitat Freiburg i. Br., Institut fur Organische Chemie und Biochemie, Albertstr. 2 1, D-79 104 Freiburg I Germany James H. Rigby, Department of Chemistry, Wayne State University, Detroit, MI 48202 I USA Hans-Dieter Scharf, Institut fur Organische Chemie, Technische Hochschule Aachen, Prof.-Pirlet-Strasse 1, D-52056 Aachen I Germany John R. Scheffer, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Y6 / Canada Harikisan R. Sonawane, Division of Organic Chemistry: Technology, National Chemistry Laboratory, Pune 41 1 008 I India Eberhard Steckhan, Institut fur Organische Chemie und Biochemie der Universitat Bonn, Gerhard-Domagk-Str. 1, D-53121 Bonn I Germany Hiroshi Suginome, Organic Synthesis Division, Faculty of Engineering, Hokkaido University, Sapporo 060 /Japan Lutz F. Tietze, Institut fur Organische Chemie der Universitat Gottingen, Tammannstr. 2, D-37077 Gottingen I Germany

Heinz Heimgartner, Organisch-Chemisches Institut der Universitat Zurich, Winterthurerstr. 190, CH-8057 Zurich / Switzerland Hans Georg Henning, Institut fur Organische Chemie, Humboldt-Universitat Berlin, Hessische Str. 1 - 2, D-10115 Berlin / Germany H. Martin R. Hoffmann, Institut fiir Organische Chemie, Schneiderberg lB, D-30167 Hannover / Germany Norbert Hoffmann, Facultk de Sciences, Universitt de Reims Champagne-Ardenne, B.P. 347, F-51062 Reims Cedex / France Henning Hopf, Institut fur Organische Chemie, Technische Universitat Braunschweig, Hagenring 30, D-38106 Braunschweig / Germany William M. Horspool, Department of Chemistry, University of Dundee, Dundee DD14HN / United Kingdom

Y. Inoue, Department of Chemical Process Engineering, Faculty of Engineering, Osaka University, Yamadaoka, Suita 565 /Japan George Just, Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, PQ H3A 2K6 / Canada Gerd Kaupp, Fachbereich Chemie - Organische Chemie I - Universitiit Oldenburg, Postfach 2503, D-26129 Oldenburg / Germany Wim H. Laarhoven, Department of Organic Chemistry, University of Nijmegen, Toernooiveld, NL-6525 ED Nijmegen / The Netherlands Giinther Maier, Institut fiir Organische Chemie, Justus-Liebig-UniversitatGieBen, Heinrich-Buff-Ring 58, D-35392 GieBen / Germany Paul Margaretha, Institut fiir Organische Chemie, Universiat Hamburg, Martin-LutherKing-Platz 6, D-20146 Hamburg / Germany Jochen Mattay, Organisch-Chemisches Institut, Universitat Munster, Orltansring 23, D-48 149 Munster / Germany Herbert Meier, Institut fiir Organische Chemie, Universitiit Mainz, J.-J. Becher-Weg 18 22, D-55128 Mainz / Germany Craig A. Merlic, Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90024 / USA

Alan C. Weedon, Department of Chemistry, University of Western Ontario, London, Ontario, N6A 5B7 I Canada Paul A. Wender, Department of Chemistry, Stanford University, Stanford, CA 94305 / USA Jeffrey D.Winkler, Department of Chemistry, University of Pennsylvania, 23 1 South 34th Street, Philadelphia, PA 19104/ USA Howard E. Zimmerman, Department of Chemistry, University of Wisconsin at Madison, 1101 University Avenue, Madison, WI 53706 I USA

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

How To Use This Book Many syntheses in this collection represent multistep procedures starting with readily available compounds which are transformed using non-photochemical methods into the necessary substrates for the photochemical "key-step".A number of sequences, however, already require substrates which must be prepared using procedures from the literature. In each case, you should consult the literature which is given by the authors and find out about a) the source for all substrates and reagents used in the synthesis, b) the photochemical set-up which was used by the authors, c) the purification of starting materials and solvents as well as the characterization of the products, d) the mechanism of the reaction. Never avoid a walk to the library before you run a reaction! Always recalculate the reaction stoichiometry. Many problems and also hazards can originate in wrong reaction stoichiometry. Never take numbers just as they are written in a textbook or a publication. Always confirm for yourself that these numbers make sense! Photochemical reactions sometimes are capricious (vide infra). Many parameters can influence the outcome of such a reaction. Always run a UV spectrum of your photoactive compound and compare it with the data given in literature. Sometimes it is useful to check the quality of the radiation source by running a standard photochemical reaction where the quantum yield is known and the products are easy to characterize.

GENERAL FEATURES a) Further reading: from introductory to sophisticated photochemistry You will find at least two dozen textbooks on photochemistry in a well equipped library and many more on special aspects covering all possible areas of inorganic, organic and physical photochemistry. Some of these books combine mechanistic with synthetic aspects, whilst some of them concentrate on one of these aspects. Finding the right text is therefore a question of how deep you want to go into a specific problem. In 1978 N. J. Turro set a landmark with his "Modern Molecular Photochemistry" which still is one of the best books combining mechanistic with synthetic aspecdl]. A modern variation is "Essentials of Molecular Photochemistry" by Gilbert and Baggott (1991)[*]. Sometimes it is worthwhile to go deeper into mechanistic thinking especially concerning the application of modern quantum theory. R. P. Wayne published "Principles and Applications of Photochemistry" in 198813] and for all who want read the non plus ultra we recommend "Electronic Aspects of Organic Photochemistry" by J. Michl and V. Bonacic-Koutecky ( 1990)14]. You won't find a word about synthetic photochemistry in this impressive work. In order to understand the more basic aspects one should read "Excited States and Photochemistry of Organic Molecules" by M. Klessinger and J. Michl (1994)15]. Half a dozen books concentrate on synthetic aspects of organic photochemistry and should be consulted in order to obtain more information about specific photoreactions. Everything from brief s ~ m m a r i e s [ ~ ]up ~ [ ~to] elaborate descriptions is J. Kopecky published "Organic Photochemistry: A Visual Approach" in 1992L1I] as an

2

How To Use This Book

interesting experiment to present photochemistry in a different way. It is up to the reader which text he wants to choose. Sometimes you will have to look up data, e.g. the triplet energy of a sensitizer, the transmission of a certain filter, the emission of a lamp, etc. In this case consult the "Handbook of Photochemistry"[l2I or the "CRC Handbook of Organic Photochemistry"[l3].If you become interested in inorganic or organometallic photochemistry, look for the books by Ferraudi[l4I and Geofffoy and Wright~n['~I. A. M. Braun et al. published an interesting book on "Photochemical Technology" in 1991 16]. The increasing importance of electron transfer processes in photochemistry is reflected in "Photoinduced Electron Transfer", edited by M. A. Fox and M. Chandon[17]. Besides the different journals on photochemistry[l*I there are two important series: "Organic Photochemistry" (now edited by A. Padwa)[19] and "Advances in Photochemistry" (now edited by D. H. Volman, G. S. Hammond and K. Gollnick)[20]. In these periodically published books special areas of photochemistry are reviewed. A specialist periodical report about photochemistry reviews the literature published over a period of twelve months[21] and is essential for all researchers active in this area. Among all important photochemical meetings only the IUPAC Conferences on Photochemistry (every two years) should be mentioned. Abstracts of all lectures appear in Pure 8c Applied Chemistry. Also in this journal a collection of experiments for teaching photochemistry appeared in 1992[22]. N. J. Turro, Modern Molecular Photochemistry 1991, University Science Books, Mill-Valley, California. A. Gilbert, J. Baggott, Essentials of Molecular Photochemistry 1991, Blackwell Scientific Publications, London. R. P. Wayne, Principles and Applications of Photochemistry 1988, Oxford University Press, Oxford. J. Michl, V. Bonacic-Koutecky, Electronic Aspects of Organic Photochemistry 1990, Wiley-Interscience Publication, New York. M. Klessinger, J. Michl, Excited States and Photochemistry of Organic Molecules 1994, VCH, New York. J. M. Coxon, B. Halton, Organic Photochemistry 1974, Cambridge University Press, Cambridge. Photochemistry in Organic Synthesis J. D. Coyle (Ed.), 1986, The Royal Society of Chemistry, London. Synthetic Organic Photochemistry W. A. Horspool (Ed.), 1984, Plenum Press, New York, London. Photochemical Synthesis I. Ninomiya, T. Naito (Eds.), 1989, Academic Press, London. W. A. Horspool, D. Armesto, Organic Photochemistry: A Comprehensive Approach 1992, Ellis Horwood, PTR Prentice Hall, New York. J. Kopecky, Organic Photochemistry: A Visual Approach 1992, VCH, Weinheim, New York. S. L. Murov, I. Carmichael, G. L. Hug, Handbook of Photochemistry, 2nd ed., 1993, Marcel Dekker, Inc., New York.

How To Use This Book

3

CRC Handbook of Organic Photochemistry, Vol. 1 and 2, J. C. Scaiano (Ed.), 1989, CRC Press, Boca Raton, Florida. G. J. Ferraudi, Elements of Inorganic Photochemistry 1988, Wiley, New York. G. L. Geoffroy, M. S. Wrighton, Organometallic Photochemistry 1979, Academic Press, New York, London. A. M. Braun, M.-T. Maurette, E. Oliveros, Photochemical Technology 1991, Wiley, Chichester, New York. Photoinduced Electron Transfer, Part A-D M. A. FOX,M. Chandon (Eds.), 1988, Elsevier. Journal of Photochemistry and Photobiology R. P. Wayne (Ed.), Elsevier Sequoia, 74 volumes published to date; Photochemistry and Photobiology P.-S. Song (Ed.), American Society of Photobiology, 59 volumes published to date. Organic Photochemistry A. Padwa (Ed.), Marcel Dekker Inc., New York, Basel, 11 volumes published to date. Advances in Photochemistry D. H. Volman, G. S. Hammond, D. C. Neckers (Eds.), Wiley, New York, Chichester, 18 volumes published to date. Photochemistry, A Specialist Periodical Report, D. Bryce-Smith, A. Gilbert, (Senior Reporters), Royal Society of Chemistry, London, 21 volumes published to date. K.Tokumaru, J. D. Coyle, "A Collection of Experiments for Teaching Photochemistry", Pure Appl. Chem. 1992,64, 1343.

b) Purity of the starting materials: a problem of reactivity and absorption Every technique in synthetic organic chemistry has its prerequisites. When working with organometallic substrates for example one usually has to exclude oxygen and water or other protic substrates. If, however, the substrates, the reagents, the intermediates, or byproducts are highly colored the reaction could proceed exactly as described in the literature. The appearance of a colored species is often useful in organometallic chemistry to follow the progress of certain reaction steps. Quite the contrary holds for most photochemical processes. In many cases the use of substrates which are contaminated with colored material or the occurrence of colored byproducts inhibits the reaction progress. Obviously, photons have to be absorbed by substrate molecules and not by contaminants or byproducts. The design of a photochemical reaction is essentially linked to the absorption properties of all components in a specific reaction mixture. Therefore, careful purification of the starting materials has a similar status in photochemistry as in organometallic chemistry.

c) UV spectra of substrates: a first hint Before starting a photochemical reaction the absorption spectrum of the "photoactive" compound(s) should be recorded. The "phoroacrive" compound is the material which should be electronically excited either to a singlet or a triplet state. This compound could further undergo (i) unimolecular transformations, (ii) bimolecular reactions with a groundstate substrate molecule, (iii) bimolecular reactions with another electronically excited molecule (a rare case), (iv) serve as a photosensitizer, i.e. activate another substrate

4

How To Use This Book

molecule by energy or electron transfer, or (v) serve as a photoinitiator, e.g. in photochemical induced radical chain reactions. It makes sense to record several spectra using different substrate concentrations, so that the extinction coefficients for all absorption bands can be calculated. In many cases the weakest bands in the long-wavelength region are the important ones. Of course, the absorption spectra should also be recorded from the reagents which are applied in the reaction. It is advised to record as well an absorption spectra from the reaction mixture to look for additional bands in the UV-spectra which could indicate ground-state interactions such as the formation of CT-complexes. These photophysical data, however, does not say anything about the success of the reaction. If the desired product is already available one should also record an absorption spectra of it. Finally a set of several spectra (Figure 1) is available which should be carefully studied to decide on the right irradiation conditions. E

76 s

t.50

1.26

1.00

0.76

0.10

0.26

0

300

350

400

spectrum of substrate; --------- after different irradiation times Figure I: UV-spectra during irradiation of a tetrazole (compound analogous to 2.7d, see page 142, 1.02 x M in ethanol, mercury high-pressure lamp, Pyrex lamp); from H. Meier, H. Heimgartner, Helv.Chim.Actu 1985,68, 1287.

d ) Solvents:finding the best medium for the desired transformation In principle photoreactions can be performed in the gas phase, in the liquid phase, and in the solid phase. In contrast to many other techniques in chemistry all of these possibilities can lead to a successful conversion of the substrate. The majority of the reactions, however, are still performed in the liquid phase. Using normal concentrations of photoactive substrates and reagents, the concentration ratio solvent to substrate is around 100 - IOOO! An extinction coefficient of the photoactive compound only ten times higher than that of the solvent (in the wavelength region used for irradiation) corresponds to a pronounced filter effect of the reaction medium. Before starting a photoreaction one should therefore consult a table with the transmission data for the solvent used (see Table 1).

5

How To Use This Book

Table 1: Solvents used for photoreactions

I Solvent

Cut-off wavelength*

Er3

ET(30)4

water 185 78.30 63.1 acetonitrile 190 35.94 45.6 n-hexane 195 1.88 31.0 204 24.5 51.9 ethanol methanol 205 32.66 55.4 cyclohexane 215 2.02 30.9 diethyl ether 215 4.20 34.5 1,Cdioxane 230 2.21 36.0 methylene chloride 230 8.93 40.7 245 4.81 39.1 chloroform tetrahydrofuran 245 7.58 37.5 255 6.02 38.1 ethyl acetate 250 6.17 51.7 acetic acid carbon tetrachloride 265 2.23 32.4 dimethylsulfoxide 277 46.45 45.1 280 2.27 34.3 benzene 285 2.38 33.9 toluene pyridine 305 12.9I 40.5 acetone 330 20.56 42.2 taken from C. Reichardt, Solvents and Solvent Effects in Organic Chemistry 1988, VCH, Weinheim. wavelength (nm) at which E is approximately 1.0 in a 10 mm cell. dielectric constant. Dimroth-Reichardt values (kcdmol) for the longest-wavelength solvatochromic absorption based on a pyridinium-N-phenoxidebetaine dye no. 30. There is a wide variety of solvents which transmit down to short wavelengths, e.g. hydrocarbons, alcohols, and water. Sometimes it is advisable to use non-transparent solvents, but in these cases the solvents change their role and function as sensitizers. Acetone which absorbs up to 330 nm is often used as a solvent and sensitizer. It is also required that the solvent is free of impurities, especially for those which absorb in the wavelength region used for excitation and for those which could interfere with relatively long lived intermediates formed during the photoreaction. The first prerequisite is easily checked by recording a UV-spectrum. The second problem is often not obvious until a new solvent fraction is used. Sometimes it is useful to treat the solvent with EDTA in order to get rid of metal traces. Certain intermediates in photochemical reactions such as biradicals or zwitterions could be stabilized or destabilized by the surrounding solvent sphere. Therefore new experiments should be prepared by testing a series of solvents with increasing solvent polarity to find the optimal medium.

I

How To Use This Book

6 e ) Direct or sensitized photolysis: you have tofind out !

The absorption behavior of the photoactive component does not say anything about the behavior of the excited state. Does it deactivate rapidly in the singlet channel with fluorescence or radiationless ? Does it undergo fast intersystem crossing into the triplet manifold ? What is the chemistry of all these excited states ? If we have the opportunity to measure them, fluorescence and phosphorescence spectra will supply us with lifetime and quantum yield data. A comprehensive up-to-date collection of photophysical data can be found in Murov’s Handbook of Photochemistry (see Table 2). Table 2: Sensitizers and quenchers in non-polar solvents1

,

I

compound

ET2

Es3

%c4

0.25 459 353 346 445 0.53 326 42g7 3325 3726 0.906/1.005 1.oo 3 10 330 310 324 1.oo 301 323 0.8@ 2915 362 1.oo 287 316 0.22 282 397 0.86 286 349 0.84 4 1.8 274 0.73 260 346 0.40 415 258 0.75 385 253 0.845 3255 249 1.oo 2675 2365 0.92 247 223 0.71 178 318 0.33 177 209 0.61 164 213 0.52 138 180 taken from ref. [121 (chapter General Features, a ) . 2 triplet energies in H/mol. first excited singlet state energies in kJ/mol. quantum yields for singlet-triplet intersystem crossing. 5 in polar solvents. taken from H. G. 0. Becker, Einfuhrung in die Photochemie, 1991, Deutscher Verlag der Wissenschaften Berlin. benzoic acid. benzene toluene methyl benzoate acetone acetophenone xanthone benzaldehyde triphenylamine benzophenone fluorene triphenylene biphenyl phenanthrene styrene naphthalene 2-acety lnaphthalene biacetyl benzil anthracene eosine rose bengale methylene blue

How To Use This Book

7

From this data we can learn if it is necessary to sensitize the formation of the triplet excited state, or if the triplet state is rapidly formed by intersystem crossing without our help. Without this luminescence data the reaction efficiency and product composition has to be investigated in the presence and absence of a triplet sensitizer. If a specific reaction does proceed in the presence of a triplet sensitizer, variation of the triplet energy of this catalyst (when not incorporated in the photoproduct) can serve as a method for determining the triplet energy of the photoactive molecule. Typical triplet sensitizers and their corresponding energies are given in Table 2. On the other hand, the application of triplet quenchers serves as a method for the determination of triplet versus singlet reactivity. There are several possible reactivity patterns and methods to determine their existence: (i)

pure singlet reactivity: no reaction in the presence of (appropriate) triplet sensitizders. (ii) pure triplet reactivity: enhanced product formation in the presence of (appropriate) sensitizers, no reaction in the presence of triplet quenchers. (iii) triplet as well as singlet reactivity: combination of methods (i) and (ii) gives a product pattern corresponding to the specifically activated states.

f3 Reaction control: spectroscopy and chromatography As the product is formed in solution, it will compete more and more with the photoactive compound for absorption of the incident wavelength which may lie within the region of overlap of their absorption spectra. If the product is known, a UV spectra should be recorded before the photoreaction is started to avoid these problems. With increasing absorption of light by the products the reaction efficiency is reduced and, if all the incident radiation lies within the region of overlap, this may lead to a premature end of the reaction. Therefore, reaction control using absorption spectroscopy often is an important method to study the progress of a reaction (see Figure 1). Analogously, byproducts could be formed which also may absorb in the wavelength region used for excitation. NMR spectroscopy can help to study the quantitative reaction progress and find the optimal point for ceasing the transformation. Thin layer chromatography as well as gas or high performance liquid chromatography also are useful to study the substrate/product composition at certain points of the reaction.

g) Side reactions: can sometimes become the major track ! There are special features in photochemical reactions where side reactions become the major track and make a well planned synthesis unsuccessful. Sometimes the photoactive compound in the reaction mixture which could be applied in stoichiometric or catalytic (photosensitizer) amounts may also be the photoinitiator of a radical chain reaction. Again, the role of the solvent has to be considered carefully. If hydrogen abstraction reactions can be induced (e.g. when reactive free radicals are produced), solvents labile to this process must be excluded. Many saturated hydrocarbons, ethers, and alcohols (which normally are useful solvents because of their optical properties) have to be avoided in these

8

How To Use This Book

cases. Benzene is a relatively inert solvent, likewise acetonitrile, acetic acid, and tert-butanol. The latter three solvents, however, are highly polar and could therefore favor electron transfer steps and the formation of radical ions which also could give rise to side reactions. Despite its low solubility in most organic solvents, oxygen is a highly efficient quencher of electronically excited triplet states and additionally can react with many radicals. Sometimes these processes are desired ("photooxygenation"),however, in most other cases oxygen has to be removed by bubbling nitrogen or argon through the reaction mixture prior to and during the photoreaction. If the essential electronically excited state is not very efficiently quenched by (triplet) oxygen, (which is often the case for short living singlet states), the use of an inert gas may not be necessary. Despite this fact, it is rewarding to exclude oxygen because of possible hazardous effects from peroxides (even in low amounts !) which could be produced in the presence of molecular oxygen. For special precautions see k).

If there are free radicals produced during the reaction, they could undergo side reactions. Consequently radical scavengers such as substituted phenols have to be added. In many cases this has to be found out by trial and error.

h) Quantum yields and chemical yields There are specific properties of photochemical reactions which do not have to be considered in normal "ground-state chemistry". The chemical yield of a reaction, the non plus ultra for any reaction of nonexcited molecules, is no longer the only relevant number when excited states are involved. The quantum yield of a photoreaction, defined as the number of events (e.g. a certain photochemical induced transformation) divided by the number of photons absorbed by the specific system, also has to be considered. Quantum yields can range from 0 to 100 and more. A quantum yield of less than 0.01 for a photochemical process gives rise to a very slow conversion of the starting material. Still the chemical yield of the desired product could be satisfactory (90 - loo%), however, long irradiation times have to be used. If such low quantum yields for photochemical processes are observed, the quantum yields for the photophysical (deactivation) pathways are normally high. Some of these are rather easily determined by luminescence spectroscopy (quantum yields for fluorescence, phosphorescence, and radiationless decay), and these data are also useful for the design (and modification) of photoreactions. In cases of photoinitiated radical chain reactions, the quantum yield for chemical processes could reach values as high as 100.000 (for certain industrial processes an exceedingly important number in order to reach low lamp-costs, e.g. for the photochlorination of acyclic alkanes). There are more complex properties such as differential quantum yields and reaction efficiency which should not be discussed here.

i) Lumps, vessels andfilters Light sources commonly used for preparative photoreactions are a) the sun (covering the visible and IR-A wavelength region of ca. 300 - 1400 nm), b) mercury lamps (low-, medium-, and high-pressure Hg lamps), and c) sodium lamps (low- and high-pressure Na

9

How To Use This Book

lamps). Of course, one can also use a laser or a xenon high-pressure lamp, however, in most cases these light sources are too expensive for preparative work. The decision to use a certain light source is directly connected to the absorption properties of the substrate which has to be electronically excited (see part c). Figure 2 shows the different emission lines for some of the light sources mentioned.

I

I

I

200 I 1 1 I

I

I

200

400

4c)

I

I

600

t--c

I

600

400

I I,

I

I

L-

b) a)

Figure 2: Emission properties of a) mercury low-pressure lamp (strong 254 line), b) mercury high-pressure lamp and c) RPR-300081 lamp for Rayonet photoreactors (300 nm line). Low-pressure resonance mercury lamps (mercury vapor pressure ca. atm) emit at 185 nm (ca. 5% of the energy) and 254 nm (ca. 95% of the energy). Coating the envelope of these lamps with phosphors can lead to a rather broad secondary fluorescence emission at 300 nm or 350 nm. These lamps (RPR-1849/2537, RPR-2537, RPR-3OO0, RPR-3500 and RPR-4190; the numbers indicate the wavelength of emission in A) are used in commercially available &yonet@ photochemical reaction chambers. The mercury vapor pressure in medium-pressure Hg lamps varies in the range of 5 atm and the spectral distribution of the emission lines constitutes a number of distinct lines between 250 and 600 nm. A set of much broader lines in the vis-region (360 - 600 nm) characterizes the output of highpressure Hg lamps (mercury vapor pressure ca. 100 atm). These lamps are more expensive and are easily damaged and therefore have to be kept in a suitable box. Low-pressure as well as high-pressure sodium lamps cover a specific region in the visible region (around 600 nm) and are often used to excite dyestuffs which strongly absorb in this region (e.g. porphyrins or other dyestuffs in photooxygenation reactions).

10

How To Use This Book

Preparative photoreactions can be performed in two principal ways: by external irradiation where the lamps are located outside the reaction mixture or in immersion-well reactors where the light source is surrounded by the reaction solution. The latter constructions are more efficient because one can take full advantage of the emitted light. Reactors with external lamps permit the performance of many photoreactions at the same time and work with large volumes of reaction mixtures. Likewise merry-go-round photoreactors are used to perform more than one photoreaction (at smaller scale) at the same time, e.g. for the determination of reaction quantum yields where identical irradiation conditions are necessary for all probes. Falling film photoreactions are often used for the irradiation of concentrated solutions where appreciable amounts of polymeric byproducts normally lead to the formation of deposits at the reaction walls. An additional advantage is the use of thin liquid films which are irradiated in special immersion-well or falling film reactors and lead to a high local concentration of excited states. The reaction vessels used in the photoreactors mentioned must fit the irradiation conditions, i.e. the wavelength region which is needed for electronic excitation of the substrate. For irradiation at 254 nm vessels made of quartz glass are needed, Pyrex and solidex glass is needed for irradiation around 300 nm, and normal lab glass (or window glass) is transparent for wavelengths > 350 nm. In all cases the glass material serves as an solid optical filter. In some cases additional liquid optical filters have to be used in order to avoid undesired short wavelength irradiation.

k) Hazards The ultraviolet region of the sun emission spectrum (at the earth's surface) consists of ca. 3% UV-A (315 - 380 nm) and ca. 0.5% UV-B (280 - 315 nm). Fortunately essentially no UV-C (100 - 280 nm) is present which constitutes a highly hazardous energy region. This wavelength composition enables us to go into bright sunlight without immediately suffering from severe cell damage. Wavelengths shorter than 300 nm are particularly dangerous to the eye and the skin. Sunburn and snow blindness symptoms could occur a relatively long time after exposure. Special care should be taken when low-pressure mercury lamps are used which have almost all of their output at 254 nm. Reaction vessels and photoreactors must be shielded (e.g. by aluminium foil) and lamps should always be turned off when manipulations (changing of reaction vessels, e.g. in Rayonet reactors, checking the reaction progress, etc.) have to be performed. All photoreactors should operate in fume hoods or in special sufficiently ventilated rooms because of the possible ozone production from molecular oxygen and short wavelength UV light. Most lamps operate at high temperatures (e.g. medium-pressure mercury lamps around 700 "C, which requires efficient cooling) and at high vapor pressures (e.g. mercury vapor pressure in high-pressure lamps around 100 atm). Handling of lamps during operation is therefore strictly forbidden. Do not touch lamps after switchmg off before they have cooled down sufficiently.

1

Carbonyl Compounds

1.1

Aldehydes and Ketones

Electronically excited carbonyl compounds serve as versatile intermediates in countless reactions. They not only operate as reactive substrates for intra- and intermolecular hydrogen abstraction and cycloaddition reactions as well as C-C cleavage steps, but many of them also are useful sensitizers for the generation of triplet excited compounds. This variety of reaction possibilities makes carbonyl photochemistry sometimes very complex, i.e. it delivers many products and depends quite sensitively on the reaction conditions (temperature, sensitizer, solvent, irradiation wavelength). The absorption properties of these substrates are convenient for irradiation around 300 nm: the characteristic absorption band for the nn* excitation lies in the 330 - 280 nm region. The low lying S, states are populated with low probability, i.e. the electronic transitions are symmetry forbidden and the &-valuesare around 10 - 30. Because of a rather small triplet-singlet energy gap (20 - 70 kJ/mol, see Table 2) the intersystem crossing rates are high and the intersystem crossing quantum yields near unity. The lifetime of the first excited singlet state is in the nanosecond region for aliphatic aldehydes and ketones and in the subnanosecond region for aromatic aldehydes and ketones. Due to these parameters, singlet photochemistry can be detected with aliphatic carbonyl compounds, however, aromatic substrates such as acetophenone or benzophenone react exclusively from their corresponding triplet states (and represent excellent triplet sensitizers for many compounds with lower lying triplet states). In general electronically excited carbonyl compounds show five reaction types: i) Norrish Type I cleavage reaction (intramolecular a-cleavage), ii) Nomsh Type I1 reaction (cleavage of the P-bond), iii) Cyclobutanol formation (Yang reaction) or formation of smallerllarger ring cycloalkanols (following p-, y-, 6-, etc. hydrogen abstraction), iv) Paternb-Buchi reaction (cycloaddition with alkenes, dienes, alkynes, etc.), and v) Photoisomerization and photoreduction (intra- or intermolecular).

(i)

Norrish Type I cleavage reactions

Norrish Type I cleavage reactions dominate in the gas phase photochemistry of many acyclic aldehydes and ketones, whereas in the liquid phase this process is less common and alternative pathways (ii, iii, v) dominate. When no suitable C-H bonds are present to allow hydrogen abstraction reactions, however, this process will also constitute an important synthetic method for the cleavage of a-C-C bonds in solution. One important subsequent reaction of the resulting acyl and alkyl radicals is carbon monoxide formation and radical combination. Overall CO extrusion results which represents a versatile method for the formation of C-C single bonds from ketones. When cyclic substrates (cycloalkanones but not conjugated cycloalkenones which exhibit a different photochemistry) are used, ring

12

1.1 Aldehydes and Ketones

contraction reactions result from a Norrish Type I reaction. An impressive approach to tetra-tert-butyltetrahedrane is described by G. Maier, where the key step is the photochemical extrusion of carbon monoxide from an appropriate precursor. Another type of photochemical extrusion of a small fragment precedes the decarbonylation step: the extrusion of carbon dioxide from a (photochemically generated!) bicyclic anhydnde.

(ii)

Norrish Type 11 reaction

Beside carbon monoxide extrusion acyl radicals formed in a a-cleavage reaction can stabilize by subsequent hydrogen migration. Thus the a-trimethylsilylmethyl substituted cyclopentanone used by L. F. Tietze gives in a clean photochemical reaction the corresponding aldehyde with a vinylsilane moiety in its side chain.

(iii)

Cyclobutanol formation

The Yang reaction (a name used to honor the exceedingly valuable contributions of N. C. Yang in this field of organic photochemistry) is the most effective method for the synthesis of cyclobutanols provided that the appropriate alignment of C=O and C-Hgroups is given and no secondary transformations prevent cyclization of the 1,4-biradical. A beautiful example for the Yang reaction is given by H. M. R. Hoffmann who uses a rather complex and constrained substrate. There is an impressive number of different y-hydrogen positions, however, due to the substrate geometry only one of the diastereotopic methyl groups of the isopropyl substituent is active. It is highly recommended to build molecular models in order to learn more about this phototransformation. Two illustrative examples for "unusual" hydrogen abstractions, i.e. not from the normally preferred y-position, are reported by H. G. Henning. In his first synthesis, a bichromophoric substrate (ketondamide) was chosen. Irradiation at 300 nm solely activates the ketone CO-group which subsequently abstracts a hydrogen atom from the P-POsition (y-, &positions are blocked). &Hydrogen abstraction can become a serious reaction pathway as shown for the second substrate, where the p-amino group is only monoacylated. In this case a highly functionalized pyrrolidine derives from the photochemically induced &hydrogen abstraction.

(iv)

Paternd-Biichi reaction

Three examples are given for the well-known Patemb-Buchi reaction, two intermolecular and one intramolecular version: in the course of his studies on pharmaceutically active oxetanes, G. Just developed the [2+2]-cycloaddition of 0-protected a-hydroxy acetic aldehyde to 2-methylfuran and an interesting further functionalization of the resulting oxetane. The use of cheap and readily available chiral auxiliaries such as menthol, 8-phenylmenthol, and trans-2-terr-butylcyclohexanolin Paternb-Buchi reactions is described by H.-D. Scharf. High diastereoselectivities are obtained in the photocycloaddition of the corresponding pyruvic esters to electron rich cycloalkenes. Both the synthesis of the chiral auxiliary as well as of the cycloalkene are interesting non-photochemical steps.

1.1 Aldehydes and Ketones

13

R. Gleiter submitted an intramolecular version which transforms 5-acetylbicyclo[2.2.2]oct-2-ene into a complex tetracyclic photoproduct.

(v)

Photoisomerization and photoreduction

This part covers the phototransformations initiated by electronic excitation which do not fit in (i) - (iv). The photoisomerization of the amino acid derivative PHT=Val-OMe is one example. In this reaction, described by A. G. Griesbeck, the first event is abstraction of a hydrogen from a y-position. Neither cyclization (Yang reaction) nor fragmentation (Norrish 11) follows this step. Another hydrogen (now from the &position) migrates and leads to the formation of a photoisomerization product which could be transformed into N,C-protected isodehydrovaline. This reaction indicates that a broad variety of transformations should be possible at the primary 1,4-biradical stage. From B. Pandey's research group comes a straightforward photochemical method for the synthesis of spirocyclic compounds. An intramolecular hydrogen abstraction by an excited enone group is followed by radical combination. It is remarkable that no product arising from photoenolization and subsequent cyclization was observed. This is usually observed in ortho-alkyl substituted benzophenone and acetophenone derivatives. A strategy developed by H. R. Sonawane which is based on a photochemical induced 1,2-aryl shift allows the efficient transformation of 2-chloropropiophenones into 2-arylpropionic acids. This method is a straightforward alternative to the classical umpolungl Lewis-acid induced 1,Zaryl shift sequence used in ground state chemistry. Photoreduction of a$-epoxy ketones is possible in the presence of an external and efficient hydrogen donor such as triethylamine. An application in carbohydrate chemistry is described by J. Cossy. In the final step of a 7-step synthesis, a cyclic a,P-epoxy ketone is reduced (with retention of configuration) to a 0-hydroxy ketone. As shown by J.-P. Pkte the hydroxyalkyl radical formed initially can also be trapped in an intramolecular reaction, for example, by an alkyne moiety. The resulting vinyl radical abstracts another hydrogen from an external source. The starting material for this reaction sequence can be prepared by photochemical Wolff ring contraction reaction (see also Chapter 2). It is again a photochemical transformation which leads to a structure modification of an unsaturated bicyclo[4.1.O]heptanone as developed by J. Mattay et al. The key step starts with a photoinduced electron transfer (PET) from the donor triethylamine to the electronically excited cyclohexanone cleaving the exocyclic c-C bond followed by 5-ex0 cyclization.

Recommendedfurther reading Hydrogen Abstraction Reactions: P. J. Wagner, Organic Photochemistry 1991, 11, 227 366. [2+2]-Cycloaddition reactions of carbonyl compounds (PaternbBuchi reaction): G. Jones 11, Organic Photochemistry 1981,5, 1 - 122. Nomsh Type I Processes: D. S. Weiss, Organic Photochemistry 1981,5,347 - 420. and the corresponding chapters in: Rearrangements in Ground and Excited States P. de Mayo (Ed.), 1980, Vol. 42 - 43 of Organic Chemistry H. H. Wassermann (Ed.);

14

1.1 Aldehydes and Ketones Photochemistry in Organic Synthesis J. D. Coyle (Ed.), 1986, The Royal Society of Chemistry, London: Synthetic Organic Photochemistry W. A. Horspool (Ed.), 1984, Plenum Press, New York, London; W. A. Horspool, D. Armesto, Organic Photochemistry: A Comprehensive Approach, 1992, Ellis Honvood, PTR Prentice Hall. New York.

1.1

15

Aldehydes and Ketones

1.1.1

Tetra-tert-butyltetrahedrane 141 (route I) submitted by

G. Maier and F. Fleischer

1.l.la Maleic acid di-tert-butylester

>-

lH2''4

56.1

COOH 116.1

228.3

120 mL of isobutene were condensed into a pressure vessel (cooling with a methanolldry ice bath). 100 mL of diethylether and 5 mL of concentrated sulfuric acid were added. After addition of 56 g (0.48 mol) of maleic acid, the vessel was capped and shaken for 15 h. The vessel was opened cautiously (ice-cooling) and the content was poured onto a mixture of 250 g of ice, 70 g of NaOH and 350 mL of water. After separation of the organic layer, the aqueous layer was extracted with two 75 mL portions of diethylether. The combined organic layer was dried over MgS04, the solvent was removed by distillation and the crude product was recrystallized from pentane, yielding 87 g (80%) of maleic acid di-tertbutylester 1.l.la as colorless crystals, mp 68 "C. 'H-NMR (CDC13): 6 = 6.09 (s, 2 H, CH=C), 1.50 (s, 18 H, OC(CH3)3).

16

1.1 Aldehydes and Ketones

1.l.lb 2-Bromo-3-tert-butyl succinic acid di-tert-butylester

228.3

365.3

To 440 mL of a 1,26 M tert-butyl magnesium chloride solution were added at -35 "C 122.6 g (0.55 mol) of 1.l.la in 550 mL of diethylether over a 30 min period. The mixture was allowed to warm to room temperature and was additionally stirred for 10 min. Beginning at -40 "C 88 g (0.55 mol) of bromine were added over a 4 min period. The temperature was maintained below -20 "C. Excess bromine was destroyed by addition of saturated Na2S03 solution. 2 N HCl was added at room temperature. The separated organic layer was washed with 2 N NaOH and water and dried over MgSO4. Evaporation of the diethylether gave 170 g (85%) of crude 1.l.lb (mixture of the diastereomers), which was used without further purification.

'H-NMR (CDCI3): 6 = 1.05 (s, C(C_H3)3), 1.16 (s, C(C&)3), 1.45 - 1.55 (2 pairs of OC(C€&)3), 2.90 (d, J = 10, CH), 3.02 (d, J = 12, CH), 4.37 (d, J = 10, C m r ) , 4.43 (d, J = 12, C w r ) .

1.1.1~ tert-Butyl maleic acid mono-tert-butylester NaOH/MeOH -HBr

0

0

0

365.3

228.3

228.3

A mixture of 173 g (0.47 mol) of crude l.l.lb, 54 g of NaOH and 1400 mL of methanol were refluxed for 2 h. The methanol was evaporated. The residue was dissolved in water and acidified to pH 2. After extraction with diethylether, drying over MgS04 and evaporation of the solvent, 96.3 g (90%) of the crude product 1 . 1 . 1 ~were obtained.

1.1 Aldehydes

17

and Ketones

lH-NMR (CDC13), one of the isomers: 6 = 1.21 (s, 9 H, C(C_H3)3), 1.50 (s, 9 H, OC(C_H3)3),12.09 (s, 1 H, COOH).

1.l.ld tert-Butyl maleic acid anhydride"]

228.3

228.3

154.2

96.3 g (0.43 mol) of crude 1.1.1~were heated at 110 "C under a reduced pressure of 15 Tom. Formed H 2 0 and isobutene were condensed in a cold trap. When crystals of 1.l.ld began to sublimate to the cold parts of the flask, the reaction was finished. The product was distilled in a sausage flask at 0.1 Tom, maintaining the temperature below 120 "C. The product was recrystallized from petrol ether, yielding 40 g (47% refered to 1.l.la) of 1.l.ld as colorless crystals, mp. 65 "C. 'H-NMR (CDC13): 6 = 1.38 (s, 9 H, C(CH3)3), 6.60 (s, 1 H, C&C).

1.l.le 2,2-Dichloro-3,3-dimethylbutane

100.2

155.1

TO 625 g (3 mol) of PC15 were added at 0 - 5 "C 300 g (3 mol) of 2,2-dimethyl-3-butanone Over a 8 - 10 h period. The mixture was stirred for additional 14 h, and then it was poured Onto 2 kg of ice. After suction filtration the product was washed with ice water until the violet color had disappeared. The product was not sucked dry, because it was very volatile. About 280 g (60%)of 1.l.le were yielded.

18

1.1 Aldehydes and Ketones

lH-NMR (CDC13): 6 = 1.21 (s, 9 H, C(C_H3)3),2.10 (s, 3 H, C&).

1.1.If

3,3-Dimethylbutyne

82.1

155.1

A 2 1 three necked flask was fitted with a thermometer, a mechanical stirrer and a reflux condenser. The reflux condenser was maintained at 50 "C and on its top equipped with a vigreux-column and a Claisen-head, which was maintained at 0 - 5 "C. The receiving flask was cooled with an ice/NaCl bath. The flask was charged with 250 mL of diglyme, 770 g of KOH and the crude product 1.l.le (suspended in 450 mL triethyleneglycol). 2 mL of triethanolamine were added to start the reaction. The mixture warmed up by itself to 90 - 100 "C. Then it was heated cautiously (the product began to form very suddenly) to 200 "C. 103 g (70%) of 1.l.lf could be obtained (bp 39 "C).

lH-NMR (CDC13): 6 = 1.20 (s, 9 H, C(C_H3)3),2.00 (s, 1 H, CU).

1.1. l g 2-Hydroxy-2,5,5-trimethylhex-3-yne

-+" EtMgBr

82.1

0

r+-~g~r-

1)

A

2) H,O 185.4

140.2

140.2 g (1.7 mol) of 1.l.lf in 150 mL of diethylether were added dropwise to a ethylmagnesium bromide solution (1.7 mol in 400 mL of diethylether). The flask was fitted with a reflux condenser, which was maintained at -20 "C in order to prevent the loss of volatile 1.l.lf. The mixture was diluted with diethylether until the 3,3-dimethyl-butyn-lyl-magnesium bromide was dissolved. 99 g (1.7 mol) of acetone in 100 mL of diethylether were added at 15 - 20 "C. The mixture was stirred for 4 h and slowly warmed to 40 "C. 2 N HCI was added until the solution showed acidic reaction. The organic layer was separated and the aqueous layer was extracted with diethylether. The combined organic layers were washed with NaHC03 solution and water, and dried over MgS04. After evaporation of the solvent, the residue was distilled at 55 - 60 "C/12 Torr yielding 214g (90%) of 1.l.lg as colorless crystals, mp 32 "C.

19

1.1 Aldehydes and Ketones

lH-NMR (CDC13): 6 = 1.20 (s, 9 H, C(C_H3)3),1.46 (s, 6 H, 2 C&), 2.38 (s, 1 H, OH).

1.l.lh 2-Chloro-2,5,5-trimethylhex-3-yne

140.2

158.7

A stream of dry hydrogen chloride was bubbled through a precooled (8 - 12 "C) mixture of 210 g (1.5 mol) of 1.1.1g and 60 g of CaC12 powder in 250 mL of pentane. After standing at room temperature for 1 d, the solution was decanted, washed with NaHC03 solution and dried over Na2S04 The solvent was removed under reduced pressure, yielding 202 g (85%)of 1.l.lh as a colorless liquid.

lH-NMR (CDC13): 6 = 1.20 (s, 9 H, C(C_H3)3), 1.80 (s, 6 H, 2 C_H3).

1.l.li

2,2,5,5-Tetramethylhex3-yne[21 MeMgBr

158.7

138.3

To 100 g (4 mol) magnesium in 1 L of diethylether CH3Br was introduced until the magnesium had dissolved. The diethylether was removed by distillation until the solution was very viscous. 238 g (1.5 mol) 1.l.lh were added slowly (temperature below 40 "C). Hydrolysis was achieved by addition of 2 N HCl. The organic layer was separated and the aqueous layer was extracted with 5 portions of diethylether. The combined organic layers were washed with 2 portions of saturated NaHS04 solution, NaHC03 solution and water and were dried over MgS04. The solvent was removed by distillation through a vigreuxcolumn. Distillation of the residue afforded 145 g (70%) of 1.l.li as a colorless liquid ( b p l l 0 - 112°C).

'H-NMR (CDC13): 6 = 1.16 (s, 18 H, 2 C(CI33)3).

20

1.1 Aldehydes and Ketones

1,3,4-Tri-tert-butyl-3-cyclobutane-1,Zdicarboxylic acid anhydrideL31

1.1.1j

138.3

154.2

292.4

40 g (0.29mol) of 1.l.li and 30.8 g (0.2 mol) of 1.l.ld were dissolved in 900 mL of dry acetone. A stream of nitrogen was bubbled through the solution for 30 min to remove the oxygen. After irradiation for 48 h at 5 "C in a Normag circulation reactor (medium-pressure mercury lamp Hanau TQ 718), the solvent was removed by distillation through a vigreux-column together with the main part of excess l.l.li, which could be used for further irradiations. Recrystallization of the residue from ethanollwater (7:l ) gave 35 g (60%) of colorless crystalline l.l.lj,mp 63.5"C. lH-NMR (CC14): 6 = 1,16 (s, 9 H,C(C€33)3), 1,25 (s, 18 H, 2 C(CH3)3), 3,38 (s, 1 H, CH). IR (CC14): v = 1860,1820,1770.

~~~~~

~

1.l.lk 2,3,4-Tri-tert-butyl-2,4-cyclopentadien-l-one

1 292.4

240.4

H 248.4

A solution of 24 g (82 mmol) of 1.l.lj in 2.4L of methylene chloride was irradiated with a low-pressure mercury lamp (Vycor-reactor, Gr2ntzel) for 12 h. After evaporation of the solvent the products were separated by column chromatography (550 g silica gel) with pentane as eluant. After collecting a fraction of 5 g (25%) of 2,3,5-Tri-tert-butyl-2,4-

21

1.1 Aldehydes and Ketones

cyclopentadien-l-one, pentane/diethylether (30:1) was used as eluant. Then a fraction of 10.5 g (50%)of 1.l.lk could be collected.

2,3,4-Tri-rerr-butyl-2,4-cyclopentadien1-one 1.l.lk: orange needles, mp 55 "C 1H-NMR (CC14): 6 = 1.38 (s, 9 H, C(CH3)3), 1.40 (s, 9 H, C(C_H3)3), 1.49 (s, 9 H, C(C_H3)3),5.18 (s, 1 H, CH). IR (CC14): v = 1695 (C=O). MS: m/z = 248 (M'). 2,3,5-Tri-rerr-butyl-2,4-cyclopentadien1-one: orange needles, mp 55 "C 'H-NMR (CCl4): 6 = 1.13 ( S, 9 H, C(CH3)3), 1.30 (s, 18 H, 2 C(C_H3)3),6.58 (s, 1 H, CHI. JR (CC14): v = 1690. MS: d z = 248 (M+).

1.1.11

2-Bromo-3,4,5-tri-tert-butyl-2,4-cyclopentadien-l-one

\ / 248.4

+Br2

Br

408.2

408.2

-

- HBr

327.3

To a solution of 10.5 g (42 mmol) of 1.l.lk in 375 mL of CC14 was added one equivalent of a solution of bromine (1.55 M) in CC14 at room temperature. After addition of 150 g KOH in 150 mL of water, the mixture was rigorously stirred for 48 h. The organic layer was separated, washed with water and dried over MgS04. After evaporation of the solvent, the residue was recrystallized from pentane, yielding 11.7 g (85%) of 1.1.11 as orange crystals, mp 108 - 109 "C. 'H-NMR (CDC13): 6 = 1.27 (s, 9 H, C(CH3)3), 1.37 (s, 9 H, C(C_H3)3), 1.41 (s, 9 H, C(CH3)3). 13C-NMR (CDC13/CD30D 2:l): 6 = 191.0, 178.3, 173.3, 147.7, 111.9, 36.5, 34.4, 31.9, 30.3,29.6. IR (KBr): v = 1701 (C=O), 1561 (C=C). MS: d z = 328/326 (M+), 271/269,247,219, 191,57 (100%).

22

1.1

Aldehydes and Ketones

1.l.lm 2,3,4,5-Tetra-tert-butyl-2,4-cyclopentadien-l-one t-BuLi ____c

327.3

304.5

To a solution of 10.5 g (32 mmol) of 1.1.11 in 1850 mL of dry 13-dimethoxyethane were added 72 mL of a rert-butyllithium solution (1.3 M in hexane) over a 20 min period at 15 "C. After stirring for 15 min at this temperature, the mixture was maintained at room temperature for 48 h. After addition of water, pentane was added to separate the layers. 1,Zdimethoxyethane was successfully removed by washing with water. The organic layer was dried over Na2S04 and the solvent was evaporated. The products were separated by column chromatography (240 g silica gel) with pentane as eluant. The first intense orange fraction was collected and gave 2.2 g (22%) of 1.l.lm as orange needles, mp 112 115 OC.

'H-NMR (CC14): 6 = 1.28 (s, 18 H, C(CI33)3), 1.38 (s, 18 H, 2 C(CH3)3). 13C-NMR(C6D12):6 = 197.17, 175.76, 143.10, 36.81, 34.71, 33.80, 31.50. IR (KBr): v = 1679 (C=O). MS: m/z = 304 (M+), 247, 184 (loo%), 165, 106,57.

23

1.1 Aldehydes and Ketones

1.l.ln Tetra-tert-butyltetrahedrane

304.5

304.5

-x

248.4

h v l -CO

A

__.c

hv

276.5

276.5

138.3

1.7 g (5.58 mmol) of 1.l.lm in 250 mL of degassed, dry 2,2-dimethylbutane/n-pentane (8:3,Rigisolve, Merck) as matrix-solvent were irradiated for 100 h at -196"C with a low-

pressure mercury lamp. The irradiation was carried out in a Vycor-reactor with an irradiation tube and a dewar-flask made of quartz-glass. Cooling was achieved by a 300L tank, charged with nitrogen and equipped with an electronically controlled unit for nitrogen supply. For a complete conversion about 400 L of liquid nitrogen were needed. Column chromatography of the crude product at -14 "C (200 g silica gel) with pentane/diethylether (501) as eluant afforded 270 mg of 1.l.ln in the first fraction. The second fraction gave 270 mg of tert-butyl( 1,2,3,-tri-tert-buty1-2-cyclopropenl-y1)ketene and at least a mixture of 1,2,4,5-tetra-tert-butyltricyclo[2.1.0.02~5]pentan-3-oneand 1.l.lm (950 mg) was obtained. This mixture could be used for further irradiations. Refered to the converted part of l.l.lm, a yield of 40% of 1.l.ln could be obtained.

1,2,4,5-Tetra-tert-butyltricycl0[2.1.0.02y5]pentan-3-one: colorless needles, mp 90 - 91 "C. 'H-NMR (CDC13): 6 = 1.27 (s, 18 H,2 C(C_H3)3). 1.37 (s, 18 H, 2 C(C_H3)3). 13C-NMR [(C2D5)20, -20"C]:6 = 188.81,59.89,34.31,32.90,30.73,30.08,29.15. IR (KBr): v = 1755 (C=O). MS: m/z = 304 (M+), 247 (loo%), 191,57.

24

1.1 Aldehydes and Ketones

rert-Butyl( 1,2,3,-tri-terr-butyl-2-cyclopropen1 -yl)ketene: colorless crystals, mp 161 - 162 "C. 'H-NMR (CDC13): 6 = 0.94 (s, 9 H,C(CH3)3), 1.15 (s, 9 H,C(CH3)3), 1.30(s, 18 H,2 C(CH3)3). 13C-NMR [(C,Ds),O]: 6 = 206.15, 129.16,44.92, 40.77,39.32, 32.72,32.03,31.72, 31.11,30.60. IR (KBr): v = 2077 (ketene), 1818 (C=O). MS: m/z = 304 (M+), 247 (loo%), 207,191,57.

1,2,3,4-Tetra-tert-butyltricyclo[l.1 .0.0274]butane 1.l.ln: colorless crystals, mp 135 "C (conversion to 1,2,3,4-tetra-tert-cyclobutadiene) 'H-NMR (CDC13): 6 = 1.18 (s, 36 H,C(CH3)3). 13C-NMR [(C2Ds),O]: 6 = 32.26,28.33,10.20. IR (Nujol):v = 1415,1360,1348,1312,1213,1170,1027,923,838,659,465,425. MS: m/z = 276 (M'), 123,81,57(100%).

[l] [2] [3]

S. R. Jensen, J. Munch-Petersen, Acru Chem. Scand. 1967,21, 1963 - 1965.

G.F.Hennion, T. F. Banigan Sr., J. Am. Chem. Soc. 1946,68, 1202 - 1204. G.Maier, F. BoBlet, Tetrahedron Lett. 1972, 1025 - 1030;F. BoSlet, Dissertation,

Universitat Marburg 1972. [4] G. Maier, S. Pfriem, U. Schiifer, K.-D. Malsch, R. Mattusch, Chem. Ber. 1981, 114, 3965 - 3987.

25

1.1 Aldehydes and Ketones

1.1.2

Tetra-tert-butyltetrahedrane[l] (route 11) G. Maier and F. Fleischer

submitted by

1.1.2a

tert-Butyl(l,2,3-tri-tert-butyl-2-cyclopropen-l-yl)diazomethane[*I

254.4

260.3

qN2 -

304.5

373.6

*

294.2

98.1 MeLi

I

104.1

To a solution of 5.09 g (20mmol) of 4-methyl-benzenesulfonic acid (2,2-dimethylpropylidene)hydrazide in 200 mL of dry diethylether was added under an argon atmosphere at 0 "C one equivalent of a rert-butyllithium solution ( 1 3 M in hexane). The point of equivalence was reached, when the color of the solution changed from colorless to yellow. The solvent was evaporated and the lithium salt was dried at 0.01 Torr for 1 h. It was heated from 80 to 110 "C over a 2 h period. The formed 2,2-dimethyl-l-dia~opropane[~] was condensed on a cooling finger, which was charged with liquid nitrogen. When the pyrolysis was finished, the nitrogen was allowed to evaporize. The diazomethane was melted and dropped into a flask, charged with precooled (-78"C) THF. At this temperature 9 mL of a methyllithium solution (1.2M in diethylether) were added. Then 2.84 g (10 mmol) of tri-tert-butylcyclopropenylium tetraflu~roborate[~], dissolved in 300 mL of

26

1.1

Aldehydes and Ketones

THF by addition of 2 g LiCl, were added. The solution was stirred for 1 h until it had warmed to -60 "C. Then 400 mL of pentane were added and the mixture was washed with three 600 mL portions of cold brine. The solvent was rota-evaporated. A column chromatography (370 g A1203, desactivated with 10%of water) of the crude product at -30 "C with pentane as eluant afforded 2 fractions: 1.430 mg (14%) of tert-butyl(1,2,3-ti-terr-butyl-2-cyclopropen-l-yl)diazomethane 2. 780 mg (2 1%) of 1-(1',2'-di-tert-butylethenylazo)-1,2,3-tri-rert-butyl-2-cyclopropene tert-Butyl(1,2,3-tri-tert-butyl-2-cyclopropen1-yl)diazomethane: orange crystals, mp 122 "C lH-NMR (CD2C12): 6 = 0.98 (s, 9 H, C(CH3)3), 1.18 (s, 9 H, C(CH3)3), 1.32 (s, 18 H, C(CH3)3). 13C-NMR [(CDZC~~), -50 "C]: 6 = 127.5,58.3,41.1, 38.8,32.0, 31.3, 30.6,30.0, 29.3. IR (CCl4): v = 203 1. MS:m/z = 276,261,247,207. 1-(1',2'-Di-?err-butylethenylazo)-1,2,3-tri-tert-butyl-2-cyclopropene: yellow crystals, not stable at room temperature lH-NMR (CD2C12): 6 = 1.14 (s, 9 H, C(CH3)3), 1.16 (s, 18 H,2 C(C_H3)3), 1.20 (s, 9 H, C(CH3)3), 1.27 (s, 9 H,C(CH3)3), 4.76 ( s , 1 H, CH). 13C-NMR(CD2C12): 6 = 163.1, 125.2, 123.8,72.7, 35.2, 34.8, 32.8, 31.1,30.8,29.6. IR (CC14): v = 1815 (C=C). MS: m/z = 317,207

1.1.2b

Tetra-tert-butyltetrahedrane

\hv

276.5

138.3

1.1 Aldehydes and Ketones

27

A solution of20 mg (0.07 mmol) of 1.1.2a in 1 mL of 2,2-dimethylbutane/n-pentane(8:3, Rigisolve, Merck) was irradiated at -196 "C in a quartz tube with a low-pressure mercury

lamp (Vycor-reactor, Grantzel; quartz dewar flask, charged with liquid nitrogen). After evaporation of the solvent 12 mg (66%) of 1.1.2b could be obtained. 1.1.2b could be purified by sublimation at 0.01 Torr and 35 "C. Spectroscopic data cf: 1.l.ln

[ 11

[2] [3] [4]

G. Maier, F. Fleischer, Tetrahedron Lett. 1991, 32, 57-60. K. A. Reuter, Dissertation, Universitiit GieBen 1985; G. Maier, K. A. Reuter, L. Franz, H. P. Reisenauer, Tetrahedron Lett. 1985, 1845 - 1848. H. Quast, F. Kees, Chem. Ber. 1981, 114,774 - 786. J. Ciabattoni, A. E. Feiring, J. Am. Chem. SOC.1972, 94, 51 13 - 51 15; J. Ciabattoni, A. E. Feiring, J. Am. Chem. SOC.1973, 95, 5266 - 5272; J. Ciabattoni, A. E. Feiring, P. J. Kocienski, Org. Synth. 1974,54, 97 - 102.

28

1.1

Aldehydes and Ketones

(E,Z)-6-Trimethylsilyl-4-hexenal~3~~

1.1.3

submitted by

1.1.3a

L. F. Tietze

N - Cyclopentylidenecyclohexylamine[1]

84.1

99.2

165.3

A solution of 50.4 g (0.60 mol) of cyclopentanone and 59.4 g (0.60 mol) of cyclohexylamine in 100 mL of anhydrous toluene is heated under reflux with a water separator until 1 1 mL (0.6 mol) of water has been collected (ca. 24 h). The reaction mixture is cooled to room temperature and all volatiles are removed in vucuo (9 Torr). The remaining ketimine is purified by distillation to give 72.3 g (73%) of a colorless oil with bp 108 - l l l ° C / 9 Torr.

lH-NMR (CDC13, 80 MHz): 6 = 1 . 0 4 - 1.95 (m, 14 H, CHz), 2.03 - 2.42 (m, 4 H, (CH2)2C=N), 3.04 (mc, 1 H, C=N-CH). IR (film): v = 2982,2984 (CH), 1678 (C=N), 1422 (CH2).

1.1.3b

2-Trimethylsilylmethylcyclopentanone

0 6 + N

165.3

IASiMe, 214.1

1.) LDA

0

2.)H,O'

170.3

29

1.1 Aldehydes and Ketones

To a solution of 13.0 mmol of lithium diisopropylamide (generated in siru from freshly distilled diisopropylamine and n-butyllithium) in 50 mL of anhydrous tetrahydrofuran is added at -78 "C with stirring 1.65 g (10.0 mmol) of the imine 1.1.3a. The solution is allowed to warm to 0 "C and stirred for 0.5 h at this temperature. Then 2.31 g (11.0 mmol) of iodomethyltrimethylsilane[2]is added at -78 "C via a syringe with stirring. The reaction mixture is slowly warmed to room temperature and stirred for 4 - 6 h. The solvent is removed in vucuo, and the residue is dissolved in 90 mL of tetrahydrofuran. To this solution is added 15 mL of 1 M aqueous oxalic acid, and the solution is stirred at room temperature for 3 - 5 h. The mixture is extracted with 50 mL of diethyl ether/ petroleum ether (1:l) and three times with 30 mL of diethyl ether, the combined organic layers are washed with 30 mL of water, 30 mL of brine, dried over magnesium sulfate, and filtered. The solvent is removed in vucuo, leaving the crude alkylated product which is purified by flash chromatography (silica gel, petroleum etheddiethyl ether 10:1) or distillation (Kugelrohr) to give 1.30 g (79%) of a colorless oil.

lH-NMR (CDC13, 80 MHz): 6 = 0.01 (s, 9 H, SiMe3), 0.32 (dd, 1 H, J = 14, 11, 1'-H), 1.06 (dd, 1 H, J = 14,3.5, 1'-H), 1.40- 2.29 (m, 7 H, CH, CH2). IR (film): v = 2956,2878 (CH),1740 (C=O),1452 (CH2), 1248 (Si-CH3), 860 (SiMe3). UV (methanol): Amax = 247 nm (lg E = 2.233), 3 13 (1.634). ~

SiMe,

170.3

hv

MeOH

0 t

H

SiMe,

170.3

A mixture of 170 mg (1.00 mmol) of 2-trimethylsilylmethylcyclopentanone in 10 mL of methanol and 92.4 mg (1.1 mmol) of sodium hydrogen carbonate in a ring reactorl4I made of pyrex is cooled to 0 "C, flushed for 15 min with argon and irradiated with a 500 W Heraeus high-pressure mercury lamp while argon was bubbled through to obtain a good Solution; the reaction was monitored by TLC (silica gel, petroleum etheddiethyl ether
30

1.1 Aldehydes and Ketones

k N M R (CDC13, 200 Mhz): (8-isomer: 6 = -0.16 (s, 9 H, SiMe3), 1.26 (dd, 2 H, J = 7.5, 0.9, 6-H), 2.21 (dt, 2 H, J = 6.5, 3-H), 2.33 (dt, 2 H, J = 6.8, 1.9, 2-H), 5.09 (ttd, 1 H, J = 15,7,0.9,4-H), 5.32 (ttd, 1 H, J = 15,7,0.9,5-H), 9.62 (t, 1 H, J = 2, 1-H). (a-isomer: 6 = -0.13 (s, 9 H, SiMe3), 1.35 (dd, 2 H, J = 7.5, 0.9, 6-H), 2.20 (dt, 2 H, J = 6.5, 3-H), 2.36 (dt, 2 H, J = 6.8, 1.9, 2-H), 5.10 (m, 1 H, 4-H), 5.29 (m, 1 H, 5-H), 9.64 (t, 1 H, J = 2, 1-H). 13C-NMR (CDC13, 20 Mhz): @)-isomer: 6 = -2.46 (%Me3), 22.21 (C-6), 25.05 (C-3), 43.43 (C-2), 125.9 (C-4), 127.3 (C-5), 201.3 (C-1). (2)-isomer: 6 = -2.25 (SiMe3), 18.07 (C-6), 19.43 (C-3), 51.97 (C-2), 124.5 (C-4), 126.6 (C-5), 201.1 (C-1). IR (film): v = 2954,2930,2804 (CH), 2706 (CH, CHO), 1728 (C=O), 1658 (C=C), 1438 (CH2), 1250 (SiCH3), 844 (SiMe3). Discussion: The obtained aldehydes with an allylsilane moiety are useful intermediates among others for the tandem Knoevenagel allylsilane cycli~ation[~]. This domino reactioni6] allows e.g. the stereoselective formation of 1,2-trans-substituted cyclopentanes (translcis = 99.6:0.4).

[l] [2] [3] [4] [5]

[6]

J. K. Whitesell, M. A. Whitesell, Synthesis, 1983,517 - 536. Prepared by Finkelstein reaction from chloromethyltrirnethyl silane and sodium iodide in acetone. L. F. Tietze, J. R. Wunsch, Synthesis, 1990,985 - 990, 1204. L. F. Tietze, T. Eicher, Reuktionen und Synthesen im orgunisch-chernischen Pruktikum, 2nd Ed., 1991,Thieme Verlag, Stuttgart, p. 17. L. F. Tietze, M. Ruther, Chem. Ber., 1990,123, 1387 - 1395. Review: L. F. Tietze, U. Beifuss, Angew. Chem., 1993, 105, 137 - 170.

31

1.1 Aldehydes and Ketones

1.1.4

9,12-Dimethyl-13-oxa-tetracyclo[4.3.3.12,s.O 1,71tridecan-7-01 submitted by

Th. Beer and H. M. R. Hoffmann

1.1.4a (5R)-2,6-Dibromo-2-isopropyl-5-methylcyclohexanone~~~

154.3

31 2.0

L-Menthone (20 g, 0.13 mol) in ether (130 mL) is introduced into a three-necked flask equipped with a CaC12 drying tube, dropping funnel and inside thermometer. Bromine (13.3 mL, 0.26 mol) is added dropwise with discoloration at 0 "C. After completed addition the reaction mixture is carefully poured into a beaker containing NaHC03 (5 g) and ice (100 g). The mixture is stirred vigorously for 10 min. The organic phase is separated and washed with an equal volume of sat. aq. NaHC03 solution (2x) precooled in ice and brine. The combined organic layers are dried (MgSO,), the solvent is evaporated on a rotavap to leave a yellow oil, which is cooled and taken up in methanol (70 mL). Dibromoketone 1.1.4a crystallizes in a freezer at -18 "C, colorless crystals 19.5 g (48%).

lH NMR (CDC13, 380 MHz): 6 = 0.98 and 1.12 (2d, 6 H, J = 6.9, CHMe2), 1.27 (d, 3 H, J = 6, CH&), 1.9 - 2.6 (m, 6 H), 5.22 (d, J = 11.5, 1 H, BrCHCO).

32

1.1 Aldehydes and Ketones

1.1.4b l-Isopropyl-7-methyl-ll-oxa-tricyclo-[4.3.l.l2~s]undec-3en-10-one[1A

312.0

220.3

A three-necked flask equipped with a dropping funnel (with septum), nitrogen inlet and stopper is charged with NaI (43 g, 280 mmol) and copper powder (8.9 g, 140 mmol). The apparatus is evacuated (0.1 Torr, oil pump), heated externally with a blow dryer and flushed with nitrogen. Acetonitrile (84 mL, 0.005% H20) is added. Crystalline dibromoketone 1.1.4a (8.75 g, 28 mmol) is dissolved rapidly in furan (14 mL, 196 mmol) in a countercurrent of nitrogen and added dropwise to the vigorously stirred suspension which is cooled externally with ice/water. The reaction mixture is stirred overnight (15 h) at room temperature and water (9 mL) is added to the mixture. The reaction mixture is evaporated on a rotavap to give an oatmeal-colored sludge which is taken up in dichloromethane (100 mL). The solid is removed by suction-filtration through a sintered glassfunnel filled with silica gel. The reaction flask is rinsed with dichloromethane until the copper residues have been transferred completely onto the funnel. Chromatography (petrol ethedether, 1 0 1) affords tricyclic adduct of 1.1.4b, white crystals (2.3 g, 37%), mp 83 OC.

'H-NMR (CDCl3, 200 MHz): 6 = 0.85 (d, 3 H, J = 7, C H m ) , 1.0 (t, J = 7, 6 H, CH(Me)2), 1.0 - 2.7 (m, 7 H), 4.7 (s, 1 H, CHOCH), 4.8 (dd, 1 H, J = 1, 2, CHOCHJ, 6.3 (t, 2 H, J = 7, CH=C€J). 13C-NMR (CDCl3, 50 MHz): 6 = 17.3 (9, MeCHMM), 18.4 (q, BCHMe), 22.9 (q, CH&), 28.2 (d, CHMe), 28.7 (t), 30.9 (t), 36.1 (d, MeCHMe), 59.7 (s, Cq), 59.8 (d), 83.1 (d, CHOCH), 84.8 (d, CHOCH), 133.9 (d), 134.8 (d), 215.5 (s, CO). IR (CHC13): v = 2970,2940,2880,1710.

33

1.1 Aldehydes and Ketones

1.1.4~ l-Isopropyl-7-methyl-ll-oxa-tricyclo[4.3.l.l2~5]undecan10-one

O

d

o

P H2

o&;

MeOH

220.3

222.3

Unsaturated tricyclic ketone 1.1.4b (2 g, 9.1 mmol) is dissolved in redistilled methanol (20mL) containing 10% Pd on charcoal (213 mg) and hydrogenated in an autoclave ,(75 bar, 24 h). Chromatography (petrol etherlether, 3:l) affords a light yellow oil, 1.56 g :'(77.1%).

,IH-NMR (CDC13, 200 MHz): 6 = 0.74 (d, 3 H, J = 7, H-12), 0.95 and 0.99 (2d, 6 H, J = e 7, H-13/H-14), 1.5 - 2.1 (m, 10 H), 2.45 (m, 1 H, H-6), 4.36 and 4.45 (m, 2 H, H-2/ H-5). iyC-NMR (CDC13, 50 MHz)I3]: Peak UP: 6 = 23.4, 27.3,27.5, 30.5 (C-4, C-3, C-8, C-9), 58.2 (C-l), 215.6 (C-10); Peak DOWN: 6 = 15.8, 18.4, 22.7 (C-12, C-14, C-13), 37.6 (C-7), 63.2 (C-6), 81.7 and 83.9 (C-2, C-5). IR (cap): v = 2956,2875, 1714, 1466, 1067. k

i 1.1.4d

9,12-Dimethyl-13-oxa-tetracyclo[4.3.3.12'5.O 1'7ltridecan-7OW

222.3

222.3

Tricyclic ketone 1.1.4~(300 mg, 1.35 mmol) is dissolved in abs. THF (30 mL) in a twonecked flask (Duran) under nitrogen. The solution is irradiated with a high-pressure merCUry lamp (HPK 125 W L , Philips, cooling finger made from quartz). The light source is placed about 2 cm from the flask. After being irradiated for 20 h at room temperature, the mixture is freed from solvent on a rotavap to give a light yellow oil. Chromatography (petrol ethedether, 12:l) affords colorless crystals (255 mg, 85 %), mp 80 - 82 "C.

34

1.1 Aldehydes and Ketones

'H-NMR (CDC13, 500 MHz): 6 = 0.96 (d, 3 H, J = 7, H-14), 0.99 (d, 3 H, J = 7, H-13), 1.18 (m, 1 H, H-lo), 1.37 (br.s, OH), 1.42 (m, 1 H, H-6), 1.63 (m, 1 H, H-3b), 1.78 (m, 1 H, H-4b), 1.85 - 1.97 (m, 2 H, H-8bA-I-lo), 2.06 (m, 1 H, H-11), 2.16 (m,1 H, H-12), 2.35 (m, 1 H, H-22), 2.5 (m,3 H, H-3a&I-4a/H-8a), 3.17 (m, 1 H, H-9), 4.02 (m, 1 H, H-2), 4.12 (m, 1 H, H-5). 13C-NMR (CDC13, 150.9 MHz): Peak UP:6 = 26.5 (C-3), 28.7 (C-1 l), 30.7 (C-lo), 31.9 (C-4), 47.4 (C-l), 51.9 (C-8), 79.3 (C-7); Peak DOWN: 6 = 13.5 (C-14), 23.7 (C-13), 33.9 (C-12), 39.7 (C-9), 50.8 (C-6), 82.3 (C-5), 83.5 (C-2). IR (KBr): v = 3392,3001,2946,2869,1459, 1125.

___------_--_----_ H. M. R. Hoffmann, D. Wagner, R. Wartchow, Chem. Ber. 1990,123,2131 - 2139, 2460. T. Schottelius, H. M. R. Hoffmann, Chem. Ber. 1991, 124, 1673 - 75; M. R. Ashcroft, H. M. R. Hoffmann, Urg. Synrh. Coll. Vol. VZ, 512, Wiley, New York, 1988. APT (attached proton test): Spin echo based selection of multiplicities of 13C signals. Quaternary C and CH2 carbon atoms give positive signals (Peak UP), while CH and CH3 give negative signals (Peak DOWN). We thank Thorsten Dieckmann (EMBL, Heidelberg) for his help with confirming the structure of tetracyclic alcohol by HOHAHA-spectrum (TOCSY) with 15 ms/ 37 ms mixing and CH-correlation.

35

1.1 Aldehydes and Ketones

1.1.5

N,N-Dibenzyl-2-hydroxy-2-phenyl-cyclopropanamides submitted by

1.1.5a

NJV-Dibenzyl-y-0x0-benzenebutanamide

ph&OH

178.2

E v

H.-G. Henning

0

+

r Ph H-NLPh

CI-COO'BU NEt, -

197.3

(Ph ph")P ;,h

357.5

0

A solution of 0.7 g (7 mmol) of triethylamine in 10 mL of chloroform was added to a solution of 7 mmol of anhydrous y-0x0-butanoic acid in 10 mL of chloroform at -20 "C. To this mixture 0.75 mL (5.3 mmol) of isobutyl chloroformate was added dropwise with stimng and exclusion of moisture. After 30 min stirring at -20 "C 1.4 g (7 mmol) of dibenzylamine was added. Stirring was continued for 3 h while slowly warming the mixture to room temperature. After rota-evaporation of the solvent the crude product was extracted with ether. Concentration of the etheric solution afforded 1.14 g (45.7%) of crystalline 1.1.5a, mp 84 - 85 "C (EtOWH20).

'H-NMR (CDCl-j, 80 MHz): 6 = 2.80 (t, 2 H, CX-CH~), 3.30 (t, 2 H, P-CHz), 4.50 (d, 4 H, N-CHz), 7.2 - 8.0 (m, 15 H, arom.). : IR (KBr): v = 1690,1645. F; W (ether): h,, (lg E) = 315 (1.95), 236 (4.22).

1.1.5b

NJV-Dibenzyl-2-hydroxy-2-phenyl-cyclopropanamides

)ph&N-ph (Ph 357.5

0

hv

Ho
0

:qH NBn,

357.5

0

A solution of 200 mg (0.56 mmol) of 1.1.5a in 200 mL of anhydrous ether was irradiated (Pyrex vessel, Hg high-pressure lamp as extern. light source) for 18 h. After rota-evapora-

36

1.1 Aldehydes and Ketones

tion 20 mg (10%) crystalline Z-1.1.5b (mp 180 - 184 "C) precepitated. Addition of a few drops of petroleum ether to the mother liquor yielded, after standing for 15 h in a refrigerator, 50 mg (25%) E-1.1.5b (mp 90 - 94 "C). 2-1.1.5b: lH-NMR (80 MHz, CDC13): 6 = 1.81 - 2.77 (m, 3 H, cyclo-Pr), 4.10 (s, 2 H, CH2-Ph), 4.41 (s, 2 H, CHZPh), 5.31 (s, 1 H, OH), 6.7 - 7.7 (m, 15 H, arom.). IR (KBr): v = 1618,1630,3280,3300. R-1.1.5b: 'H-NMR (80 MHz, CDC13): 6 = 1.86 - 2.81 (m, 3 H, cyclo-Pr), 4.17 (s, 2 H, CH2-Ph), 4.46 (s, 2 H, CHZPh), 5.51 (s, 1 H, OH), 6.7 - 7.7 (m,15 H, arom). IR (KBr): v = 1625, 1630,3300,3450.

37

1.1 Aldehydes and Ketones

N-(2-Hydroxy-2-phenyl)cyclopropyl-N-tosylglycinester and l-Acyl-3-hydroxy-prolinester

1.1.6

submitted by

H.-G. Henning

1.1.6a N-(Benzoylethyl)glycinester-hydrochloride 0 Phl\

R’

+

H,NACOOR2 HCI

CH,O

-

Ph;irNhCOOR2 R’ H * H C I

0.15 mol glycinesterhydrochloride,0.15 mol of alkyl-aryl-ketone, and 4.5 g (0.3 mol) of paraformaldehyde, were dissolved in tert-butanol with addition of cyclohexane. The solution was refluxed for some hours using a water-separator. The precipitated Mannichbase-hydrochlorides 1.1.6a were separated. ~

~

1.1.6a

~~

~~

~

R1

R2

time(h)

yield(%)

mp (“C)

I

H

Me

14

25

141

11

H

Et

14

32

Ph

Me

40

15

150 147-9

~

III

(Mef20hleOH) (20% AcOH)

(Me2COEt20)

Usually the hydrochloride 111 was formed as an oil, which after rota-evaporation of the solvent was extracted with chloroform and dissolved in aceton. Crystalline III precipitated after cooling and addition of some drops of ether.

I: ‘H-NMR (DMSO-d6, 80 MHz): 6 = 3.08 - 3.63 (m, 4 H, CH2-CH2), 3.68 (s, 3 H, Me), 3.96 (s, 2 H, N-CH2-CO), 7.42 - 7.65 (m, 3 H, arom.), 7.80 - 7.97 (m, 2 H, arom.).

IR (KBr): v = 1754,1687. II:

‘H-NMR (DMSO-d6, 80 MHz): 6 = 1.18 (t, 3 H, CH2-CH3), 3.13 - 3.68 (m, 4 H, CH2-CH9, 3.98 (s, 2 H, N-CH2-CO), 4.15 (9, 2 H, CI&-CH3), 7.56 - 7.83 (m, 3 H, arom.), 7.97 - 8.15 (m, 2 H, arom.). IR (KBr): v = 1760,1695.

38

1.1 Aldehydes and Ketones

111: lH-NMR (CDC13, 80 MHz): 6 = 3.25 - 4.05 (m, 2 H, CH2-N), 3.60 (s, 3 H, Me), 3.76 (s, 1 H, N-CHTCO), 5.58 - 5.78 (m, 1 H, CH), 7.05 - 7.40 (m, 8 H, arom.), 7.80 - 7.98 (m, 2 H, arom.). IR (KBr): v = 1745, 1684.

1.1.6b N-Acyl-N-(benzoylethy1)glycinester and

" 0

Ph

pyridine

N/\COOR2 H HCI

TsCl

" 0

* Ph

NA COOR2 I Ts

190.7

Tosylation: A solution of 5 mmol of Mannich-base-hydrochloride 1.1.6a in 10 mL of carefully dried pyridine was cooled to -10 "C and then mixed with 1.9 g (10 mmol) of tosylchloride. After stirring for 1 h at -10 "C and standing at room temp. for another 48 h the dark-colored reaction mixture was poured into crushed ice and acidfied with dilute hydrochloric acid. The precipitated N-tosylcompounds 1.1.6b were washed with dilute HCI and water and then recrystallized.

Acyl-CI

R'

H*HCI

P

base

h qNA COOR2 R Ac

Benzoylation: 2.3 g (10 mmol) of benzoic anhydride was added to a solution of 10 mmol of 1.1.6a in 30 mL of water. After addition of 1.7 g of NaHC03 the reaction mixture was stirred for 2 h at room temp. and then extracted with 50 mL of ether three times. The organic phase was washed with NaHC03 solution and water. After drying with sodium sulfate the solution was concentrated to 1/10 of the volume. The 1.1.6b crystallized. 1.1.6b

R1

R2

Acyl

yield(%)

mP ("C)

I

H

Me

Ts

80

76

(MeOH)

11

H

Et

Ts

90

63 - 65

(EtOHM20)

111

H Ph

Me Me

Bz Bz

60 52

58 oil

(J320)

Iv

39

1.1 Aldehydes and Ketones

I: lH-NMR (CDC13, 80 MHz): 6 = 2.31 (s, 3 H, Me/Ts), 3.19 - 3.69 (m, 4 H, CH2-CH2), 3.49 (s, 3 H, COOMe), 4.08 (s, 2 H, N-CH2-CO), 7.12 - 7.90 (m, 9 H, arom.). IR (CHC13):v = 1754, 1683. 11: lH-NMR (CDC13, 80 MHz): 6 = 1.09 (t, 3 H, CH2-CH3), 2.33 (s, 3 H, Me/Ts), 3.30 3.68 (m, 4 H , CH2-CH2), 3.96 (q, 2 H , CH2-CH3), 4.08 (s, 2 H , N-CH2CO), 7.13 7.91 (m, 9 H, arom.). IR (CHC13):v = 1747, 1682. 111: lH-NMR (CDC13, 80 MHz): 6 = 3.18 - 3.98 (m, 4 H, CH2-CH2), 3.65 (s, 3 H, COOMe), 4.15 (s, 2 H, N-CH2CO), 7.25 - 7.53 (m, 8 H, arom.), 7.65 - 8.03 (m, 2 H, arom.). IR (CHC13): v = 1749, 1637, 1683.

IV:

lH-NMR (CDC13,80 MHz): 6 = 3.39 (s, 3 H, COOMe), 3.65 - 4.25 (m, 4 H, CH2-N und N-CH2CO), 5.27 - 5.48 (m, 1 H, CH), 7.07 - 7.31 (m, 13 H, arom.), 7.68 - 7.81 (m, 2 H, arom.). IR (CHC13): v = 1747, 1677, 1636.

1.1.6~ N-(2-Hydroxy-2-phenyl-cyclopropyl)-N-tosyl-glycinethylester Ph

L A

N COOEt Ts

389.5

hu ether

-

HO

Ph37+COOEt Ts

389.5

A solution of 150 mg (3.86 x mol) of N-tosyl-(benzoylethy1)glycin-ethylester 1.1.6.b (11) in 150 mL of anhydrous diethylether was irradiated (Pyrex cuvette, Hg high-pressure lamp as an external light source) at room temp., until 1.1.6b (11) was no longer detectable by TLC. After rota-evaporation of the ether the crude product was purified by column chromatography (sephadex LH-20; Rf(5)= 0.25) with chlorofodethyl formate/methanol (100: 10:1) as eluant. The 1.1.6~-fraction was concentrated and the residue recrystallized from methanol yielding 18.6 mg (12.5%) of 1.1.6c, mp 163 - 165 "C.

'H-NMR (80 MHz, CDC13): 6 = 1.09 (t, 3 H, CH2-C&), 1.80 - 2.10 (m, 1 H, CH2-CH), 2.35 (s, 3 H, MeITs), 2.37 - 2,94 (m, 2 H, C&-CH), 3.06 (s, 1 H, COH), 3.70 (s, 2 H,

1.1

40

Aldehydes and Ketones

N-CHZCO), 3.98 (q, 2 H, CHZ-CH~), 6.95 - 7.25 (m, 7 H, arom.), 7.40 - 7.55 (m, 2 H, arom.). IR (KBr): v = 3501,1754.

1.1.6d 1-Acyl-3-hydroxy-prolinester (General procedure) "gL[N

hu cyclohexane / benzene (80/ 20 )

Acyl

R'

H

Ph

-Acyl COOR2

Solutions of 150 mg (ca. 3 x mol) of 1.1.6b in 150 mL of an anhydrous mixture of cyclohexanehenzene (80/20) were irradiated (Pyrex cuvette, Hg high-pressure lamp as an external light source) until the educts 1.1.6b were no longer detectable by TLC. After rotaevaporation of the solvent the crude products were purified by column chromatography (sephadex LH-20) with chlorofodmethanol (see table) as eluant. 1.1.6d

I I1

III

lv

R1

R2

Acyl

H

Me

Ts

0.21 (A)

76

134- 6

(MeOH)

H

Et

Ts

0.20 (A)

85

107- 8

(Et20/PE)b

H Ph

Me Me

Bz Bz

0.16 (B) 0.24 (B)

65 70

135 163-5

(Et20) (Et20)

Rf(solvent)a yield(%) mp("C)

I: lH-NMR (80 MHz, CDC13): 6 = 1.93 - 2.03 (m, 2 H, C_H2-CH2-N),2.40 (s, 3 H, Me/%), 3.25 (s, 1 H, OH), 3.38 - 3.75 (m, 2H, CH2-CH2-N), 3.64 (s, 3 H, COOMe), 4.45 (s, 1 H, CH-N), 7.12 - 7.38 (m, 7 H, arom.), 7.60 - 7.82 (m, 2 H, arom.). IR (CHC13): v = 3575, 1735.

n:

'H-NMR (80 MHz, CDC13): 6 = 1.08 (t, 3 H, CH2-C&), 1.90 - 2.25 (m, 2 H, CH2-CH2-N), 2.38 (s, 3 H, Mems), 3.29 (s, 1 H, OH), 3.40 - 3.75 (m,2 H, CH2-CH2N), 4.08 (4,2 H, CH2-CH3). 4.40 (s, 1 H, CH-N), 7.13 - 7.35 (m, 7 H, arom.), 7.62 7.80 (m, 2 H, arom.). IR (CHC13): v = 3579, 1733

The Rf-values were determined on a 8 cm-flow distance with saturation of the chamber; A = (CHCl$HCOOEt/MeOH = 100: 10:1); B = (CHC13MeOH = 100: 1). PE = petroleum ether.

1.1 Aldehydes and Ketones

41

111: IH-NMR (80 MHz, CDC13): 6 = 2.08 - 2.35 (m, 2 H, CH2-CH2-N), 3.41 (s, 1 H, OH), 3.48 - 4.0 (m, 2 H, CH2-CH2-N), 3.61 (s, 3 H, COOMe), 4.85 (s, I H, CH-N), 7.05 7.57 (m,10 H, arom.). IR (CHC13): v = 3580, 1738, 1631.

Iv:

lH-NMR (80 MHz, CDC13): 6 = 2.75 (s, 1 H, OH), 3.61 (s, 3 H, COOMe), 3.79 - 4.0 (m, 2 H, CH-C&-N), 4.30 - 4.55 (m, I H, CH-CHTN), 5.13 (s, 1 H, CH-N), 6.98 - 7.10 (m, 2 H, arom.), 7.23 - 7.48 (m, 11 H, arom.), 7.53 - 7.75 (m. 2 H, arom.). IR (CHC13): V = 3565, 1747,1635.

42

1.1

1.1.7

Aldehydes and Ketones

2a-Acetoxy-3a-methyloxalyloxymethyl-4~-propionyloxymethyloxetane"] submitted by

G. Just

1.1.7a 1-O-Propionyloxy-3-methyl-2-butene I

HO

EtCOCI, CH2CI2

4

I

L

EtCOO

pyridine, DMAP

86.1

4 142.2

A solution of 3-methyl-2-butene-1-01 (86.1 g, 1.00 mol) in dry methylene chloride (1.5 L) under nitrogen at ambient temperature containing NN-dimethylaminopyridine (12.2 g, 0.1 mol), pyridine (283.1 mL, 3.5 mol) and propionyl chloride (130.3 mL, 1.5 mol) was stirred for 18 h. The solution was washed with 5% hydrochloric acid (1.5 L), saturated aqueous sodium bicarbonate (1.5 L), brine (1.5 L), dried (Na2S04), filtered and the solvent removed under reduced pressure to yield a yellow oil. Distillation of the crude product (57 - 58 "C, 0.7 mm Hg) gave the title compound in virtually quantitative yield (141.49 g) as a clear oil. ~~

~~~~~

'H-NMR (CDCl3, 200 MHz): 6 = 1.12 (t, 3 H, J = 7.6, C&CH2), 1.69 (d, 3 H, J = -1.3, C€&C), 1.74 (d, 3 H, J = -1.1, CHjC), 2.30 (9, 2 H, J = 7.6, CH3C€&), 4.55 (d, 2 H, J = 7.3, C_H2CH),5.32 (m, 1 H, CHCH2). 13C-NMR (CDC13, 75.4 MHz): 6 = 8.7 KH3CH2), 25.3 (Me2C), 27.1 (CH3_CH2), 60.7 (OCH2CH), 118.6 (OCH2CH), 138.2 (Me2Q, 173.8 (CO).

1.1.7b Propionyloxyacetaldehyde"] I EtCOO

1. 0, CH,CI, 2.) Me,S

142.2

EtCOO116.1

Ozone was bubbled through a solution of 1.1.7a (28.4 g, 0.2 mol) in dry methylene chloride (1.7 L) at -78 "C until the solution turned blue (12 h). Dimethyl sulfide (146.9 mL,

43

1.1 Aldehydes and Ketones

10 equiv.) was added to the reaction mixture under an atmosphere of nitrogen and it was allowed to warm to ambient temperature gradually overnight. The solution was washed with water (2 x 1 L), brine (1 L), dried (Na2S04), filtered and the solvent removed in vucuo to give a light yellow syrup. Purification by flash chromatography on silica (petroleum ethedethyl acetate 4: 1) gave the title compound (19.74 g 85% yield) as a clear oil. -

IH-NMR (CDCl3, 200 MHz): 6 = (t, 3 H, J = 7.6, CH3CH2). 2.46 (q, 2 H, J = 7.6, CH3C_H2),4.65 ( s , 2 H, C&CHO), 9.59 ( s , 1 H, CHO). I3C-NMR (CDCl3, 75.4 MHz): 6 = 8.6 (CH3CH2), 26.6 (CH3CH2), 68.3 (OCH2), 173.4 (EtCO), 195.7 (CHO).

1.1.7~ 3-Methyl-6~-propionyloxymethyl-2,7-dioxabicyclo[3.2.0]hept-3-ene and 1.1.7d l~-Methyl-6~-propionyloxymethyl-2,7-dioxabicyclo[3.2.0]hept-3-ene[ 11 EtCOO-o

116.1

+

ahy

82.1

C6H6

E t C O O q 198.2 EtCOO

a +

I

198.2

A mixture of 2-methylfuran (17.3 mL, 192 mmol) and 1.1.7b (1 1.14 g, 96 mmol) in benzene (1.8 L) (other solvents may be possible if the photochemical properties are similar to those of benzene) was placed in a 2 L photo-reaction vessel, cooled to 8 "C and saturated with argon. The solution was then irradiated (Hanovia 450 W medium-pressure Hg lamp with Vycor filter) for 8 h. The solvent was removed under reduced pressure to give a yellow syrup. Purification by flash chromatography (petroleum ethedethyl acetatehiethylamine 10:1:O.Ol) gave 1.1.7~and 1.1.7d (mixture of 2 inseparable regioisomers, 16:11, 6.4 g, 33% yield) as a light yellow oil and recovered starting material (4.6 g of aldehyde 1.1.7b). In the absence of triethylamine, 1.1.7d decomposed on the column and photo-adduct 1.1.7~was isolated (4.37 g, 23% yield) as a light yellow oil along with recovered starting material (4.64 g aldehyde 1.1.7b).

1.1.7~: 'H-NMR (CD2C12,200 MHz): 6 = 1.15 (t, 3 H, J = 7.5, C_H3CH2), 1.92 (dd, 3 H, J = 1.4, -1.4, C_H3), 2.40 (q, 2 H, J = 7.5, CH3C_H2), 3.59 (dddd, 1 H, J = 4.4, 2.8, 2.7, 1.4,

44

1.1 Aldehydes and Ketones

5-H), 4.22 (A Of ABX, 1 H, J = -12.4,4.4,6',-H), 4.26 (B of ABX, 1 H, J = -12.4, 3.2, 6'b-H), 4.63 (dddd, 1 H, J = 4.4, 3.2,2.8, -0.8, 6-H), 4.97 (dd, 1 H, J = 2.7, -1.4, 4-H), 6.22 (dd, 1 H, J = 4.4, -0.8, 1-H). I3C-NMR (CD2C12, 75.4 MHz): 6 = 9.1 (CH~CHZ),13.7 (Me), 27.6 (CH$H2), 47.9 (C-5), 65.8 (C-6'),88.6 (C-6), 98.8 (C-4), 108.3 (C-I), 158.2 (C-3), 174.0 (CO). LRMS (CI-NH3): m/z = 199 ([MH'], 0.5%), 181 ([MH' - H20], 100%). HRMS (CI-NH3): m/z calcd. for C 10Hl3O3 [MH+ - H20], I 8 1.0865; found, 181.0864. 1.1.7d: 'H-NMR (CDCl3, 200 MHz): 6 = 1.15 (t, 3 H, J = 7.6, CH3CH2), 1.71 (s, 3 H, CI43), 2.39 (4,2 H, J = 7.6, CH3C&), 3.37 (ddd, 1 H, J = 4.3, 2.9, -1.0, 5-H), 4.26 (d, 2 H, J=4.1,6',-H9 6'b-H), 4.59 (dt, 1 H, J = 4.3, 4.1, 6-H), 5.23 (t, 1 H, J = 3.0, 2.9, 4-H), 6.54 (dd, 1 H, J = 3.0, -1.0, 3-H). 13C-NMR (CD2C12, 75.4 MHz): 6 = 9.2 (CH3CH2), 23.1 (Mk), 27.6 (CH3GH2). 48.4 (C-5), 65.7 (C-6'), 85.7 (C-6), 104.3 (C-4), 116.1 (C-l), 148.4 (C-3), 174.2 (CO). LRMS (CI-NH3): m/z = 199 ([MH'], 0.5%), 181 ([MH' - H20], 100%). HRMS (CI-NH3): m/z calcd. for C1&I13O3 [MH+ - H201, 181.0865; found, 181.0864.

1.1.7e 2a-Acetoxy-3a-methyloxalyloxymethyl-4~-propionylox~ methyloxetane"1 1.) 0,, CH,CI,

I

2.)M e 8

,coo* 0

198-2

-

3.) 10% NaBH, on AI,O, E t C O O ~ ~ O c o o M e 318.3 4.) MeOOCCOCI, NEt,, DMAP

Ozone was bubbled through a solution of the photo-adduct 1.1.7~(198 mg, 1.00 mmol) in dry methylene chloride (100 mL) at -78 "C until the solution turned blue (45 min). Dimethy1 sulfide (727 kL, 10 equiv.) was added to the stirring reaction mixture under nitrogen and it was allowed to warm to ambient temperature gradually overnight. The solution was (804 mg, 2.18 mmol) was cooled to 0 OC, sodium borohydride on alumina gel added and the reaction mixture was warmed to ambient temperature gradually over 1 h. After 5 h, reduction of the aldehyde was complete. The mixture was filtered through a bed of dry Celite/Na2SO4 and the solvent removed in vucuo to afford a yellow syrup which was dried under high vacuum (0.1 mm Hg) for 2 h. The product was redissolved in dry methylene chloride (100 mL) under nitrogen at 0 OC and N,N-dimethylaminopyridine (12 mg, 0.10 mmol), triethylamine (697 kL, 5.00 mmol) and methyl oxalyl chloride (184 pL, 2.00 mmol) were added. The solution was gradually warmed to room temperature (1 h) and it was allowed to stir for 16 h. The reaction mixture was diluted with methylene chloride (50 mL), washed with 5% hydrochloric acid (100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL), dried (Na2S04), filtered and the

1.1 Aldehydes and Ketones

45

solvent removed in vucuo to yield a yellow syrup. Purification by flash chromatography on silica (petroleum etherlethyl acetate 2:l) afforded the title compound (130 mg, 41% yield) as a colorless oil. ~

lH-NMR (CDC13,200 MHz): 6 = 1.15 (t, 3 H, J = 7.5, CH3CH2), 2.1 1 (s, 3 H, CH3CO), 2.39 (9,2 H, J = 7.5, CH3C_H2), 3.44 (dddd, 1 H, J = 7.3, 7.2, 6.2, 5.9, 3-H), 3.89 (s, 3 H, &O), 4.19 (A Of ABX, 1 H, J = -12.7, 4.3, 4',-H), 4.34 (B of ABX, 1 H, J = -12.7, 3.3, 4'b-H), 4.55 (A Of ABX, 1 H, J = -11.6, 7.3, 3',-H), 4.60 (B of ABX, 1 H, J = -11.6, 7.2, 3'b-H), 4.82 (ddd, 1 H, J = 6.2, 4.3, 3.3, 4-H), 6.46 (d, 1 H, J = 5.9, 2-H). 13C-NMR (CD2C12,75.4 MHz): 6 = 9.1 gH3CH2), 20.9 (CH3CO), 27.5 (CH3CH2), 39.7 (C-3), 53.8 (MeO), 63.0 (C-3'), 64.9 (C-4'), 79.6 (C-4), 96.0 (C-2), 157.6, 158.0 (OcOcOOMe), 169.6 (CH3CO), 174.1 (EtCO). LRMS (CI-NH3): m/z = 336 ([M + NHq+], 56.8%), 259 ([MH' - AcOH], 25.8%). HRMS (CI-NH3): m/z calcd. for C13H22NOg [M + NH4+], 336.1296; found, 336.1294.

[11

[2]

[3]

R. Hambalek, G. Just, Tetrahedron Lett. 1990,3I, 5445-5448. Kieselgel 60, Merck 230-400 mesh. Thin-layer chromatography was performed on silica gel (Kieselgel 60 F254, Merck) aluminium-backed plates (0.2 mm thickness) and visualized by UV and/or dipping into a solution of 2.5 g ammonium molybdate and 1 g ceric sulfate in 10 mL sulphuric acid/90 mL water, followed by heating. Purchased from Aldrich Chemical Company, Inc., Milwaukee, WI, USA.

46

1.1 Aldehydes and Ketones

1.1.8

Synthesis of a Chiral L-Erythrose Building Block submitted by

P. Esser, H.-D. Scharf

1.1.8a (-)-[(1R,2S,5R)-5-Methyl-2-(l-methylphenylethyl)cyclohexyl]phenylglyoxylate; (-)-8-Phenylmenthylglyoxylate

232.4

150.1

364.5

To a mixture of 20 mL of DMF in 200 mL of absolute methylene chloride a solution of 9 mL oxalylchloride in 15 mL of methylene chloride was added dropwise at -15 "C. 15 min later 15.0 g (0.1 mol) phenylglyoxylacid[lI was added. After warming up to room temperature the reaction mixture was stirred for 1 h. Again the solution was cooled to -15 "C and a solution of 23.2 g (0.1 mol) of (-)-8-phenylmenth01[~1in 50 mL of methylene chloride was added slowly. For complete conversion the reaction mixture was stirred overnight. The reaction mixture was cooled with an ice bath and stirring was continued while 100 mL of a 10% sodium carbonate solution was added dropwise for the hydrolysation. The organic phase was separated, washed with a saturated solution of sodium bicarbonate, dried over magnesium sulphate and evaporated to dryness. For purification the ester was recrystallized from methyl alcohol. Yield 25.5 g (70%), mp 88 "C, = -6.9" (0.915 ethanol). ~~

~~

'H-NMR (CDC13, 300 MHz): 6 = 0.86 (m, 1 H, 4-Ha,), 0.91 (d, 3 H, J = 6.4, 10-H), 1.09 (dq, 1 H, J = 13.0, 3.0, 3-Ha,), 1.20 (4, 1 H, J = 11.4, 6-Ha,), 1.31 (s, 3 H, 8-, 9-H), 1.37 (s, 3 H, 9-, 8-H), 1.51 (m, 1 H, 5-H), 1.60 (m, 2 H, 3-, 4-Heq),2.07 (m, 1 H, 2-H), 2.13 (m, 1 H, 6-Heq), 5.03 (dt, 1 H, J = 10.7, 4.4, 1-H), 7.00 (m, 2 H, p-H), 7.11 (m, 2 H, m-H), 7.24 (m, 2 H, o-H), 7.49 (m, 2 H, rn-H, COPh), 7.63 (m, 1 H, p-H, COPh), 7.95 (m, 2 H, o-H, COPh). 13C-NMR (CDCl3, 75 MHz): 6 = 21.7 (C-lo), 26.2 ((2-8,- 9), 26.9 (C-3), 27.5 (C-9, -8), 31.5 (C-5), 34.4 (C-4), 40.0 (C-7), 41.4 (C-6), 50.5 (C-2), 77.5 (C-l), 125.3 (p-C), 125.5 (0-C), 128.0 (m-C), 128.7 (m-C, COPh), 130.2 (0-C, COPh), 132.6 ( ~ ~ s o - C , ) , (COO), 185.7 (CO). COPh), 134.6 (p-C, COPh), 150.2 ( ~ ~ s o - C162.7 IR (KBr): v = 3OOO,2960,2930,2870, 1720, 1690, 1600, 1450, 1320, 1200, 1180.

1.1 Aldehydes and Ketones

1

W (CH3CN): A,

1.1.8b

i

47

= 254 (lg E = 12200), 345 (38).

(-)-[(l'R,2'S,5'R)-5'-Methy1-2'-(1'-methylphenylethyl)cyclohexyl]-3,3-dimethyl-endo-6-phenyl-2,4,7trioxybicyclo[3.2.0] heptane-exo-6-carboxylate

100.1

+

to< 0

major diastereomer

A solution of 18.2 g (0,05 mol) of (-)-8-phenylglyoxylate 1.1.8a and 5.5 g (0,055 mol) of dimethyldi~xole[~] in 200 mL of toluene was irradiated (Pyrex immersion photochemical reactor with gas introduction, HPK 125 W Philips) for 12 h under a nitrogen atmosphere. The solution was evaporated and filtered over silica gel (CH Cl,). After removal of the solvent the residue was dried. Yield 22.1 g (95%), de > 96% (f3C-NMR, no signals of the minor diastereomer), mp 94 "C (CH2C12), [a],22 = -14,8" (1.34 ethanol). R*

de

lit.

(-)-menthy1

58

[41

> 96

PI

92

[51

(-)-8-Phenylmenthyl (-)-truns-2-t-butyl-cyclohexanol

'H-NMR (CDC13, 300 MHz): 6 = 0.78 (m, 1 H, 4'-Hax), 0.77 (d, 3 H, J = 6.5, 10-H), 0.88 (q, 1 H, J = 11.4, 6'-Hax), 1.04 (s, 3 H, CH3-acetonide), 1.12 (s, 3 H, 8'-, 9'-H), 1.17 (dq, J = 13.0, 3.0, 1 H, 3'-Hax), 1.19 (s, 3 H, 9'-, 8'-H), 1.28 (m, 1 H, 5'-H), 1.33 (s, 3 H, CH3-acetonideh 1.52 (m, 2 H, 3'-He , 4'-He ), 1.62 (m, 1 H, 6-He& 2.03 (m, 1 H, 2'-H), 4.72 (d, 1 H, J = 3.1, 5-H), 4.81 (It, 1 H,? = 10.1, 4.3, 1'-H), 6.04 (d, 1 H, J = 3.2, 1-H), 7.16 - 7.34 (m, 10 H, Ph, Ph'). 13C-NMR (CDC13, 75 MHz): 6 = 21.7 (C-lo'), 26.6 (C-8', -97, 26.9 (C-3'), 27.0 (CH3acetonide), 27.3 (C-9', -8'), 28.8 (CH3-acetonide), 3 1.3 (C-S), 34.4 (C-47, 40.0 (C-77, 41.3 (C-67, 49.9 (C-2'), 77.0 (C-l'), 83.1 (C-5), 86.2 (C-6), 103.2 (C-I), 117.3 (C-3),

48

1.1 Aldehydes and Ketones 125.4 (p-C, Ph'), 125.6 (O-C,Ph'), 126.4 (m-C, Ph'), 127.7 (m-C, Ph), 127.9 (O-C,Ph), 128.1 @-C, Ph), 135.0 (ipso-C, Ph), 150.8 (ipso-C, Ph'), 170.4 (ester-CO).

1.1.8~ (-)-(lR/S)-l-O-Methyl-l,2-isopropylidene-3-C-phenyl-~erythro-teturonacid-[(l'R,2'S,5'R)-5'-methyl-2'-(1'-methylphenylethyl)cyclohexyl]esteracetale

06

OPh-menthyl

464.6

dioxane

w o . 0<

.

z

o*OPh-menthyl 496.6 After silica gel filtration the oxetane 1.1.8b (22.1 g) was used without further purification. It was dissolved in a mixture of 200 mL of dry dioxane and 40 mL of abs. methanol and 30g ion exchange resin (Lewatit S 100, dry) was added. The mixture was stirred overnight. Filtration and removal of the solvent at reduced pressure yielded a material pure enough for the next step. Yield 21,2 g (90%) as a viscous oil, E/Z = 9:l (13C-NMR), [a],**= -5 1.9" (0.9 15 ethanol).

'H-NMR (CDC13, 300 MHz): 6 = 0.86 (d, 3 H, J = 6.4, 10-H), 1.09 (s, 3 H, 8'-, 9-H), 1.13 (s, 3 H, 8'-, Y-H), 1.38 (s, 3 H, CH3-acetonide), 1.41 (s, 3 H, CH3-acetonide), 0.8 - 2.2 (m, 8 H, 2'-, 3'-, 4'-, 5'-, 6'-H), 3.20, 3.41 (s, 3 H, E / Z = 9/1, OMe), 4.45 (d, 1 H, J = 2.7, 2-H), 4.81 (dt, 1 H, J = 4.0, 10.7, l'-H), 5.01 (d, 1 H, J = 2.7, 1-H), 6.8 - 7.6 (m, 10 H, Ph). 13C-NMR (CDC13, 75 MHz): 6 = 21.7 (C-lo'), 24.7 (C-8', -97, 26.66 (C-37, 26.68 (CH3acetonide), 28.2 (C-8', -9'), 31.3 (C-S), 34.5 (C-47, 39.4 (C-79, 41.1 (C-6'), 50.0 (C27, 55.2 (C-2), 77.7 (C-ll'), 78.6 (C-3), 83.4, 87.5 (OMe, ZJE = 1:9), 104.0 (C-1), 111.8 (C-acetonide), 125.1 (p-C, Ph'), 125.1 (o-C, Ph'), 126.5 (m-C, Ph'), 127.9 (m-C, Ph), 128.0 (o-C, Ph), 128.2 (p-C, Ph) 137.9 (ipso-C, Ph), 151.2 (@so-C, Ph'), 170.0 (ester-CO).

11

49

Aldehydes and Ketones

1,1.8d (-)-(1R)-1-O-Methyl-l,2-O-isopropylidene-3-C-phenyl-~erythroseacetale

2.) chromatography 496.6

232.4

chiral auxilary

A suspension of 1.9 g of LiAlH4 in 100 mL of dry ether was cooled with an ice/salt bath. 21.2 g of teturonacid ester 1 . 1 . 8 ~dissolved in 100 mL of dry ether was added dropwise. After complete addition the solution was stirred two hours at room temperature and 30 min under reflux. The mixture was cooled with an ice bath and hydrolysed with water until hydrogen development stopped. To the mixture glacial acetic acid was added until it was weakly acid. After filtration the organic solution was washed with a 5% sodium bicarbonate solution, dried over magnesium sulfat and evaporated to dryness. The product and the auxillary were separated by column chromatography (silica gel 0.1 - 0.2 mm mesh) with cyclohexane/acetone (6:l) as eluant. Yield 8.9 g (75%), mp 141 OC, [a],22= -74.4" (0.906, ethanol) and 9.5 g (96%) (-)-8-phenylmenthol. For the use of the L-erythrose building block in the synthesis of apiose see [6].

IH-NMR (CDCI3, 300 MHz): 6 = 1.33 (s, 3 H, CH3-acetonide), 1.45 (s, 3 H, CH3-acetonide), 2.15 (t. 1 H, J = 6.4, OH), 3.13 (s, 1 H, OH), 3.36 (s, 3 H, OMe), 3.81 (dd, 1 H, J = 5.4, 11.4,4-H), 3.92 (dd, 1 H, J = 6.7, 11.4,4-H), 4.39 (d, 1 H, J = 3.4, 2-H), 4.91 (d, 1 H, J = 3.4, 1-H), 7.2 - 7.4 (m, 3 H, m-,p-H), 7.5 - 7.6 (m, 4 H, o-H). 13C-NMR (CDC13, 75 MHz): 6 = 26.2 (CH3-acetonide), 26.7 (CH3-acetonide), 55.5 (OMe), 67.5 (C-4), 75.6 (C-3), 84.8 (C-2), 103.9 (C-1), 110.8 (C-acetonide), 126.3 (oC, Ph), 127.8 (p-C, Ph), 128,O (m-C, Ph), 139.9 (ipso-C, Ph).

[l] [2]

Phenylglyoxlacid can be synthesized from benzoylcyanid. T. S. Oakwood, C. A. Weissgerber, Org. Synth. 1944,24, 16 - 18. E. J. Corey, H. E. Ensley, J. Am. Chem. Soc. 1975, 97, 6908 - 6909; For the synthesis of (-)-8-phenylmenthol see: H. Herzog, H.-D. Scharf, Synthesis 1986, 420 -

50

[3]

[4] [5]

[6]

1.1 Aldehydes and Ketones 421; For the synthesis of (+)-8-phenylmenthol see: H. Buschmann, H.-D. Scharf, Synthesis 1988, 827 - 830. For a six step synthesis of dimethyldioxol from ethylencarbonat see: N. D. Field, J. Am. Chem. SOC.1961,83,3504 - 3507. Menthol is in both enantiomers available at a low price. Synthesis of both enantiomers. P. Esser, H. Buschmann, M. Meyer-Stork, Angew. Chem. 1992,104,1254 - 1255; Angew. Chem. Int. Ed. Engl. 1992,31, 1190 - 119 1. A. Nehrings, H.-D. Scharf, J. Runsink, Angew. Chem. 1985, 97, 882 - 883; Angew. Chem. Int. Ed. Engl. 1985,24,817 - 818.

51

61 Aldehydes and Ketones

1.1.9

5-Methyl-10-methylene-4-oxatetracyclo[4.3.1.02,s.O 3,7Idecane submitted by

R. Gleiter

1.1.9a 5-Acetyl-6-methylenebicyclo[2.2.2]oct-5-ene~~~ 0 &C4 82.1 +

0 80.1

60"c

&k,

&+ 0

162.2

9.22g (0.11 mol) of a~etylallene[~] was added at ambient temperature to 120g (0.15mol) of 1,3cyclohexadiene[2] and the mixture stirred at 60"C for 3.5 d. The yellow solution was purified by column chromatography (silica gel (40-63mesh)) with petroleum ether/ ether (9:l)as eluant (Rf = 0.20);yield (enddexo) 10.7g (60%). GC: endolexo = 91:9; yield (endo) 9.74g (55%). ~~

'H-NMR (CDC13, 200 MHz): 6 = 1.30- 1.40(m, 2 H,CH2), 1.55- 1.65(m,2 H, CH& 2.04(s, 3 H, CH,), 2.85- 2.93(m, 1 H, CH), 3.05- 3.13(m, 1 H, CH), 3.20- 3.28(m, 1 H, CHI, 4.57- 4.60(m, 1 H, HC=), 4.92- 4.97(m,1 H, HC=), 6.12- 6.22(m, 1 H, HC=), 6.28- 6.38(m, 1 H, HC=). 13C-NMR (CDC13, 50.32MHz): 6 = 25.0(t, CH2), 25.9 (t, CH2), 27.9(4,CH$ 34.7(d, CH), 40.9 (d, CH), 59.1 (d, CH), 107.6(t, H@), 131.78 (d, CH=), 133.3 (d, CH=), 148.0(s, C:), 208.8(s, CO). MS (GC): m/z = 162 (M', 21%), 134 (18), 119 (14),104 (17),91 (C7H7, loo), 77 (12), 65 (26),51 (10).

52

1.1 Aldehydes and Ketones

1.1.9b 5-Methyl-lO-rnethylene-4-oxatetracyclo[4.3.1.02,s.O 3,71decane"1

162.2

162.2

A solution of 3.78 g of endolexo-1.1.9a (91%, 21.2 mmol endo-1.19a) in 2.5 L of dry ether was degassed with a dry nitrogen stream for 45 min. The solution was irradiated for 20 h with a medium-pressure mercury immersion lamp (450 W Hanovia) equipped with a special quartz M 282-filter (h = 280 nm). The crude oxetane was obtained by evaporation of the ether at reduced pressure. The product was purified by column chromatography (silica gel (40-63 mesh)) with dichloromethane as eluant (Rf = 0.20), yielding 3.17 g (92%) of a colorless oil; crystallization from petroleum ethedether (12:l) at -20 "C gave colorless crystals, mp 30-32 "C.

lH-NMR (CDCl3, 300 MHz): 6 = 1.22 - 1.33 (m, 1 H, CH), 1.36 (s, 3 H, CH3), 1.52 1.63 (m, 2 H, CH2), 1.71 - 1.81 (m, 1 H, CH), 2.20 (m, 1 H, CH), 2.48 (m, 1 H, CH), 2.55 -2.59 (m, 1 H, CH), 2.90 - 2.93 (m, 1 H, CH), 4.37 (dd, 1 H, J = 2.6, 1.9, 0-CH), 4.61 (s, br, 1 H, HC=), 4.77 (s, br, 1 H, HC=). 13C-NMR (CDCl3, 75.47 MHz): 6 = 16.8 (9, CH3), 18.7 (t, CH2), 27.2 (t, CH2), 37.2 (d, CH), 44.8 (d, CH), 55.3 (d, CH), 56.0 (d, CH), 81.6 (d, CH-0), 95.9 (s, C-0), 103.7 (t, H2C=), 157.2 (s, C=). IR (thin film): v = 2966,2936,2856,1668,1384,944,881,855. W (n-Hexan): &ax = 202 (Ig E = 3.91). MS (GC): m/z = 162 (M', 5 % ) , 147 (M+-CH3, 7), 133 (Cg$O+, 5 ) , 119 (21), 105 (16), 92 (22)- 91 (C7H7+, loo), 79 (lo), 77 (15), 65 (18), 51 (11).

[ 11

121

[3]

Diplomarbeit T. Herb, 1992, Heidelberg. Organikum, 16. Aufl., 1986, VEB Deutscher Verlag der Wissenschaften, Berlin, 236; Organikum, 16. A u .., 1986, VEB Deutscher Verlag der Wissenschaften, Berlin, 255. G. Buono, Synthesis 1981, 872.

1.1

53

Aldehydes and Ketones

1.1.10 (-)-(S)-N-Phthaloylisodehydrovaline methyl e s t e r [ 3 ]

*

submitted b y

Axel G. Griesbeck

1.1.10a (-)-(S)-N-Phthaloylvaline[l] H2N

+

@:

COOH

117.1

--l$:t A

COOH

0

0

148.1

247.2

To 14.8 g (0.10 mol) of melted phthalic anhydride was added at 145 "C 11.7 g (0.10 mol) of (+)-(3-valine in five portions and the mixture stirred at 140 "C for 20 min. After cooling to RT 15 mL of methanol were added and the suspension heated under reflux for 10 min. Filtration and cooling to 0 "C gave 23.2 g (94%) colorless needles, mp 116 117 "C, [a],= -65.5" (1.0, MeOH)

'H-NMR (CDC13,250 MHz): 6 = 0.92 (d, 3 H, J = 6.7, CH3), 1.17 (d, 3 H, J = 6.7, CH3), 2.76 (dsept, 1 H, J = 8.2,6.7, CHMe2), 4.64 (d, 1 H, J = 8.2, NCHCOOMe), 7.75 (dd, 2 H, J = 5.5, 3.1, Ar.-H), 7.89 (dd, 2 H, J = 5.5,3.1, Ar.-H), 10.54 (br.s, IH, COOH). 13C-NMR (CDC13, 63 MHz): 6 = 19.5 (9, CHEH&), 20.9 (4. CH(CH3)2), 28.4 (d, CHMe2), 57.5 (d, NCHCOOMe), 123.7 (d, 2C), 131.6 (s, 2C), 134.3 (d, 2C), 167.8 (s, 2C), 174.5 (s,COOH). IR (KBr): v = 2920,2820, 1730,1680,1360, 1260, 1160,707. ~~

1.1.1Ob (-)-(S)-N-Phthaloylvaline methyl ester

cl$t 0

247.2

COOH

MeOH / HCI

@:t 0

261.3

COOCH,

54

1.1 Aldehydes and Ketones

A slow stream of hydrogen chloride was bubbled through a precooled (0 'C) solution of 12.0g (48.5mmol) 1.1.10a in 150mL of methanol for 2 min. The solution was stirred for 10 min at RT cooled to 0 "C and again saturated with gaseous HC1 for 2 min. For complete conversion the solution was stirred for 4h at RT and the solvent removed at reduced pressure. Distillation of the residue afforded 11.6g (91%) of 1.1.10b as a viscous colorless oil with bp 135 - 140 "C/O. 1 Torr, which crystallized after some days at RT, mp 49 - 50 "C, [a], = -66.7'(1.2, MeOH).

'H-NMR (CDC13, 250MHz): 6 = 0.89(d, 3 H, J = 6.8,CH3), 1.13(d, 3 H, J = 6.8,CH3), 2.74 (dsept, 1 H, J = 8.3,6.8,CEJMe2), 3.69(s, 3 H, OCH3), 4.45(d, 1 H, J = 8.3, NCHCOOMe), 7.73(dd, 2 H, J = 5.5,3.1,Ar.-H), 7.86(dd, 2 H, J = 5.4,3.1,Ar.-H). 13C-NMR (CDC13, 63 MHz): 6 = 19.4 (q, CH(CH3)2), 20.9 (4,CH(CH3)2), 28.6 (d, CHMez), 52.4(q, OCH3), 57.5 (d, NCHCOO- Me), 123.6(d, 20,131.7(s, 2C), 134.2 (d, 2C), 167.7(s, 2C). 169.3.5(s, COOMe). IR (thin film): v = 3000,2900,1770,1740,1402,1290,728.

1.l.1Oc (+)-(1*S,lR)-l'-Methoxycarbonyl-2'-methyl-N-2'-propenyll-hydroxyimindolinone[21 hv, CH,CN

0

261.3

COOCH,

d N 7

COOCH,

0

261.3

A solution of 500 mg (1.91mmol) of 1.1.1Ob in 100 mL of acetonitrile was irradiated (Rayonet photoreactor RPR, h = 300 nm) under a nitrogen atmosphere for 24 h at 13 "C. After rota-evaporation of the solvent the crude product was purified by column chromatography (silica gel 60-230mesh) with petroleum ethedethyl acetate (2:l)as eluant (Rf= 0.33), [a], = -21.1'(1.0MeOH) , yielding 485 mg (85%) of 1.1.10~.The product can be crystallized from chloroform, mp 168 - 170"C.

'H-NMR (CDC13, 250 MHz): 6 = 1.79(s, 3 H, CqMe), 3.79(s, 3 H, OMe), 4.72(br.s, 1 H, OH), 5.03(s, 1 H, C=CH2), 5.25(s, 1 H, C=CH2), 5.59 (s, 1 H, NCHCOOMe), 5.82 (s, 1 H, NCHOH), 7.55 (dd, 1 H, J = 7.6,4.1,Ar.-H), 7.59 (d, 2 H, J = 3.9,Ar.-H), 7.78(d, 1 H, J = 7.1, Ar.-H). I3C-NMR (CDC13, 63 MHz): 6 = 21.4 (4, C@H3), 52.9 (q, OCH3), 59.2 (d, NCHCOOMe), 80.3(d, NCHOH), 117.4(t, C=CH2), 123.3(d), 123.6(d), 129.5(d), 129.9(d), 132.8(d), 137.5(s), 144.5(s, C=CH2), 168.1(s, COOMe), 172.8(NCO). IR (thin film): v = 3350,2900,1670,1520,1340,1200,1050, 900.

55

1.1 Aldehydes and Ketones

1.1.1Od (-)-(S)-N-Phthaloylisodehydrovaline methyl esterL31

QJ$$ 0

PCC / CH,CI, COOCH,

261 -3

c

t

COOCH,

0

259.3

To a stirred solution of 100 mg (0.38 mmol) of 1.1.10~in 5 mL of methylene chloride were added 500 mg of pyridinium chlorochromate (PCC) on aluminium oxide (6.1 mmol PCU7.5 g A1203). The reaction mixture darkened from orange to black and after 24 h additionally 500 mg of PCC/alox were added. After completion (62 h, TLC control) the mixture was filtered through a small silica gel column and washed with 50 mL of CH2C12. The solvent was removed under reduced pressure, yielding 79 mg (80%) of a colorless viscous oil, [a] = -70.1 (1.O, MeOH). O

%NMR (CDC13, 250 MHz): 6 = 1.84 (s, 3 H, CqMe), 3.71 (s, 3 H, OCH3), 5.03, 5.06 (2s, 2 H, C=CH2), 5.30 (s, 1 H, NC_HCOOMe),7.69 (dd, 2 H, J = 5.4, 3.1, Ar.-H), 7.81 (dd, 2 H, J = 5.5,3.1, Ar.-H). 13C-NMR (CDCl,, 63 MHz): 6 = 20.4 (q, CqMe), 52.8 (q, =H3), 57.0 (d, NCHCOOMe), 117.3 (t, C=CH2), 124.5 (d, 2C), 131.7 (s, 2C), 134.2 (d, 2C), 138.2 (s, C=CH2), 167.1 (s, 2C, NCO), 168.0 (s, COOMe). IR (thin film): v = 2980, 1790, 1730, 1120,925.

[ l] [2] [3]

S. Shankman, Y. Schvo, J. Am. Chem. Soc. 1958,80,1164 - 1168. A. G. Griesbeck, M. Mauder, Angew. Chem. 1992,104,97 - 99. A. G. Griesbeck, M. Mauder, I. Miiller, Chem. Ber. 1992,125,2467 - 2475.

56

1.1

Aldehydes and Ketones

1.1.11 l'-Keto-3'-methoxy-l,2'-spirobiindane submitted by

B. Pandey

1.1.11a 3-[2-Methoxymethylbenzoyl]-indene 0 \

1 1 6.2

LDA / THF

+ OMe

182.2

-78OC

276.3

25 mL of dry THF and 2.44 g (3.48 mL, 24.1 mmol) of diisopropylamine were added with a syringe/septum technique to an oven dried 100 mL two-neck round-bottomed flask under nitrogen atmosphere. The flask was cooled in an ice-water bath. To this magnetically stirred solution, 8.74 mL (20.1 mmol) of 2.4 M n-butyllithium in hexane was slowly added with a syringe. The stirring was continued at this temperature for 10 min. Subsequently, the ice-water bath was replaced by a dry ice/acetone bath. 2.8 g (24.1 mmol) of indene was added to the above solution slowly with a syringe. The colorless solution turned yellow, indicating formation of indene-anion. The reaction mixture was allowed to warm to 0 "C, stirred for 10 min and again was cooled to -78 "C. The solution of 3.62 g (20.1 mmol) of methyl (0-methoxymethyl) benzoate in 3 mL of dry THF was added slowly by syringe. The stirring at -78 "C was continued for 30 min and then the reaction mixture was warmed up to 0 "C, where it was stirred for an additional 1 h. The work-up of reaction mixture involved slow addition of reaction mixture to separatory funnel containing 100 mL of 1 N HCI. The resulting emulsion was extracted with 3 x 25 mL of ether. Combined organic extracts were washed with aq. sodium bicarbonate solution, water and finally with brine solution, dried over sodium sulfate. Removal of the solvent at rota.-vap. led to a reddish residue which was chromatographed on silica gel (60-120 mesh) column using petroleum ethedethyl acetate (98:2) as eluant to afford 4.6 g (72%) of 1.l.lla as yellow viscous semisolid.

'H-NMR (CDC13, 90 MHz): 6 = 3.25 (s, 3 H, CH3), 3.55 (d, 2 H, CH2), 4.55 (s, 2 H, CH2-OMe), 6.9 (t, 1 H, C=C_H),7.2 - 7.6 (rn,7 H, Ar-H), 8.0 - 8.1 (m, 1 H, Ar-H). "C-NMR (CDC13,90 MHz): 6 = 38.8 (t, CH2), 58.4 (q, OCH3), 72.1 (t. CH2), 123.3 (d), 123.9 (d), 126.1 (d), 126.3 (d), 126.5 (d), 126.9 (d), 128.4 (d), 128.6 (d), 137.9 (s), 138.7 (s), 141.3 (s), 143.4 (s), 144.1 (s), 147.3 (d), 194.8 (s, C=O).

57

1.1 Aldehydes and Ketones

IR (thin film): v = 1660, 1560, 1480, 1.460, 1380, 1250, 11 10, 1100.

1.1.11b l'-Keto3'-methoxy-1,2'-spirobiindane

276.3

276.3

A solution of 200 mg (0.01 mol) of 1.l.lla in 75 mL of dry benzene was purged with nitrogen for 15 min and was photolysed with a 200 W Hanovia lamp in a Pyrex vessel (Pyrex filter) under usual cooling conditions for 6 h. The progress of the reaction was monitored by TLC. After rota-evaporation of the solvent, the crude reaction mixture was purified by column chromatography (silica gel 60- 120 mesh) using petroleum ethedethyl acetate (98:2) to get 130 mg (65%) 1.l.llb as a yellow viscous liquid.

lH-NMR (CDCl3, 90 MHz): 6 = 2.2 - 2.6 (m, 2 H, CH2),3.2 (m, 2 H, CH2), 3.4 and 3.5 (s, 3 H, OCH,), 5.9 (s, 1 H, CH-OMe), 6.8 (d, 1 H, Ar-H), 7.0 - 7.6 (m, 6 H, Ar-H), 7.9 (m, 1 H, Ar-H). 13C-NMR (CDC13, 90 MHz): 6 = 34.0, 36.1, 40.2, 62.7, 63.0, 90.5, 90.8, 127.5, 128.3, 128.8, 129.5, 129.9, 130.9, 131.5, 131.8, 132.6, 133.8, 134.8,205.6. IR (thin film): v = 1715, 1470, 1290.

[l] [2]

U. R. Khire, S . N. Naik, B. Pandey, N. R. Ayyangar, Znd. J. Chem. 1987,26B, 195. B. Pandey, U. R. Khire, N. R. Ayyangar, J. Chem. Soc., Chem. Commun. 1990, 1791 - 1792.

58

1.1 Aldehydes and Ketones

1.1.12 a-(4-Isobutylphenyl)propionic acid (Ibuprofen)[ll submitted by

H. R. Sonawane, B. S . Nanjundiah and D. G . Kulkarni

1.1.12a a-Chloro-1-(4-isobutylpheny1)propan-1-one

CH,CHCICOCI AICI, 134.2

224.7

To a stirred mixture of 13.4 g (0.10 mol) of isobutylbenzene and 20.0 g (0.150 mol) of aluminium chloride in 75 mL of 1,2-dichloroethane at 5 - 10 "C was added dropwise 15.3 g (0.12 mol) of a-chloropropionyl chloride over a period of 20 min. After stirring at 5 - 10 "C for 2 h and at 30 "C for 2 h, the reaction mixture was poured over crushed ice. The organic layer was separated, successively washed with water, dilute sodium bicarbonate, water and brine and dried over sodium sulfate. The residue, after removal of solvent, was distilled under reduced pressure, bp 145 - 150 "C/2 - 3 mm Hg, to give 20.2 g (90%) of the product as pale yellow oil, which solidified on standing, mp 52 - 53 "C. Alternatively, the residue can be crystallized from methanol.

'H-NMR (CDC13, 90 MHz): 6 = 0.89 (d, 6 H, J = 7, -CH(C&)2), 1.74 (d, 3 H, J = 7, -CHC&), 1.6 - 2.1 (m, 1 H, -CH(CH3)2), 2.52 (d, 2 H, J = 7, Ar-C&), 5.15 (4,1 H, J = 7, -CHClCH3), 7.23 (d, 2 H, J = 9, Ar-HJ, 7.90 (d, 2 H, J = 9, Ar-HJ. IR (Nujol): v = 2950, 1695, 1610, 1425, 1355, 1265, 1175,855.

1.1

59

Aldehydes and Ketones

po0

1.1.12b a-(4-Isobutylphenyl)propionic acid

p

c

/

'

hv aq. acetone

224.7

-

0

206.3

Nitrogen was bubbled for five minutes through a solution of 2.0 g (8.9 mmol) of 1.1.12a and 5 mL of propylene oxide in 100 mL of aq. acetone (acetone/water, 955). The solution was irradiated (Rayonet photoreactor RPR 208,3L = 300 nm) for 4 h. After rota-evaporation of the solvent, the residue was dissolved in ether and extracted with 5% sodium bicarbonate solution. The alkali extract was then cooled and acidified with dil. sulfuric acid. Extraction of the separated oil in ether and concentration of the ether layer gave a solid which was crystallized from petroleum ether to yield 1.28 g (70%) of 1.1.12b, mp 76 -

77 "C.

'H-NMR (CDC13,90 MHz): 6 = 0.89(d, 6 H,J = 7,-CH(C_H3)2),1.48 (d, 3 H, J = 7, -CHCH3),1.6 - 2.1 (m, 1 H, -C_H(CH&), 2.47 (d, 2 H, J = 7,Ar-C_H2), 3.67 (9, 1 H, J = 7,-C_HCH3), 7.20(m, 4 H,Ar-_H),9.60(br.s, 1 H,COO_H). IFt (Nujol): v = 3300 - 2500, 1720, 1605, 1465, 1420, 1375, 1320, 1270, 1235, 1185, 1075,1005,940,870,785. ~

Discussion a-Arylpropanoic acids are an important group of non-steriodal anti-inflammatory agents, of which ibuprofen is a typical example.[2] As regards the practical methods, reactions involving 1 ,2-aryl shifts in ketals of a-substituted propiophenones have become popular[3].

Interestingly, these thermal transformations are not known to proceed unless the carbonyl carbon hybridization is changed to sp3 by way of protection, eg. as a ketal. It is in this context that an analogous change in the exited carbonyl carbon (sp2+sp3) was envisaged to promote the desired rearrangement and we have found that such is indeed the ~ a se . 1 ~ 1

60

[I] [2] [3]

1.1

Aldehydes and Ketones

H. R. Sonawane, D. G. Kulkarni, N. R. Ayyangar, Tetrahedron Lett. 1990.31.74957496. J. P. Rieu, A. Boucherle, H. Cousse, G. Mouzin, Tetrahedron 1986, 42.4095 - 41 3 1 . H. R. Sonawane, N. S. Bellur, J. R. Ahuja, D. G . Kulkarni, Tetrahedron: Asymmetry 1992,3, 163 - 192.

1.1

61

Aldehydes and Ketones

1.1.13 3-Deoxy-~-D-glucero-pentopyranoside-4-ulose. submitted by

J.Cossy, S. Ibhi

1.1.13a Methyl-P-D-arabinopyranoside

150.1

164.2

A slow stream of hydrogen chloride was bubbled through a precooled (-5 "C) solution of 1.00 g (6.6 mmol) of D-arabinose in 20 mL of methanol for 15 min. The solution was stirred for 20 min at room temperature. The solvent was removed at reduced pressure and 1.06 g (96%) of 1.1.13a was obtained. [a], = -172.0" (2.0, DMSO)

lH-NMR (DMSO-d6, 300 MHz): d = 3.25 (s, 3 H, OCH3), 3.30 - 3.65 (m, 3 H), 4.50 6.65 (m, 6 H). 13C-NMR (DMSO-d6,75 MHz): d = 64.0 (q,OCH3), 73.0 (t), 78.0 (d), 78.5 (d), 79.0 (d), 110.0 (d). IR (NaCl): n = 3400,1450,1000. MS (NH3): m/z = 182 (M', loo), 150 (42), 102 (22), 85 (14), 35 (78).

1.1.13b Methyl-3,4-O-isopropylidene-~-D-arabinopyranoside. C~SO,/ H,SO,

HO\8''

acetone

c

OH 164.2

204.2

62

1.1 Aldehydes and Ketones

To a solution of 1.00 g (6.09 mmol) of 1.1.13a in 50 mL of acetone at room temperature was added 4.37 g (27.43 mmol) of copper sulfate and a few drops of sulfuric acid. After 18 h, ammonia was bubbled through the solution until [ C U ( N H ~ ) ~ ] Swas O ~precipitated. The solution was filtered, evaporated and 1.1.13b was purified by flash chromatography using hexane/ethyl acetate (7:3) as eluant. (Rf = 0.22), [a],= -200.0' (2.0, CHC13), yielding 0.74 g (60%) of 1.1.13b.

'H-NMR (CDC13,300 MHz): 6 = 1.35 (s, 3 H, CH3), 1.60 (s, 3 H, CH3), 2.50 (d, 1 H, J = 7.2), 3.45 (s, 3 H, OMe), 3.90 - 4.30 (m, 5 H), 4.75 (d, 1 H, J = 3.5). 13C-NMR (CDCl3, 75 MHz): 6 = 26.0 (4,CH3), 28.0 (4,CH,), 56.0 (9, OCH3), 60.0 (t), 71.0 (d), 74.0 (d), 76.0 (d), 99.0 (d), 110.0 (s). IR (NaCl): v = 3460,1380, 1050,850. MS (NH3): NIJZ = 222 (M', 82), 205 (68), 190 (loo), 172 (lo), 35 (28)

1.1.13~Methyl-3,4-O-isopropyl~dene-2-O-toluen~~fonyl-~-~arabinopyranoside.

204.2

190.7

358.4

To a solution of 0.65 g (3.20 mmoles) of 1.1.13b in 20 mL of pyridine was added at room temperature 1.20 g (6.40 mmoles) of tosyl chloride. After 24 h, the mixture was extracted with a solution of HCl(1 N) and chloroform. The organic phase was separated and evaporated in vucuo. The crude product was purified by flash chromatography using hexane/ ethyl acetate (7:3) as eluant. (Rf = 0.32), [aID= -1 18.0" (2.0, CHC13), yielding 0.96 g (80%)of 1.1.13~.

'H-NMR (CDC13, 300 MHz): 6 = 1.10 (s, 3 H), 1.20 (s, 3 H), 2.50 (s, 3 H), 3.40 (s, 3 H), 3.90 - 3.95 (m, 2 H), 4.20 - 4.30 (m, 3 H), 4.90 (d, 1 H, J = 3.5), 7.30 (d, 2 H, J = 8.1), 7.80 (d, 2 H, J = 8.3). 13C-NMR (CDC13, 75 MHz): 6 = 22.2 (q), 26.8 (q), 28.1 (4). 56.6 (9). 58.8 (t), 73.3 (d), 74.5 (d), 79.6 (d), 98.4 (d), 109.9 (s), 128.8 (2 d), 130.3 (2 d), 133.9 (d), 145.5 (d). IR (NaCl): v = 1350, 1200,800. MS (NH3): m / = ~ 376 (M', loo), 344 (58), 222 (22), 190 (42).

63

1.1 Aldehydes and Ketones

1.1.13d Methyl-2-0-p-toluenesulfonyl-fl-D-arabinopyranoside. HCOOH

OH

358.4

318.3

To a solution of 0.90 g (2.52 mmol) of 1.1.13~in 20 mL of acetone was added 20 mL of a solution of formic acid (1 N). The acetone was removed in vacuo. The residue was extracted with a saturated solution of NaHC03 and dichloromethane. The organic layer was separated and evaporated in vacuo. The crude product was purified by flash chromatography with hexane/ethyl acetate (3:7) as eluant. (Rf = 0.27), [a],= -108.0' (1.8, CHC13), yielding 0.82 g (80%) of 1.1.13d. ~~

'H-NMR (CDC13, 300 MHz): 6 = 2.40 (s, 3 H), 2.90 (s, 1 H), 3.10 (s, 1 H), 3.30 (s, 3 H), 3.70 (m, 2 H), 4.60 (m, 2 H), 7.35 (d, 2 H, J = 8.1), 7.85 (d, 2 H, J = 8.3). 13C-NMR (CDC13, 75 Mz): 6 = 23.0 (q), 56.0 (q), 62.3 (t), 67.0 (d), 72.0 (d), 80.0 (d), 98.0 (d), 128.0 (2 d), 132.0 (2 d), 136.0 (d), 146.0 (d). IR (NaC1): v = 3500,1600, 1350, 1150, 1OOO. MS (NH3): m / ~= 336 (M', loo), 304 (25), 182 (40), 134 (61), 80 (21), 35 (86).

1.1.13e Methy1-2,3-anhydro-P-D-lyxo-pentopyranoside.

318.3

146.1

To a solution of 0.20 g (8.69 mmol) of sodium in 20 mL of methanol was added 0.78 g (2.46 mmol) of 1.1.13d. After 12 h, the reaction was quenched with 5 mL of a solution of sulfuric acid (2N). The solvent was evaporated and the residue was extracted with chloroform. The organic layer was evaporated and the crude product was purified by flash chromatography with hexane/ethyl acetate (3:7) as eluant. (Rf = 0.31), [a],= -37.0" (2.0, CHC13), yielding 0.21 g (60%) of 1.1.13e. 'H-NMR (CDC13, 300 MHz): 6 = 3.20 (m, 2 H), 3.40 (dd, 1 H, J = 2.5, 9.9), 3.45 (s, 3 H), 3.60 (m, 1 H), 3.80 (dd, 1 H, J = 3.20,9.2), 3.90 (s, 1 H), 4.85 (s, 1 H).

64

1.1 Aldehydes and Ketones

I3C-NMR (CDC13,75 MHz): 6 = 52.4 (d), 52.5 (d), 56.4 (d), 62.3 (t), 62.5 (d), 96.0 (d). IR (NaCl): v = 3450, 1250,950.

MS (NH3): m/z = 164 (M', loo), 132 (38), 35 (48).

1.1.13f Methyl-2,3-anhydro-~-~-erythro-pentopyranoside-4-ulose.

146.1

144.1

To a solution of 0.17 mL (2.53 mmol) of DMSO in 1 mL of CH2C12 was added a solution of 0.10 mL (1.26 mmol) of oxalyl chloride in 1 mL of CH2C12 at -60 'C. After 10 min, a solution of 0.15 g (1.05 mmol) of 1.1.13e in 1 mL of CH2C12 was added followed by the addition of 0.70 mL (0.52 mmol) of triethylamine. After 15 min, the temperature was allowed to warm to room temperature. The reaction mixture was extracted with water and dichloromethane. The organic phase was evaporated. The crude product was purified by flash chromatography with hexane/ethyl acetate (7:3) as eluant. (Rf = 0.3). [aID= -244.0' (2.1, CHC13), yielding 0.10 g (70%) of 1.1.13f.

'H-NMR (CDC13, 300 MHz): 6 = 3.40 (d, 1 H, J = 4.1), 3.50 (s, 3 H), 3.60 (dd, 1 H, J = 1.30,4.10), 4.15 (d, 2 H, J = 3.20), 5.10 (s, 1 H). 13C-NMR (CDC13,75 MHz): 6 = 53.1 (d), 53.4 (d), 56.4 (q), 65.7 (t), 94.9 (d), 202.0 (s). IR (NaCl): v = 1720,1078,800. MS (NH3): m/z = 162 (M', 65), 144 (32), 130 (42), 119 (loo), 102 (72)

1.1.13g 3-Deoxy-~-~-glycero-pentopyranoside-4-ulose.

144.1

146.1

1.1 Aldehydes and Ketones

65

To a solution of 0.20 g (1.38 mmol) of 1.1.13f in 10 mL of acetonitrile was added 1 mL (7.00 mmol) of triethylamine. The resulting solution was irradiated (quartz tube) at 254 nm. After one hour the solvent was evaporated and the reaction mixture was purified by flash chromatography with hexane/ethyl acetate (3:7) as eluant. (Rf = 0.29), [aID= -1 18.0" (2.0, CHCl3), yielding 0.106 g (53%) of 1.1.13j. ~

'H-NMR (CDC13, 300 MHz): 6 = 2.25 (s, 1 H), 2.60 (dd, 1 H, J = 4.4, 12.1), 2.90 (dd, 1 H, J = 4.6, 12.1), 3.55 (s, 3 H), 3.90 - 4.20 (m, 3 H), 4.65 (d, 1 H, J = 3.0). 13C-NMR (CDCl,, 75 MHz): 6 = 44.0 (t), 56.0 (q), 68.0 (t), 70.0 (d), 102.0 (d), 206.0 (s). IR (NaCI): v = 3450,1750. MS (NH3): m/z = 164 (M+, loo), 132 (lo), 74 (70).

66

1.1 Aldehydes and Ketones

1.1.14 4-Aza-2-methylene-5-oxo-4,8,8-trimethyl[ 4.3.01bicyclononan-1-01 submitted by

J. P. Pbe

209.3

207.3

A solution of the P-ketoamide[l] (300 mg) and triethylamine (1.45 g) in acetonitrile (30 mL) is deoxygenated by argon bubbling and then irradiated for 5 h in a Rayonet photochemical reactor using 254 nm radiation lampd2]. The solvent is evaporated and the residue separated by flash chromatography on silicagel using a mixture of CHC13/methanol (93:7) as eluant. Yield 6596, mp 96 - 97 "C. ~~

~

~

~

'H-NMR (CDC13, 300 MHz): 6 = 1.01 (s, 3 H), 1.21 (s, 3 H), 1.68 (d, 1 H, J = 14.2), 1.85 (dd, 1 H, J = 13, 7), 1.90 (d, 1 H, J = 14.2), 2.13 (dd, 1 H, J = 13, 8), 2.75 (s, 1 H, exchangeable), 2.80 (t, 1 H, J = 7.5), 2.96 (s, 3 H), 3.95 (s, 2 H), 5.08 (d, 1 H, J = OS), 5.29 (d, 1 H, J = 0.5). 13C-NMR (CDCl3,75.5 MHz): 6 = 30.6 (q), 31.0 (q), 34.5 (q), 37.9 (s), 44.7 (t), 52.7 (t), 53.3 (t), 55.8 (d), 81.9 (s), 110.5 (t), 144.4 (s), 171.8 (s). MS (70 eV): m/z = 209 (3696, M+). 194 (33), 152 (32), 125 (58), 124 (63), 112 (95), 110 (54), 98 (42), 97 (58), 96 (52), 95 (32), 70 (loo), 55 (53). IR:v = 3580,3380,1655,1630,1500,1400,1310,1140,1050,920.

[l] [2]

J. Cossy, D. Belotti, A. Thellend, J. P. Pbte, Synthesis 1988, 720 - 721. J. Cossy, D. Belotti, J. P. P&e, Tetrahedron Lett. 1987,28,4545 - 4546.

67

1.1 Aldehydes and Ketones

1.1.15 8-Methylspiro[4.5]decan-3-one[1] subrnirted by

Th. Kirschberg and J. Mattay

L kEt

1.1.15a 3-(3-Butenyl)-cyclohex-2-en-l-one 1.) BrMgCH,CH,CH=CH,

140.2

150.2

14.0 g (0.1 mol) of 3-ethoxycyclohexenone in 40 mL ether were added dropwise to a freshly synthesized Grignard reagent of 13.1 g (0.09 mol) of 4-bromo-1-butene and 2.7 g (0.1 1 mol) of magnesium turnings in 100 mL of ether[2]. (4-bromine-1-butene is available by dehydrohalogenation of 1,Cdibromobutane and HMPAD]). After addition was complete at 0 "C the reaction mixture was stirred at room temperature for 30 min and refluxed for additional 60 min. The reaction was quenched by addition of 300 mL of ice/water. The solution was acidified with 5% hydrochloride and extracted 5 times with ether. The organic layers were dried with magnesium sulfate. Filtration and evaporation of the solvent afforded the crude product which was stirred in 40 mL of methanol with 2.5 g of potassiumhydroxide for 14 h. The mixture was acidified with 10% hydrochloride, the methanol was evaporated and 10 mL of water were added to the resulting solid. Extraction with ether, washing of the organic layers with water and drying with magnesium sulfate afforded 4.9 g (35.8%) of the product by distillation (123 "C/12 Torr). ~

'H-NMR (CDC13, 300 MHz): 6 = 1.99 (m, 2 H, 5-H), 2.31 (m, 8 H, 4-, 6-, 7-, 8-H), 5.00 (dm, 1 H, J = 11.0, 10-HCis), 5.05 (dm, 1 H, J = 18, 1O-Htrans), 5.78 (ddt, 1 H, J = 17, 10,6.5,9-H), 5.86 (s, 1 H, 2-H). 13C-NMR (CDC13, 75 MHz): 6 = 22.6 (CH2) 29.6 (CH2,), 30.5 (CH2), 37.2 (CH2), 37.9 (CH2), 115.5 (CH3, C-lo), 125.9 (CH, C-2), 137.0 (CH, C-9), 165.4 (Cq, C-3), 199.5 (Cq, c-1). IR (neat): v = 3065, 2925, 2880, 2860, 1660 (s), 1620, 1600, 1425, 1322, 1250, 1138, 910, 884. MS (GC): m/z = 151 (30, M++l), 150 (lo), 132 (20), 121 (22), 104 (20), 94 (30), 91 (21), 80 (28), 79 (IOO), 77 (22), 53 (25), 41 (28), 39 (88).

68

1.1 Aldehydes and Ketones

1.1.15b 1-(3-Butenyl)bicyclo[4.1.0]heptan-5-one 0

0

(CH,),S'OCHi 150.2

164.2

1.6 g (0.033 mol) of NaH dipersion in mineral oil (55 - 60%) were washed under argon atmosphere with light petroleum ether (3 times, each 10 mL). Vaccum was applied to remove last traces of light petroleum ether. Argon was again introduced to the system and not removed until the quenching step. 6.0 g (0.027 mol) of trimethyloxosulfonium iodide (available by refluxing DMSO and methyliodide for five daysL4]) and 35 mL of dry dimethylsulfoxide were added seperately. After the hydrogen evolution ceased (30 min) 3.8 g (0.025 mol) of the enone 1.1.15a were added dropwise with waterke cooling. The reaction mixture was stirred for additional 3 h at room temperature and quenched by pouring it into 75 mL of ice water. The mixture was extracted with ether (3 times, each 75 mL) and the combined organic layers were washed with water (2 times, each 50 mL). Drying over magnesium sulfate, filtration, evaporation of the solvent and chromatography on silica gel (ethylacetatekyclohexane 10:90) yielded 1.89 g (46%) of 1.1.15b. ~~~

~

~

~

lH-NMR (CDC13,300 MHz): 6 = 0.94 (dd, 1 H, J = 10,5, 1 x 7-H), 1.36 - 1.83 (m, 4 H), 1.93 - 2.08 (m, 3 H), 2.12 - 2.38 (m, 5 H), 4.95 (dm, 1 H, J = 10, lI-Hcis), 5.01 (dm, 1 H, J = 18, Il-Htrans), 5.79 (ddt, 1 H, J = 17.5, 10,7, 10-H). "C-NMR (CDCl3, 75 MHz): 6 = 17.3 (CH2), 18.5 (CH2), 25.7 (CH2), 26.1 (Cq, C-l), 30.8 (CH2), 33.7 (CH, C-6) 36.5 (CH2), 38.6 (CH2), 114.9 (CH2, C-ll), 138. 3 (CH, C-lo), 209.1 (Cq, C-5). IR (neat): v = 3060,2910,2835, 1675 (s), 1630, 1440, 1315, 1245,905. MS (GC): d z = 164 (10, M+), 149 (12), 136 (16), 135 (17), 121 (20), 110 (loo), 95 (78), 93 (58), 91 (40), 79 (84), 77 (38), 67 (66), 55 (80), 41 (46), 39 (34).

0

0

164.2

166.2

1.1 Aldehydes and Ketones

69

A solution of 0.85 g (5.18 mmol) of 1.1.15b, 1.4 g (13.85 mmol) of triethylamine (2.5 eq.) and 100 pL of decane in 20 mL of dry acetonitrile was degassed by argon bubbling and distributed among 10 mL Duran glass tubes. After purging the tubes with argon for 1 min, they were sealed and irradiated for 120 h in a Rayonet reactor fitted with 300 nm lamps and a merry-go-round inset. The solvent was evaporated and purification by HPLC (cyclohexane/ethylacetate93:7) yielded 0.352 g (41%)of 1.1.15~.

lH-NMR (CDC13,300 MHz): 6 = 0.97 (d, 3 H, J = 7, 11-H), 0.98 (m, 2 H), 1.19 (m, 1 H, 8-H), 1.37 - 2.10 (m, 8 H), 2.22 - 2.30 (m, 4 H, 2 - 4-H). 13C-NMR (CDC13, 75 MHz): 6 = 20.7 (CH3, C-Il), 23.8 (CH2), 33.5 (CH, C-8), 33.7 (CH2), 38.3 (CH2), 41.2 (CH2), 47.2 (CH2), 47.7 (Cq, C-l), 53.9 (CH2, C-4), 54.9 (CH2, C-2), 21.9 (Cq, C-3). IR (neat): v = 2930,2860, 1710 (s), 1455, 1440, 1310, 1225. MS (GC): m/z = 166 (30, M"), 148 (18), 133 (24), 123 (loo), 108 (28), 95 (42), 93 (28), 81 (55), 67 (62), 55 (36), 41 (35),39 (59).

[ 11

[2] [3] [4]

Th Kirschberg, J. Mattay, Tetrahedron Lett. 1994, in print. D. Becker, Z. Harel, M. Nagler, A. Gillon, J. Org. Chem. 1982,47, 3297 - 3306. G. A. Kraus, K. Landgrebe, Synthesis 1984,885. E. J. Corey, M. Chaykovsky, J. Am. Chem. SOC.1965,1353 - 1364.

1.2

Enones and Dienones

In most cases the photochemistry of enones (a$- as well as P,y-unsaturated) and dienones is completely different compared with the carbonyl reactivity (vide supra). Because the extra double-bond(s) will now interfere, the reactivity often resembles that of alkene chromphores. For example, the well-known di-x-methane rearrangement (see chapter 4 for this reaction) could be modified by simply exchanging one of the C-C double bonds by a carbonyl group, thus leading to a substrate for the oxa-di-n-methane rearrangement. This reaction has been thoroughly studied by M. Demuth who submitted two versions of the oxa-di-x-methane rearrangement using racemic as well as enantiomerically pure bicyclo[2.2.2]oct-5-en-2-one as substrates. The photoreaction leads to semibullvalene derivatives which constitute versatile starting materials for the synthesis of complex terpenoid structures. Conjugated enones could undergo, quite similar to carbonyl substrates, a multitude of reactions. The photodeconjugation of a$-unsaturated carboxylic esters (to the corresponding P,yunsaturated isomers) has been studied in detail by J.-P. Pete. Using a carbohydrate derived ester substituent (actually a simple glucose derivative) high enantiomeric excesses could be obtained. The reactions conditions are crucial for the amount of %ee, especially the use of the proper hydrogen donor (an amino alcohol in this case). This transformation is initiated by a y-hydrogen abstraction. Likewise the photodeconjugation of P-methyl cinnamic ethyl ester as described by A. C. Weedon is an efficient process for the synthesis of the P,y-unsaturated isomer. Like simple carbonyl compounds a$-unsaturated ketones and esters easily undergo photochemical -addition of alcohols. Pinacols can be synthesized from carbonyl compounds, whereas addition of alcohols to a$-unsaturated substrates leads to the formation of y-hydroxy carbonyl compounds. A remarkable synthesis of enantiomerically pure terebic acid, described by N. Hoffmann, takes advantage of this methodology. Photooxygenation of furfural - (an excellent example of a powerful singlet oxygen reaction (see also chapter 6) - leads to a hydroxy butenolide which serves as the starting material (after conversion to its corresponding menthyl ether) for the photoaddition of isopropanol. When no y-hydrogens are available or their geometry is unfavorable for abstraction, EIZ-isomerization gets the important process. This type of isomerization is often found for chalcone-type substrates (1,3-diaryIpropenones) as described by H. G. Henning for an enamido chalcone. Obviously this process is not possible for small-ring substrates such as cyclopentenones or cyclohexenones. Therefore they constitute reactive substrates for intrac and intermolecular [2+2] reactions. Electron-rich alkenes are often used as addends for this type of cycloaddition. As described by R. Neier a cyclic P-amido cyclohexenone (compare with the open-chain substrate before) undergoes clean [2+2] cycloaddition to tetramethylethylene. Additionally a useful method for the enhancement of diastereomeric purity is described. Many starting materials, which are used for [2+2] photocycloaddition reactions, are protected enols of 1,3-dicarbonyl compounds. 1,3-diketones are largely enolized in solution. Thus, they can be used directly for [2+2] photocycloaddition reactions which are named de Mayo reactions.

1.2

Enones and Dienones

71

An intermolecular [2+2] cycloaddition using an enantiomerically pure enone substrate is described by M. Demuth. His menthone derived bicyclic acetal adds to cyclopentene with high diastereoselectivity (with both diastereoisomers obviously being enantiomerically pure). This chiral auxiliary also has been used in several syntheses of (+) and (-)-grandisol, a potent aggregation pheromone of the boll weevil. A menthol-based route to grandisol is described by H.-D. Scharf using the [2+2] cycloaddition of ethylene with an enantiomerically pure menthyl-substituted furanone as the photochemical key step. The asymmetric induction of this reaction is relatively poor, the diastereomeric photoproducts, however, can be easily separated. Both enantiomers of grandisol can be synthesized using this methodology. A variety of heterocyclic compounds of the indole and benzofuran type can be made via photoaddition of alkenes to 2-amino- or 2-hydroxy- 1,4-naphthoquinone. These products, described by H. Suginome probably derive from an intramolecular trapping reaction of the intermediary 1,4-biradicals or I ,4-zwitterions. An intramolecular variation of the ene/enone photocycloaddition is described by J. D. Winkler. As already described for the intermolecular transformation (see Demuth's enone cycloaddition reaction), a dioxenone is formed via cyclization of a P-ketoester and subsequently irradiated. Intramolecular cycloaddition then leads to a strained tetracyclic photoproduct which can be ring-opened and decarboxylated to give the trans-fused bicyclo[5.3. llundecan- 1 1-one. Strained cage compounds can be made by intramolecular photocycloaddition of properly designed ene/enone substrates. In an interesting example from J. R. Scheffer, a benzoquinone derived Diels-Alder product is regioselectively transformed into a (half) cage compound. This is a more complicated version of the classical intramolecular photochemical cyclization reactions of benzoquinone derivatives (for example see B. Pandey's cage synthesis from a naphthoquinone-cyclopentadienein Chapter 3). The norbornadiene-quadricyclane photoisomerization has received some attention due to possible applications as a solar energy storage and conversion system. However, shortwavelength irradiation is necessary a achieve [2+2] cycloaddition in the absence of triplet sensitizers. T. Miyashi describes an easily accessible substrate absorbing in the longwavelength region due to the naphthoquinone chromophore. The synthesis of the starting material is described in the literature and is based on simple [4+2] cycloaddition chemistry. Substituted furan-3(2H)-ones, generated by Claisen-rearrangement from 3-allyloxy furanes can also serve as versatile substrates in photocycloaddition chemistry, as described by P. Margaretha. The cycloadducts, which are formed with high regioaelectivity, can be ring-opened with sodium methoxide to afford diastereomerically pure bicyclo[3.2.0]heptane derivatives. Interesting rearrangement processes are known for electronically excited cyclohex-2-en1 -ones and cyclohexa-2,5-dien-1-ones and have been extensively studied in the group of H. E. Zimmerman. Thus triplet excited 4,4-diphenylcyclohex-2-en-1-one gives the phenyl migration product 5,6-bicyclo[3.1.O]hexan-2-onein high trans (or endo) diastereoselectivity (> 250: 1). A different pathway (named Type A rearrangement) was found for cyclohexadienones (obviously directly connected with the di-x-methane rearrangement): 4,4-diphenylcyclohexa-2,5-dien-1-one gives exclusively the skeleton migration product

72

1.2 Enones and Dienones

6,6-bicyclo[3.1.O]hex-3-en-2-one.Many other examples have been intensively investigated by Zimmerman and coworkers.

Recommended further reading Oxa-di-n-methane rearrangement: M . Demuth, Organic Photochemistry 1991, ZZ, 37 110. Intramolecular [2+2] cycloaddition reactions of enones: D. Becker, N. Haddad, Organic Photochemistry 1989, 10, 1 - 162. Intermolecular [2+2] cycloaddition reactions of enones: S . W. Baldwin, Organic Photochemistry 1981,5, 123 - 226. and the corresponding chapters in: Rearrangements in Ground and Excited States Vol. 42 - 43, P. de Mayo (Ed.), 1980; Photochemistry in Organic Synthesis J. D. Coyle (Ed.), 1986, The Royal Society of Chemistry, London; Synthetic Organic Photochemistry W. A. Horspool (Ed.), 1984, Plenum Press, New York, London; W. A. Horspool, D. Armesto, Organic Photochemistry: A Comprehensive Approach, 1992, Ellis Horwood, PTR Prentice Hall, New York.

73

1.2 Enones and Dienones

1.2.1

Oxa-di-n-MethaneRearrangement submitted by

1.2.la

M. Demuth

5-Cyanobicyclo[2.2.2]oct-2-ene[~~

cc" a

80.1

53.1

133.2

140 g (1.73 mol) of 1,3-cyclohexadieneand 100 g (1.89 mol) of acrylonitrile were heated for 12 h to 120 "C in an autoclave. The crude product was purified by distillation (104 106 "C/12 Torr). Yield: 80% of 1.2.la, mp 58 "C.

1.2.lb

5-Chloro-5-cyanobicyclo[2.2.2]oct-2-ene~~~

133.2

167.6

5-Cyanobicyclo[2.2.2]oct-2-ene1.2.la (88.2 g, 0.65 mol) was added slowly, to a stirred solution of pyridine (106 g, 1.33 mol) and phosphorous pentachloride (207 g, 0.99 mol) in 1.5 L of dry chloroform. After refluxing for 16 h, the mixture was poured onto 2 kg of ice. After the ice had melted, the layers were separated and the aqueous phase was washed twice with ether. The organic extracts were combined and washed once with saturated aqueous sodium chloride and once with 10% aqueous sodium carbonate. Removal of the solvent and distillation gave 67.2 g (60.8%) of chloronitrile 1.2.lb, mp 88 - 90 "C.

74

1.2 Enones and Dienones

KOH, H,O

DMSO

=

167.6

Q" 122.2

A hot solution of 106 g (1.61 mol) of 85% potassium hydroxide in 30 mL of water was added to a solution of 66.7 g (0.40 mol) of chloronitrile 1.2.lb in 600 mL of DMSO. There was a gradual darkening of color from yellow to black and a mild increase of temperature to 50 - 60 "C. After 12 h the reaction mixture was added to 1 kg of ice-water and extracted five times with petroleum ether (bp 30 - 60 "C). Drying over magnesium sulphate and distilling off the solvent left a semi-solid material which was sublimed (at ca. 80 "C/ 12 Torr) to give 33.0 g (68%) of ketone 1.2.lc, mp 84 - 86 "C.

13C-NMR (CDCl3): 6 = 22.5 (t), 24.3 (t), 32.4 (d), 40.5 (t), 48.6 (d), 128.5 (d), 137.0 (d), 212.9 (s).r31

1.2.Id Tricyclo[3.3.0.02~*]octan-3-one~41

Q" 122.2

hu

t

acetone 122.2

Method A: A solution of bicyclo[2.2.2]oct-5-en-2-one(1.2.1c, 5.0 g, 41 mmol) in acetone (500 mL, serves as solvent and sensitizer) is purged with argon for 15 min prior to irradiation in a water-cooled quarz vessel placed in a Rayonet RPR-208 photoreactor equipped with RUL-300 nm-lamps (the solution to be irradiated is surrounded by a battery of lamps within a chamber). After 20 h, 96% of the starting material is converted into 1.2.ld. The acetone is distilled off. Column chromatography of the residue (75 g silica gel of 70-230 mesh) with toluene as eluant affords unreacted 1.2.1~(0.15 g) in addition to Nomsh Type I material (0.11 g, 2% yield), and with toluenelether (9: 1) the rearrangement produkt 1.2.ld (4.475 g, 89.5% yield, >98% purity by GC and IH-NMR). A purity of 99.5% is reached upon distillation of 1.2.ld at 50 "C/1 Torr.

Method B: A solution of 1.2.1~(5.0 g, 41 mmol) and acetophenone (1 g) as sensitizer in acetone (200mL) (note: acetone can be replaced in this procedure by any other solvent which is light resistant and transparent > 340 nm, eg., benzene or cyclohexane) is purged with argon for 15 min prior to irradiation in a water-cooled Pyrex vessel placed in a

1.2

75

Enones and Dienones

Rayonet RPR-208 photoreactor (RUL-350 nm-lamps). After 18 h, 94% of the starting material is converted into 1.2.ld. The acetone is removed in vucuo and pure 1.2.ld (4.31 g, 86% yield) is obtained by column chromatopraphy of the residue (silica gel 100-fold; pentanelether 1:l). The acetophenone and unreacted 1.2.1~(5 - 6%) are separately eluated with the initial fractions.

Method C: Alternatively the reaction mixture employed in method B can be irradiated (16 - 18 h) in a Pyrex vessel, which surrounds a centrally arranged water-cooled mediumpressure mercury lamp (250 W Hanovia). A jacket containing a filter solution (thickness 1 cm; 750 g NaBr and 8 g Pb(N03)2 in 1 L of water; transmission > 340 nm) is placed between the lamp and the solution to be irradiated.

lH-NMR and MS data see ref ( 5 ) .

1.2.le (1R)-and (1s)-Diethyl Tartrate Acetal of l.2.lcr61

Q" HoYooEt +

122.2

HO "''COOEt

206.2

TsoH benzene

310.4

A solution of racemic 1.2.1~ (10 g, 82 mmol), p-toluenesulphonic acid (0.35 g, 1.84 mmol) and diethyl (R,R)-(+)-tartrate (35 g, 170 mmol; [a],= +7.9", neat) in 20 mL of benzene is refluxed in a Dean-Stark apparatus. After 50 h the reaction mixture is cooled to room temperature and washed with five 100 mL portions of water. The organic layer is separated and dried, and the solvent is evaporated. The residue is 25.89 g (96%) of a 1:l mixture of the diasteroisomeric acetals 1.2.le (94% purity by GLC; about 3% of the remainder is diethyl (+)-tartrate). The material is passed in 5 g portions through two Merck ready-made columns (Li-Chroprep SI 60, Type C, mesh 63 - 125; solvent toluene/ ether 99:l; pressure 2.4 bar) connected in series. A typical separation is as follows: fractions 1 and 5 contain each 0.75 g of (-)-U.le and (+)-1.2.1e, respectively, with purities of 99%. Fraction 2 and 4 (each ca. 1.45 g) are strongly enriched with (-1-1.2.1e and (+)-1.2.1e, respectively, and fraction 3 (about 0.5 g) is a 1:1 mixture. The enriched fractions are passed once more through the same columns using the same solvent mixture, affording another 0.85 g of each isomer in pure form. The yield from 5 g of crude 1.2.1~is thus about 1.6 g of each diastereoisomer (separation of 64% of the total).

76

1.2

Enones and Dienones

(+)-1,2,1e: lH-NMR (CDC13, 270 MHz): 6 = 1.13 + 1.17 (2 t, 4 H, J = 7), 1.2 - 2.1 (m, 6 H), 2.5 (m, 2 H), 4.11 + 4.15 (2 q, 4 H, J = 7), 4.59 + 4.66 (2 d, 4 H, J = 4.5),6.1 + 6.2 (2 m, 2 H). IR (CC14): v = 1770,1755, 1610, 1380,1215,1135, 1035. MS: m / = ~ 310 (M+, C16H2206). 231 (loo), 115,80,43,29. [a],= +65" (0.5). (-)-1.2.1e: 'H-NMR (CDC13, 270 MHz): 6 = 1.12 + 1.16 (2 t, 3 H, J = 7), about 1.2 - 2.1 (m, 6 H), about 2.5 (m, 2 H), 4.11 and 4.15 (2 q, 4 H, J = 7), 4.63 and 4.67 (2 d, 2 H, J = 4.9, about 6.1 and 6.2 (2 m, 2 H). IR and MS data identical with those of (+)-1.2.1e. [a],= -68.6" (2.31).

1.2.lf

(1R,4R)-(+)-and (1S,4S)-(-)-Bicyclo[2.2.2]oct-5-en-2-one[6]

310.4

122.2

A solution of (+)-1.2.le (1.33 g, 4.29 mmol) in 50 mL of EtOH and 20 mL of 10% aqueous HCl is heated to 50 "C for 48 h. After cooling to room temperature 100 mL of H20 is added and the mixture is extracted with three 30mL portions of hexane. The combined organic layers are washed with aqueous NaHC03 solution. Evaporation of the solvent gives 492 mg (94%) of (+)-1.2.lc ([a], = +512" (0.55)) as a colorless semicrystalline material. Hydrolysis of (-)-1.2.1e gives correspondently (-)-1.2.1c ([a], = -520" (0.26)); both preparations exhibit enantiomeric purities of > 98%.

[l] [2] [3] [4] [5] [6]

K. Alder, H. Krieger, H. Weiss, Chem. Ber. 1955,88, 144 - 155. P. K. Freemann, D. M. Balls, D. J. Brown, J. Org. Chem. 1968,33,2211 - 2214. G. E. Langford, J. A. Auksi, G. E. Gosbee, F. N. Mac Lachan, P. Yates, Tetrahedron 1981,37, 1091 - 1104. M. Demuth, G. Mikhail, Synrhesis 1989, 145 - 162. S.A. Monti, D. J. Bucheck, J. C. Shepard, J. Org. Chem. 1969,34,3080 - 3084. M. Demuth, S. Chandrasekhar. K. Schaffner, J. Am. Chem. SOC. 1984, 106, 1092 1095.

1.2

77

Enones and Dienones

1.2.2

(2R)-(1,2:5,6-Di-0-isopropylidene-a-~-glucofuranose3-0-y1)2,4-dimethyl3-pentenoate[ll submitted by

+god-

J. P. Pkte

hv

\

0

A

s

370.4

n-hexane, -50°C n -N OH \

0k0

370.4

To a solution of 1 mmol of (1,2:5,6-di-O-isopropylidene-a-~-glucofuranose-3-~-yl)2,4dimethyl 2-~entenoate[~] (370 mg), in n-hexane (100 mL) is added 1 mmol of N,N-dimethylaminoethanol (89 mg). The mixture is poured into 7 quartz tubes (10 mm diameter) and deoxygenated with argon for 5 min. The tubes are disposed around a quartz Dewar in which a short wave lamp (254 nm) is placed. This system is cooled by an external ethanol bath at -50 "C. Irradiation is performed at this temperature for 6 h. After evaporation of the solvent, the crude product is purified by flash-chromatography on SiO2 using ethyl acetate/petrol ether (10:90) as solvent (Rf = 0.48). Yield: 204 mg (56%), [a],, = -88.6" (0.7, CH2C12), de = 97% according to IH-NMR.

'H-NMR (CDC13, 250 MHz): 6 = 1.20 (d, 3 H, J = 6.9). 1.27 (s, 3 H), 1.29 (s, 3 H), 1.31 (s, 3 H), 1.40 (s, 3 H), 1.51 (s, 3 H), 1.67 (d, 3 H, J = 1.3), 1.71 (d, 3 H, J = 1.2), 3.34 (dq,1H,J=9.3,6.9),3.97(dd,1H,J=4.8,8.3),4.08-4.15(m,1H),4.17-4.22(m, 2 H), 4.44 (d, 1 H, J = 3.6), 5.12 (dq, 1 H, J = 9.3, 1.3), 5.26 (d, 1 H, J = 2.5), 5.87 (d, 1 H, J = 3.6). 13C-NMR (CDC13, 75.5 MHz): 6 = 17.6, 18.0, 25.1, 25.6, 26.2, 26.7, 39.0, 53.4, 67.3, 72.3,75.7,80.2, 83.4, 105.1, 109.2, 112.2, 123.3, 134.4, 173.7. MS (70 eV): m/z = 355 (20, M+-15), 312 (15), 101 (82), 83 (100). IR: v = 2990,2940,1735,1450,1385,1375,1260- 1200,1160,1080 - 1060,1030.

[l] [2]

0. Piva, J. P. Pkte, Tetrahedron Asymmetry 1992, 3, 759 - 768. From 2,4-dimethyl 2-pentenoic acid, obtained by Wittig-Horner reaction; F. Henin, R. Mortezai, J. Muzart, J. P. Pbte, 0. Piva, Tetrahedron 1989,45,6171 - 6196.

78

1.2

1.2.3

Enones and Dienones

Ethyl 3-phenyl-3-butenoate[*l submitted by

1.2.3a

Alan Weedon

Ethyl 3-hydroxy-3-phenylbutanoate[2]

4

Ph

+

120.1

-

Zn

Br>OEt 0

65.4

167.0

r,,, 0

Ph

OH

208.3

The hydroxyester is prepared by Reformatsky reaction of acetophenone with ethyl bromoacetate.[2] 8 g (0.12 mol) of zinc dust was stirred in 25 mL benzene. A 10 mL portion of a solution of 12 g (0.1 mol) acetophenone and 20 g (0.12mol) ethyl bromoacetate in 50 mL benzene was added to the zinc suspension and the mixture was heated to reflux to initiate the reaction. The remainder of the benzene solution containing the ketone and the bromoester was added over 30 min. The reaction mixture was then refluxed for a further 30 min. Before being cooled to room temperature, washed with 50mL of dil. H2SO4 and dried (MgS04). Filtration and evaporation under reduced pressure gave an oil which was distilled (106 "C/0.8 Torr; lit.[2] 146 - 147 "C/15 Torr) to give a 50% yield of ethyl 3-hydroxy-3-phenylbutenoate 1.2.3a.

1.2.3b

Ethyl 3-acetoxy-3-phenylbutanoate

tom

Ph

OH

208.3

CH,COCI PhNMe,

78.5

-

tom

Ph OAc

250.3

A solution of 10.4 g (50 mmol) of ethyl 3-hydroxy-3-phenylbutanoate 1.2.3a, 4.3 g (55 mmol) of acetyl chloride and 6.7 g (55 mmol) of N,N-dimethylaniline in chloroform (50 mL) was refluxed for 4 h. The solution was cooled to room temperature and washed with 50 mL of water, 50 mL of saturated aqueous NaHC03,50 mL of dil. HCI, and 50 mL

79

1.2 Enones and Dienones

of water. The solution was dried (Na2S04) and evaporated to yield an oil which was distilled (106 - 118 "C/ 0.4 Torr) to give ethyl 3-acetoxy-3-phenylbutenoate1.2.3b in 80% yield.

'H-NMR (CDC13,60 MHz): 6 = 1.18 (t, 3 H, J = 7, OCH2CH3), 2.0 (s, 3 H), 2.2 (s, 3 H), 3.12 (s, 2 H, CH2C02Et), 4.1 (q,2 H, J = 7, OCH2CH3), 7.4 (br.s, 5 H).

1.2.3~ trans-Ethyl 3-phenyl-2-butenoate JOEt

B U ~ K

2 0 E t

m

Ph

OAc 250.3

Ph 112.2

190.2

A solution of potassium tert-butoxide was prepared under dry nitrogen gas by dissolving 2 g (51 mmol) of potassium in 40 mL of tert-butanol. 9 g (36 mmol) of ethyl 3-acetoxy-3phenyl-butanoate 1.2.3b was dissolved in 15 mL of tert-butanol and the solution was added dropwise to the stirred tert-butoxide solution over 5 min. with slight cooling by a cold water bath. Halfway through the addition a white gelatinous solid appeared. When the addition was complete the solution was stirred for a further 15 min. and poured into water (100 mL). The aqueous solution was extracted with diethyl ether (3 x 50 mL) and the combined extracts were dried (MgS04), filtered and evaporated. The crude product was distilled to give trans-3-phenyl-2-butenoate(96 - 98 "C/O.S Torr; lid3] 135 - 1361 1 Tom) in 79% yield.

'H-NMR (CDCI3, 60 MHz): 6 = 1.26 (t, J = 7, OCH2C&), 2.57 (d, 3 H, .I= 1, =C(Ph)CH3), 4.2 (q, 2 H, J = 7, OCH2CH3), 6.0 (q, 1 H, J = 1, =CHC02Et), 7.4 (br.s, 5 H).

1.2.3d Ethyl 3-phenyl-3-butenoate hu

Ph

1,2-dimethyl irnidazole 190.2

96.1

-

2

OEt

Ph

190.2

80

1.2

Enones and Dienones

A solution of 1.19 g (6.3 mmol) of ethyl 3-phenyl-2-butenoate 1.2.3~ and 0.40 g (0.043 mmol) of 1,2-dimethylimidazole in 350 mL of benzene was irradiated with a Hanovia 450 W medium-pressure mercury lamp. The light source was housed in a Pyrex water jacket which was immersed in the solution being irradiated. The reaction was followed by GC and conversion was found to be complete after 56 h. The benzene was removed under reduced pressure and the residue was dissolved in 100 mL of diethyl ether (a small amount of polymeric material did not dissolve and was discarded. The ether solution was washed with 100 mL of 5% aqueous sulfuric acid and 100 mL of 1% aqueous NaHCO3 solution. It was then dried (MgS04) and evaporated to give a light yellow oil which was distilled (bulb-to-bulb, 96 "U0.4 Torr) to give 1.01 g of ethyl 3-phenyl-3butenoate (85%). The reaction can also be successfully carried out using imidazole instead of 1,2-dirnethylimidazole.

'H-NMR (CDCl,, 200 MHz): 6 = 1.16 (t, 3 H, J = 7, OCHZCH3), 3.49 (d, 2 H, J = 1, C&C02Et), 4.08 (9.2 H, J = 7, OCH~CHQ), 5.21 (q, 1 H, J = 1, C=C€l), 5.52 (d, 1 H, J = 1, C=CHJ, 7.3 - 7.5 (m, 5 H). IR (neat): v = 1750, 1640.

[l] [2] [3]

R. M. Duhaime, D. A. Lombardo, I. A. Skinner, A. C. Weedon, J. Org. Chern. 1985,50,873 - 879. S . Lindenbaum, Chem. Ber. 1917,50, 1270 - 1274. D. Lipkin, T. D. Stewart, J. Am. Chem. Soc. 1939,61,3295 - 3300.

1.2

81

Enones and Dienones

1.2.4

Synthesis of Terebic Acidrll submitted by

1.2.4a

N. Hoffmann

Hydroxy-2[5Hl-furanone[*l

100.1 96 g (1.0 mol) of furfural and 0.3 g of rose bengale are dissolved in 375 mL of methanol or ethanol: The solution is filled into the irradiation vessel. During irradiation, the reaction mixture is flushed with air and a second solution of 0.7 g of rose bengale in 100mL of methanol or ethanol is added with a rate of about 1 drop per 12 sec. The reaction solution is irradiated for 24 h with a Hg medium-pressure lamp (TQ 150 Z 2, Haereus) through suprasil (immersion well) filter. The solution is then evaporated carefully so that the bath temperature does not exceed 35 "C. The resulting syrup is cooled to 4 "C. Crystallization is induced by adding some crystals. The crystalline material is washed with cold chloroform. The resulting product is pure enough for further conversion. lH-NMR (acetone-dg, 300 MHz): 6 = 3.05 (s, 1 H, Om, 6.22 (m, 2 H, OOC-CHSH, 0-C_H-0),7.44 (dd, 1 H, J = 1.0,5.5, OOC-CH). 13C-NMR (acetone-dg, 75 MHz): 6 = 99.5 (0-CH-0), 124.5 (OOC-CH=CH), 153.8 (OOC-CH), 171.5 (C=O).

82

1.2

Enones and Dienones

1.2.4b (-)-(5R)-5-Menthyloxy-2[5~-furanone[3]

+ 100.1

156.3

238.3

40 g (0.4 mol) of 5-hydroxy-2[5H]-furanone, 26.4 g (0.4 mol) of (-)-menthol and about 0.2 g of p-toluenesulfonic acid are dissolved in 200 mL of chloroform. The solution is heated at a water trap until the water separation is complete. The reaction mixture is extracted twice with saturated NaHC03 solution and subsequently with water. The organic phase is dried with MgS04. After filtration the solvent is evaporated with a rotavapor. The residue is treated with n-hexane. The resulting crystalline fraction is recrystallized from n-hexane several times until mp 79 "C is reached. Pure fractions are obtained from ratios: solvent/product = 20: 1 to 30: 1. From the mother liquor, sometimes a crystal fraction with mp 39 "C may also be obtained. It containes mainly the 5s-diastereomer. Yield: 21 g (22%), [a]D25 = -134" (1.004, CHC13). For equilibration see [3b, 3c]. 'H-NMR (CDCl3, 300 MHz): 6 = 0.81 (d, 3 H, J = 7.0, 8-', 9'-H), 0.88 (d, 3 H, J = 7.0, 8'-, 9'-H), 0.96 (d, 3 H, J = 6.5, 10-H), 0.99 (m, 1 H, 3'-H,), 1.26 (m, 1 H, 2'-H), 1.41 (m, 1 H, 5'-H), 1.67 (m,2 H, 3'-, 4'-Heq), 2.1 1 (m, 1 H, 7'-H), 2.15 (m,1 H, 6-Heq), 3.66 (dt, 1 H, J = 4.5, 10.5, 1'-H), 6.09 (t, 1 H, J = 1.0, 5-H), 6.20 (dd, 1 H, J = 5.5, 1.0,3-H),7.17 (dd, 1 H, J = 5.5, 1.0,4-H). 13C-NMR (CDC13, 75 MHz): 6 = 15.8 (C-S', 9'). 20.9 (C-8', 97, 22.2 (C-lo'), 23.2 (C-37, 25.3 (C-7'), 31.5 (C-57, 34.2 (C-47, 40.3 (C-67, 47.8 (C-27, 79.1 (C-l'), 100.5 (C-5), 124.7 (C-3), 150.9 (C-4), 170.8 (C-2). IR (KBr): v = 3500, 3118,2930,2870, 1800, 1768, 1755, 1655, 1610, 1505, 1350, 1130, 925,905,830. MS (70 eV): m/z = 238 (0.6, M+), 138 (94), 123 (20), 95 (54), 83 (54), 82 (22), 81 (loo), 69 (45),55 (39), 43 (21), 41 (46). W (CH3CN): h = 185 (E = 12600),247 ( ~ 4 0 ) . UV (n-hexane): h = c 180,253 (E = 30).

(5S)-(-)-Menthyloxy-2[5H]-furanone(minor isomer, mixture with the main isomer): 'H-NMR (CDC13, 300 MHz): 6 = 0.82 (d, 3 H, J = 7.0, 8'-, 9'-H), 0.92 (d, 3 H, J = 7.0, 8-, 9'-H), 0.93 (d, 3 H, J = 6.5, 10-H), 1.00 (m, 1 H, 3'-HaX), 1.30 (m,1 H, 2'-H), 1.42 (m, 1 H,5'-H), 1.66 (m, 2 H, 3'-, 4'-Heq), 2.13 (dsep, J = 4.5, 7.0, 1 H, 7'-H), 2.25 (m,

1.2

83

Enones and Dienones

1 H, 6'-Heq), 3.52 (dt, 1 H,, J = 4.5, 10.5, 1'-H), 5.96 (t, 1 H, J = 1.2 - 1.3, 5-H), 6.21 (dd, 1 H, J =5.7, 1.2,3-H), 7.21 (dd, 1 H, J=5.7, 1.3,4-H). 13C-NMR (CDCl3, 75 MHz): 6 = 16.3 (C-8', 9'), 20.9 (C-8', 97, 22.1 (C-lo'), 23.3 (C-37, 25.7 (C-77, 31.6 (C-5'), 34.1 (C-4'), 42.5 (C-6'), 48.1 (C-2'), 82.9 (C-l'), 104.6 (C-5), 124.6 (C-3), 150.5 (C-4), 170.7 (C-2).

OH

hv

acetone

238.3

59.1

298.4

23.8 g (100 mmol) of (-)-(5R)-5-menthyloxy-2[5H]-furanone are dissolved in 140 mL of isopropanol and 50 mL of acetone. The mixture is irradiated for about 4.5 h (Hg highpressure lamp, HPK-150 W, Philips, Pyrex immersion well). After evaporation of the solvents, 29.4 g of crude material is obtained. Recrystallization from n-hexane gives 25.7 (86%) of pure product, mp 86 "C, [a],29= -150" (1.056, CHC13). ~~~~~~

lH-NMR (CDCl,, 300 MHz): 6 = 0.8 - 1.08 (m, 3 H, 3'-, 4'-, 6-Hax), 0.79 (d, 3 H, J = 7.0,8'-, 9'-H), 0.88 (d, 3 H, J = 7.0, 8'-, 9'-H), 0.94 (d, 3 H, J = 6.5, 10-H), 1.16 - 1.28 (m, 1 H, 2'-H), 1.21 (s, 3 H, 7-, 8-H), 1.28 (s, 3 H, 7-, 8-H), 1.38 (m, 1 H, 5'-H), 1.66 (m, 3 H, 3'-, 4'-Heq, OH), 2.14 (dsep, 1 H, J = 2.5, 7.0, 7'-H), 2.16 (m, 1 H, 6'-H ), 2.32 (ddd, 1 H, J = 3.0, 5.5, 9.5, 4-H), 2.53 (dd, 1 H, J = 9.5, 18.0, 3-Hb), 2.70 1 H, J = 9.5, 18.0, 3-Ha), 3.55 (dt, 1 H, J = 4.0, 10.5, l'-H), 5.70 (d, 1 H, J = 3.3,5-H). 13C-NMR (CDC13,75 MHz): 6 = 15.7 (C-8', 9'), 20.9 (C-8', 9'), 22.3 (C-lo), 23.1 (C-37, 25.4 (C-7'), 27.8 (C-7, 8), 27.8 (C-7, 8), 30.1 (C-3), 31.4 (C-57, 34.4 (C-4'), 39.9 (C-6'),47.9 (C-2'), 51.9 (C-4), 69.9 (C-6), 77.3 (C-l'), 102.3 (C-5), 176.4 (C-2). IR (CDC13): v = 3550,2960,2950,2925,1790,1645, 1180, 1100,940. MS (70 eV): m/z = 298 (0.4, M+), 280 (l), 139 (74), 138 (75), 125 (25), 123 (19), 115 (93), 114 (31), 97 (63), 95 (38), 83 (loo), 81 (69), 71 (47), 69 (63), 59 (44),57 (38), 55 (48), 4 3 (30), 41 (55).

gd,

84

1.2 Enones and Dienones

1.2.4d (-)-Terebic Acidrs] BCOOH

HO

F.

1.) Glycole, H' 2.)0,

3.)KOH / HO , 4.) HCI

298.4

-

+

158.2

156.3

3.1 g (10.4mmol) of (4S,5R)-4-(2-hydroxy-2-propyl)-5-menthyloxy-2[5H]-furanone and a catalytic amount of p-toluenesulfonic acid are dissolved in 50 mL of glycol. The mixture is heated to 110 "C for about 14 h. After cooling to room temperature, the mixture is treated with saturated NaHC03 solution and ether. The aqueous phase is extracted 12 times with ether. The organic phases are dried with MgS04. The crude material obtained after evaporation of the ether is dissolved in 50 mL of ethyl acetate. The resulting solution is ozonized for 100 min at -78 "C. The excess of ozone is then removed by a Nptream. After evaporation of the solvent (T < 45 "C), the resulting mixture is added to 30 mL of a 1 N KOH solution and stirred for about 14 h at room temperature. The (-)-menthol is removed by extraction with ether (4 times, yield of recovery: 1.3 g (80%)). The aqueous solution is then acidified with diluted hydrochloic acid and saturated with NaCl. The mixture is perforated with ether for 3 d. The etheral solution is dried with MgS04. The residue of the evaporation is recrystallized with water and a small quantity of ethanol. = -13.7"(1.052,acetone). Yield: 0.55 g (32%), mp 198 "C, ~~

'H-NMR (DMSO-ds, 300 MHz): 6 = 1.29 ( s , 3 H,CH3), 1.51 ( s , 3 H, CH3), 2.72(dd, J = 8.5, 18.0,1 H, CH2), 2.84(dd, 1 H, J = 8.5, 18.0,CHz), 3.23 (t, 1 H, J = 8.5,CH). 13C-NMR (DMSO-d6, 75 MHz): 6 = 23.1 (CH3). 27.8 (CH3), 31.6 (CH2), 49.5 (CH), 83.9(C-0), 171.7(COOH), 174.3(COOR).

[ 13

Hoffmann, N. in preparation. [2] G. O.Schenck, German Pat. No881 193 (1953);G.Bolz, W.-W. Wiersdorff, German Pat. No 2111119 (BASF) (1972); P. Esser, B. Pohlmann, H.-D. Scharf, Angew. Chem. in press. J. Martel, J. Tessier, J. P. Demoute, Eur. Pat. No 23454 (Roussel-Uclaf) (1981); [3] B.L. Feringa, B. de Lange, J. Org. Chem. 1988,53,1125 - 1127;B. L. Feringa, B. de Lange, Tetrahedron 1988,44,17213- 7222. [41 G. 0.Schenck, G. Kolzenburg, H. Grossmann, Angew. Chem. 1957,69, 177 - 178; L. Homer, J. Klaus, Liebigs Ann. Chem. 1979, 1232 - 1257;R. VaSen, J. Runsink,

1.2

[5]

Enones and Dienones

85

H.-D. Scharf, Chem Ber. 1986, 119, 3492 - 3497; J. Mann, A. Weymouth-Wilson, Carbohydr. Res. 1991,216,511 - 515. A. Fredga, Svensk Papperstidn. 1947, 50, 91 (CA 42, 123); R. Sandberg, Arkiv for Kemi 1960, 16, 255 - 265; K. Gollnick, G. Schade, S. Schroeter, Tetrahedron 1966, 22, 139 - 144; P. Delongchamps, P. Atlani, D. FrChel, A. Malaval, C. Moreau, Can. J. Chem. 1974,52,3651 - 3664.

86

1.2

Enones and Dienones

(E)-N-Benzyl-N-(3-oxo-l,3-diphenyl)propenylbenzamide

1.2.5

submitted by

H.-G. Henning

1.2.5a (2)-3-Benzylamino-1,3-diphenyl-1-propenone A Phm

p

h

+

224.3

Ph*NH,

0 H'NAPh

___t

Ph-Ph

107.2

313.4

A mixture of 10 g (45 mmol) of dibenzoylmethane, 10.9 g (90 mmol) of benzylamine and a drop of conc. hydrochloric acid was refluxed for 8 h. After cooling to room temperature and addition of ether the mixture was washed with water. After evaporation of the ether and addition of petroleum ether (bp 60 - 70 "C) the crude product precipitated. Purification with petroleum ether and ether afforded 12.2 g (86%) colorless 1.2.5a, mp 101 "C.

lH-NMR (CDC13, 300 MHz): 6 = 4.41 (d, 2 H, CH2), 5.85 (s, I H, CH), 7.2 - 7.4 (m, 13 H, arom.), 7.90 - 7.93 (m, 2 H, arom), 11.73 (s, 1 H, NH). IR (KBr): v = 1601,1588, 1568, 1553, 1336,732.

1.2.5b (Z)-N-Benzyl-N-(3-0~0-1,3-diphenyl)propenyl benzamide 0 H'NAPh Ph-Ph

31 3.4

Ph-CO-CI pyridine

UPhP o*

t

Ph

Ph

A

417.5

A solution of 2 g (6.4 mmol) of 1.2.5a in 20 mL of anhydrous pyridine was cooled to 0 "C and then mixed with 2.7 g (19.2 mmol) of benzoylchloride. After standing for 3 d 5 mL of water were added and the mixture then acidified with dil. hydrochloric acid. Extraction with ether and washing the extract with dil. NaOH and water afforded, after drying with

1.2

87

Enones and Dienones

Na2SO4,an oil which crystallized on treatment with etherln-hexane. 0.5 g (1 9%) of 1.2.5b; mp 128 - 129 "C.

lH-NMR (CDC13, 300 MHz): 6 = 5.0 (s, 2 H, CH2), 6.74 (s, 1 H, CH), 7.10 - 7.59 (m, 20 H, arom.). IR (KBr): v = 1670,1650, 1600, 1590, 1570.

1.2.5~ (E)-N-Benzyl-N-(3-oxo-l,3-diphenyl)propenyl benzamide Ph

ether 417.5

0A Ph 417.5

A solution of 100 mg (0.24 mmol) 1.2.5b in 100 mL ether was irradiated for 2 h (Pyrex vessel, Hg high-pressure lamp as an external light source). TLC showed complete conversion of 1.2.5b into 1.2.5~. After rota-evaporation of the solvent the oily product was solidified by treatment with etherln-hexane. 95 mg (95%) 1.2.5~.

IH-NMR (CDC13, 300 MHz): 6 = 4.95 (s, 2 H, CH2), 6.15 (s, 1 H, CH), 7.06 - 7.69 (m, 20 H, arom.). IR (KBr): v = 1670, 1650, 1620, 1600, 1580.

1.2 Enones and Dienones

88

1.2.6

(rac)Methyl-7,7,8,8-tetramethyl-5-oxo-cis-2azabicyclo [4.2.0] octan-2-oneand (rac)methyl-7,7,8,8-tetramethyl-5-oxo-trans-2azabicyclo [4.2.0] octan-2-one[ll submitted by

1.2.6a

R. Neier

4-Methoxy pyridine N-oxide[*l MeOH I K&O, 0-

0

140.1

125.1

To 50.0 g (0.36 mol) of 4-nitropyridine N-oxide in 360 mL of methanol 50 g (0.5 mol) of potassium carbonate were added and the mixture was stirred at reflux for 8 h. After cooling to room temperature the solution was filtered and the solvent removed under reduced pressure. The residue was treated five times with 100 mL of dichloromethane. After rota-evaporation of the dichloromethane 35.8 g (92%) of a white crystalline solid was obtained, mp 78 - 79 OC, Rf = 0.39 (chlorofodmethanol4:l on silica gel). ~~~~~~~~

'H-NMR (CDCl3, 90 MHz): 6 = 3.96 (s, OMe), 6.86 (d, 2 H, J = 7, Ar-H), 8.20 (d, 2 H, J = 7, Ar-H). 13C-NMR (CDCl3, 91 MHz): 6 = 56.1 (q, OCH3,), 111.7 (d, 2 C), 139.9 (d, 2 C), 158.2 (s, 1 C). IR (CHC13): v = 2980,1492,1438,1292,1030,834.

89

1.2 Enones and Dienones

1.2.6b 4-Methoxypyridine[3] OCH,

c3 N

OCH,

H P Zn / H,SO,

0

125.1

109.1

35 g (0.31 mol) of 4-methoxypyridine N-oxide 1.2.6a are dissolved in 360 mL of aqueous 2 M sulfuric acid. 36 g (0.55 mol) of zinc powder are added and the mixture is rigorously stirred under reflux for 6 h with a mechanical stirrer. After cooling to room temperature sufficient 4 M sodium hydroxide is added to reach pH 10. The resulting mixture is filtered over celite and sodium chloride is added until saturation is reached. The water phase is extracted 3 times with 150 mL of ethyl acetate. The unified organic phases are dried with sodium carbonate and the solvent is rota-evaporated. The colorless liquid is distilled at reduced pressure (bp 85"/15 Torr) yielding 28.0 g (90%) 1.2.6b, Rf = 0.64 (chlorofondmethanol 4: 1 on silica gel)

lH-NMR (CDC13, 90 MHz): 6 = 3.80 (s, OMe), 6.70 (m, 2 H, Ar.-H), 8.63 (m, 2 H, Ar-H).

13C-NMR (CDC13,91 MHz): 6 = 54.9 (q,OCH3), 109.7 (d, 2 C), 150.8 (d, 2 C), 165.3 (s, 1 C). IR (thin film): v = 1590,1569,1502, 1284, 1028,818,802.

1.2.6~ 1-Methoxycarbonyl-2,3-dihydropyridin-4(l~-one [31 MeOH CICOOCH, / 'NaBH,

I

COOCH, 109.1

155.1

To a solution of 10 g (9.2 mmol) of 1.2.6b in 200 mL of absolute methanol kept at -78 "C under nitrogen are added 4.17 g (1 1 mmol) of sodium borohydride. The suspension is stirred for 30 min until it gets homogenous. Then a solution of 9.5 g (10 mmol) of methyl chloroformate in 30 mL of absolute ether are added dropwise during 45 min. The mixture is stirred for 5 h at -78 "C and then the reaction is quenched by adding the organic solvent

90

1.2

Enones and Dienones

to 200 mL of ice cooled water. The two phase mixture is stirred for 1 h and then extracted 3 times with 150 mL of dichloromethane. The organic phases are washed against 150 mL of brine and dried over magnesium sulfate. After rota-evaporation of the solvent the crude material is recrystallized from dichloromethane/ether to yield 11,4 g (89%) of a white solid, mp = 69 - 70 "C, Rf = 0.5 1 (ethyl acetatekexane 1 :1 on silica gel).

'H-NMR (CDC13, 90 MHz): 6 = 2.56 (t, 2 H, J = 8, COCH2), 3.89 (s, 3 H, OCH3), 4.03 (t, 2 H, J = 8, NCH,), 5.30 (d, 1 H, J = 8, COCH), 7.83 (d, 1 H, J = 8, NCH). 13C-NMR (CDC13, 91 MHz) : 6 = 3.56 (t,COCH,), 42.5 (t, NCH,), 54.1 (q, OCH3), 107.5 (d, COCH), 143.2 (d, NCH), 153.1 (s, COOCH,), 195.1 (s, CO). IR (CHC13): v = 1665, 1605, 1442, 1355,1343,1332,1308. UV (ethanol): h = 286 nm ( E = 16 700).

1.2.6d (rac)Methyl-7,7,8,8-tetraethyl-5-oxo-cis-2azabicyclo[4.2.0]octne-2-carboxylate 1.2.6e

(rac)Methyl-7,7,8,8-tetraethyl-5-oxo-trans-2azabicyclo[4.2.0]octane-2-carboxylate

A+x-

acetone hv

NI

COOCH,

155.1

&+& I

I

COOCH, 84.2

COOCH, 239.4

A solution of 1.24 g (8 mmol) of 1.2.6~and 3.36 g (39.9 mmol) of 2,3-dimethylbutene in 125 mL of acetone was irradiated with an immersion-lamp Philips HPK 125 behind Pyrex

and under nitrogen atmosphere during two hours. After rota-evaporation of the solvent the crude photoproduct was purified by flash ~hromatography[~] with etherlhexane (3: 1) as eluant. Three fractions were obtained. Fraction 1: Rf = 0.28 (etherhexane 3:l on silica gel), 580 mg (30%) of 1.2.6d, mp = 48 - 49°C; fraction 2: Rf = 0.28 and 0.24 (ether/ hexane 3:l on silica gel), 292 mg (15%) of a mixture of 1.2.6d and 1.2.6e (1:9); fraction 3: Rf = 0.24 (etherkexane 3:l on silica gel), 751 mg (39%) of 1.2.6e, mp 59 - 61 "C.

1.2.6d: lH-NMR (CDC13, 360 MHz): 6 = 0.86, 0.99, 1.09, 1.18 (4 s, 4x3 H, 4 CqMe), 2.39 (dddd, 1 H, J = 16.4, 8.0, 5.4, 0.9, COCH-H), 2.50 (ddd, 1 H, J = 16.4, 7.0, 4.6, CO CH-H), 2.74 (dd, 1 H, J = 10.0, 0.9, COCH), 3.72 (s, 3 H, OCH3), 3.81 (ddd, 1 H, J = 13.5, 8.0,4.6, N CH-H), 3.87 (ddd, 1 H, J = 13.5, 7.0, 5.4, NCH-H), 4.38 (d, 1 H, J = 10.0, NCH).

1.2

91

Enones and Dienones

W - N M R (CDC13, 91 MHz): d = 19.9, 20.4, 23.7, 22.4 (4 9, 4 CH3), 41.4, 45.4 (2 S, 2 Cq), 51.4 (d, COCH), 52.6 (9, OCH3), 57.3 (d, NCH), 156.6 (s, COOCH3), 208.1 (s, CO). IR (KBr): v = 1705, 1445, 1401, 1370, 1348, 1270,1255,1190. 1.2.6e: lH-NMR (CDC13, 360 MHz): 6 = 1.02, 1.03, 1.09, 1.15 (4 s, 4x3H, 4 Me), 2.29 (ddd, 1 H, J = 18.4, 3.2, 2.0, COCH-H), 2.57 (ddd, 1 H, J = 18.4, 13.2, 5.8, COCH-H), 2.92 (d, 1 H, J = 13, COCH), 3.51 (td, 1 H, J = 13.2, 3.2, NCH-H), 3.66 (d, 1 H, J = 13.0, NCH), 3.72 (s, 3 H, OCH3) 4.1 1 (ddd, 1 H, J = 13.2,2.0,5.8, NCH-H). 13C-NMR (CDC13, 91 MHz): 6 = 17.3, 19.1, 22.1, 23.7, (4 S, 4 CH,), 40.1 (s, Cq), 40.2 (t, NCHz), 42.5 (t, NCH2), 44.8 (s, Cq), 52.4 (4, OCHQ), 53.5 (d, COCH), 59.6 (d, NCH), 156.4 (s, COOCH3), 206.7 (s, CO). IR (KBr): v = 1695,1448, 1393, 1344, 1232,1222.

Isomerisation of the mixture 1.2.6d1.2.6e to pure 1.2.6d. 0

0

0 Et,O I Alox

I

I

COOCH,

COOCH, 239.4

I

COOCH, 239.4

To 292 mg (1.3 mmol) of a mixture of 1.2.6d1.2.6e (1:9) dissolved in ether 500 mg of aluminium oxide neutral was added and this heterogenous mixture was stirred for 2 h at room temperature. Filtration and rota-evaporation of the solvent gave an oily raw product which was crystallized at -20 "C from etherhexane to yield 270 mg (93%) of pure 1.2.6d, mp 48 - 49 "C.All spectroscopic datas were identical with the sample obtained by chromatography of the photoproduct.

[l] [2] [3] [4]

P. Guerry, P. Blanco, H. Brodbeck, 0. Pasteris, R. Neier, Helv. Chim.A c t ~ ,1991, 74, 163 - 178. E. Profft, W. Krueger, P. Kuhn, W. Lietz, see also Chem. Abstr., 1970, 72, P 90309~. S. Raucher, J. E. Macdonald, Synth. Commun., 1980, 10,325 - 331. W. C. Still, M. Kahn, A. Mitra, J. Org. Chem., 1978,43,2923 - 2925.

92

1.2.7

1.2 Enones and Dienones

Asymmetric Induction Concept with Optically Active Spirocyclic 1,3-Dioxacyclohexenones submitted by

1.2.7a 1.2.7b

M. Demuth

(2S,7S,10R)-7-Isopropyl-l0,6-dimethyl-l,3-dioxaspiro[1,7]undec-5-en-4-0ne[1~2~3~~1 and

(2R,7S,1OR)-7-Isopropyl-10,6-dimethyl-1,3-dioxaspiro[1,7]undec-5-en-4-one[ 192,3941 I

(-)-1.2.7&

240.3

b,

238.2

+

A

154.2

158.2

A mixture of (-)-1.2.7a and (-)-1.2.7bcan be obtained via two routes: By rearrangement of the dioxacyclohexadione[5] after acetylation (acetyl chloride, pyridine; analogously as in ref. [ 6 ] )into a 1:1 mixture of (-)-1.2.7a and (-)-1.2.7b(diglyme, 120 "C, analogously as in ref. [7])(Route I; ca. 10%yield) or in one step by condensation of (-)-menthone with ferfbutyl acetoacetate in acetic anhydride in present of sulphuric acid (Route 11; ca. 34% yield).

1.2 Enones and Dienones

93

Route II: 11.71g (0.076mol) of (-)-menthone and 12.2mL (1 1.94g, 0.076mol) of tertbutyl acetoacetate were dissolved in 25.9g (24.0mL, 0.25mol) of acetic anhydride. The mixture was cooled to -10"C before 3.4mL of conc. sulfuric acid were added slowly maintaining this temperature. Continued stirring of the mixture at -10"C for 4 d followed. The solution, which meanwhile turned reddish, was then poured onto 250 mL of an icecold satd. aqu. NaZC03 solution, followed by stirring for 2 - 3 h until RT. The reaction mixture was then concentrated in vucuo (rotary evaporator) and the residue taken up in diethylether before shaking consecutively with water and aqu. NaCl (brine). The organic layer was separated, dried over Na2S04 and evaporated, yielding 14.5g of crude material. Flash chromatography on 500 g of silica gel 60 with n-hexane/diethylether (9:1) afforded 8.81 g of a mixture of the diastereoisomers (-)-1.2.7a and (-)-1.2.7b (6:l ratio as determined by 'H-NMRusing Eu(fod), shift reagent). This mixture could be separated by medium-pressure column chromatography (columns of size A + C, Merck Lobar LiChroprep S 60, connected in series, a pressure of 4 bar was applied) using n-hexanel diethylether (9:l). 5.605 g of (-)-1.2.7a (98% purity by GLC, 31% yield based on consumed menthone, [a]D = -27.4'(0.48)) and 0.907g of (-)-1.2.7b (97% purity by GLC, 5.1% yield, [a], = -22.5'(0.4),mp = 49 - 51 'c) were obtained. (Notably, when the condensation was carried out at +10 "C (48 h), 4.52g of the diastereoisomeric mixture (-)-1.2.7a/bwere obtained only in a 1: 1 ratio): (-)-1.2.7a: 1H-NMR:6=0.84(d,3H,J=6),0.87(d,3H,J=7),0.91(d,3H,J=7),0.97(t,J= 13, 1 H),1.42- 1.80(m,6H), 1.94(s, 3 H),ca. 2.17 (dsept, 1 H,J = 2.5,7), 2.56(ddd, 1 H,J = 2.5,3.5, 13.5), 5.12(s, 1 H). "C-NMR: 6 = 18.5(4).20.1 (9). 21.6(q), 22.2(t). 23.2(q)25.6 (d), 25.6(d), 34.1 (t), 41.0(t), 49.4(d), 93.1(d), 109.8(s), 161.0(s), 168.7 (s). MS:m/z = 238 (M+), 196,154,139,112 (100),69,55,41. IR:v = 1710,1630,1225,1180,1140,1075. W: &ax = 244(E = 5992). (-)-1.2.7b: 'H-NMR: 6 = 0.83(d, 3 H, J = 7), 0.85(d, 3 H, J = 7),0.90(d, 3 H,J = 7), 1.05 (t, 1 H, J = 13.2),1.44- 1.56(mm, 4 H),about 1.65(m, 1 H),about 1.74(dm, 1 H, J = 13.2), 1.95(s, 3 H), 2.29(dsept, 1 H, J = 1,7),2.57(ddd, 1 H, J = 1, 2,14),5.16(s, 1 H). 13C-NMR: 6= 18.1(q), 20.0(q), 21.5(q), 21.8(t), 23.1(q), 25.0(d), 29.7(d), 33.9(t), 40.5 (t), 49.2(d), 93.7(d), 109.4(s), 161.5(s), 168.0(s). MS: d z : cf. (-)-1.2.7ab. IR: v = 1710,1630,1275,1210,1095,1075. UV: = 241 (E = 5769).

ha

94

1.2

Enones and Dienones

1.2.7~ (lS,2R,2'S,4S,5'R,7S,8R)-2'-Isopropyl-2,5'-dimethylspiro[cyclohexan-l',4-[3,5]-dioxa-tricyclo[6.3.O.O2~7] -

undecan]-6-one[8] and

(lR,2S,2'S,4R,5'R,7R,8S)-2'-Isopropyl-2,5'-dimethylspiro[cyclohexan-1',44331-dioxa-tricyclo[6.3.0.0297]undecan]-6-one[*l

1.2.7d

1 A

0

238.2

+

68.1

306.3

A solution of (-)-1.2.7b (520 mg, 2.1 mmol) in CH3CN (4 mL) and acetone (1 mL) is purged with argon for 10 - 15 min before cyclopentene (1 mL, 11.4 mmol) is added dropwise. The solution is then irradiated in a water-cooled quarz vessel (reaction temperature 10 "C) with a medium-pressure mercury lamp (250 W) for 15 h. For work-up the solvent is evaporated and the residue chromatographed (25 g silica gel of 70-230 mesh) with n-hexane/Et20, 955, to afford a) unreacted (-)-1.2.7b (48 mg), b) (-)-1.2.7c (389 mg, 64% yield, > 97% purity by GLC and 'H-NMR): [a],= -31" (CHC13, c = 0.116) and c) the stereoisomer resulting from the attack of cyclopentene, occuring on the face opposite the isopropyl group, (-)-1.2.7d in 9% yield (57.3 mg): [a]D = -23.8" (CHCL3, c = 0.063). 1.2.7~: 'H-NMR (CDCl3, 270 MHz): 6 = 0.83 (d, 3 H, J = 6.5), 0.90 (m, 1 H), 0.92 (d, 3 H, J = 2.5), 0.94 (d, 3 H, J = 2.5), 1.26 (s, 3 H), 1.31 (dd, 1 H, J = 12.5, 14), 1.90 - 1.39 (m, 12 H), 2.24 (m, 1 H), 2.29 (dd, 1 H, J = 1.5, 5 . 3 , 2.61 (t, 1 H, J = 8), 2.91 (m, 1 H). 13C-NMR (CDC13, 100 MHz): 6 = 19.0 (q), 21.2 (q), 22.6 (t), 23.5 (q), 25.2 (t), 25.6 (d), 26.9 (t), 29.7 (d), 31.6 (t), 34.2 (t), 42.0 (d), 43.4 (d), 46.6 (t), 48.4 (d), 51.3 (d), 76.2 (s), 109.7 (s), 171.7 (s). MS: m/z = 306 (M+. ClgH30O3), 239, 155 (loo), 124,85,41. JR(CHC13): v = 2925,1700,1445, 1320,1100.

1.2

95

Enones and Dienones

1.2.7d: lH-NMR (CDC13, 270 MHz): 6 = 0.84 (d, 3 H, J = 6.5), 0.88 (d, 3 H, J = 7.0), 0.90 (m, 1 H), 0.92 (d, 3 H, J = 7.0), 1.20 (s, 3 H), 1.90 - 1.00 (m, 11 H), 2.00 (m, 1 H), 2.26 (m, 1 H), 2.47 (dd, 1 H, J = 1.5, 5 . 3 , 2.48 (m, 1 H), 2.77 (t, 1 H, J = 8 . 5 ) , 2.95 (m, 1 H). 13C-NMR (CDC13, 100 MHz): 6 = 18.6 (q), 21.7 (q), 22.6 (q), 22.7 (t), 24.0 (q), 25.2 (t), 25.9 (t), 27.9 (t), 30.4 (d), 32.1 (t), 34.4 (t), 40.8 (d), 45.9 (d), 46.8 (t), 48.6 (d), 52.1 (d), 77.2 (s), 110.1 (s), 170.8 (s). MS: m/z = 306 (M+, CIgH30O3), 239,155 (loo), 124,81,41 IR (CHC13): v = 2940, 1700,1420.

[ 11

1.2.7a and 1.2.7b can be alternatively synthezised according to a route reported by Dehmlow, elaborated by R. Hoffmann: Reaction of (-)-menthone with diketene to the corresponding adducts 1.2.7a and 1.2.7b:

154.3

84.0

239.3

It is necessary to carry out the reaction in two portions, otherwise the yield will be reduced. For each portion 4.6 g (30 mmol) of (-)-menthone, 2.52 g (30 mmol) of diketene and 45 mg (0.26 mmol) of p-toluolsulfonic acid are filled in a sealed glass-tube and heated at 80 "C for 24 h. The deep brown reaction mixtures are combined and dissolved in 200 mL of diethyl ether, washed twice with 30 mL of 5 N NaOH, three times with 30 mL of water and dried over MgS04. After rota-evaporation of the solvent the residue is placed in a water-bath - the temperature should not exceed 35 "C - to remove the excess (-)-menthone and other low-boiling compounds at a pressure of 0.01 Torr. This procedure yields approximately 10 g of a crude yellow oil. Column chromatography (6 cm internal diameter, 30 cm long; cyclohexane/ ethyl acetate 4:l; silica gel 60) affords a mixture of the diastereoisomeric compounds 1.2.7a and 1.2.7b which is further separated by medium-pressure column chromatography (Column: Buchi Code Nr. 17980; silica gel 60, 0.04 0.063 mm, eluant 7% ethyl acetate in cyclohexane). Fractional chromatography yields 3.3 g (13.8 mmol) of 1.2.7a - colorless crystals, mp 29 - 31 "C, 3.1 g (13.0

96

[2] [3] [4] [5]

[6] [7] [8]

1.2

Enones and Dienones

mmol) of 1.2.7b - colorless crystals, mp 51 - 52 "C - and ca. 0.3 - 0.5 g of a mixture of 1.2.7a and 1.2.7b which could be used in further separations. The yields are 23 % of 1.2.7a and 22 % of 1.2.7b referring to starting compound (-)-menthone. Crystallization proceeds via pure crystal or by cooling in liquid nitrogen and following storing at room temperature. E. V. Dehmlow, A. Sleegers, 2. Nuturforsch 1980, 43 b, 921 - 922 modified by R Hoffmann., J. Mattay, to be published. M. Demuth, A. Palomer, H.-D. Sluma, A. Dey, A. Kriiger, Y.-H. Tsay, Angew. Chem. 1986,98, 1093 - 1095;Angew. Chem. Int. Ed. Engl. 1986,25, 11 17. A. Palomer. Ph. D. Thesis, Max-Planck-Institut / University of Essen, 1988. H.-P. Rink. Ph. D. Thesis, Max-Planck-Institut / University of Essen, 1990. Procedure 1: Condensation of (-)-menthone and tert-butyl acetoacetate in acetic anhydrid, catalytic amount of sulphuric acid, room temperature, 24 h. The sole, previously described analogous condensation of (+)-camphor with cx-methylmalonic acid required 200 d: A. Michael, N. Weiner, J. Chem. SOC. 1936, 58, 680 - 684; B. Eistert, F. Geiss, Chem. Ber. 1961, 94,929 - 947. Y. Oikawa, K. Sugano, 0. Yonemitsu, J. Org. Chem. 1978,43,2087 - 2088. M. Sato, H. Ogasawara, K. Oi, T. Kato, Chem. Pharm. Bull. 1983, 31, 1896. M. Demuth, G. Mikhail, Synthesis 1989, 145 -162.

1.2

97

Enones and Dienones

Synthesis of (+)- and (-)-Grandisol[ll

1.2.8

submitted by

N. Hoffmann and H.-D. Scharf

1.2.8a 4-Methyl-5-hydroxy-2[5~-furanone[2]

+ 58.1

o\u(o OH

74.0

HZ

dioxane 113.1

123 g (1.0 mol) of pulverized morpholinium chloride and 1.0 mol of glyoxylic acid (50% aqueous solution) are suspended in 400 mL of dioxane. The mixture is stirred at room temperature for 30 - 40 min. 64 g (1.1 mol) of propionic aldehyd are added. The resulting mixture is stirred for 1 h at room temperature and then at reflux temperature for 24 h. The dioxane is carefully removed (bumping !) at a rota vapor. Water is added before the residue begins to crystallize. The resulting solution is saturated with ether and perforated for 3 d. The etheral solution is dried with MgSO4 After filtration and removal of the ether, the residue is distillated in high vacuum. Bp 140 "(30.7 Torr, yield: 91 g (80%),mp 47 "C. ~

~

~

'H-NMR (CDC13, 300 Mz): 6 = 2.1 1 (d, 3 H, J = 1.5, CH$ 5.87 (m, 1 H, CH), 6.02 (s, 1 H, 0-CH-0), 5.2 - 6.2 (s, 1 H, OH). 13C-NMR (CDCl3,75 MHz): 6 = 13.3 (CH3), 100.1 (0-CH-0), 118.2 (HC=), 166.5 (C=), 172.7 (C=O).

1.2 Enones and Dienones

98

1.2.8b (+)-(5S)-4-Methyl-5-rnenthyloxy-2[5NJ-furanone[31 0 &o*

/

0 3c=JOH 0 113.1

+

toluene H

O 156.3

G

H

-

+

H'/-H,O

I

/

251.4

80 g (0.75 mol) of 4-methyl-5-hydroxy-2[5H]-furanone1.2.8a, 99 g (0.68 mol) of (+)-menthol and about 0.6 g of p-toluenesulfonic acid are dissolved in 130 mL of toluene. The solution is heated at a water trap until the water separation is complete. The reaction mixture is extracted with saturated NaHCO3 solution and subsequently with water. The organic layer is dried with MgS04. After filtration the solvent is evaporated with a rota vapor. The residue is treated with n-hexane. A 80 g fraction of mixed crystalls is obtained. This fraction is recrystallized several times from n-hexane until mp 98 "C is reached. Pure fractions are obtained from a ratio solventlproduct = 20: 1 to 30: 1. From the mother liquor a crystal fraction (diastereomericratio 1:l) with mp 99 "C may also be obtained. Equilibration of the diastereomeric mixture: 50 g of a mixed crystal fraction are dissolved in 300 mL of toluene. 0.4 g of p-toluenesulfonic acid and 5 mL of water are added. The mixture is heated under reflux for 16 h and then at a water trap. The reaction mixture is treated as described above. The crystallizations from n-hexane give about 8.5 g of diastereomerically pure material. Yield 30 - 40% of the (4S)-diastereomer, [a],25= +161" (1.01, CHC13).

'H-NMR (CDC13, 300 MHz): 6 = 0.81 (d, 3 H, J = 7.0, H-8',9'), 0.88 (d, 3 H, J = 7.0, H-8',9'), 0.95 (d, J = 6.5, 3H, H-lo'), 1.00 (m, 1 H, Hax-3'), 1.26 (m, 1 H, H-2'), 1.42 (m, 1 H, H-5'), 1.67 (m, 1 H, Heq-3',4'), 2.04 (dd, 3 H, J = 1.0, 2.0, H-6), 2.13 (m, 2 H, %q-6,7'), 3.63 (dt, 1 H, J = 4.5, 10.5, H-l'), 5.79 (s, broad, 1 H, H-5), 5.82 (dq, 1 H, J = 2.0, 1.0, H-3). 13C-NMR (CDC13, 75 MHz): 6 = 13.3 (C-6), 15.8 (C-8',9'), 20.9 (C-8',9'), 22.3 (C-lo'), 23.2 (C-37, 25.3 (C-7'), 31.5 (C-57, 34.3 (C-47, 40.4 (C-6'), 47.8 (C-2'), 79.4 (C-l'), 101.7 (C-5), 118.7 (C-3), 163.9 (C-4), 171.1 (C-2). IR (KBr): v = 3490,3110,2960,2925,2870, 1807, 1780, 1745, 1655, 1458, 1295, 1120, 950,900,860. MS (70 eV): m/z = 252 (M+, 6), 138 (loo), 98 (52), 97 (89), 95 (46), 81 (84), 69 (38), 55 (29), 41 (46). UV (CH3CN): h = 191 (E = 13900), 248 ( ~ 5 7 ) .

1.2

99

Enones and Dienones

UV (n-hexane): A = 185 (E = 16700), 266 (68).

(5R)-4-Methyl-5-(+)-menthyloxy-2[5Hl-furanone(minor isomer, mixture with the main

isomer): 'H-NMR (CDC13, 300 MHz): 6 = 0.82 (d, 3 H, J = 7.0, H-8', -97, 0.94 (m, 6 H, H-8', -9', H-lo'), 1.35 (m,1 H, H-27, 1.43 (m,1 H, H-57, 1.67 (m, 1 H, H, -3', -47, 2.08 (m, 3 H, H-6), 2.32 (dm, 1 H, J = 12.2, %q-6), 3.53 (dt, 1 H, J = 4.5,10.5, H-l'), 5.69 (s, broad, 1 H, H-5), 5.85 (m, 1 H, H-3). 13C-NMR (CDC13, 75 MHz): 6 = 13.5 (C-6), 15.8 (C-8',9'), 21.0 (C-8',9'), 22.1 (C-lo), 22.9 (C-3'), 25.5 (C-7'), 31.7 (C-57, 34.1 (C-4'), 42.4 (C-6), 48.2 (C-2'), 83.4 (C-l'), 105.5 (C-5), 118.8 (C-3), 163.6 (C-4), 170.9 (C-2).

1.2.8~ (lR,4S,5S)-, (1S,4S,5R)-4-(+)-Menthyloxy-5-methyl-3-oxa2-oxobicyclo[3.2.0]heptane

0&Go* + "'H

251.4

CH* II CH*

32.1

oso+

hv acetone, -25OC

0 '

283.5 A solution of 6 g of (+)-(5S)-4-methyl-5-menthyloxy-2[5H]-furanone1.2.8b in 250 mL of acetone is carefully flushed with ethylene and irradatiated for 8 h at -25°C (quarz glass immersion well with vacuum jacket, HPK 125 (Philips)). The solvent is evaporated and the residue is chromatographed (silica gel, 3% ethylacetatekyclohexane, column: 210 mL) in order to seperate the diastereomers. Yield: quant., 9% de for (lR,4S,SS)-4-(+)-mentyloxy-5-methyl-3-oxa-2-oxobicyclo[3.2.0]heptane, major diastereomer: [a],29= +143.4" (1.13, CHC13). ~~

'H-NMR (CDC13, 300 MHz): 6 = 0.76, 0.86 (2d, 3 H, J = 6.7, CH3-9', lo'), 0.92 (d, 3 H, J = 6.4, CH3-7'), 0.99 (m, 1 H), 1.28 (s, 3 H, CH3-8), 1.2 - 1.4 (m, 2 H), 1.64 (m, 1 H), 1.82 (m, 1 H), 2.02 (m, 1 H, Hq-6), 2.20 (dt, 1 H, J = 10, l l S ) , 2.54 (pen, J = 10, 1 H), 2.67 (m, 1 H), 3.53 (dt, 1 H, J = 4, 10.4, H-5'),5.27 (s, H-4). 13C-NMR (CDC13, 75 MHz): 6 = 15.9, 20.8 (C-9', lo), 17.4 (C-8), 21.0 (C-6), 22.3 ((2-77, 23.4 ((2-37, 25.6 (C-8'), 29.4 (C-7), 31.4 (C-l'), 34.4 (C-2'), 39.8 (C-67, 42.7 (C-1), 45.0 (C-5), 47.8 (C-47, 76.5 (C-5'), 105.1 (C-4), 180.0 (C-2). IR (CDC13): v = 2960,2930,2870, 1785, 1650, 1550, 1460, 1345, 1305.

100

1.2 Enones and Dienones

MS (70 eV): m/z = 280 (M+, 6), 252 (6), 139 (loo), 125 (51), 83 (58), 81 (97), 41 (55). minor diastereomer: [a],29= +205.1 (1.06, CHC13). 'H-NMR (CDC13, 300 MHz): 6 = 0.85 (d, J = 7, CH3-9',10'), 0.91 (d, 3 H, J = 6.5, CH3-7), 0.93 (d, 3 H, J = 6, CH3-9',10'), 1.00 (m, 1 H), 1.30 (s, 3 H, CH3-8), 1.94 2.08 (m,2 H), 2.25 (m,1 H), 2.40 (m, 1 H), 2.60 - 2.74 (m, 2 H), 3.56 (dt, 1 H, J = 4, 11, H-5'),5.31 ( s , H-4). 13C-NMR (CDC13, 75 MHz): 6 = 15.9 (C-lo), 19.8 (C-6), 20.7 (C-8), 21.0 (C-Y), 22.3 (C-77, 23.2 (C-3'), 24.8 (C-7), 25.6 (C-87, 31.4 (C-l'), 34.3 (C-27, 39.9 (C-6'), 44.4 (C-1), 47.8 (C-47, 78,l ((2-57, 106.3 (C-4), 178,l (C-2). IR (CDC13): v = 2960,2915,2870,1765,1655, 1550, 1455, 1295. MS (70 eV): m/z = 280 (M+,l), 252 (9, 139 (loo), 83 (50),81 (56), 68 (36), 41 (38).

1.2.8d (lS,5R,2-RS)-, (lR,5S,2-RS)-2-Hydroxy-l,4,4-trirnethyl-3oxabicyclo[3.2.0] heptane

O

0 ,.d)* p H "4

2 MeLi/THF

'I

Lr

HO-

156.2

156.3

283.5

HO A stirred solution of 10.7 mmol of (lR,4S,5S)-, or (1S,4S,5R)-4-(+)-menthyloxy-5-methyl-

3-oxa-2-oxobicyclo[3.2.0]heptane 1.2.8~in anhydrous ether is cooled to -20 to -40 "C. Two equivalents of methyllithium (5% solution in ether) are added under a nitrogen athmosphere. The solution is allowed to warm up to RT and is stirred for additional 30min. After it has been cooled to 0 "C,water is added until a clear water phase is formed. It is extracted twice with ether. The combined ether phases are dried with MgSO4 and are evaporated. The residue is chromatographed (silica gel, 15% ethylacetatel cyclohexane, column: 210 mL).

Yields: menthol: 95 - 98%, (lS,5R,2-RS)-2-hydroxy-1,4,4-trimethyl-3-oxabicyclo-[3.2.0]heptane: 73% (byproduct: 7%), (lR,W,2-RS)-2-hydroxy- 1,4,4-trimethyl-3-oxabicyclo[3.2.0]-heptane: 65% (byproduct: 13%). (two diastereomers, ratio: 1:1).

1.2

101

Enones and Dienones

lH-NMR (CDC13, 300 MHz): 6 = 1.17 (s, CH3), 1.23 (CH3), 1.26(CH3), 1.28 (CH3), 1.34(s, CH3), 1.35 (s, CH3), 1.6- 2.3(m, CH, CH2), 4.00(s, 1 H, OH), 4.65(d, 1 H, J = 5.7,OH), 5.05(d, 1 H, J = 5.7,O-CH-0), 5.16(s, 1 H, O-CH-0). 13C-NMR (CDC13,75 MHz): 6 = 16.4(CH2), 16.5,22.4,29.6,48.5(C), 51.3,52.0(CH), 52.7,80.0(C-0), 84.0,102.8(O-CH-0), 104.4. IR (CDC13): v = 3490,2975,2875,1655,1545,1460,1365,1335. MS (70eV): m/z = 156 (M+, 0.03), 110(34), 95 (loo), 81 (32),67(42),43 (36).

1.2.8e

(1R,2R)-,(1S,2S)-l-Ethenyl-2-(l-hydroxy-l-methylethyl)1-methyIcy clobutane 2 Ph,P=CH, 156.2

THF

-9 '0

154.3

To a suspension of 20.5 mmol of potassium r-butoxide in 20 mL of anhydrous THF, 20mmol of methyltriphenylphosphoniumbrornideare added at 0 "C. After stirring at RT or for 15 - 30 min, the suspension is cooled to -78"C, and 10 mmol of (lS,5R,2-RS)(1R,5S,2-RS)-2-hydroxy-1,4,4-trimethyl-3-oxabicyclo[3.2.0]heptane 1.2.8d dissolved in 5 mL of anhydrous THF are added. After 15 min at low temperature, the reaction mixture is stirred at RT overnight. The reaction is quenched with water and most of the THF is evaporated carefully. The residue is extracted with ether and the combined ether phases are dried with MgS04. The solvent is carefully evaporated and triphenylphosphane oxide is separated by flash chromatography with 5% ethedpentane and silica gel. The crude product can be used for next conversion. A further chromatography yields pure product. Yield: 78%. (lR,2R)- 1-Ethenyl-2-(1-hydroxy-1-methylethyl)-1-methylcyclobutane: [CXlD25= -34.lo (1.25,CHC13).

(lS,2S)-1-Ethenyl-2-(1-hydroxy-1-methylethyl)-1-methylcyclobutane: = -33.0"(0.97,CHC13). 'H-NMR (CDC13, 300 MHz): 6 = 1.01(s, 3 H, HO-C-C_H3), 1.18(s, 3 H, HO-C-C&), 1.25 (s, 3 H, CH3), 1.65- 1.95(m, 4 H), 2.00 - 2.18(m, 2 H), 5.11 (d, 1 H, J = 11.5, =CHH), 5.13(d, 1 H, J = 17.5,=C_HH), 6.42(dd, 1 H, J = 17.5,11.5,HC=). "C-NMR (CDC13, 75 MHz): 6 = 17.5(CH2), 27.8(CH3), 28.1 (CH3), 28.3(CH3), 30.5 (CH2), 45.0(C), 56.5(CH), 72.2(C-OH), 112.6(H2C=), 143.8(HC=). IR (CDC13): v = 3560,3450,3085,2975,2870,1635, 1550,1470,1370. MS (70eV): m/z = 154 (M+, 0.9),121 (19),93 (25),81 (22),68 (loo), 67 (61),59 (58).

102

1.2

Enones and Dienones

1.2.8f (lR,2R)-, (lS,2S)-1-(2-Hydroxyethyl)-2-(1-hydroxy-1methylethyl)-l-methylcyclobutane[41 1 .) BH,. '0

154.3

THF

2.)NaOH/H,O,

172.3

6 mmol of (1R,2R)- or (lS,2S)-l-etheny1-2-( 1-hydroxy-l-methylethyl)-l-methylcyclobutane 1.2.8e are dissolved in 10 mL of anhydrous THF. The resulting solution is cooled to -78 "C. A solution of 6 mmol of BH3 in THF is added. The mixture is then stirred at RT for about 2 h. After cooling with ice/water, 10% NaOH is carefully added until foaming ceases. 0.8 mL of H202 (30% in H20) is added. Most of the THF is evaporated and the residue is treated with water and ether. The water layer is extracted three times with ether. The combined organic layers are dried with MgS04. The ether is evaporated. The resulting product is pure enough for further conversion. Yield: 89%. Chromatography with 50% ethylacetatekyclohexane and silica gel yields pure product. (1R,2R)-1-(2-Hydroxyethyl)-2-(1-hydroxy-1-methylethyl)-1-methylcyclobutane: [a],'' = 4-18' (0.96, CHCl,), mp 57 - 61 "c. ( lS,2S)- 1-(2-Hydroxyethyl)-2-(1-hydroxy- 1-methylethyl)-1-methylcyclobutane: [a]DZ5 = -17" (0.91, CHC13).

'H-NMR (CDC13, 300 MHz): 6 = 1.09 (s, 3 H, CH3), 1.10 (s, 3 H, CH3), 1.23 (s, 3 H, CH3), 1.50 (m, 1 H), 1.71 (m, 2 H), 1.83 - 2.14 (m, 2 H), 3.5 - 3.75 (m, 2 H) 3.1 - 4.1 (s, 2 H, OH). 13C-NMR (CDCl3, 75 MHz): 6 = 18.0 (CH2), 28.2 (CH3), 29.0 (2C, CH3), 30.5 (CH& 37.5 (CH2), 41.7 (C), 56.1 (CH), 59.4 (CH2OH), 72.1 (COH). IR (CDC13): v = 3450,2970,2870,1655,1545, 1465,1380. MS (70 eV): m/z = 154 (M+, 4), 139 (8), 129 (8), 111 (34), 81 (25), 71 (42), 69 (100),68 (47), 59 (38), 43 (50),41 (47).

1.2.8g (1R,6S)-,(1S,6R)-1,5,5-Trimethyl-4-oxabicyclo[4.2.0]octane[4,5,61

172.3

154.3

103

1.2 Enones and Dienones

To a solution of (1 R,2R)- or (lS,2S)-1-(2-hydroxyethyl)-2-(l-hydroxy-l-methylethy1)-lmethylcyclobutane 1.2.8f in 20 mL of pyridine, 10 mmol of TsCl and a catalytic amount of DMAP are added at 0 "C. The mixture is refluxed for 2 h under nitrogen atmosphere. The solution is then poured into 50 mL of 10% HC1 and extracted with ether. The combined ether layers are washed with 10% HCl, twice with saturated NaHC03 solution and then with water. The organic layer is dried with MgS04/K2C03. The crude product is chromatographed with 5 % ethedpentane (silica gel). Yield: 84%.

(1R,6S)-1,5,5-Trimethyl-4-oxa-[4.2.0]-bicyclooctane: (1S,6R)-1,5,5-Trimethyl-4-oxa-[4.2.0]-bicyclooctane:

-21' (0.98,CHC13), = +21'

(1.04,CHC13).

'H-NMR (CDC13, 300 MHz): 6 = 1.01 (s, 3 H, CH3), 1.13 (s, 3 H, CH,), 1.16 (s, 3 H, CH3), 1.31 (m, 1 H), 1.40 - 1.73 (m, 4 H), 1.90 (m, 2 H), 3.59 (m, 2 H, CH20). 13C-NMR (CDC13, 75 MHz): 6 = 18.4(CHz), 24.9 (CH3), 26.4 (CH3), 28.1 (CH3), 32.8 (CH2), 34.2 (CH2), 35.6 (C), 47.9 (CH), 57.8(CH20), 70.8 (CO). IR (kap): v = 2975,2950,2865,1465,1375,1215,1075. MS (70 eV): m/z = 154 (M+. 2), 1 1 1 (42),81 (83),71 (24),69 (loo),55 (22),41 (55).

1.2.8h (+)-, (-)-Grandisol[6>7]

154.3

LDNhexane b

-

*OH

% ,

154.3

55 mmol of butyllithium (2.5 molar solution in n-hexane) is added under a nitrogen atmosphere with cooling and stirring to a solution of 5 mmol of (1R,6S)-or (lS,6R)-1,5,5-

trimethyl-4-oxabicyclo[4.2.O]octane in 8 mL of diisopropyl amine. The last portion is added at RT. The mixture is then refluxed for 24 h. Conversion is controlled by TLC (20% ethylacetatekyclohexane).The reaction mixture is carefully poured in a two phase system of saturated NH4C1-solution and ether. The water phase is extracted with ether. The combined organic layers are washed twice with 1% HCl and brine and dried with MgSO4. After evaporation of ether, the residue is chromatographed (silica gel, 10% etherlpentane). Yield: 90%. (+)-Grandisol: [a],23= +17.0"(0.99,hexane). (-)-Grandisol: [a],23= -17.7' (1.07,hexane).

104

1.2

Enones and Dienones

lH-NMR (CDC13, 300 MHz): 6 = 1.17 (s, 3 H, CH3), 1.67 (s, broad, 1 H, CH3, allyl), 1.37 - 1.48 (m,1 H), 1.54 - 1.86 (m,4 H), 1.86 - 2.50 (m,2 H), 2.54 (t, 1 H, J = 8, CHI, 3.63 (m,2 H, C&OH), 4.64 (s, broad, 1 H, HHC=), 4.83 (m, 1 H, _HC=). 13C-NMR (CDC13, 75 MHz): 6 = 19.2 (CH& 23.2 (CH3, allyl), 28.4 (CH3), 29.4 (CH2), 36.9 gH2CH20H), 41.4 (C), 52.6 (CH), 59.8 (CH*OH), 109.8 (H2C=), 145.2 (C=). IR (kap): v = 3340,3080,2950,2870,1645, 1455, 1375,1055,885. MS (70 eV): mlz = 154 (M+, O.l), 139 (2), 121 (3,109 (29), 68 (lOO), 67 (61), 41 (26).

[ 11

[2] [3] [4]

[5] [6] [7]

N. Hoffmann, H.-D. Scharf, Liebigs Ann. Chem. 1991,1273 - 1277. J. J. Bourguignon, C. G. Wermuth, J. Org. Chem. 1981,46,4889 - 4894. B. L. Feringa, B. de Lange, J. C. de Jong, J. Org. Chem. 1989,54,2471 - 2475. J. H. Tumlinson, R. C. Gueldner, D. D. Hardee, A. C. Thompson, P. A. Hedin, J. P. Minyard, J. Org. Chem. 1971,36,2616 - 2621. R. Zerfliih, L. L. Dunham, V. L. Spain, J. B. Siddall, J. Am. Chem. SOC. 1970, 92, 425 - 427; R. C. Gueldner, A. C. Thompson, P. A. Hedin, J. Org. Chem. 1972, 37, 1854 - 1856. K. Langer, J. Mattay, A. Heidbreder, M. Moller, Liebigs Ann. Chem. 1992, 257 260. I. Aljancic-Sola, M. Rey, A. S. Dreiding, Helv. Chim. Acru 1987, 70, 1302 - 1306.

1.2

105

Enones and Dienones

1.2.9

7,8,9,10-Tetrahydrobenzo[b]carbazole-5,1l-dione~~~ submitted by

H. Suginome, K. Kobayashi

1.2.9a 2-Amino-1,4-naphthoquinone [I] NaN, 0

aq. AcOH

0

158.2

173.2

To a solution of 5.0 g (32 mmol) of 1.4-naphthoquinone in 50 mL of acetic acid at 40 "C was added a solution of 3.4 g (52 mmol) of sodium azide in 10 mL of water. After one and a half hours the brown, crystalline material was collected and recrystallized from ethanol to give 4.7g (87%) of 1.2.9a, mp 204 - 205 "C.

lH-NMR (CDC13, 270 MHz): 6 = 5.15 (br. s, 2 H, NH2), 6.00 (s, 1 H, 3-H), 7.64 (td, 1 H, J = 7.6, 1.3,6- or 7-H), 7.73 (td, 1 H, J = 7.6, 1.3,6- or 7-H), 8.0-8.1 (m, 2 H,

5-, 8-H). IR (Nujol): v = 3390, 3283, 1686, 1620, 1564.

1.2.9b 1-Methoxycyclohexene[2] 0

OMe HC(OMe),, TsOH 112.2

98.2

A mixture of 95 g (0.97 mol) of cyclohexanone, 103 g (0.97 mmol) of trimethyl orthoformate, and 0.95 g (5.0 mmol) of p-toluenesulfonic acid monohydrate was stirred for 21 h at room temperature. Fractional distillation of the resulting mixture gave 87 g (80%) of 1.2.9b, bp 137 - 138 "C. _____

~

_____

'H-NMR (CDC13, 90 MHz): 6 = 1.45 - 1.8 (m, 4 H, 4- and 5-CH2), 1.95 - 2.15 (m, 4 H, 3- and 6-CH2), 3.49 (s, 3 H, OCH3), 4.61 (t, 1 H, J = 3.5, CH=C(OCH3)). Ut (neat): v = 1029, 1221, 1668.

106

-6 1.2 Enones and Dienones

6 OMe

&NH2+

benzene hv

0 235.3

0 173.2

112.2

A solution of 70 mg (0.40 mmol) of 1.2.9a and 0.90 g (8.0 mmol) of 1.2.9b in 70 mL of benzene was irradiated (500 W high-pressure Hg arc, h > 300 nm) under a nitrogen atmosphere for 2.5 h at room temperature. After rota-evaporation of the solvent the crude product was purified by preparative TLC (silica gel) with chloroform yielding 68 mg (68%) of 1.2.9c, mp 290 "C (dec.) (chloroform).

lH-NMR (CDC13, 270 MHz): 6 = 1.75 - 1.95 (m, 4 H, 8, 9-CH2), 2.71 (t, 2 H, J = 5.9, 7 or lO-CH2), 2.89 (t. 2 H, J = 5.9, 7 or 10-CH2), 7.6 - 7.75 (m, 2 H, 2- and 3-H), 8.1 - 8.2 (m, 2 H, 1- and 4-H). JR (Nujol): v = 3200, 1645, 1587.

1.2.9d 2-Methyl-lH-benzo~indole-4,9-dione[3] 0

O

H

hv

OMe

0

173.2

72.1

benzene

0 21 1.2

A solution of 70 mg (0.40 mmol) of 1.2.9a and 0.58 g (8.0 mmol) of 2-methoxypropene in 70 mL of benzene was irradiated (a 500 W high-pressure Hg arc, h > 300 nm) under a nitrogen atmosphere for 3 h at room temperature. After rota-evaporation of the solvent the crude product was recrystallized from chloroform to give 70 mg (72%) of 1.2.9d, mp 300 "C (dec.).

'H-NMR (CDC13, 90 MHz): 6 = 2.37 (d, 3 H, J = 0.9, 2-CH3), 6.45 (q, 1 H, J = 0.9, 3-H), 7.1 - 8.25 (m, 5 H, ArH, NH). IR (Nujol): v = 1664, 1641, 1585. [l] [2] [3]

L. F. Fieser, J. L. Hartwell, J. Am. Chem. S O ~ 1935,57, . 1482 - 1484. R. H. Wohl, Synthesis 1974, 38 - 40. K. Kobayashi, H. Takeuchi, S. Seko, H. Suginome, Helv. Chim. Actu 1991, 74, 1091 - 1094; K. Kobayashi, H. Takeuchi, S. Seko, H. Suginome, Helv. Chim.

.

-,.a-

-,.-,.

1.2

107

Enones and Dienones

1.2.10 2,3-Dihydro-2,2-dimethylnaphtho[2,3-b]furan-4,9&one[ 11 submitted by

H. Suginome and K. Kobayashi

0

0

hv

acetone

0 56.1

174.2

0

230.3

A solution of 0.17 g (1 mmol) of 2-hydroxy-l,4-naphthoquinone(Janssen) and 0.56 g (10 mmol) of isobutene in 40 mL of acetone under a nitrogen atmosphere was irradiated (a 500 W high-pressure Hg arc, h > 300 nm) for 15 h at room temperature. After excess isobutene and acetone were removed under reduced pressure, the residue was subjected to preparative TLC (silica gel) with hexane/ethyl acetate (3: 1) to give 0.21g (92%) of 1.2.10, mp 188 - 190 "C (hexane/diethyl ether). 'H-NMR (CDC13, 90 MHz): 6 = 1.59 (s, 6 H, 2-(CH3)2), 2.00 (s, 2 H, 3-CH2), 7.6 7.8 (m, 2 H, 6- and 7-H), 8.0 - 8.15 (m, 2 H, 5- and 8-H). JR (Nujol): v = 1684, 1640, 1620, 1593. ~

[l]

K. Kobayashi, H. Shimizu, A. Sasaki, H. Suginome, J. Org. Chem. 1993, 58, 4614 - 4618.

108

1.2

Enones and Dienones

1.2.11 trans-Bicyclo[5.3.l]undecan-ll-one['] submitted by

J. D. Winkler and B. Hong

1.2.11a tert-Butyl-3-(4'-Pentenyl)-2-oxocyclohexanecarboxylate

NaH, n-BuLi CH2=CH(CH2),I 198.3

266.4

To a solution of NaH (0.812 g, 50% in oil, 1.1 eq.) in THF (30 mL) was added a solution of t-butyl-2-cyclohexanonecarboxylate[2](2.968g) in THF (5 mL) at 0 "C under nitrogen atmosphere. After stirring for 10 min at 0 "C, the solution was treated dropwise with n-BuLi (6.48mL, 2.43 M, 1.05 eq.). After stirring for 10 min at 0 "C, the pale yellow reaction mixture was treated with HMPA (2.87mL, 1.1 eq.), and 10 min later, with a solution of 4-pentenyl iodide (3.242g, 1.leq.) in THF. The reaction was allowed to warm up slowly to 25 "C with stirring over 3 h. The reaction mixture was poured into pH 7 aqueous phosphate buffer and extracted with diethyl ether. The combined etheral layers were washed with water, dried over MgS04, concentrated and purified by chromatography (5% ethyl acetate/petroleum ether) to give 1.2.11a (3.562g, 89%).

'H-NMR (CDC13, 500 MHz): 6 = 1.20- 1.50(m, 6 H), 1.50(s, 9 H),1.65 - 1.85 (m, 2 H),2.00 - 2.40 (m, 5 H),3.20- 3.32 (m,1 H),4.90- 5.00 (m,2 H),5.70- 5.82 (m,1 H). IR (neat): v = 2978,2862,1738,1714,1641,1393,1314,1255,1237,1160. MS:m/z = 267,253,225,211,193, 165,155,142,117.

1.2

109

Enones and Dienones

1.2.11b 5,6,7,8-Tetrahydro-2,2-dimethyl-8-(4'-pentenyl)-4H1,3-benzodioxin-4-one

Coot-Bu

CF,COOH (CF,CO),O acetone

0

* 250.3

266.4

A solution of 1.2.11a (857 mg), acetone (11.8 mL), trifluoroacetic anhydride (0.91 mL), and trifluoroacetic acid (6.20 mL) was stirred at 25 "C under a nitrogen atmosphere for 24 h. The solution was concentrated to provide 924 mg of crude material, which was purified by chromatography with 10% ethyl acetate in petroleum ether (Rf=0.30) to give 1.2.11b (473 mg, 59% yield).

'€I-NMR (CDC13, 500 MHz): 6 = 0.80 - 1.80 (m, 9 H), 1.66 (s, 3 H), 1.67 (s, 3 H), 1.90 - 2.30 (m, 4 H), 4.90 - 5.00 (m, 2 H), 5.70 - 5.82 (m, 1 H). 13C-NMR (CDCI,, 125 MHz): 6 = 19.6 (CH2), 21.7 (CH2), 24.8 (CH3), 25.6 (CH3), 26.5 (CH2), 26.9 (CH2), 30.8 (CH2), 33.7 (CH2), 37.0 (CH), 102.4 (C), 105.9 (C), 114.5 (CH2), 138.3 (CH), 162.0 (C), 167.3 (C). IR (neat): v = 2939,2862, 1727, 1644,1398,1389,1370,1303,1268,1206, 1152. MS:d z = 250 (M+, 4), 234 (2), 192 (87), 151(13), 137 (83), 124 (loo), 111 (20). exact mass calc. for CI5H22O3:250.1569; found: 250.1574.

1.2.11~ (1S,2S,6S,lOR)-13,13-Dimethyl-l2,14=dioxatetracyclo[S.4.0.12~'0.019~pentadecan-1l-one

0

250.3

hv

-

CH,CN/acetone (9/1)

wo x

H

250.3

A solution of 1.2.11b (360 mg, 1.44 mmol) in 9:l acetonitrile/acetone (300 mL) was degassed by passing a stream of N2 through the solution for 30 min. The resulting solution was then cooled to 0 "C, and irradiated through a Pyrex filter sleeve using a 450 W Hanovia lamp in an immersion well for 2 h. The resulting solution was concentrated and purified by flash column chromatography using 10% ethyl acetate in petroleum ether to provide 1.2.11~(325 mg, 90% yield).

110

1.2

Enones and Dienones

IH-NMR (CDC13, 500 MHz): 6 = 1.10 - 1.75 (m,7 H), 1.68 (s, 6 H), 1.80 - 1.95 (m, 3 H), 2.00 - 2.05 (m, 2 H), 2.08 - 2.15 (m, 1 H), 2.52 (dd, 1 H, J = 4, 5 ) , 2.58 2.65 (m, 1 H), 2.85 - 2.92 (m, 1 H). 13C-NMR (CDC13, 125 MHz): 6 = 22.3 (CH2), 22.5 (CHz), 24.2 (CH2), 26.0 (CHZ), 28.0 (CHz), 29.9 (CH2), 30.4 (CH3), 30.6 (CH3), 35.2 (CH), 35.3 (CH), 37.0 (CH2), 44.0 (C), 80.5 (C), 106.4 (C), 173.5 (C). IR (neat): v = 2940,2860, 1736, 1270, 1261. MS: m/z = 250 (M', 0.2), 192 (27), 164 (4), 137 (36), 124 (loo), 105 (5). exact mass calc. for C15H22O3: 250.1569; found: 250.1563.

1.2.11d (1R,3R,7R)-3-Carboxybicyclo[5.3.1]undecan-l1-one

x

LiOH, MeOH *O H

H

250.3

21 0.3

A solution of 1.2.11~(982 mg, 4.38 mmol) and LiOH (480 mg) in methanol (50 mL) was stirred at 25 OC for 10 h. The solution was diluted with diethyl ether, acidified to pH 1 with 6 N aqueous HCl, extracted with methylene chloride, dried overMgS04, and purified by flash column chromatography using 80% ethyl acetate in petroleum ether to give 1.2.11d (737 mg,80% yield) as a white solid, mp 108 - 109 "C. Crystals of this acid suitable for X-ray crystallographic analysis were obtained by slow evaporation of a methanol solution of this acid at room temperature.

'H-NMR (CDC13, 500 MHz): 6 = 1.30 - 2.20 (m, 13 H), 2.30 - 2.42 (m, 1 H), 2.50 2.60 (m, 2 H), 3.30 - 3.40 (m, 1 H). IR (neat): v = 3000 - 3400,2960,2880,1705,1725, 1460,1420. MS: m/z = 210 (M+, loo), 192 (54), 164 (72), 149 (30), 136 (36), 122 (34), 109 (52).

1.2.11e trans-Bicyclo[5.3.1]undecan-ll-one 1.) (COCI),, DMF, benzene 2.) toluene, DMAP, t-BUSH 21 0.3

0

N' SNa 0-

166.3

1.2

Enones and Dienones

111

To a solution of 1.2.11d (219 mg, 1.04 mmol) in benzene (25 mL) was added oxalyl chloride (1 mL). The reaction flask was then charged with nitrogen, and dimethylformamide (50 mL) was added. The resulting solution was stirred for 1 h at 25 "C and then evaporated under reduced pressure. The crude acid chloride was dissolved in toluene (10 mL) and added dropwise to a refluxing slurry of the sodium salt of 2-mercaptopyridine-N-oxide(1 85 mg), DMAP (14 mg), and terr-butyl mercaptan (2 mL) in toluene (10 mL).l3l After refluxing for 1.5 h, the solution was cooled and extracted with aqueous sodium bicarbonate, 1 N aqueous HCl, and water. The organic layers were evaporated and purified by flash column chromatography with 5% THF in petroleum ether to give 1.2.11e (1 10 mg, 64% yield). lH-NMR (CDC13, 500 MHz): 6 = 1.00 - 2.10 (m, 16 H), 2.35 - 2.42 (m, 1 H), 3.20 3.30 (m, 1 H). 13C-NMR (CDC13, 75.5 MHz): 6 = 23.8, 24.2, 28.5, 28.8, 29.1, 33.4, 34.6, 34.7, 46.9,5 1.2,222.4. IR (neat): v = 2930,2860, 1728, 1457,1441. MS: m/z = 166 (M', 51), 123 (19), 111 (70), 98 (100). exact mass calc. for CllHI80: 166.1358; found: 166.1354.

[l]

[2] [3]

J. D. Winkler, B.-C. Hong, J. P. Hey, P. G. Williard, J. Am. Chem. Soc., 1991, 113,8839 - 8846. D. K. Banerjee, S. N. Mahapatra, Tetrahedron, 1960, 11, 234 - 240. D. H. R. Barton, D. Crich, W. B. Motherwell, J. Chem. Soc., Chem. Cummun., 1983,939 - 941.

112

1.2

Enones and Dienones

1.2.12 Tetracyclo[6.4.0.02~11.O4~9]dodec-6-en-3,lO-dione~~~ submitted by

J. R. Scheffer

1.2.12a Sa-Viny1-4aP,5,8,8aP-tetrahydro-l,4-naphthoquinone[ 11

80.1

108.1

188.2

A mixture of 4.0 g (0.05 mol) of 1,3,5-hexatriene (Aldrich, mixture of isomers, mainly trans) and 1.6 g (0.014 mol) of freshly recrystallized p-benzoquinone was stirred at 60 "C for 2 h during which time the benzoquinone slowly dissolved. The solution was then stirrred for 4 h at rmm temperature and the hexatriene removed in vacuo to leave a yellow solid. Two recrystallizations of this material from petroleum ether afforded 1.2 g (43%) of light yellow crystals, mp 58 - 60 "C.

lH-NMR (CDC13, 100 MHz): 6 = 2.0 - 3.5 (m, 5 H), 4.9 - 5.1 (m, 2 H, -CH=C&), 5.4 - 5.9 (m, 3 H), 6.7 (ABq, 2 H, J = 10, -COC&CHCO-). IR (CHC13): v = 1695, 1610 cm-*.

6

1.2.12b Tetracyclo[6.4.0.02,11.O 4'9]dodec-6-en-3,10-dione[1]

@'

H0

188.2

hu benzene

188.2

A solution of 200 mg (1.1 mmol) of 1.2.12a in 200 mL of freshly distilled, anhydrous benzene deoxygenated by purging for 1 h with nitrogen. The vessel containing the solution was placed 15 cm away from a water-cooled 450 W Hanovia mediumpressure mercury lamp and irradiated with light of h 2 340 nm by means of an interposed 17 x 17 x 0.2 cm plate of Corning #7380 glass. The reaction was monitored

1.2

Enones and Dienones

113

by TLC (alumina, ethyl acetate), which showed the disappearance of the starting material after 2.5 h and the development of only one significant new spot. Removal of benzene in V ~ C U Oand column chromatography (alumina, ethyl acetate) afforded a 60% yield of crude solid photoproduct. Recrystallization from a mixture of petroleum ethedether afforded colorless crystals, mp 9 1.5 - 92.5 "C, in 50% overall yield.

1H N M R (CDC13, 100 MHz): 6 = 1.6-3.2 (m, 10 H), 5.8 (m, 2H, -C_H=C_H-). IR (KBr): v = 1735 cm, 1715 cm-l.

Ultimate proof of structure came from an X-ray crystal structure determination.[']

[l]

Y.-M. Ngan, S. J. Rettig, J. R. Scheffer, J. Trotter J. Can. J. Chem. 1975, 53, 2068 - 2075.

114

1.2

Enones and Dienones

1.2.13 Benzopentacyclo[5.4.0.01'3.O 2'6.O 5'7]undeca-9-en-8,11dionel I 1 submitted by

T. Miyashi

hv CH,CI,

0

222.2

0

222.2

A solution of 0.4 mmol of naphthoquinonorbornadiene[2] (88 mg) in dry dichloromethane (20 mL) was deoxygenated by nitrogen bubbling, and irradiated by a 150 W high-pressure Hg-lamp using glass cut filter (Y-43, h > 400 nm) until total conversion. Evaporation of the solvent at 20 OC in the dark afforded pale yellow solid (mp > 100 "C [dec.]) of the quadricyclane derivative in quantitative yield. ~-

'H-NMR (90 MHz, CDCI,): 6 = 2.42 (t, 2 H, J = 1.2), 2.96 (d, 2 H, J = 4 3 , 3.14 (at, 2 H, J = 4.5, 1.2), 7.59 - 7.82 (m, 2 H), 8.05 - 8.28 (m, 2 H). MS (25 eV): m/z = 222 (M+, 81), 221 (156), 165 (100). IR (KBr): v = 154. UV (CH2C12): A,, = 231 nm (lg E = 4.57), 252 (4.17), 287 (3.57, sh), 300 (3.65, sh), 307 (3.69), 353 (3.22, sh), 372 (2.95, sh). ~

[l] [2]

~~

~

~~

~~

T Suzuki, Y. Yamashita, T. Mukai, T. Miyashi, Tetrahedron Left. 1988, 29, 1405 - 1408. 0. Diels, K. Alder, Chem. Ber. 1929,62,2337 - 2372.

1.2

115

Enones and Dienones

1.2.14 Methyl 3-em-acetyl-2-oxabicyclo[3.2.01heptaneendo-carboxylate[ll submitted by

P. Margaretha

1.2.14a l-[3-(Prop-2-enyloxy)furan-2-yl]ethanone CH,=CHCH,Br

0

c

0

K*CQ

126.1

166.2

A solution of isomaltol[2] (8.17 g, 0.065 mol), 3-bromopropene (14.3 g, 0.12 mol) and anhydrous K2CO3 (17 g, 0.12 mol) in dry acetone (120 mL) is refluxed for 18 h. After addition of H20 (100 mL) and ethoxyethane (200 mL) the organic phase is separated, washed with aq. NaHC03- and NaC1-solutions, dried (MgS04) and evaporated to afford 5.6 g (52%) of a colorless liquid (purity > 92%) which is used without further purification. 'H-NMR (CDC13, 400 MHz): 6 = 2.47 (s, 3 H, CH3), 4.65 (m, 2 H, OCH2), 5.40 (m, 2 H, =CH2), 6.02 (m, 1 H, =CH-), 6.36 and 7.42 (d, 2 H, J = 2.0, CH=CH).

1.2.14b 2-Acetyl-2-(prop-2-enyl)furan-3(2H)-one

&? 166.2

0

195 OC

--

& 0 166.2

The neat propenyl ether 1.2.14a (5.6 g, 0.034 mol) is heated under Argon for 5 h at 195 "C and then bulb-to-bulb distilled at 175 "U0.25 Torr to afford 4.3 g (76%) of white crystalls, mp 41 "C. 'H-NMR (CDCl3, 400 MHz): 6 = 2.22 (s, 3 H, CH3), 2.75 and 2.90 (dd, 2 H, J = 7.4, 14.4, CH2), 5.19 (m, 2 H, =CH2), 5.62 (m, 1 H, =CH), 5.72 and 8.45 (AB, 2 H, J = 2.4, CH=CH). 13C-NMR (CDC13, 100.6 MHz): 6 = 25 (9, CH3), 38 (t, CH2), 97 (s), 107 (d, =CH), 121 (t, =CH2), 129 (d, CH=CO), 178 (d, OCH=), 197 (s, CO), 198 (s, CO).

116

1.2 Enones and Dienones

166.2

166.2

An argon-degassed solution of 1.2.14b (1.66 g, 0.01 mol) in benzene (10 mL) is irradiated in an uranium glass vessel (cut-off at 340 nm) for 30 h in a Rayonet-RPR-100 photoreactor equipped with 350 nm lamps. After evaporation of the solvent the residue is bulb-to-bulb distilled at 170 "U0.25 Torr to afford 1.28 g (77%) white crystalls, mp 45 "C.

13C-NMR (CDC13, 100.6 MHz): 6 = 28 (4, CH3), 29 (t, CH2), 38 (t, CH2), 39 (d, CH), 47 (d,CHCO), 78 (d,OCH),92 (s),201 (s,C0),206 (s,CO). IR (KBr): v = 1767, 1718.

1.2.14d Methyl 3-exo-Acetyl-2-oxabicyclo[3.2.0]heptane-7endo-carboxylate 0 1

166.2

198.2

To a solution of NaOMe (300 mg, 0.0055 mol) in MeOH (20 mL) cooled down to -78 "C is added a solution of 1.2.14~ (830 mg, 0.005 mol) in MeOH (10 mL). After 2 min the reaction is quenched by addition of water and ethoxyethane, the organic phase separated, washed with dil. aq. NH4CI solution and then with water, dried (MgS04) and evaporated. The residue is then bulb-to-bulb distilled at 170 "C/ 0.25 Torr to afford 644 mg (65%) of a colorless liquid. 13C-NMR (CDC13, 100.6 MHz) 6 = 24 (q, CH3), 25 (t, CH2), 34 (t, CH2), 35 (d, CH), 38 (d, CHCO), 50 (9, OCH,), 81 (d, OCH), 87 (d, OCHCO), 175 (s, COO), 21 1 (s, CO). IR (film): v = 1736, 1717.

1.2

117

Enones and Dienones

1.2.15 Photolysis of 4,4-diphenylcyclohexenone[1l submitted by H. E. Zimmerman

0

248.3

0

248.3

A 2.00 g (8.07mmoles) sample of 4,4-diphenylcyclohexenonein 500 mL of 95% ethanol was irradiated under nitrogen through a Pyrex filter using a 450 W Hanovia medium-pressure lamp in a cooled immersion well. The reaction was monitored by NMR. Concentration in vucuo at 40°C left a yellow oil. Chromatography afforded 1.95 g of 5,6-truns-diphenylbicyclo[3.l.0]hexan-2-one,mp 73 - 74 "C after recrystallization. 60 mg of the cis-stereoisomer of the bicyclic photoproduct were also isolated WaS.

[I]

H. E. Zimmerman, J. W. Wilson, J. Am. Chem. SOC. 1964, 86, 4036 - 4042; H.E.Zimmerman, K. G. Hancock, J. Am. Chem. Soc., 1%8,90,3749 - 3760.

1.2

118

Enones and Dienones

1.2.16 Sensitized photolysis of 4,4-diphenyl-2,5cyclohexenoner11 submitted by H. E. Zimmerman

0

hv, sens. Ph

Ph

246.3

benzene / MeOH

-

0

@Ph Ph

246.3

Three filter cells of pathlength 2.4cm each, containing 26.3 g/L of nickel sulfate, 225 g/L of cobalt sulfate, and 4.5 g/L of stannous chloride, respectively, were employed. The tin salt was in 10%hydrochloric acid and the nickel and cobalt in 10% sulfuric acid. This filter combination gave a band-width of 325 - 385 nm. An apparatus with a 5 inch linear beam from a lo00 W high-pressure mercury lamp was directed through the triple filter cell into a stirred solution of 1.02g of the 4,4-diphenylcyclohexadienoneand 20.3 g of acetophenone in 700 mL of benzene and 50 mL of methanol. Three such runs were carried out and concentrated in vucuo to afford solid mp 96 - 138 "C. Recrystallization from methanol and then hexane/ethyl acetate afforded 900 mg of 6,6-diphenylbicyclo[3.l.O]hex-3-en-2-one,mp 137.8 - 139.9 "C. From the filtrates there was isolated by chromatography 1.16g of reactant dienone and an additional 700 mg of bicyclic photoproduct.

[l]

H. E. Zimmerman, J. Nasielski, R. Keese, J. S. Swenton, J. Am. Chem. Soc., 1966,88, 4895 - 4903; H. E. Zimmerman, D. I. Schuster, J. Am. Chem. Soc., 1962,84,4527- 4540.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

2

Nitrogen-containing Chromophores

The presence of a nitrogen atom often alters the photophysical and photochemical behavior of a given chromophore. Thus, amides and imides still showing normal carbonyl reactivity when electronically excited, can exhibit quite different selectivities and efficiencies. The presence of an amine or amide substituent at a C-C double bond could lead to drastic differences in reactivity. Analogies between carbonyl photochemistry and the photochemistry of analogous compounds such as imines and nitriles holds true only for a limited number of substrates. Different ways for energy dissipation (e.g. C=N bond rotation) have to be considered and, most important for nitrogen containing substrates, many of them are much easier to oxidize. This makes these compounds excellent candidates for photoinduced electron transfer (PET) chemistry as the impressive developments in the last decade clearly showed. This chapter describes photoreactions of nitrogen containing chromophores which are different from the principal reactions of electronically excited carbonyl compounds. Five groups of substrates were included: cyclic and acyclic imines, nitriles, amine oxides, azo and diazo compounds, and enamides. The photochemistry of alkenes with a hydrazo or N-acyloxy substituted imino group in conjugation or separated by one methylene unit has been investigated by D. Armesto and W. A. Horspool. N-benzoyloxy substituted 1-azabutadienes underwent an efficient photochemical 6n-cyclization and subsequent aromatization with formation of substituted quinolines. When the C-C double bond and the imino group are separated by one methylene unit the aza-di-z-methane rearrangement becomes the dominant photochemical reaction. It is important to note that P,y-unsaturated nitriles, although easier to synthesize, do not undergo the aza-di-n-methane rearrangement. Dihydropyrazoles result when P,y-unsaturated hydrazones were irradiated in the presence of a triplet sensitizer. In contrast to these efficient intramolecular reactions most intermolecular photoreactions involving acyclic imines proceed with very low quantum yields. This is probably due to the rapid deactivation of the excited imine chromophore by C-N bond rotation. Cyclic imines, however, which lack this possibility, can undergo photoaddition to alkenes. 2-(Methy1thio)benzthiazole for example gives two products when irradiated in the presence of trans-stilbene. This reaction was investigated by G . Kaupp and seems to proceed via two different biradical intermediates. Whereas one biradical leads to an azetane simply by radical recombination, the other rearranges to a seven-membered heterocycle. Thermolysis of the latter cycloadduct leads to an I-azabutadiene which can be subsequently transformed into its geometrical isomer. This isomerization is reversible at another wavelength and thus constitute a simple photochromic system (see also Chapter 8). Direct irradiation of amino substituted azirines leads to neutral nitrile ylides which can be trapped with electron-deficient double bonds. H. Heimgartner described the synthesis of triazolines and oxazolines via trapping of a nitrile ylide with diethylazodicarboxylate and methyl trifluoroacetate, respectively. An elegant application of 1,3-dipolar cycloaddition chemistry is the photolysis of a tetrazole leading to a reactive nitrile imine which is trapped in an intramolecular fashion.

120

2.

Nitrogen-containing Chrornophores

Photochemical nitrogen extrusion also is the key reaction in a cross coupling reaction between reactive sides of a polymer chains as described by H.Meier. In this case a thiadiazole linked to a polyethylene chain (prepared from 3-pentanone in five steps) serves as the chromophore and double denitrogenation leads to chain dimerization with formation of a 1,4-dithiine. The extrusion of nitrogen is the predominant photoreactions for all kinds of azo and diazo compounds, azides and diazonium salts. When nitrogen is eliminated from a-diazoketones, a-ketocarbenes are formed which undergo the well-known Wolff rearrangement with formation of ketenes. An elegant version of this reaction with subsequent intramolecular trapping of the ketene is described by A. Padwa. After photolysis of an alkynyl substituted a-diazoketone and photo-Wolff rearrangement, electrophilic attack at the alkyne moiety and subsequent electrophilic aromatic substitution leads to a bridged phenyl substituted P-naphthol. Several instructive experiments describing singlet carbene addition reactions to styrene and styrene derivatives (a-, P-methyl styrene and 4-methyl styrene) were submitted by H.Diirr.These reactions are highly efficient and, as demonstrated for trans- 1-phenylpropene as trapping reagent, also highly stereoselective. Another important class of nitrogen-containing chromophores are nitro compounds and nitrones. Especially in heterocyclic chemistry these functional groups serve as valuable chromophores for structural transformations. Nitrones undergo photochemical cyclization to oxaziridines which can subsequently suffer N-0 bond cleavage. As one synthetic example from A. Albini shows, this cyclization can be used for ring expansion of quinolines. The photochemical reaction of ortho-alkylsubstituted nitroarenes is tautomerization to form the aci-nitro compound. An alternative cyclization with elimination of acetic acid (rearomatization) was observed for the 2,4-dinitroaniline derivative. Nitrosubstituted aromatic compounds have found some applications as protecting groups for amino and carboxyl functionalities. Photocycloaddition of alkenes and cycloalkenes (Chapter 4) with indole often lead to less satisfying results concerning yields and the number of side-products. When transformed into the corresponding carbamate, the enamido group undergoes clean [2+2] cycloaddition to cyclopentene as described by A. C.Weedon. The tetracyclic photoproduct can subsequently be deprotected. When irradiated in absence of an alkene, photodimers are formed in good yields.

Recommendedfurther reading General: The photochemistry of Amino, Nitroso, and Nitro Compounds S . Patai (Ed.), 1982, Wiley, New York; The Photochemistry of Heterocyclic Compounds 0.Buchardt (Ed.), 1976, Wiley, New York. and the corresponding chapters in: Rearrangements in Ground and Excited States Vol. 42 - 43 P. de Mayo (Ed.), 1980; Photochemistry in Organic Synthesis J. D. Coyle (Ed.), 1986, The Royal Society of Chemistry, London; Synthetic Organic Photochemistry W. A. Horspool (Ed.), 1984, Plenum Press, New York, London; W. A. Horspool, D. Armesto, Organic Photochemistry: A Comprehensive Approach, 1992, Ellis Horwood, PTR Prentice Hall, New York.

2.

121

Nitrogen-containing Chromophores

2.1

7-Chloro-2,3-diphenylquinoline~~l submitted by

2.la

D. Armesto, M. G. Gallego, A. Ramos and W. M. Horspool

3-Chloro-3-p-chlorophenyl-l,2-diphenylpropanone~*~ PhCOCH,Ph CI 140.6

HCI (9)

-

0 5 P h CI Ar Ar = p-CIC,H,

357.3

Deoxybenzoin (4g, 20 mmol) and p-chlorobenzaldehyde (3.5 g, 25 mmol) were dissolved in dry ether and the solution was cooled to 0 OC. Dry HC1 was then passed through the mixture for 8 h, keeping the temperature at 0 "C during this time. The crude product was allowed to stand at room temperature overnight. After rotary evaporation of the solvent the resulting solid was washed with ethanol, yielding 3.0 g (42%) of the chloro ketone 2.la as colorless crystalls, mp 122 - 124 "C.

'H-NMR (CDC13,250 MHz): 6 = 5.2 (d, 1 H, J = 10,CH), 5.7 (d, 1 H, J = 10,CH), 7.2 7.7(rn,lOH,ArH),7.8-8.0(m,lH,ArH),8.2(m,2H,ArH). IR (KBr): v = 1670.

2.lb

3-p-Chlorophenyl-l,2-diphenyl-2-propen-l-one 0 5 P h CI Ar Ar = p-CIC,H,

357.3

KOAc Na,CO,

c

Ar

320.8

The chloro ketone 2.la (1.3 g, 3.6 mmol), fused potassium acetate (1.1 g, 10.8 mmol) and sodium carbonate (0.38 g, 3.6 mmol) were heated at reflux in 150 mL of methanol for

122

2.

Nitrogen-containingChromophores

10 h. After cooling to room temperature and removing the solvent under reduced pressure, the crude product was purified by flash chromatography (silica gel 60 230-400 mesh) using hexaneltoluene (4:6) as eluant. The chromatography yielded 1.0 g (70%) of the enone 2.lb as colorless crystals, mp 91 - 93 “C from ethanol.

IH-NMR (CDC13, 250 MHz): 6 = 7.0 - 7.5 (m, 13 H, ArH and CH), 7.8 - 8.0 (m, 2 H, ArH). IR (KBr): v = 1650.

2.lc

3-p-Chlorophenyl-l,2-diphenyl-2-propen-l-one oxime Ph

O J y h

Ar Ar = p-CIC,H,

320.8

NH,OH- HCI pyridine

c

H O N y

Ar

335.8

The enone 2.lb (0.9 g, 2.8 mmol), hydroxylamine hydrochloride (0.3 g, 4.2 mmol) and pyridine (0.3 g, 4.2 mmol) were heated at reflux in 100 mL of ethanol for 52 h. After cooling the mixture to room temperature, the solvent was removed under vacuum and the crude dissolved in ether, washed with 3 x 100 mL portions of 10% aqueous HCl and then with water. The organic layer was dried over magnesium sulfate. The desiccant was filtered off and the solvent was removed under reduced pressure. The crude product obtained was purified by flash chromatography (silica gel 60 230-400 mesh) using hexane/ethyl acetate (1:l) as eluant. The chromatography yielded 0.9 g (95%) of the oxime 2.lc as colorless crystals, mp 185 - 187 OC from ethanol.

lH-NMR (DMSO-d6, 250 MHz): 6 = 6.4 (s, 1 H, CH), 6.8 - 7.3 (m, 14 H, ArH), 11.5 (s, 1 H, OH). IR (KBr): v = 3300.

2.

123

Nitrogen-containing Chrornophores

2.ld

N-Benzoyloxy-4-p-chlorophenyl-2~-diphenyl-1-azabuta1,3-diene

..

Ph

Ph

Ar = p-CIC,H,

335.8

439.9

To a stirred solution of the oxime 2.lc (0.45 g, 1.35 mmol) in 2 mL of pyridine at 0 "C 0.15 mL (1.35 mmol) of benzoyl chloride were added dropwise. The mixture was kept at 0 "C for 30 min, and then at room temperature for 1 h. The crude was dissolved in ether, washed with 3 x 25 mL portions of 10% aqueous HC1 and then with water. The ethereal layer was dried with MgS04. After rotary evaporation of the solvent, the crude product was purified by flash chromatography (silica gel 60 230-400 mesh) using hexane/ethyl acetate (8:2) as eluant. The chromatography yielded 0.5 g (84%) of 2.ld as colorless crystals, mp 169 - 170 "C from MeOWH20.

IH-NMR (CDC13, 250 MHz): 6 = 6.9 - 7.8 (m, 19 H, ArH). 13C-NMR (CDC13, 250 MHz): 6 = 128.5 - 138.2 (ArC and C=C), 163.6 (C=N), 168.6 (C=O). IR (KBr): v = 1740. W (CH2C12): A = 31 1 (E = 19000), 238 (E = 38000).

2.1e

7-Chloro-2,3-diphenylquinoline

Ph PhCOONvh

Ar Ar = p-CIC6H,

439.9

hu CH2CI,

-

CI

31 5.8

A solution of 2.ld (300 mg, 0.69 mmol) in 400 mL of anhydrous methylene chloride was purged with deoxygenated nitrogen for 1 h and then irradiated under a positive pressure of nitrogen for 40 min. The irradiation was carried out in an immersion well apparatus with a Pyrex filter and a 400 W medium-pressure Hg arc-lamp. After rotary evaporation of the solvent, the crude product was flash chromatographed (silica gel 60 230-400 mesh) using hexane/ethyl acetate (94:6) as eluant. The chromatography yielded 151 mg (70%) of 2.le,

124

2. Nitrogen-containing Chrornophores

as colorless crystals, mp 146 - 148 "C from ethanol; 52 mg (36%) of azadiene 2.ld and 23 mg (27%)of benzoic acid.

lH-NMR (CDC13,250 MHz): 6 = 7.2 - 7.9 (m, 12 H, ArH), 8.2 - 8.3 (m, 2 H, ArH). 13C-NMR (CDC13, 250 MHz): 6 = 125.6 - 129.8, 134.8, 135.4, 137.1, 137.6, 139.7, 140.1, 147.7, 159.5. IR (KBr): v = 1610, 1585, 1575, 1550, 1490,1480, 1470, 1440, 1410,810,700,650.

[I] [2]

D. Armesto, M. G. Gallego, W. M. Horspool, J. Chem. SOC.,Perkin Trans 1 1989, 1623 - 1626. J. L. Soto, C. Seoane, N. Martin, L. A. Blanco, Heterocycles 1983, 20, 803 - 812.

2.

125

Nitrogen-containing Chromophores

2.2

2,2-Dimethyl-3,3-diphenylcyclopropanecarbaldehyde O-benzoyloxime[ll submitted by

2.2a

D. Armesto, W. M. Horspool, M. J. Mancheiio, M. J. Ortiz and A. Ramos

2,2-Dimethyl-4,4-diphenylbut-3-enal Oxime NH,OH

HCI

PYr*idine

250.3

-

Ph4 Ph N. OH

265.4

2,2-Dimethy1-4,4-diphenylb~t-3-enal[~] (4g, 0.016 mmol), hydroxylamine hydrochloride (1.67g, 24 mmol) and 2 mL of pyridine were heated at reflux in 100 mL of ethanol for 2 h. After cooling the mixture to room temperature, the solvent was removed under vacuum and the crude product dissolved in ether, washed with 3 x 100 mL portions of

10% aqueous HCl and then with water. The organic layer was dried over MgSO4 The desiccant was filtered off and the solvent was removed under reduced pressure. The crude product obtained was purified by flash chromatography (silica gel 60 230-400mesh) using hexane/diethyl ether (1:l) as eluant. The chromatography yielded 3.8 g (90%) of the oxime 2.2a as colorless crystals, mp 169 - 170 O C from hexane.

IH-NMR (CDCl3, 300 MHz): 6 = 1.2 (s, 6 H, 2 CH3), 5.9 (s, 1 H, vinyl H), 6.9 (s, 1 H, CH=N), 7.0- 7.3 (m, 10 H,ArH), 8.5 (s, 1 H,OH). 13C-NMR (CDCl,, 300 MHz): 6 = 27.2 (2 CH3), 39.0 (Cq), 127.0 - 142.9 (Arc and C=C), 156.8 (C=N). IR (KBr): v = 3320,1620.

126

2.2b

2.

Nitrogen-containingChromophores

2,2-Dimethyl-4,4-diphenylbut-3-enalO-benzoyloxime PhCOCl

pyridine

265.4

369.5

To a solution of 0.47 g (1.8 mmol) of the oxime 2.2a in 3 mL of pyridine at 0 'C, 0.15 mL (1.35 mmol) of benzoyl chloride were added dropwise. The mixture was stirred at room temperature for two hours and then poured into 10% aqueous sulfuric acid and extracted with diethyl ether. The organic layer was washed with saturated solution of sodium bicarbonate, and then with water. The organic layer was dried over magnesium sulfate. The desiccant was filtered off and the solvent was removed under reduced pressure. The crude material obtained was purified by flash chromatography (silica gel 60 230-400 mesh) using hexane/diethyl ether (9:l) as eluant. The chromatography yielded 1.3 g (93%) of 2.2b as colorless crystals, mp 40 - 42 "C from hexane.

'H-NMR (CDc13, 300 MHz): 6 = 1.4 (s, 6 H, 2 CH3), 6.0 (s, 1 H, vinyl H), 7.1 - 7.9 (m, 16 H, ArH and CH=N). 13C-NMR (CDC13, 300 MHz): 6 = 27.0 (2 CH3), 39.9 (Cq), 126.8 - 142.1 (ArC and C=C), 164.2 (C=N), 171.4 ( G O ) .

IR (KBr): v = 1750,1270,1100,1080.

w (CH2C12): &ax

2.2~

= 245 (E = 21000).

2,2-Dimethyl-3,3-diphenylcyclopropanecarbaldehyde0benzoyloxime hv /CH,CI, acetophenone

369.5

- Phx Ph-

11

N. 369.5 'OCOPh

A solution of 2.2b (3 10 mg, 0.84 mmol) and acetophenone (1.8 g ) in 400 mL of anhydrous CH2C12 was purged for 1 h with deoxygenated nitrogen and irradiated under a positive pressure of nitrogen for 20 min. The irradiation was carried out in an immersion well aparatus with a Pyrex filter and a 400 W medium-pressure Hg arc-lamp. After rotary evaporation of the solvent the crude was flash chromatographed (silica gel 60 230-400 mesh)

2.

Nitrogen-containing Chromophores

127

using hexanelethyl acetate as eluant. The chromatography yielded 10 mg (0.3%) of 2.2b and 280 mg (90%)of 2 . 2 ~as colorless crystals, mp 110 - 114 "C from hexane. 'H-NMR (CDC13, 300 MHz): 6 = 1.I (s, 3 H, CH$ 1.3 (s, 3 H, CH3), 2.6 (d, 1 H, J = 9, cyclopropyl-H), 7.1 - 8.1 (m, 16 H, ArH and CH=N). 13C-NMR (CDCl3, 300 MHz): 6 = 20.6 (CH3), 25.3 (CH3). 29.8 (cyclopropyl C-2), 33.3 (cyclopropyl C-l), 48.3 (cyclopropyl C-3), 126.3 - 133.1 (Arc and C=C), 143.4 (CH=N), 160.4 (C=O). IR (KBr): v = 1745, 1620, 1440, 1330, 1165.

[l]

[2]

D. Armesto, W. M. Horspool, M. J. Manchefio, M. J. Ortiz, J. Chem. SOC.,Perkin Trans. I 1992,2325 - 2329. H. E. Zimmerman, A. C. Pratt, J. Am. Chern. Soc. 1970,92,6259 - 6267.

128

2.3

2.

Nitrogen-containing Chromophores

3,4,4-Trimethyl-5-diphenylmethyl-l-tosyl-4,5-dihydropyrazoler* 1 submitted by D. Armesto, W. M. Horspool, M. J. Mancheiio, M. J. Ortiz and A. Ramos

2.3a

3,3-Dimethyl-5,5-diphenylpent-4-en-2-one Tosylhydrazone

264.4

186.2

432.6

To a solution of 0.3 g (1.1 mmol) of 3,3-dimethyl-5,5-diphenylpent-4-en-2-one[*I in 60 mL of toluene, 0.23 g (1.2mmol) of tosylhydrazine and 20 mg of ZnC12 were added and the mixture was refluxed for 12 h. The catalyst was removed by filtration and the

solvent by rotary evaporation. The crude product was purified by flash chromatography (silica gel 60 230-400 mesh) using hexane/ethyi acetate (8:2)as eluant. The chromatography yielded 0.37 g (78%) of 2.3a as colorless crystals, mp 176 - 177 “C from ethanol.

‘H-NMR (CDC13, 300 MHz): 6 = 1.2( s , 6 H, 2 CH3), 1.3 ( s , 3 H, CH3C=N), 2.4 ( s , 3 H, ArCH3), 5.9 (s, 1 H, vinyl H), 6.8- 7.8 (m,15 H,ArH and NH). 13C-NMR (CDC13, 300 MHz): 6 = 13.7 (CH$=N), 21.5 (ArCH3), 27.8 (2 CH3), 45.1 (Cq), 127.0- 143.7(ArC and C=C), 161.8 (C=N). IR (KBr): v = 3090,1690,1440,1330,1165. UV (CHZC12): h, = 230 (E = 24000).

2.

129

Nitrogen-containingChromophores

2.3b

3,4,4-Trimethyl-5-diphenylmethyl-l-tosyl-4,5-dihydropyrazole hv /CH,CI, acetophenone

432.6

Ph

I

Ts

432.6

A solution of 2.3a (300 mg, 0.69 mmol) and acetophenone (3 g) in 400 mL of anhydrous CH2C12 were purged for 1 h with deoxygenated nitrogen and irradiated under a positive pressure of nitrogen for 50 min. The irradiation was carried out in an immersion well apparatus and a 400 W medium-pressure Hg arc-lamp. After rotary evaporation of the solvent, and elimination of the acetophenone under vacuum, flash chromatography of the crude product on silica gel (60 230-400 mesh) using hexanelethyl acetate (8:2) as eluant yielded 50 mg (17%) of 2.3a and 225 mg (75%) of 2.3b as colorless crystals, mp 122 123 "C from ethanol.

'H-NMR (CDC13, 300 MHz): 6 = 0.8 (s, 3 H, CH3), 1.0 (s, 3 H, CH3), 1.9 (s, 3 H, CH3C=N), 2.3 (s, 3 H, ArcH3), 3.9 (d, 1 H, J = 10, CHPh2), 5.0 (d, J = 10, CH-N), 7.1 - 7.3 (m, 14 H, ArH). 13C-NMR (CDC13,300 MHz): 6 = 12.2 (CH3), 20.0 (CH3), 21.4 (CH& 26.8 (CH3), 52.7 (Cq), 53.5 (CHPh2), 68.5 (CH), 126.1 - 143.5 (Arc). IR (KBr): v = 1620,1600, 1500,1455,1330,1170.

[ll [21

D. Armesto, W. M. Horspool, M. J. Mancheiio, M. J. Ortiz, J. Chem. Soc., Chem. Commun. 1993,721 - 722. A. Pratt, J. Chem. SOC.Perkin Trans. I 1973,2496 - 2499.

130

2.4

2.

241,2-Diphenylethenyl)benzothiazole submitted by

2.4a

Nitrogen-containing Chrornophores

G. Kaupp

trans-2,3-Dihydro-4-methylthio-2,3-diphenyl-1,5-benzothiazepine and 2,2a-dihydro-2a-methylthio-1,2-diphenyllH-azeto[2,1-b]benzothiazole[l]

181.3

180.3 361.5

Ph

A solution of 1.0 g (5.5 mmol) of trans-stilbene and 9.4 g (51.8 mmol) of freshly distilled (at 5 x Tom) 2-(methy1thio)-benzothiazole in 150 mL of benzene was flushed with nitrogen and irradiated for 1 d with a high-pressure mercury lamp (Hanau TQ 718, 500 W)through a Solidex filter at room temperature. After filtration and rota-evaporation of the solvent, most of the excess reagent was removed by short-path distillation at 80 "C under vacuum prior to preparative layer chromatography on 200 g silica gel with cyclohexane. 380 mg of stilbene dimers, phenanthrene and residual excess reagent are separated from the mixture of (cyc1o)addition products, which are separated by an additional preparative layer chromatography on 200 g of silica gel with benzendcyclohexane (1: 1) to give 165 mg (8%) of the faster running azetane, mp 157 - 158 OC (ethanol) and 425 mg (21%) of the thiazepine, mp 174 - 175 "C (ethanol).

'H-NMR (CDCl3, 250 MHz): Thiazepine deriv.: 6 = 2.41 (s, 3 H, SCH3), 4.59 (BA, J = 12, 1 H),5.24 (AB, J = 12, 1 H), 7.01 - 7.18 (11 H, Ar-H); azetane deriv.: 6 = 2.43 (3 H, SCH3), 4.39 (BA, J = 8, 1 H),4.97 (AB, J = 8, 1 H), 6.86- 6.90 (1 H), 6.90 - 6.97 (1 Ar-H), 6.98 - 7.05 (1 Ar-H), 7.17 - 7.23 (2 Ar-H), 7.29 - 7.45 (7 Ar-H), 7.59 - 7.65 (2 Ar-H).

2.

131

Nitrogen-containing Chromophores

13C-NMR (CDC13,20 MHz): Thiazepine deriv.: 6 = 14.1 (q, J = 141, SCH3), 56.4 (d, J = 134, C-2), 62.2 (d, J = 136, C-3), 121.9, 124.4, 124.6 (s), 126.4 (2 C), 127.4, 127.8, 128.3 (2 C), 128.7 (2 C), 129.9 (2 C), 130.2, 135.3, 135.8 (s), 142.7 (s), 152.2 (C-5a), 174.6 (C-4); azetane deriv.: 13.2 (9, J = 139, SCH3), 55.7 (d, J = 137, C-2), 71.1 (d, J = 142, C-l), 119.1, 121.6 (C-2a), 121.6, 125.3, 126.0, 126.9 (2 C), 127.5 (2 C), 127.6, 128.2, 128.6 (2 C), 128.9 (2 C), 137.1 (s), 138.0 (s), 140.3 (s), 149.3 (C-7a). UV (CH3CN): Thiazepine deriv.: Amax = 255 (lg E = 4.04), 260 (sh, 4.02), 270 (3.99), 275 (3.98), 300 (3.78), absorption onset ca. 360 nm; azetane deriv.: A,, = 252 (sh, lg E = 3.65), 263 (sh, 3.57), 268 (sh, 3.49), 278 (sh, 3.42), 290 (sh, 3.37).

2.4b

a'ph

( E )-2-(1,2-Diphenyletheny1) benzothiazole121 H

/

/

SCH,

361.5

2OOOC

-

Ph

313.4

500 mg (1.39 mmol) of the benzothiazepine from 2.4a were sealed in a thick-walled Pyrex tube of 50 - 100 mL volume under vacuum and heated at 200 "C after covering it with a safety iron tube (alternatively a lab autoclave may be used) for 20 h. After cooling with liquid nitrogen the tube was opened and the CH3SH and CH3-S-S-CH3 condensed to a cooled vessel (77 K) under vacuum (at the end with heating up to 40 "C) to give 65 mg (97%) of solid residue. This was layer-chromatographed in the dark on 200 g SiO2 with benzene under a fume hood to give 340 mg (78%) of the stilbene derivative, mp 108 "C (methanol) besides 96 mg (22%) of its dihydro-derivative. Alternatively the hydrogenated product may be oxidized with 250 mg of DDQ in 50 mL benzene (8 h reflux, then addition of 5 mL ethanol) prior to the chromatography, in order to increase the yield to nearly quantitative. 'H-NMR (CDC13, 80 MHz): 6 = 7.01 - 7.22 (5 H), 7.29 - 7.52 (7 H), 7.71 - 7.84 (1 H), 7.96 (s,l H), 7.98 - 8.11 (1 H). 13C-NMR (CDC13,20 MHz): 6 = 121.4 (dd, J = 162,8), 123.1 (dd, J = 162, 8), 124.8 (dd, J = 161, 8), 126.3 (dd, J = 161, 8), 128.2 (d, J = 163, 2 C), 128.3 (d, J = 162), 128.7 (d, J = 156), 129.2 (d, J = 156, 2 C), 130.2 (d, J = 158, 3 C), 130.4 (d, J = 174), 132.9 (d, J = 153), 135.4(s), 135.9, 138.1, 140.7, 154.1, 171.8. MS (70 eV): d z = 313(64, M+), 312 (100); appearance potential 19.5 eV. UV (CH30H): A, = 258 (sh, lg E = 3.96), 336 (4.54).

132

2.

2.4~

Nitrogen-containing Chromophores

(Z)-2-(1,2-Diphenylethenyl)benzothiazole[21

313.4

313.4

200 mg (0.64 mmol) of the (@-isomer from 2.4b in 50 mL of methylene chloride were irradiated under nitrogen with a Hg high-pressure lamp (Hanau Q-81) through a bandpass filter glass (Wertheimer UVW-55,330 < h < 410 nm) for 1 h. lH-NMR-analysis indicated 180 mg (90%) (2)-besides 20 mg (10%) @)-isomer. The (2)-isomer was obtained pure by recrystallization from methanol, mp 98 - 100 "C.Irradiation at 253.7, 302, or 313 nm leads to photostationary EIZ-mixtures (isosbestic point at 302 nm). Heating of the (2)-isomer to 150 "C for 20 h (vacuum) leads to the (E)-isomer quantitatively.

lH-NMR (CDCl3, 80 MHz): 6 = 7.16 - 7.20 (5 H), 7.30 (s, 1 H), 7.27 - 7.67 (7 H), 7.70 7.90 (1 H), 7.95 - 8.16 ( 1H). 13C-NMR (CDC13, 20 MHz): 6 = 121.6, 123.7, 125.4, 126.0, 127.4 (2 C), 128.1, 128.3 (3 C), 128.5 (2 C), 129.6 (2 C), 133.9. W (80% CH30H): Lax = 273.5, 288 (sh), 296 (sh), 308 (sh), 327 (sh); (CH2C12): 272, 292,306 (sh), 320 (sh), 325 (sh).

2.4d

threo- and erythro-2-[2-(Methylthio)-l,2-diphenylethyl]benzothiazole[31 Ph a I & P h H

SCH, 361.5

15OoC

AcOH

-

CH,S

Ph

361.5

200 mg of the (,!?)-isomer from 2.4b and 2.0 mL acetic acid (100%) were sealed under vacuum in a Pyrex tube and heated at 150 OC for 10 h. The solvent was removed by rotaevaporation and the solid residue layer-chromatographed on 50 g Si02 with benzene. One obtained 97 mg (56%) of the mixture of the diastereomeric pair of enantiomers ((RS)I(SR):(RRI(SS) = 3.3:l.O) in addition to 16 mg (9%) 2-benzylbenzothiazole . Heating of the diastereomers to 200 "C gave methylthiole and the stilbene derivative.

2.

Nitrogen-containing Chromophores

133

'H-NMR (CDCl3, 80 MHz): 6 = 1.70 (s, 0.77 x 3 H, SCHQ),1.84 (s, 0.23 x 3 H, SCH3), 4.8 - 4.9 (2 H), 7.00 - 7.75 (14 H). MS (70 eV): m/z = 361 (M+), 313,312.

[l] [2] [3]

G. Kaupp, H. W. Grueter, Chem. Ber. 1981,ZZ4,2844 - 2858. G. Kaupp, Chem. Ber. 1984,117,1643 - 1646. G. Kaupp, Chem. Ber. 1985,118,4271 - 4275.

134

2.5

2.

Diethyl-2,3-dihydro-3,3-dimethyl-5-(N-methyl-Npheny1amino)-1,2,4-triazole-1,2-dicarboxylate[l] submitted by

2.5a

Nitrogen-containing Chromophores

H. Heimgartner

28-Dimethyl-N-phenylpropanamide

106.6

107.2

177.2

To a solution of 7.0 g (66 mmol) of N-methylaniline in 150 mL of dry CHzC12, containing 2.5 equiv. of dry pyridine (150 mmol), a solution of 6.4 g (60 mmol) of 2-methylpropanoyl chloride in 30 mL of dry CH2C12 was dropped slowly over a period of 2.5 h at 0 "C. After completion of the addition, the reaction mixture was stirred for another 5 - 6 h raising the temperature to room temperature. Then 50 mL of ice/H20 and concentrated HCl were added until pH 1 - 2 was reached. The organic layer was separated and the aqueous layer extracted with 25 mL of CH2C12. The combined organic layers were dried over MgS04, the solvent rota-evaporated and the residue recrystallized from ether: 9.35 g (88%) colorless prisms.

-

lH-NMR (CDC13, 300 MHz): 6 = 1.02 (d, 6 H , J = 7, 2 CH3), 2.4- 2.6 (m, IH, (CH3)2CEI), 3.25 (s, 3 H, CH3N), 7.15 - 7.45 (m, 5 H, ArH). 13C-NMR (CDC13, 50.4 MHz): 6 = 19.5 (q, (CH3)2CH), 30.8 (q, CH3N), 37.2 (d, (CH&CH), 127.0, 127.4, 129.5 (3 d, 5 arom. CH), 144.1 (s, 1 arom. C), 175.0 (s, CO). IR (CHC13): v = 1610, 1600, 1500, 1470, 1425, 1390, 1270,1120,1040,700.

2.

135

Nitrogen-containing Chromophores

1.) LDA, THF

3.)NaN,, DMF

177.3

-

N

174.3

To a solution of 10.0 g (56.4 mmol) of 2.5a in 250 mL of dry THF at 0 "C under Argon atmosphere, 1.1 equiv. (42 mL) of LDA (1.5 M in cyclohexane, H u h ) was added. The solution was stirred at 0 "C for 60 - 75 min, then 15.5 g (57.7 mmol) of diphenyl phosphor0 chloridate was added via a syringe at 0 "C. After 20 - 30 min the ice bath was removed and the mixture was stirred for 20 - 24 h. The precipitated solid was filtered off under Ar, the THF solution was dropped into 5 - 25 mL of a dry DMF suspension containing 11.0 g (169.2 mmol) of NaN3, and the mixture was then stirred for 3 - 4 d at room temperature. After this time, ether was added, the mixture filtered through a celite pad, and the solvent rota-evaporated. The resulting residue was dissolved in ether, washed twice with NaHC03 5%, and the aqueous layer extracted with ether. The combined organic layers were dried over MgS04. Removal of the solvent under reduced pressure, and distillation through a vigreux column at 110 "C/2 x Torr yielded 9.24 g (94%) 2.5b as a colorless oil.

'H-NMR (CDC13, 300 MHz): 6 = 1.23 (s, 6 H, 2 CH3), 3.22 (s, 3 H, CH,N), 6.85 - 6.90 (m, 2 arom. H), 7.15 - 7.25 (m, 3 arom. H). 13C-NMR (CDC13, 50.4 MHz): 6 = 25.5 (9, (CH3)2CH), 34.4 (broad q. CH3N), 42.5 (s, C-2), 115.8, 122.8, 129.3 (3d, 5 arom. CH), 142.3 (s, 1 arom. C), 167.1 (s, C-3). IR (CHC13): v = 1750, 1600, 1500, 1435,1370, 1330, 1285, 1235, 1125,950,690.

2 . 5 ~ Diethyl-2,3-dihydro-3,3-dimethyl-5-(~-methyl-~-phenylamino)-1,2,4-triazole-1,2-dicarboxylate[1]

A2y-J N

EtOOC,

\

174.2

+

EtOOC-N=N- COOEt

174.1

hu

DME

COOEt N-N' %NAN'

tJ

348.5

136

2.

Nitrogen-containingChromophores

A solution of 222 mg (1.28 mmol) 2.5b and 242 mg (1.39 mmol) diethyl azodicarboxylate in 80 mL dimethoxyethane was irradiated with a Hg low-pressure lamp (A = 257 nm, TNN 15/32, Quarzlampenges. m. b. H., Hanau; Quartz apparatus with magnetic stirring, H. Mangels, Bomheim-Roisdorj) under an Argon atmosphere for 2.5 h at ca. 20 "C. After rota-evaporation of the solvent the crude product was purified by thick layer chromatography (Alox, hexane/ethyl acetate 4: 1). The main fraction (298 mg) proved to be a mixture of 77% 2 . 5 ~and an unknown compound (IH-NMR). A second thick layer chromatography (silica gel, hexane/ethylacetate 4: 1 and then etherlmethanol 98:2) yielded after distillation at 75 - 85 "C/O.Ol Ton (Kugelrohr) 182 mg (41%) 2 . 5 ~as a colorless oil.

'H-NMR (CDC13, 60 MHz): 6 = 1.08, 1.35 (2 t, 6 H, J = 7.0, 2 OCH2CH3). 1.70 (s, 6 H, C(CH3)2), 3.50 (s, 3 H, CH3N), 4.03,4.26 (2 q, 4 H, J = 7.0, 2 OCH4CH3), 6.95 - 7.50 (m, 5 arom. H) IR (CHCI3): v = 1740,1722,1640, 1599,1499.

[ 11

[2]

K. Dietliker, H. Heimgartner, Helv. Chim. Acfa 1983,66,262 - 295. J. M. Villalgordo, H. Heimgartner, unpublished; cf. J. M. Villalgordo, H. Heimgartner, Helv.Chim. Actu 1992, 75, 1866 - 1871

2.

137

Nitrogen-containing Chromophores

2.6

2,5-Dihydro-5-methoxy-2,2-dimethyl-4-(N-methyl-Npheny1amino)-5-trifluoromethyl-l,3-oxazole~ 11 submitted by

2.6a

H. Heimgartner

2,iV-Dimethyl-N-phenylpropanamide I

106.6

107.2

177.2

To a solution of 7.0 g (66 mmol) of N-methylaniline in 150 mL of dry CH2C12, containing 2.5 equiv. of dry pyridine (150 mmol), a solution of 6.4 g (60 mmol) of 2-methylpropanoyl chloride in 30 mL of dry CH2C12 was dropped slowly over a period of 2.5 h at 0 "C. After completion of the addition, the reaction mixture was stirred for another 5 - 6 h raising the temperature to room temperature. Then 50 mL of kern20 and concentrated HCl were added until pH 1 - 2 was reached. The organic layer was separated and the aqueous layer extracted with 25 mL of CH2C12. The combined organic layers were dried over MgS04, the solvent rota-evaporated and the residue recrystallized from ether: 9.35 g (88%), colorless prisms.

-

k N M R (CDC13, 300 MHz): 6 = 1.02 (d, 6 H, J = 7, 2 CH3), 2.6 - 2.4 (m, 1 H, (CH&CHJ, 3.25 (s, 3 H, CH3N), 7.15 - 7.45 (m, 5 H, ArH). 13C-NMR (CDC13, 50.4 MHz): 6 = 19.5 (9, (CH&CH), 30.8 (4, CH3N), 37.2 (d, (CH3)2CH), 127.0, 127.4, 129.5 (3 d, 5 arom. CH), 144.1 (s, 1 arom. C), 175.0 (s, CO). IR (CHC13): v = 1610, 1600, 1500, 1470, 1425, 1390, 1270, 1120, 1040,700.

138

2.6b

2.

Nitrogen-containing Chromophores

2,2-Dimethyl-3-(N-methyl-N-phenylamino)-2H-a~irine~~~~l

177.3

3.)NaN,, DMF

174.3

To a solution of 10.0 g (56.4 mmol) of 2.6a in 250 mL of dry THF at 0 "C under Argon atmosphere, 1.1 equiv. (42 mL) of LDA (1.5 M in cyclohexane, Fluku) was added. The solution was stirred at 0 ° C for 60 - 75 min, then 15.5 g (57.7 mmol) of diphenyl phosphorochloridate was added via a syringe at 0 "C. After 20 - 30 min the ice bath was removed and the mixture was stirred for 20 - 24 h. The precipitated solid was filtered off under Argon, the THF solution was dropped into 5 - 25 mL of a dry DMF suspension containing 11.0 g (169.2 mmol) of NaN3, and the mixture was then stirred for 3 - 4 d at room temperature. After this time, ether was added, the mixture filtered through a celite pad, and the solvent rota-evaporated. The resulting residue was dissolved in ether, washed twice with NaHC03 (5%), and the aqueous layer extracted with ether. The combined organic layers were dried over MgS04 Removal of the solvent under reduced pressure, Torr yielded 9.24 g (94%) of and distillation through a vigreux column at 110 "C/2 x 2.6b as a colorless oil.

lH-NMR (CDC13, 300 MHz): 6 = 1.23 (s, 6 H, 2 CH3), 3.22 (s, 3 H, CH3N), 6.85 - 6.90 (m, 2 arom. H), 7.15 - 7.25 (m, 3 H, ArH). 13C-NMR (CDC13, 50.4 MHz): 6 = 25.5 (9, (CH3)2CH), 34.4 (broad q, CH3N), 42.5 (s, C-2), 115.8, 122.8, 129.3 (3 d, 5 arom. CH), 142.3 (s, 1 arom. C), 167.1 (s,C-3). IR (CHC13): v = 1750,1600,1500,1435,1370,1330,1285,1235,1125,950,690.

2.

139

Nitrogen-containing Chromophores

$yN? CF3

N 174.2

+

CF3

0

4

OCH3

128.1

hv

DME

-

N

302.3

A solution of 212 mg (1.22 mmol) of 2.6b and 1.92 g (15 mmol) of methyl trifluoroacetate in 80 mL of dimethoxyethane was irradiated with a mercury low-pressure lamp (h = 257 nm, TNN 15/32, Quarzlampenges. m.b.H., Hanau; Quartz apparatus with magnetic stirring, H. Mangels, BornheindRoisdoM under an Argon atmosphere for 1.75 h at 20 "C. After rota-evaporation of the solvent and excess of the ester, the crude product was purified by thick layer chromatography (silica gel, ethedmethanol 98:2) and distillation at 60 - 65 "C/ 0.001 Torr (Kugelrohr) yielding 213 mg (60%) of 2.6~.

lH-NMR (CDC13, 100 MHz): 6 = 1.50, 1.54 (2 s, twice 3 H, (CH&C), 3.32, 3.35 (2 s, twice 3 H, CH3N, CH30), 7.05 - 7.45 (m, 5 H, ArH). 13C-NMR (CDC13, 25.2 MHz): 6 = 28.5 (4,(CH3)2C), 39.7 (99. J(C,F) = 2, CH3N), 50.9 (q, CH30), 105.0 (q, J(C,F) = 67, C - 3 , 105.1 (s, C-2), 121.1 (q, J(C,F) = 287, CF,), 126.0, 126.4, 128.8 (3 d, 5 arom. CH), 144.8 (s, 1 mom. C), 153.5 (s, (2-4). IR (CCl4): v = 1636,1600,1500,1383,1368,1196,1186,1124, 1086.

[ll [21

K. Dietliker, H. Heimgartner, Helv. Chim. Acta 1983,66,262 - 295. J. M. Villalgordo, H. Heimgartner, unpublished; c j J. M. Villalgordo, H. Heimgartner, Helv. Chirn. Acta 1992,75, 1866 - 1871.

2.

140

2.7

3a-Methyl-2-phenyl-2,3,3a,4-tetrahydrochromeno[4,3c]pyrazole[11 submitted by

2.7a

Nitrogen-containing Chromophores

H. Heimgartner

2-(2-Methylallyloxy)benzaldehyde[2] H,O/DMF, NaOH

40-50°C

CHO 122.1

CHO

90.6

176.2

To a solution of 36.6 g (0.3 mol) of salicylic aldehyde and 13.2 g (0.33 mol) of NaOH in 30 mL of water and 270 mL of DMF at 40 - 50°C were added 27.2 g (0.3 mol) of 2-methylallyl chloride. After 4 h stirring the mixture was cooled to 20 "C, 300 mL of water was added, and the mixture was extracted 3 times with 100 mL pentane. The organic layer was washed twice with 50 mL of 10% NaOH, 2 N H2SO4 and water and dried over MgS04. After rota-evaporation the residue was distilled at 71 - 72 "C/ 0.01 Torr yielding 35.9 g (68%) 2.7a as a colorless oil. h N M R (CDC13, 60 MHz): 6 = 1.7 - 1.8 (m, 3 H, CH3), 4.53 (br. s, 2 H, CH2), 4.9 - 5.2 (2 m, 2 H, =CH2), 6.8 - 7.2 (m, 2 H, ArH), 7.2 - 7.9 (m, 2 H, ArH), 10.55 (s, 1 H, CHO). IR (thin film): v = 2870,2770, 1693, 1602, 1587, 1488, 1460, 1243, 1012,908, 760. MS (70 eV): m/z = 176 (6, M+), 161 (16), 121 (34), 120 (79), 92 (16), 77(10), 66 (12), 55 (loo).

2.7b

2-(2-Methylallyloxy)benzaldehyde tosylhydrazone[1~3] H,NNHTs CHO 176.2

EtOH, 80°C 186.2

CHzN-NHTs 344.4

2.

141

Nitrogen-containing Chromophores

A solution of 8.8g (50 mmol) of 2.7a in 50 mL of ethanol was mixed with 9.3g (50 mmol) of 4-methylphenylsulfonylhydrazide. After 30 min at 25 "C, the precipitated solid product was filtered, washed with ethanol/water 1:1 and petroleum ether, and dried at 0.01Torr yielding 14.9g (86%) of 2.7b, colorless needles, mp 93 - 94OC.

IH-NMR (CDC13, 100MHz): 6 = 1.7- 1.8(m, 3 H, CH3), 2.31 (s, 3 H, CH3), 4.34(br. s, 2 H, CHz), 4.85- 5.1 (2m, 2 H,=CHz), 6.7- 7.0(m, 2 H, ArH), 7.1- 7.35(m, 3 H, ArH), 7.7- 7.95(m,3 H, ArH), 8.26(s, 1 H, CH=N), 8.63(br. s, 1 H, NH). IR (KBr): v = 3150,1654,1598,1485,1453,1359,1321,1220,1165,1155, 1035,890,

759. MS (70eV): m/z = 344 (3,M+),314 (6), 189 (ll), 174 (12), 159 (loo), 158 (22), 145 (54), 131 (32),105 (25),91 (90),77 (35),55 (57)

-

0 N ; C I -

CH=N- NHTs 344.4

pyridine

292.3

A solution of 960mg (10.3mmol) of aniline in 16 mL of ethanol/water 1:l at 0 - 5 "C was treated with 2.6mL of conc. HC1 and 715 mg (10.4mmol) of NaN02 dissolved in 2 mL of water. This solution was added slowly to a solution of 3.55g (10.3mmol) of 2.7b in 60 mL of pyridine at -10 "C. After 30 min 300 mL. of water were added. Extraction with 3 x 50 mL of CHC13, washing with 3 x 100 mL of 2 N H2S04, 2 x 100 mL of water, drying over Na2S04, rota-evaporation of the solvent, and recrystallization of the residue from ethanol yielded 1.95g (65%) 2.7~as colorless crystals, mp 99- 100 "C.

lH-NMR (CDC13, 100 MHz): 6 = 1.89(br. s, 3 H, CH3), 4.56(br. s, 2 H, CH,), 4.955.05, 5.30- 5.40(2 m, each 1 H, =CH2), 6.95- 7.20 (m, 2 H, ArH),7.30- 7.65(rn, 4 H, ArH), 8.05-8.30 (m, 3 H, ArH). IR (KBr): v = 1660,1607,1587,1522,1498,1486,1450,1430,1282,1260,1208,1110, 1013,986,901,748. MS (70eV): m/z = 292 (1, M+), 264 (92),263 (58),249 (lo), 144 (1 I), 91 (loo), 77 (30). UV (ethanol): ha= 291 sh (E = 11750), 280 sh (12790), 275 (12960). 246.5 (14570); &in = 264 (12220).

142

2.7d

2.

Nitrogen-containing Chromophores

3a-Methyl-2-phenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole"]

qN)o O

N=N

292.3

A

hu

benzene

0

N-N

292.3

A solution of 236.8 mg (0.8 mmol) of 2.7~in 80 mL of benzene (c = 0.01 M) was irradiated with a mercury high-pressure lamp (TQ-150, Quarzlampenges. m.b.H. Hanau, Pyrex-filter, 1 > 300 nm) under an Argon atmosphere for 2 h at 20 "C. After rotaevaporation of the solvent the crude product was recrystallized from petroleum ethedether. Sublimation at 140 - 150 "C/O.Ol Torr yielded 192 mg (90%) of 2.7d, colorless crystals, mp 159 - 161 "C.

'H-NMR (CDC13, 100 MHz): 6 = 1.42 (s, 3 H, CH3), 3.38, 3.80 (AB, 2 H, J = 10, CH2), 4.14, 4.36 (AB, 2 H, J = 10.5, CH2), 6.85 - 7.40 (m, 8 H, ArH), 7.75 - 7.95 (m, 1 H, ArH). IR (KBr): v = 1599, 1572, 1500, 1480, 1372, 1304, 1210, 1098, 1060, 1020, 800, 763, 758,748,740. MS (70 eV): m/z = 264 (100, M+), 263 (65), 249 (8), 130 (lo), 104 (13), 91 (17), 77 (48). UV (ethanol): kax = 358 sh (E = 17310), 301 (4850), 254 (13640), 242 sh (11410); = 308 (4720), 278.5 (3150).

b,,

[l]

[2] [3]

H. Meier, H. Heimgartner, Helv. Chim. Actu 1985,68, 1283 - 1300. R. Vollrath, W. Boell, G. Scheurer, H. Adolfi, BASF, Deutsche Offenlegungsschrift 210 89 32,31.8. 1972; C.A. 1972,77, P 151 886j. S. Ito, Y. Tanaka, A. Kakehi, K. Kondo, Bull. Chem. SOC. Jpn. 1976,49, 1920 1923.

2.

143

Nitrogen-containing Chromophores

2.8

Photocrosslinked Poly(4-ethenyl-S-methyl-1,2,3thiadiazole)[51 submirted by

2.8a

H. Meier, N. Hanold

3-Pentanone-p-toluenesulfonylhydrazone"]

H3C-CH,- C-CH2 -CH, I1 0 86.1

TsNHNH, 'C

H,C-CH2-C-C II

i2 -CH,

N. 'NHTS 186.2

254.4

To a stirred solution of 18.6 g (0.1 mol) of p-toluenesulfonic acid hydrazide in 50 mL of boiling ethanol was added 8.6 g (0.1 mol) of 3-pentanone. After 1 h half of the solvent was removed and the solution kept at 5 "Covernight. The precipitate formed was washed with cold methanol and recrystallized from ethanol yielding 21.7 g (80%) of 2.8a, mp 104 106 "C.

'€I-NMR (CDC13, 200 MHz): 6 = 0.95 (t. 6 H, CH3), 2.13 (q, 2 H, CH2), 2.16 (9, 2 H, CH2), 2.38 (s, 3 H, CH3), 7.54 (AA'BB', 4 H, Aryl-H). IR (KBr): v = 3175,2940,1330,1160,920,810.

2.8b

4-Ethyl-5-methyl-l,2,3-thiadiazole[2]

254.4

128.2

A small portion of 2.8a of was added while stirring vigorously at room temp. to 40 mL of freshly distilled thionyl chloride. Evolution of HCl indicated the beginning of the reaction. The flask was cooled in an ice bath and the reaction mixture treated with further portions of 2.8a within 1 h. After the addition of 21.7 g (do mmol) of 2.8a (all at once), the ice bath was removed and the mixture stirred for 2 h at room temp. The excess amount of SW12

144

2. Nitrogen-containingChromophores

was carefully evaporated under reduced pressure and the residue purified by column chromatography (4 x 80 cm silica gel, toluene). The first fraction contained p-toluenesulfonic acid chloride; the second fraction afforded the raw product, which was distilled in vucuo, bp 34 - 36 "U0.4 Torr, yield 8.1 g (79%).

'H-NMR (CDC13, 200 MHz): 6 = 1.36 (t, 3 H, CH3), 2.58 (s, 3 H, CH3CH2), 2.95 (q, 2 H, CH2). 13C-NMR (CDC13, 50 MHz): 6 = 8.2 (CH3CH2), 12.8 (CH3), 19.1 (CH2), 144.5 (C-5), 161.1 (C-4). IR (thin film): v = 2950,2910,2860, 1520, 1450, 1380, 1240,900, 815.

(Wohl-Ziegler Bromination)

1:;

H3C

N

H3C

128.2

NBS 178.0

5

H3C 207.1

A mixture of 8.1 g (63 mmol) of 2.8b dissolved in 70 mL of dry tetrachloromethane and 11.2 g (63 mmol) of NBS was heated under reflux. Small portions of dibenzoyl peroxide were added from time to time. As soon as the whole NBS was transformed to succinimide, which rose to the surface of the liquid phase, the heating was stopped, the succinimide filtered off and the solvent removed by rota-evaporation. Purification by column chromatography (120 x 5 cm silica gel, benzene/petroleum ether (60 - 90 "C) 4: 1) afforded 10.7 g (82%) of the pale yellow, oily compound.

'H-NMR (CDC13,200 MHz): 6 = 2.24 (d, 3 H, CH3), 2.54 (s, 3 H, C€&CH), 5.37 (q, 1 H, CH). 13C-NMR (CDC13, 50 MHz): 6 = 9.4 (CH$H), 25.0 (CHQ),38.0 (CH), 148.3 (C-5), 160.1 (C-4). IR (thin film): v = 3020,2960,1450, 1385,1260, 1200,1084,972,900,808. ~~

2.

145

Nitrogen-containingChromophores

2.8d

4-Ethenyl-5-methyl-l,2,3-thiadiazole[3~4~ Br

207.1

152.2

126.2

To a stirred solution of 10.7 g (52mmol) of 2 . 8 ~and 1 - 5 mg hydroquinone in 80 mL of dry THF 30.4g (200mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was added dropwise in a nitrogen atmosphere. The solution turned deep red at room temperature. After 5 h heating under reflux 80 mL of water and 80 mL of ether were added. The organic layer was extracted three times with 30 mL of ether, the combined extracts were dried over Na2S04 and the solvent was evaporated. Filtration through 50 g of silica gel with toluene afforded the raw product which was purified by distillation in the presence of 2 mg of hydroquinone, bp 33 - 36 "Cf0.4Tom, yield 4.6 g (70%).

lH-NMR (CDCl3, 400 MHz): 6 = 2.60 (s, 3H,CH3),5.65 (1 H), 6.34 (1 H),6.84 (ABC, 1 H,3Jtrans = 17.5,3Jcis = 10.7,2J = 1.8,olefinic H). 13C-NMR (CDC13,100 MHz): 6 = 9.4 (CH3),119.6 (CHZ), 124.6 (CH), 145.9 (C-3, 157.3 (C-4). IR (thin film): v = 2940,1630,1495,1270,985,925,905,810.

2.8e

Poly(4-ethenyl-5-methyl-l,2,3-thiadiazole)~~l

126.2

40000 - 340000

A solution of 4.6g (36mmol) of pure 2.8d and 30 mg of dibenzoyl peroxide in 60 mL of dry toluene was heated for 24 h to 80 "C in a reaction vessel which was carefully liberated from water and oxygen (pump and freeze technique). After 8 and 16 h further portions of 30 mg of dibenzoyl peroxide were added in a nitrogen atmosphere. The solution was concentrated to 30mL and poured slowly while stirring into 600mL of cold ether (-30"C). The precipitate was washed with ether and dried in vucuo at room temperature. The yield of the isolated polymer amounted to 2.76 g (60%).Above 165 "C the colorless material began to darken and to decompose. (Average molecular masses between 40000

146

2.

Nitrogen-containing Chromaphores

and 34oooO dalton could be determined by viscosimetry using polystyrene standards. The upper range of the molecular mass was only achieved when traces of dibenzoyl peroxide were used in a completely water- and oxygen-free medium).

IR (KBr): v = 3435,2920, 1625, 1505, 1440, 1380, 1240.

2.8f

0

0

Photocrosslinked Poly(4-ethenyl-5-methyl-l,2,3-thiadiazole)[51

,c%

0 / /

CH

CH

8

S-N

hv

N-S

- N2

'

'+CH3 CH

CH, 0 4

.

'CH,

A) Photocrosslinking in solution[5]: 1.0 g of 2.8e was dissolved in 50 mL of dry dichloromethane and irradiated with a Hanovia 450-watt mercury vapor lamp equipped with a Vycor filter (h 2 225 nm). The extrusion of nitrogen could be determined volumetrically. Soon after the beginning of the irradiation the crosslinked polymer precipitates. (If the irradiation was extended till complete denitrogenation was achieved, the formation of a polymer film on the walls of the photoreactor occured. This could be done by avoiding the contact between the solution and the wall through which the light falls in). The solid material was filtered off, washed with dichloromethane and ether and dried in vacuo at room temperature. The yield of the totally insoluble, colorless polymer amounts to 0.62 - 0.70 g (80 - 90%).

B) Photocrosslinkingin a thin polymer layer[6]: A silicon wafer was cleaned with ethanol and coated with a thin layer (about 0.5 p n ) of 2.8e (3% solution in THF) by the application of a spin-coater. Irradiation through a mask (or any other device which provides irradiated and unirradiated zones) with W light, X-rays or electron beams generated a pattern which was developed by a short immersion into THF. The unchanged polymer was dissolved and the irradiated parts with the crosslinked polymer remained. (Principally, this imaging technique with a negative resist

2.

147

Nifrogen-containing Chromophores

shows an extremely high resolution; a more sophisticated arrangement allowed a lithography with a resolution of 10 - 4 mm.)

U L T R f i DUEN N E

POLY M E R S C H I C H T E N

I

I

I I

QL H

Figure 3: Scanning electron microscopy of the legend ‘Ultraduenne Polymerschichten’ written by an electron beam on the prepared resist. Scale: 0.1 mm in the upper part, 10 pm in the lower part. The thickness of a letter amounts to 4 pm.

IR (KBr): v = 2420,2920, 1700, 1440, 1370.

[l] [2] [3] [4] [5] [6]

J. F. W. Keana, D. P. Dolata, J. Ollerenshaw, J. Org. Chem. 1973,38,3815 - 3816. 0. Zimmer, T. Echter, U. Merkle, H. Meier, Liebigs Ann. Chem. 1982, 683 - 698. N. Hanold, H. Kalbitz, M. Pieper, 0. Zimmer, H. Meier, Liebigs Ann. Chem. 1986, 1344 - 1352. M. Pieper, W. Teichert, H. Meier, Liebigs Ann. Chem. 1986, 1334 - 1343. M. Pieper, H. Meier, Liebigs Ann. Chem. 1986, 1353 - 1359. Hoechst AG (H. Meier, N. Hanold, W. PraS, R. Zertani, J. Lingnau, Inv.), Ger. Offen. DE 3835039 (1990) and Eur. Pat. Appl. EP 363817 (1990).

148

2.

Nitrogen-containing Chromophores

7-Hydroxy-6H-benzo[b]naphtho[ 1,2d]pyran[l]

2.9

submitted by

2.9a

A. Padwa, U. Chiacchio and J. M. Kassir

re

Methyl 2-(3-phenoxy-l-propynyl)benzoate

aCo2ye H-CH,OPh

Br

NEt,

PdCI,( Ph,P),

\\

266.3

215.0

CH,OPh

To a degassed solution containing 1.O g (4.6mmol) of methyl o-bromobenzoate[2] and 0.78g (6.0 mmol) of 3-pheno~y-l-propyne[~] in 40 mL of anhydrous triethylamine was added 25 mg of trans-bis(triphenylphosphine)palladium(II) chloride and 50 mg of cuprous iodide. The reaction mixture was stirred at 25 "C for 12 h. The resulting slurry was filtered through a pad of Celite. Removal of the solvent under reduced pressure followed by silica gel chromatography using a hexandethyl acetate mixture (4:l) as the eluant afforded 870 mg (70%)of methyl 2-(3-phenoxy-l-propynyl)benzoateas a clear oil.

lH-NMR (CDC13, 80 MHz): 6 = 3.80 (s, 3 H),4.86 (s, 2 H),6.92 - 8.05 (m, 9 H). IR (neat): v = 1720,1590,1430,1250,1070,820,750. Anal. calcd. for Cl7HI4O3:C 76.67,H 5.30;found: C 76.63,H 5.33.

2.9b

o-(3-Phenoxy-l-propynyl)-a-diazoacetophenone

re

1.) Me,SiOK

266.3

\\

2.) CIC0,Me

CH20Ph

3.)CH2N2

*

KHN \\

276.3

CH,OPh

To a stirred solution containing 650 mg (5.0 mmol) of potassium trimethylsilanolate in 100 mL of anhydrous ether was added, in one portion, 800 mg (3.0mmol) of methyl 2-(3-phenoxy-1 -propynyl)benzoate2.9a. The reaction mixture was heated at reflux for 2 h under a nitrogen atmosphere. After being cooled to 0 "C, 450 mg (5.0mmol) of methyl chloroformate was added and the resulting mixture was stirred for 2 h at 25 "C. The mixture was filtered through a pad of Celite. The filtrate was concentrated to about 20 mL and

2.

149

Nitrogen-containingChromophores

to this solution was added a 30mmol excess of an etheral diazomethane solution[4] at 0 "C. The resulting mixture was allowed to stir at 25 "C for 16 h and the excess diazomethane and ether were removed under reduced pressure. The residue was chromatographed on silica gel using a hexane/ethyl acetate mixture (411) as the eluant to give 623 mg (75%) of 0-(3-phenoxy-1-propynyl)-a-diazoacetophenone2.9b as a clear oil.

lH-NMR (CDC13, 80 MHz): 6 = 4.98 (s, 2 H), 5.93 (s, 1 H), 6.87 - 7.69 (m, 9 H).

LR (neat): v = 1600, 1500, 1440, 1350,1200, 1010,750. UV (ethanol): h,, = 292 (sh, E = 19.800), 306 (22.500), 328 (sh, 17.000), 333 (sh, 11.900).

H

1

248.3 A solution containing 100 mg (3.5 mmol) of o-(3-phenoxy-1-propyny1)-a-diazoacetophenone 2.9b in 300 mL of methylene chloride was irradiated under an Argon atmosphere with a 450 W Hanovia lamp equipped with an Uranium filter sleeve for 20 min. Removal of the solvent under reduced pressure left a dark red oil which was subjected to silica gel chromatography using a 5% ethyl acetate/cyclohexane mixture as the eluant. The major product isolated from the column contained 63 mg (70%) of 7-hydroxy-6H-benzo[b]as a white solid, mp 148 - 149 "C. naphtho[ 1,ZdJpyran 2 . 9 ~

lH-NMR (CDCI,, 80 MHz): 6 = 5.22 (s, 2 H), 5.70 (bs, 1 H), 6.99 - 8.55 (m, 9 H). 13C-NMR (CDC13, 63 MHz): 6 = 64.4, 109.5, 117.6, 121.7, 124.0, 124.3, 124.8, 125.3, 126.1, 127.1, 128.1, 128.9, 134.9, 148.5, 156.5. IR (KBr): v = 1620,1600,1430,1340,1240,1100,990,820,730.

150

2.

Nitrogen-containingChromophores

UV (ethanol): Amax

= 232 ( E = 1655),242 (sh, E = 1480),310 (sh, 470),320 (500),350 (sh, 283). MS: m/z = 248 (M+, base), 247,236,231,219,189,167,149,137,123,111, 97,95,84,

69. Anal. calc. for C17H1202: C 82.24,H 4.87;found: C 82.21,H 4.84.

A solution containing 60mg (0.27mmol) of 7-hydroxy-6H-benzo[b]naphtho[1,2-d]pyran 2 . 9 ~and 40mg (0.33mmol) of phenylisocyanate in 25 mL of anhydrous benzene was heated at reflux for 6 h. At the end of this time, the solvent was removed under reduced pressure and the residue was chromatographed on a silica gel column using a 10% ethyl acetatekyclohexane mixture as the eluant. The major fraction contained 68 mg (70%) of the expected urethane as a white solid, mp 155 - 156 "C. The structure of the urethane derivative was unambigously established by an X-ray crystallographic structure determinatiodl].

lH-NMR (CDC13, 80MHz): 6 = 5.12 (s, 2 H),6.83- 8.79(m, 15 H). IR (KBr): v = 1710,1590,1420,1230,1120,1080,790.

MS: m/z = 249,248,247,231,219, 181,119,101,91. Anal. calc. for C24H17N03: C 78.46,H 4.66,N 3.81;found: C 78.43,H 4.67,N 3.80.

[l]

A. Padwa, D. J. Austin, U. Chiacchio, J. M. Kassir, Tetrahedron Lett. 1991,5923 -

[2] [3] [4] [5] [6] [7]

A. R.Katritzky, R. A. Jones, J. Chem. SOC.1959,3670- 3674. I. Iwai, J. Ide, Chem. Pharm. Bull. 1963,II.1042. Th. J. de Boer, H. J. Backer, Org. Syn., Coll. Vol. 4,1963,943 - 946. R.L. Danheiser, S. K. Gee, J. Org. Chem. 1984,49,1672- 1674. L. S. Liebeskind, S. Iyer, C. F. Jewelljr., J. Org. Chem. 1986,51, 3065 - 3067. S. T. Perri, H. W. Moore, J. Am. Chem. SOC.1990,112,1897 - 1905.

5926.

2.

151

Nitrogen-containing Chromophores

2.10

Spirocyclopropanes submitted by

2.10a

A.A. Abdel-Wahab and H. Diirr

l-Phenylspiro[cyclopropane-2,9'-thioxanthene]S,Sdioxide[ 11

hv

+ 256.3

104.2

A solution of 1 .OOg (3.9mmol) of 9-dia~othioxanthene-S,S-dioxide[~] was irradiated using a Hanovia lamp (450W) in 20 mL of styrene, placed in a 25 ml-size Vycor glass tube with a side arm,until the photolysis was complete and the red color of the solution turned yellow. The excess styrene was distilled at 0.01 Tom and the residue was separated by column chromatography (silica gel) with petrolether (bp 60 - 80 "C)/ ether (1:4).After evaporation of solvent and recrystallization from ether 1.05g (82%), mp 171 "C were obtained.

'H-NMR (CDC13, 90 MHz): 6 = 2.21- 2.46 (m, 3 H,CH2, CH);6.46- 8.15 (m, 13 H, Ar-H). 13C-NMR (CDC13, 90 MHz): 6 = 12.2(t, CH2), 32.2(s, Cq), 39.0(d, CH), 123.8- 141.8 (m, Ar-C). MS:m/z = 332 (M+). IR (KBr): v = 3085,3065,1588,1302,1290,1160. Anal. calc. for C21H16S02: C 75.90,H 4.80;found: C 76.40,H 4.90.

152

2. Nitrogen-containing Chromophores

2.10b 1-(p-Methylphenyl)spiro[cyclopropane-2,9’-thioxanthene]S,S-dioxide[1]

Photolysis of 1.OO g (3.90mmol) of 9-dia~othioxanthene-S,S-dioxide[~] in 20 mL of p-methylstyrene, contained in 25 mL-size Vycor glass, using a Hanovia lamp (450W), was continued until disappearance of the starting diazo-red color. After vacuum distillation of the unreacted styrene, column chromatographic separation of the residue (silica gel, methylene chlorideln-pentane (1 :2)), solvent removal and recrystallization from ether afforded 1.10 g (81%) of 2.10b, mp 190 “C.

‘H-NMR (CDC13, 90 MHz): 6 = 2.06 (s, 3 H, CH3), 2.18 - 2.39 (m, 3 H, CH2, CH), 6.39 - 8.09 (m, 12 H, Ar-H). MS:m/z = 346 (M+). IR (KBr): v = 3085,3060,2905,1580,1300,1285,1160. Anal. calc. for C22H18S02: C 76.30,H 5.20; found: C 76.16,H 5.34.

+ 256.3

d

hu

118.2

A magnetically stirred degassed solution of 1.00 g (3.9 mmol) of 9-diazothioxanthene-S,Sdioxidef2I in 20 mL of E-0-methylstyrene placed in Vycor glass tube (20mL-size) was irradiated using a Hanovia lamp (450W) until disappearance of the starting diazothioxanthene. Evaporation of unreacted styrene and chromatographic separation of the residue

2.

153

Nitrogen-containing Chromophores

(silica gel column, petroleum ether (60 - 80 "C) eluant) after removal of solvent and recrystallization from ether afforded 0.95 g (70%) of 2.10c, mp 236 "C.

lH-NMR (CDC13, 90 MHz): 6 = 1.10 (d, 3 H,CH3),1.97 - 2.41 (m, H, CPH), 3.26 (d, 1 H, CH), 6.42 - 8.16 (m, 13 H, Ar-H). IR (KBr): v = 3082,3062,2920,1575,1290,1280, 1157. Anal. calc. for C22H18S02: C 76.30, H 5.20; found: C 75.98, H 5.25.

2.10d

4,5-Diazafluoren-9-one

180.2

182.2

To a refluxing solution of 9.00 g (0.05mol) of 1,lO-phenanthrolene and 5.00 g (9 mmol) of potassium hydroxide in 750 mL of water, a solution of 25.30 g (0.16 mol) of potassium permanganate in 400 mL of water was added with stirring during one hour. The reaction mixture was refluxed for additional 30 min. The boiling reaction mixture was filtered, cooled and then extrated with chloroform. The extract was dried and the solvent evaporated. A yellow precipitate was formed and recrystallized from water. The product was 4,5-diazofluorene-9-one,3.30 g (36%), mp 212 "C.

IR (KBr): v = 3040 (C-H aromatic), 1720 (C=O), 1650 - 1600 (C=N, C=C).

2.10e

4,5-Diazafluoren-9-hydrazone

A mixture of 5.00 g (2.75 x mol) of 2.10d, 1.5 mL (2.5 x mol) of glacial acetic acid, 50 mL of methanol and 7.8 mL (2.2 x 10-1 mol) of hydrazine hydrate (80%) was

154

2.

Nitrogen-containing Chromophores

refluxed for 30 min. The solution was evaporated under reduced pressure and the residue was filtered and washed several times with water and dried. The hydrazone was recrystallized from ethanol, (3.50 g, 65%), mp 198 - 208 "C (lit.r3] 208 - 211 "C).

IR (KBr): v = 3400,3340 and 3240 (NH2), 3060 (CH aromatic), 1660, 1570 (C=N, C=C), 1420, 1200, 800 and 750 (aromatic).

2.10f

9-Diazo-4,5-diazafluorene

A suspension of 4.00 g (0.02 mol) of 2.1Oe in 40 mL benzene and 10 g of yellow mercuric oxide were placed in a 100 mL round bottom flask capped with a calcium chloride tube. The reaction mixture was stirred in the dark for one day at room temperature and then filtered. The filtrate was evaporated under reduced pressure. Orange crystals of 2.1Of were separated (2.2 g, 57%), mp 158 - 160 "C.

lH-NMR (CDC13): 6 = 7.38 (m, 2 H, aromatic), 7.89 (d, 2 H, J = 7.84, aromatic), 8.70 (d, 2 H, J = 4.24, aromatic). IR (KBr): v = 3040 (CH aromatic), 2090 (C=N2), 1630 and 1580 (C=N, C=C>.

2.

155

Nitrogen-containing Chrornophores

2.1Og

-

4,5-Diazafluorene-9-spiro1'-[2'-@-methylphenyl)] cyclopropane[4]

hu

194.2

118.2

284.4

A solution of 0.30 g (1.5 mmol) of 9-diaz0-4,5-diazafluorene[~I2.1Of in 20 mL of p-methylstyrene, in a 25 mL Vycor glass tube with a side arm, was irradiated for four hours with stirring using Hanovia lamp (450 W). Column chromatographic separation of the residue, after vacuum distillation of the unchanged p-methylstyrene, using silica gel and ethyl acetate/methanol (1O:l) as eluant afforded after solvent removal and recrystallization from ether 0.18 g (38%) of the spirocyclopropane 2.10g, mp 160 "C (ether/CH2C12,20:1).

'H-NMR (CDC13, 400 MHz) 6 = 2.25 (dd, 1 H, 3J, = 6.36, 2Jab = 8.50, Ha), 2.27 (dd, 1 H, 3 J b = 6.36, *Jba = 8.50, Hb), 3.38 ((dd)t, 1 H, 3Jc, = J h = 6.36, HJ, 2.36 (s, 3 H, CH3), 5.5 - 8.87 (m, 10 H, Ar-H). 13C-NMR (CDC13, 400 MHz): 6 = 31.91 (C-l'), 33.96 (C-2', CH), 21.13 (C-3', CH2), 21.02 (C, CH3), 121.50 - 157.60 (16 C, Ar-C). MS:m/z = 284 (M+). IR (KBr): v = 3080,3020,2940,1610,1595,1520.

2.1Oh 4,5-Diaz~uorene-9-spiro-1'-(2'-methyl-2'-phenyl)cyclopropane[sl

hv

194.2

118.2

284.4

156

2.

Nitrogen-containing Chromophores

A solution of 0.30 g (1.5 mmol) of 9-diazo-4,5-diazafluorene 2.1Of (vide supra) in 20 mL of a-methylstyrene was irradiated with a Hanovia lamp (450 W) for six hours in a 25 mL Vycor glass tube while stirring. The reaction mixture was distilled under vacuum and the residue chromatographed on a silica gel column (ethyl acetate/methanol, 25:2). Solvent removal and recrystallization from ether yielded 0.23 g (54%)of 2.10h, mp 178 "C.

'H-NMR (CDC13, 400 MHz): 6 = 1.78 (s, 3 H, CH3) 2.15 (d, 1 H, 3J,b = 5.52, Ha), 2.47 (d, 1 H, H,,, 3Jba = 5.56), 6.1 - 8.7 (m, 11 H, Ar-H). MS: m/z = 284 (70, M'), 269 (loo), 168 (13.7). IR (KBr): v = 3060,3010,2980,1600, 1570. Anal. calc. for C1oH16N2:C 84.51, H 5.63, N 9.86; found: C 83.86, H 5.67, N 9.82.

[I] [2] [3] [4] [5]

A. A. Abdel-Wahab, S. H. Doss, H. Diirr, N. J. Turro, I. R. Gould, J. Org. Chem. 1987,52,429 - 434. M. Regitz, Chem. Ber. 1%4,97,2742 - 2754. J. Mlochowski, Z. Szulc, Pol. J. Chem. 1983, 57, 33; A. Schonberg, K. Junghans, Chem. Ber. 1962,95,2137 - 2143. 0. S. Mohamed, H. Diirr, M. T. Ismail, A. A. Abdel-Wahab, Tetrahedron Letters 1989,30,1935 - 1938. A. A. Abdel-Wahab, M. T. Ismail, 0. S. Mohamed, H. Diirr, Chem. Ber. 1994, submitted.

Experimental: Irradiation experiments were carried out with a) Hanovia 450 W Hg lamps or b) with Hanau Q 80 W Hg lamps or c) with Philips HPK 125 W Hg lamps using Pyrex filters (> 290 nm). The photolysis was carried out at room temperature after 15-20 min of flushing with nitrogen.

2.

157

Nitrogen-containing Chromophores

2.11

2-Methoxy-3,l-benzoxazepine[~l submitted by

2.1 l a

A. Albini and M. Mella

2-Hydroxyquinoline[2]

H 145.2

193.2

A solution of 90 g of Fe2S04.7H20 (0.324 mol), 150 g of Ba(OH)yH20 (0.79 mol) and 10 g of o-nitrocinnamic acid (0.052 mol) in 2 L of water in an Erlenmeyer flask was heated while stirring for 1 h. A red-brown precipitate of Fe(II1) hydroxide formed and was filtered out. A stream of carbon dioxide was passed through the solution. The precipitate of BaC03 was filtered, the solution evaporated under vacuum, the residue treated with excess conc. aq. HCl and refluxed for 10 h. On cooling and neutralizing with conc. aq. ammonia carbostyril precipitated out as almost colorless crystals, mp 193 - 195 "C (4.5 g, 58% yield).

2.11b

2-Chloroquinoline[31 PCI, POCI,

H 145.2

163.6

A mixture of 4.5 g (30 mmol) of 2.11a, 8 g of phosphorus pentachloride and 1 mL of phosphorus oxychloride was heated at 135 "C for 2 h. After cooling, the mixture was poured into 70 g of water and 70 g of ice, and neutralized with conc. aq. ammonia. Steam distillation of this mixture gave 4 g (79 %) of colorless needles, mp 35 "C.

158

2.

Nitrogen-containingChromophores

'H-NMR (CDC13, 80 MHz): 6 = 7.3 (d, 1 H, J = 8, 3-H), 7.95 (d, 1 H, J = 8, 4-H), 7.4 7.85 (m, 4 H, Aryl-H). IR (melt): v = 1585,1500,1420,1145,1095.

NaOMe

159.2

163.6

A mixture of 4 g (24 mmol) of 2.11b, 6 g of sodium methoxide and 60 mL of methanol was refluxed for 6 h. Evaporation under vacuum gave a solid which was treated with 20 mL of chloroform and 10 mL of water. The organic layer was separated, dried over sodium sulfate and evaporated under vacuum to yield 3.7 g (95%) of colorless oil.

'H-NMR (CDC13, 80 MHz): 6 = 3.1 (s, 3 H, Me), 6.9 (d, 1 H, J = 7, 3-H), 7.6-7.4 (m, 2H, 6-H, 7-H), 7.7 (d, 1 H, J = 7, 5-H), 7.9 (d, 1 H, J = 7, 8-H), 7.95 (d, 1 H, J = 7, 4-H). IR (neat): v = 1615,1600,1315,1275,1240,1015.

2.11d

2-Methoxyquinoline-l-oxide~~l

g""'" CO,H

D

0' 159.2

175.2 (anh.)

To a mixture of 5 g of 30% hydrogen peroxide and 2.9 g (18 mmol) of 2 . 1 1 ~contained in a wide-necked, round bottomed flask, 6 g of finely powdered maleic anhydride were added in portions while magnetically stirring. Mild heating caused an exothermic reaction to set in; the course of the reaction was moderated by cooling with a water bath. After 24 h the solid obtained was basified with 10% aq. NaOH and extracted with 2 x 30mL of

2. Nitrogen-containing Chromophores

159

chloroform. The organic phase was dried over sodium sulfate, evaporated under reduced pressure and treated with a little water-equilibrated diethyl ether to yield 0.7 g (dried under vacuum, 19%) of colorless crystals, mp 85 'C (showed by Karl Fisher analysis to contain 1.5 mols water per mol of N-oxide).

lH-NMR (CDC13, 80 MHz): 6 = 6.7 (d, 1 H, J = 7, 3-H), 7.15 (d, 1 H, J = 7, 5-H), 7.65 (d, 1 H, J = 7,4-H), 7.4 - 7.8 (m, 2 H, 6-H, 7-H), 8.7 (d, 1 H, J = 7, 8-H). IR (KBr): v = 1655, 1640, 1330, 1095.

2.11e

2-Methoxy-3,1-benzoxazepine~11 hv

OCH,

I

0175.2 (anh.)

175.2

A suspension of 0.25 g (1.2 mmol) of 2.11d in 300 mL of cyclohexane was placed in a cylindrical immersion well apparatus to which a distillation head and a cooler were fitted. The suspension was first boiled until ca 30 mL of solvent had passed over and then cooled while magnetically stirring and passing through a slow stream of dry nitrogen. When cooled to room temperature, the solution was irradiated by means of a 125 W mediumpressure mercury arc for 30 min. Evaporation, extraction with 15 mL of cyclohexane, filtration and evaporation gave 0.22 g (90%) of product as an oil. 'H-NMR (CDC13, 80 MHz): 6 = 3.95 (s, 3 H, OMe), 5.9 (d, 1 H, J = 6, 5-H), 6.1 (d, 1 H, J = 6,4-H), 6.9 - 7.2 (m, 4 H, Aryl-H). IR (neat): v = 1690, 1645.

[l] [2] [3] [4] [5]

A. Albini, E. Fasani, L. Maggi. Dacrema, J. Chem. Soc., Perkin Trans. 1 1980, 2738 - 2742. F. Tiemann, J. Oppermann, Ber. Dtsch. Chem. Ges. 1880, 23,2056 - 2073. P. Friedlaender, H. Ostermaier, Chem. Ber. 1882, 1.5, 332 - 338. A. Kaufmann, V. Petheou de Petherd, Chem. Ber. 1917,50,336 - 344. M. Colonna, A. Risaliti, Ann. Chim. (Rome) 1954,44, 1029.

1 60

2. Nitrogen-containing Chromophores

2.12

2-Nitrophenazine-lO-oxide[Il submitted by

2.12a

A. Albini and E. Fasani

2,4-Dinitro-N-phenylaniline[2] CI PhNH,

NO*

202.6

bN" NHPh

93.1

w

No2

259.2

A solution of 10 g (54.6 mmol) of 2,4-dinitrochloroben~ene~ and 10 mL (1 10 mmol) of aniline in 100 mL of ethanol was brought to the boil. When the initial exothermic reaction had subsided (ca. 15 min) the solution was refluxed for 1 h. On cooling 11.4 g (88%) of red needles were obtained.

lH-NMR (CDCI3, 80 MHz): 6 = 7.3 (d, 1 H, J = 10, 6-H), 7.4 - 7.7 (m, 5 H, Aryl-H), 8.2 (dd, 1 H, J = 10,2.5,5-H), 9.15 (d, J = 2.5, 1 H, H-3), 10.0 (br, 1 H, NH). IR (KBr): v = 3310, 1615,1330, 1140.

a

2,4-Dinitrochlorobenzeneis commercially available (e.g. Aldrich). Alternatively it can be

obtained by nitration of chlorobenzene and recrystallization of the raw product[3] or, conveniently for lab scale preparations, by brief heating of the commercially available 2,4-dinitrophenol with FQC13 and dieth~laniline[~].

2.

161

Nitrogen-containing Chromophores

2.12b

2',4'-Dinitro-N-phenylacetanilide[5] Ac

NHPh

'N'

Ph

Ac,O, ZnCI, c

NO2

NO*

259.2

301.3

A mixture of 5 g (19.3 mmol) of 2.12a, 2 g of fused zinc chloride and 50 mL of acetic anhydride was stirred for 5 h, and the homogeneous solution was left for 24 h. Dilution with 100 mL. of water gave 5.5 g (95%) of pale yellow needles.

lH-NMR (CDC13, 80 MHz): 6 = 2.1 (s, 3 H, Me), 7.25 (d, 1 H, J = 8, 6-H), 7.5 (s, 5 H, Aryl-H), 8.35 (dd, 1 H, J = 2.5, 8,5-H), 8.8 (d, 1 H, J = 2.5, 3-H). IR (KBr): v = 1670,1595, 1350,1300.

&..

Ac

Ph

hv

-

NO2

0-

301.3

241.2

NO2

A solution of 0.5 g (16.6 mmol) of 2.12b in 300 mL of benzeneb was irradiated for 1 h in an immersion well apparatus at room temperature by means of a 125 W high-pressure mercury arc. The solution was then filtered over 20 g of active alumina, which was further

The irradiation can equally well be carried out in acetonitrile, but in the other solvents tried a much less clean reaction results.

162

2.

Nitrogen-containing Chromophores

eluted with 600 mL of benzene"ethy1 acetate 9: 1. Evaporation of the combined solutions gave 0.38 g (95%) of orange needles.

IH-NMR (CDC13, 200 MHz): 6 = 7.75 - 8.05 (m, 2 H, 6-H, 7-H), 8.3 (dd, 1 H, J = 2, 7, 5-H), 8.5 (ABX,2 H, 6-H, 7-H), 8.7 (dd, 1 H, J = 2,7,8-H), 9.65 (d, 1 H, J = 2, 1-H). IR (KBr): v = 1570, 1405, 1355, 1330.

[l] 121 [3] [4] [5]

E. Fasani, S. Pietra, A. Albini, Heterocycles 1992,33, 573 - 584. T. L. Davis, A. A. Ashdown, J. Am. Chem. SOC.1924,46, 1051 - 1054. E. J. Hoffmann, P. A. Dame, J. Am. Chem. SOC. 1919,41, 1013 - 1020. E. T. Borrows, J. C. Clayton, B. A. Hems, A. B. Long, J. Chem. SOC. 1949, Part V, S190 - S199. F. Kehrmann, E. Baumgartner, Helv. Chim. Acta 1926,9,673 - 675.

In order to avoid carring out the chromatography with toxic benzene as the eluant, one can add 10 g of alumina to the photolyzed solution, evaporate under vacuum, add the residue (where the product is absorbed) on top of a column containing 10 g of alumina and elute with the less toxic toluene (same amounts).

2.

163

Nitrogen-containing Chromophores

2.13

Photodimers and cyclopentene photocycloadducts of

N-phenoxycarbonylindoler 1921 submitted by

2.13a

A. Weedon

N-Phenoxycarbonylindole~~~41

117.1

156.6

237.3

A solution of 4.19 g of phenylchloroformate (27 mmol) in 25 mL of dichloromethane was added over a period of an hour to an ice cooled, stirred suspension of 2 g (17.1 mmol) of indole, 2 g (50 mmol) of freshly powdered NaOH, and 0.16 g of tetra-butylammonium bromide (50 mmol) in 25 mL of dichloromethane. The mixture was stirred for a further 2 h. 50 mL of water were added and the mixture was extracted with 3 x 30 mL of dichloromethane. The combined extracts were dried with anhydrous sodium sulfate, filtered and evaporated to give pink crystals. These were recrystallized from diethyl ether to yield 3.05 g (75%) of colorless crystals, mp 94 - 95 "C.

IH-NMR (CDC13, 200 MHz): 6 = 6.69 (d, 1 H, J = 4, indole 3-position), 7.24 - 7.36 (m, 5 H), 7.40 - 7.52 (m, 2 H), 7.61 (m,1 H), 7.75 (m, 1 H), 8.24 (d, 1 H, J = 8, indole 7-position). 13C-NMR (CDC13, 50 MHz): 6 = 108.95, 115.31, 121.15, 121.50, 123.43, 124.82, 125.54, 126.42, 129.65 (all aromatic methines), 130.62, 135.38, 135.40, 150.26 (all quaternary). IR (Nujol): v = 1754, 1239.

164

2.13b

2. Nitrogen-containing Chrornophores

Photocycloaddition of N-phenoxycarbonylindole with cyclopentene[*l

237.3

68.1

305.4

1 g of N-phenoxycarbonylindole2.13a (4.2 mmol) and 20 mL of freshly distilled cyclopentene were dissolved in 220 mL of benzene which had previously been purged with nitrogen gas. The reaction mixture was stirred under dry nitrogen gas and irradiated with light from a 450 W Hanovia medium-pressure mercury lamp. The lamp was housed in a Pyrex water jacket which was immersed in the solution being irradiated. The progress of the reaction was monitored by GC; the reaction was terminated when conversion of the remaining starting material became slow. This occurred after 96 h and at 58% conversion of the indole derivative. Removal of solvent under reduced pressure gave an oil which was chromatographed on a column of 90 g of silica gel using hexaneddiethyl ether (97:3) as eluant to give 0.43 g of unconverted N-phenoxycarbonylindole and 0.45 g (58%) of a solid consisting of a mixture of the anti and syn cycloadducts in a ratio 3.2: 1. The major product was the anti adduct, which has the structure shown above. In the syn adduct the hydrogens H,and q,and the hydrogens Hb and H,are oriented cis to each other. Recrystallisation of the mixture of adducts from diethyl ether gave 0.174 g of the pure anti adduct, mp 90 92 "C.The irradiation times were shortened considerably and the yield of adducts was increased to 75% by using acetophenone (8 nVL) as a sensitizer.

lH-NMR (CDC13,200 MHz): 6 = 1.53 (m, 2 H), 1.80 - 2.16 (m, 4 H), 2.74 (dt, 1 H, Jbc = 3, Jcd = 7, Hc), 2.98 (dt, 1 H, J,d = 7, Jad = 2, Hd), 3.36 (dd, 1 H, Jab = 8, Jbc = 3, Hb), 4.40 (dd, 1 H, Jab = 8, J,d = 2, Ha), 7.02 (m, 1 H), 7.15 - 7.28 (m, 5 H), 7.39 (m, 2 H), 7.90 (m,1 H). 13C-NMR (CDCl3, 50 MHz): 6 = 25.39, 31.53, 32.55 (all aliphatic methylenes), 44.62, 46.15, 47.35, 62.60 (all aliphatic methines), 115.32, 121.62, 123.48, 124.53, 125.44, 127.811, 129.33 (all aromatic methines), 135.53, 142.99, 150.85, 151.01 (all quaternary).

2.

165

Nitrogen-containingChromophores

2 . 1 3 ~ Removal of the activating group from the photocycloadduct of N-phenoxycarbonylindole with cyclopentene[2]

305.4

185.3

58 mg of a mixture of the syn and anti cycloadducts 2.13b (0.19 mmol) were dissolved in 4 mL of aq. THF (1:l) saturated with NaOH and the solution was refluxed for 5 h. The reaction mixture was cooled and acidified with conc. HCl. The solution was briefly heated to effect decarboxylation, cooled to room temperature and neutralized by addition of saturated aqueous NaHC03. The mixture was extracted with 3 x 20 mL of diethyl ether and the combined extracts were dried (MgS04) and evaporated to yield 40 mg of a solid. Thin layer chromatography on silica gel (hexaneldiethyl ether, 7525) gave 17.5 mg (50%) of the anti adduct, mp 96 - 97 "C, and 2 mg (6%) of the syn adduct, mp 90 - 91 "C. anti adduct (Ha and Hd, and Hb and H, trans): IH-NMR (CDCl,, 200 MHz): 6 = 1.40 - 1.51 (m,2 H), 1.66 - 1.88 (m, 4 H), 2.67 (m, 2 H,H, and Hd), 3.33 (dd, 1 H, Jab = 7.7, J h = 2.5, Hb), 3.72 (dd, 1 H, Jab = 7.7, Jad =

2.5, Ha), 3.81 (br.s, 1 H, NH), 6.61 - 6.73 (m, 2 H), 6.97 - 7.08 (m, 2 H). 13C-NMR (CDCl,, 50 MHz): 6 = 25.6, 31.8, 32.6 (all aliphatic methylenes), 47.2, 47.3, 49.1, 60.8 (all aliphatic methines), 109.9, 118.8, 124.3, 127.1 (all aromatic methines), 134.1, 151.4 (quaternary).

syn adduct (Ha and Hd, and Hb and H, cis): lH-NMR (CDC13,200 MHz): 6 = 1.13 - 1.56 (m, 6 H), 3.05 (m, 2 H, H, and Q), 4.12 (t. 1 H, Jab = J h = 8.9, Hb), 4.43 (t, 1 H, Jab = Jad = 8.9, Ha), 3.73 (br.s, 1 H, m),6.52 6.66 (m, 2 H), 6.87 - 7.00 (m, 2 H). 13C-NMR (CDC13, 50 MHz): 6 = 26.6, 28.3, 28.8 (all aliphatic methylenes), 42.6, 45.2, 46.1,56.4 (all aliphatic methines), 109.1, 117.8, 126.0, 127.1 (all aromatic methines), 130.0, 154.0 (quaternary).

2.

166

2.13d

Nitrogen-containing Chromophores

Photodimerisation of N-phenoxycarbonylindole[1]

237.3

A solution of 3.01 g of N-phenoxycarbonylindole 2.13a (12.7 mmol) and 2.5 g of acetophenone (2 1 mmol) in 4 mL of benzene was purged with nitrogen and irradiated for 300 h in front of a medium-pressure mercury lamp housed in a Pyrex water jacket. GC indicated 68% conversion of the N-phenoxycarbonylindole. A white solid which had precipitated from the reaction mixture during the irradiation was filtered off and washed with diethyl ether. 10 mL of hexane were added to the combined filtrate and washings; this produced a solid precipitate which was also filtered off.and was washed with hexane. The filtrate and washings were combined and cooled overnight in the fridge. This produced a further precipitate which was also filtered off. The three solids were combined to give 1.395 g of a mixture of the two dimers containing the head-to-head and head-to-tail isomers in a 4.8: 1 ratio. This corresponds to a 68% yield of dimers based on converted N-phenoxycarbonylindole. Recrystallization from dichlorornethane gave the head-to-tail dimer as a colorless crystalline solid, mp 311 - 312 "C. The mother liquors yielded the head-to-head dirner which was recrystallized from pentane/dichloromethane to give a colorless crystalline solid, mp 245 - 246 "C.

head-to-head dirner: k N M R (CDC13, 200 MHz): 6 = 4.14 (d, 2 H, Jab = Jaw = 7, Ha and Hat), 5.29 (d, 2 H, Jab = Jaw = 7, Hb and Hw),6.87 (br.s, 2 H), 7.0 - 7.4 (m, 14 H), 8.00 (d, J = 8 , 2 H). 13C-NMR (CDC13, 50 MHz): 6 = 49.06, 66.11 (aliphatic methmes), 116.26, 121.78, 124.06, 124.99, 125.56, 128.87, 129.10 (all aromatic methines), 129.66, 132.86, 143.05, 150.48 (all quaternary). head-to-tail dirner: 1 ~ - N M R(CDC13, 200 MHZ):6 = 4.36 (m, A, A' part of AA'XX' pattern, 2 H, Jab = J , ! ~ = 8, Jab = Jab = 2.9, Hb and Hb), 4.96 (m, X, X part of AAXX' pattern, 2 H, Ha and Hal), 6.85 (br.s, 2 H), 7.0 - 7.5 (m, 14 H), 7.75 (d, 2 H, J = 8).

2.

Nitrogen-containing Chromophores

167

13C-NMR (CDC13, 50 MHz): 6 = 49.93, 64.43 (aliphatic methines), 115.49, 121.67, 124.19, 125.05, 125.27, 125.99, 129.13 (aromatic methines), 131.00, 132.73, 142.99, 150.64 (quaternary).

[l]

[2] [3] [4]

D. L. Oldroyd, N. C. Payne, J. J. Vittal, A. C. Weedon, B. Zhang, Tetrahedron Left. 1993,34,1087 - 1090. A. C. Weedon, B. Zhang, Synthesis 1992,95 - 100. V. 0. Illi, Synthesis 1979, 387 - 388. D. Boger, M. Patel, J. Org. Chern. 1987,52, 3934 - 3936.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

3

Aromatic Compounds

For a long time aromatic compounds were believed to be stable when exposed to ultraviolet irradiation. The interest in the photochemistry of arenes only started in the late 1950s when several groups observed both isomerization and addition reactions of benzene and its derivatives. Among the pioneers who were active at that time are the groups of Bryce-Smith and Schenck. Since then the photochemistry of aromatic compounds has become the subject of innumerable papers dealing with their conversion to other aromatic systems (by substitution or isomerization) or even to nonaromatics. The origin of the high reactivity of arenes in the electronically excited state results from the changes in the electron distribution and, as a consequence, ring isomerizations belong to the first processes observed. For example, benzene in its S1-state (1B2u) forms benzvalene and fulvene probably via a biradical intermediate called prefulvene. Irradiation at a shorter wavelength, 203 nm rather than 254 nm, generates the S2-state ('BlU) and results in the formation of Dewar benzene. Isomerizations of these types have often been observed for benzenoic compounds carrying alkyl, fluoro or perfluoromethylgroups. Similar reports on heteroaromatic systems have also been published and the isomerizations of pyridines, pyrylium salts as well as five-membered heterocycles like furan, pyrrol and thiophene may serve as examples. Both excited states of benzene differ in their reactivity leading either to meta-type or para-type intermediates. However, although substituents strongly influence the absorption pattern a correlation between the excited state and isomer formation is not apparent.

8

benzvalene

6

fulvene

Dewar benzene

A second type of reaction is the cycloaddition to alkenes, which can be camed out both intra- and intermolecularly. In general three types exist, i.e. the ortho, meta and para cycloaddition, of which the last one has only occasionally been observed. Beside these transformations acyclic additions to the benzenoic ring mainly leading to 1,4-cyclohexadiene adducts have been reported. Similar addition reactions can also be carried out with higher aromatic compounds and heteroarenes. All these processes generally require a certain degree of charge transfer between the partners indicating an electron transfer mechanism.

170

6 -6 s’3.

z

Y

Y

Aromatic Compounds

ring substitution

side chain substitution

In addition, there is another type of reaction which does not change the aromatic character involving either a substitution at the ring or a substitution at the side group. As in the case of acyclic addition an electron transfer mechanism operates.

mc&& 0 NR2

H

ortho

meta cycloaddition

para

acyclic addition (para)

All these transformations which have been discovered during the last three decades illustrate the high potential of the arene photochemistry for synthetic purposes. Although the mechanism of the ortho and the metu cycloaddition is still only partly understood the rationalizations which have been proposed so far are the basis of the beautiful synthetic examples from the last decade. The reader is referred to the reviews written by Albini, Cornelisse, Gilbert, Mattay and Wender. Summarizing the current view of the arene photochemistry the photoinduced charge transfer can be regarded to control the general course of reaction. In case the electronic features of the substrates allow an exergonic electron transfer, generally, acyclic additions or substitution reactions occur.

Cycloaddition

AG’o

Arene

Substitution

AG:free enthalpy of electron transfer The free enthalpy of electron transfer can easily be calculated from the electrochemically measured redox potentials of the substrates and the excitation energy of the arene using

3.

Aromatic Compounds

171

the Weller equation (for examples see Albini and Mattay). If AG is positive (endergonic electron transfer), in general, arenes add to alkenes. Surprisingly, the AG values also serve as a factor controlling the ortho/meta ratio of the cycloaddition (Mattay). The simultaneous formation of two or more o-bonds has always attracted synthetic chemists since complex molecules can be built up in one single step. Therefore it is not surprising that highly developed syntheses of natural and artificial products often made use of cycloaddition procedures. The metu photocycloaddition of aromatic compounds to alkenes certainly belongs to this category and has reached its summit of application in the admirable work of Wender's group. Hence this chapter describes photocycloadditions of various types covering mainly meta [3+2], ortho [2+2] and para [4+2] ones. Even an unusual example of an [6+6] cycloaddition is presented. The fact that only one substitution reaction is described may indicate that synthetic studies of electron transfer activation only started recently. Although the ortho cycloaddition was discovered more than three decades ago its application to organic synthesis is scarce. Two recent examples are described by A. Gilbert. By an intermolecular procedure 1,Cdimethoxybenzene is added regioselectively to acrylonitrile in excellent yield, reflecting by the way the applicability of the empirical AG-correlation (see above). The intramolecular version is elegantly utilized in a sequence of ortho cycloaddition followed by electrocyclic ring opening alternately performed in the ground and excited state leading to a single tricyclic product. Another example is presented by B. Pandey starting from the endo Diels-Alder adduct of naphthoquinone and cyclopentadiene. The intramolecular cycloaddition to the arene leads to a cage compound in very high yield. These examples show the high potential of the ortho cycloaddition in organic synthesis which may become comparable to metu cycloaddition in the near future. The high efficiency of an intramolecular course of reaction is, yet again, illustrated by the third example of the Reading group providing a very rare case of a specific mode of cyclopropane ring formation in metu cycloaddition. D. de Keukeleire also made use of this method in the synthesis of a hydroxylated tricyclic ketone via the intramolecular meta cycloadduct of 4-phenoxybut-1-ene. As usual the alkoxy substituent controls the regioselectivity leading preferentially to an adduct with the oxygen at the cyclopropane. This high directing effect of alkoxy compared to other electron donating substituents is also illustrated in the total synthesis of a-credene presented by P. Wender. Here the starting material is a methyl alkenyl anisole derivative. Despite various possibilities of the mode of addition only one primary attack of the alkenyl group to the arene ring is observed leading to a product with methoxy at the cyclopropane unit. Two isomers are formed in a 5:4 ratio simply by the fact that the formation of the cyclopropane generally is unselective (for an exception see Gilbert's example). D. Dopp provides an example of the para cycloaddition which, apparently, is observed with dienes or as a secondary process of preformed ortho cycloadducts. Here the reactions involve the triplet state of a-acetylnaphthalene finally leading to formal ketene cycloadducts in a [4+2] mode. The spectacular synthesis of pagodane by H. Prinzbach involves a [6+6] cycloaddition of two benzene rings. Such a cycloaddition obviously requires face-to-face oriented arenes as realized in the [3.3]orthocyclophane derivative. The characteristic interaction of the benzene rings is already visible in the longwavelength shifted absorption compared to the

172

3.

Aromatic Compounds

UV-spectrum of indane. Direct irradiation at 254 nm finally leads to the cage compound which can be converted to pagodane in a multistep sequence. Finally, upon electron transfer activation acceptor-substituted arenes such as dicyanobenzene and dicyanonaphthalene react with allylsilanes under replacement of one cyan0 group by the ally1 unit. These examples are only two of several ones which have been extensively investigated by K. Mizuno. A cyclization of a dimethoxy cinnamic acid to a coumarin derivative is presented by G. Pandey. Upon electron transfer sensitization of the donorsubstituted arene by means of dicyanonaphthalene oxidation occurs to form a radical cation which is intramolecularly trapped by the acid group to form the coumarin.

Recommendedfurther reading General and electron transfer reactions: A. Gilbert in Synthetic Organic Photochemistry, W. M. Horspool (Ed.), 1984, Plenum Press, New York, p. 1 - 60; J. Mattay, Tetrahedron 1985, 41, 2393 - 2404; Angew. Chem. Internat. Ed. Engl. 1987, 26, 825 845; J. Photochem. 1987,37,167 - 183; Chem. Rev. 1993,93,99 - 117. Cycloadditions: A. Gilbert and J. Mattay, see above; D. Bryce-Smith, A. Gilbert, J. Mattay, Tetrahedron 1986, 42, 601 1 - 6014 (an historical summary); P. A. Wender, L. Siggel, J. M. Nuss in Organic Photochemistry, Vol. 10, A. Padwa (Ed.), 1989, Marcel Dekker Inc., New York, p. 357 - 473; J. Cornelisse, Chem. Rev. 1993, 93, 615 - 669. Isomerization: A. Gilbert, J. Baggott in Essentials of Molecular Photochemistry 1991, Blackwell Scientific Publications, Oxford, p. 357 - 365; W. M. Horspool, D. Armesto in Organic Photochemistry 1992, Ellis Horwood, PTR Prentice Hall, New York, p. 55 - 65.

3.

173

Aromatic Compounds

1-Cyano-4-methoxybenzocyclobutene~~~

3.1

submitted by

3.la

A. Gilbert and N. Al-Jalal

1,4-Dimethoxy-8-cyanobicyclo[4.2.0]buta-2,4-diene~~~

Me0

D O M e 138.2

+

hv

fCN

C,HI*

Me0

53.1

191.2

A solution of 1.38 g (0.01 mol) of 1P-dimethoxybenzene and 5.3 g (0.1 mol) of acrylonitrile in 100 mL of cyclohexane in a fused silica tube was irradiated (six 15 W lowpressure mercury arc lamps) under nitrogen until complete consumption of the areneD1 had occured. The cyclohexane solution of 3.la was decanted from the immiscible orange oil of the acrylonitrile cyclobutane dimers and rotary evaporated. The photocycloadduct 3.la comprised 95% of the oily residue (ca. 2.0 g) and was further purified by flash chromatography (32 - 62mm silica) with petroleum ether (bp 30 - 40 "C)/diethyl ether (5:3) as eluant[3].

'€I-NMR (CDC13, 220 MHz): 6 = 1.69 (dd, 1 H, J = 14.0, 7.0), 2.47 (dd, 1 H, J = 7.0), 3.15 (s, OCH3), 3.32 (overlapped dd, 1 H, J = 7.0), 3.55 (s, OCH3), 3.50 - 3.80 (m, 1 H), 4.81 (br.d, 1 H, J = 7.0), 5.83 (d, 1 H, J = 7.0), 6.34 (dd, 1 H, J = 7.0, 2.0). IR (thin film): v = 3080, 3000, 2950, 2830, 2240, 2210, 1660, 1625, 1605, 1450, 1410, 1250,870,790.

3.lb

l-Cyano-4-methoxybencyclobutene[3~ BBr,

Me0

CH,CI, 190.2

-

Me0 159.2

174

3.

Aromatic Compounds

To a stirred solution of 1.55 g (8 mmol) of 3.la in 20 mL of dichloromethane under nitrogen at -10 "C was added 2.0 g (8 mmol) of boron tribromideL4].Stirring was continued for a further 15 min and then 10 mL of water was added. The reaction mixture was extracted three times with 25 mL of diethyl ether and the combined extracts were dried over anhydrous magnesium sulfate. Rotary evaporation gave 1.2 g (93%)of 3.lb. Recrystallisation from diethyl ether gave the purified material (mp 90 - 92 0C)[31.

'H-NMR (CDC13, 220 MHz): 6 = 3.50 (d, 2 H, J = 3), 3.85 (s, OCH3), 4.15 (t, 1 H, J = 3), 6.50 - 7.25 (m, 3 H, Ar-H). IR (KBr): vmax = 2240.

[I] [2] [3] [4]

T. Kametani, Y. Kato, T. Honda, K. Fukumoto, J. Am. Chem. S O ~1976, . 98, 8185 8 190. N. Al-Jalal, A. Gilbert, J. Chem. Research (S) 1983,266 -267. The photocycloadduct 3.la from experiments not run to completion is readily freed from residual 1,4-dimethoxybenzeneduring purification by flash chromatography. J. S.H. Kueh, M. Mellor, G. Pattenden, J. Chem. SOC.,Perkin Trans. I 1981, 1052 1057.

3.

175

Aromatic Compounds

1l-Cyano-4-oxatricycl0[7.2.O.O~~~]undeca-2,l0-diene~~~

3.2

A. Gilbert and K. B. Cosstick

submitted by

4

3.2a

4-(4'-Cyanophenoxy)-but-l-ene

+

BrCH2CH,CH=CH,

MeCOEt

CN

119.1

K2CO3

CN 135.0

173.2

To a vigorously stirred mixture of 7.9 g (66 mmol) of 4-cyanophenol and 45 g of anhydrous potassium carbonate in 100 mL of refluxing butan-Zone 8.9 g (0.66 mol) of 4-bromobut-l-ene (Aldrich) was added over 20 min. The reaction mixture was refluxed until complete consumption of the phenol was evident by TLC (silica gel plates, petroleum ether (bp 30 - 40 "C)/diethyl ether (1:4), ca. 6 h). The cooled mixture was filtered and rotary evaporated. The residue from rotary evaporation was dissolved in 50 mL of diethyl ether and this solution was washed twice with 30 mL of 2 N aqueous sodium hydroxide and then dried over anhydrous magnesium sulfate. Removal of the diethyl ether by rotary evaporation and distillation of the residue (bp 110 - 115 "C/0.1 Tom) gave 9.1 g (80%) of 3.2a as a colorless liquid. '€ NI M R (CDC13, 220 MHz): 6 = 2.5 (dd t, 2 H, J = 8.5, 2.0, 1.75), 4.0 (t, 2 H, J = 8.5), 4.9 - 5.3 (m, 2 H, J = 17.0, 12.5, 2.0, 1.75), 5.8 (qt, 1 H, J = 17.0, 12.5, 8.0),6.8 (dd, 1 H, J = 8.5,2.0), 7.5 (dd, 2 H, J = 8.5, 2.0). IR (thin film): vmaX= 2231, 1641.

176

3.

Aromatic Compounds

yj

ll-Cyano-4-oxatricyclo[7.2.O.O3~']undeca-2,lO-diene~~~

3.2b

0

CN

173.2

-

CN

/

NC

NC 173.2

A solution of 1.0 g (5.8 mmol) of 3.2a in 100 mL of cyclohexane was irradiated (six 15 W low-pressure mercury arc lamps) under nitrogen until complete consumption of the starting materiali2] had occured. The cyclohexane solution was rotary evaporated and the residue was crystallized from methanol to give 0.85 g (85%) of 3.2b (mp 78 - 79 "C).

1HNMR(CgDg,220MHz):6=0.64(m, l H , J = 1 3 . 0 , 11.5,6.0), 1.08(m, 1 H,J=20.5,

11.5, l.O), 1.50 (m, 2 H, J = 20.5, 13.0, 5.5, 2.0), 1.76 (m, 1 H, J = 11.5, 5.5,0.5), 2.56 (m,1 H, J = 6.0,4.0, 2.0, l.O), 3.20 (ddd, 1 H, J = 6.0, 4.0, l.O), 3.50 (dd, 1 H, J = 12, 5.3,3.78 (dds, 1 H, J = 9.0, 1.0, OS), 4.89 (br.dd, 1 H, J = 5.0, 2.5, 1.0), 6.00 (br d, 1 H, J = 1.1,0.5). 13C-NMR (CDC13, 22.49 MHz): 6 = 31.1, 33.7, 42.9, 44.2, 69.1, 87.7, 113.9, 121.4, 128.3, 150.8, 161.9. IR (KBr): vmax = 2220.

_-_--__-_----_---[l] [2]

S.Y. A1 Qaradawi, K. B. Cosstick, A. Gilbert,. Chem. SOC.,Perkin Trans. I 1992,

1145 - 1148. 3.2b can be readily freed from residual starting material in incomplete photoreactions by flash chromatography using 32 - 62 pm silica and petroleum ether (bp 30 40 "C)/diethyl ether (4: 1) as eluant.

3.

177

Aromatic Compounds

e m-Tetracyclo[ 10.2.1.029' '.0499]pentadeca-4,5,7,13tetraen-3,lO-dione

3.3

submitted by

EtOH, hu Et3N

66.1

0 134.1

B. Pandey

7&$

HO

200.2

To a solution of 4.0 g of 1,4-naphthoquinone in 800 mL (31.6 x M) ethanolhiethylamine (5050) in a Pyrex tube, 0.8 g of freshly cracked cyclopentadiene (15.1 x M) was added and the reaction mixture was purged with a slow stream of nitrogen for 10 min. Above solution was irradiated at 300 nm in a Rayonet photochemical reactor with constant stirring and cooling at room temperature for 6 h. Progress of the reaction was monitored by TLC and GC, until more than 95% of the dienophile is consumed. After removal of the solvent and triethylamine under reduced pressure, the residue was chromatographed over silica gel (60-120 mesh). Elution with 5% acetonehexane gave 2.44 g (43%) of 3.3, mp 160 "C.

lH-NMR (CDC13, 200 MHz): 6 = 1.5 (m, 2 H, CH2), 2.35 (m, 2 H, CH), 4.15 (m, 2 H, CH), 6.8 (m, 2 H, vinylic), 7.5 - 7.7 (m, 2 H,Ar-H), 7.9 - 8.1 (m, 2 H, Ar-H). 13C-NMR (CDCI3, 50.32 MHz): 6 = 48.44 (t), 73.02 (d), 125.82 (d), 132.53 (d), 132.91 (d), 142.25 (d), 162.66 (s), 181.23 (s). IR (nujol): v = 1650, 1590, 1320,790.

111 [2]

B. Pandey, P. V. Dalvi, A. A. Athawale, B. G. Pant, P. P. Kewale, J. Chem. SOC., Chem. Commun. 1990,1505 - 1506. B. Pandey, P. V. Dalvi,Angew. Chem. 1993,105, 1724 - 1726.

178

3.

Aromatic Compounds

3.4 submitted by

3.4a

Q

OH 94.1

Br

D. De Keukeleire

- - Q,, \

135.0

0 148.2

To DMSO (2 mL) was added powdered KOH (224 mg, 4 mmol). After stirring for 5 min phenol (94.1 mg, 2 mmol) was added, followed immediately by 4-bromobut-1-ene (270 mg, 2 mmol). Stirring was continued for 10 min at ambient temperature after which the mixture was poured into water (20 mL) and extracted with dichloromethane (3 x 20 mL). The combined organic extracts were washed with water (5 x 10 mL) and filtered through cotten wool to remove water. Rotary evaporation of the filtrate gave 4-phenoxybut-1-ene (96 mg, 65%).

lH-NMR (CDC13,360 MHz): 6 = 2.56 (m, 2 H, J = 6.5, 1.3, CH2), 4.03 (dd, 2 H, J = 6.7, CH2), 5.12 (dq, 1 H, J = 17.2, 1.6, CH=), 5.18 (dq, 1 H,J = 17.2, 1.6, CH=), 5.92 (m, 1 H, J = 10.3,6.8, CH=), 6.94 (m, 3 H, Ar-H),7.28 (dd, 2 H,J = 8.7,7.4, Ar-H). IR (thin film): v = 3074,2926, 1600, 1496, 1244.

3.4b

3-0xatetracyclo[4.4.1.02’7.O 210 ’ lundec-8-ene H

hv (254nm)

H

9

cyclohexane 148.2

5

148.2

A solution of 96 mg (65 mmol) of 3.4a (4-phenoxybut-1-ene) in 60 mL of cyclohexane is brought into a quartz tube and deoxygenated by argon bubbling. Irradiation is carried out by means of a Rayonet photochemical reactor using 254 nm radiation lamps during 4 h.

3.

179

Aromatic Compounds

The solvent is evaporated and the residue is separated by preparative HPLC (RSL, 10 mm, 25 x 1 cm, 5 mL/min) using hexane/ethyl acetate (30:l) as eluanti3I. 3-Oxatetracycl0[4.4.1.02~7.02~10]~ndec-8-ene (30 mg) is obtained as an colorless oil, while the substrate is partially recovered (32 mg). The yield of isolated material is 31% or 46% if based on consumed substrate. IH-NMR (CDC13, 500 MHz): 6 = 1.43 (ddd, J = 2.5,6.5,7.5, 1-H), 1.46 (m, J = 3.0,4.5, lla-H), 1.50 (m, J = 3.0, 4.5, 5a-H), 1.75 (ddd, J = 2.7, 6.4, 9.1, llb-H), 1.95 (m, 5b-H), 2.57 (m, 5b-H), 2.57 (m, 7-H), 2.72 (m, 6-H), 3.20 (dq, J = 2.0,7.5, 10-H), 4.08 (ddd, J = 5.0, 10.6, 15.6, 10-H), 4.08 (ddd, J = 5.0, 10.6, 15.6, 4a-H), 4.10 (ddd, J = 0.5-7.4, 10.6,4b-H), 5.63 (ddd, J = 1.3,2.3,6.0, 8-H), 5.66 (dd, J = 2.5, 6.0,9-H). 13C-NMR (CDC13, 200 MHz): 6 = 25.3 (CH), 26.6 (CHz), 32.5 (CH2), 46.8 (CH), 53.3 (CH), 58.7 (CH), 69.5 (CH2), 88.7 (C), 127.9 (CH=), 130.5 (CH=). MS (70 eV): m/z = 148 (74, M+), 120 (70), 91 (63), 94 (71), 44 (100). IR (thin film): v = 3040,2918,1650,1580,950.

0

H .lQHl

5

HCI

c

acetone 148.2

166.2

Hydrogen chloride (35%, 0.2 mL) is added to a solution of 3.4b (32 mg) in 20 mL of acetone and the solution is stirred for 1 h at room temperature. After dilution with diethyl ether, washing with aqueous disodium carbonate (10%) and drying (MgS04), the solvent is evaporated and the residue is separated by preparative HPLC (RSiL, 10 mm, 25 x 1 cm, 5 mL/min) using hexane/ethyl acetate (7:3) as eluanti3]. The isolated reaction product 3 . 4 ~ (32 mg, 89%) is exo-2-(2-hydroxyethyl)bicyclo[3.2.lloct-6-en-8-one together with the corresponding lactol(7: 1). 'H-NMR (CDC13, 500 MHz): 6 = 1.30 (dd, J = 5.1, 14.1, 3a-H), 1.59 (m, l'a-H), 1.68 (m, J = 7.1, 13.4, l'b-H), 1.71 (m, 4a-H), 1.84 (dddd, J = 2.2, 5.2, 12.8, 4b-H), 1.96 (m, 3b-H), 2.69 (k,1-H),2.71 (m, 5-H), 3.70 (m,2a-H), 3.71 (m, 2'b-H), 6.20 (dd, J = 2.9,7.0,6-H), 6.30 (dd, J 3.0,7.0,7-H). 13C NMR (CDC13, 200 MHz): 6 = 22.1 (CH2), 25.7 (CH2), 33.1 (CH2), 35.1 (CH), 49.4 (CH), 53.1 (CH), 60.8 (CH2), 129.2 (CH=), 130.9 (CH=), 217.2 ((30). MS (70 eV): m/z = 166 (10, M+), 138 ( 2 0 120 (42), 105 (45),91 (loo), 79 (85). IR (thin film): v = 3400, 3060,2936, 1757, 1450, 1060.

180

3.

Aromatic Compounds

Lactol: lH NMR (CDC13, 500 MHz): d = 1.30 (m, 1 H), 1.6 - 2.0 (m, 5 H), 2.1 (m, 1 H), 2.45 (m, 1 H), 2.52 (m, J = 3.0, 1 H), 3.85 (m, 2 H), 5.9 (dq, J = 3.0,6.1, 2 H). 13C NMR (CDC13, 200 MHz): 6 = 21.2 (CHz), 25.3 (CH& 30.1 (CHz), 35.1 (CH), 45.4 (CH), 50.1 (CH), 60.3 (CHz), 106.4 (0-C-OH), 131.5 (CH=), 132.3 (CH=).

_______________--[l]

121 [3]

D. De Keukeleire, S.-L. He, 14rh ZUPAC Symposium on Photochemistry, Leuven, 19 - 25 July 1992, Abstract, pp. 159 - 160. R. A. W. Johnstone, M. E. Rose, Tetrahedron 1979,35,2169 - 2173. Preparative HPLC can be substituted by preparative TLC or by conventional column chromatography.

3.

181

Aromatic Compounds

3.5

The Total Synthesis of (+)-a-Cedrene[ll submitted by

3.5a

P. A. Wender, J. J. Howbert and T. M. Dore

2-Chloro-5-methylanisole~*~ OMe

OH

Me2S0,, NaOH 142.6

Bu,BnN'CI' CH2CI2,H20

156.6

Sodium hydroxide (8.77 g, 219 mmol) and benzyltributylammonium chloride (4.37 g, 14.0 mmol) were dissolved in 500 mL of water. Dimethylsulphate (40.0 mL, 423 mmol) in dichloromethane (500 mL) was added. A solution of 2-chloro-5-methylphenol (20.10 g, 140.9 mmol) in 100 mL of dichloromethane was added rapidly to the reaction with stirring. The reaction was stirred vigorously at room temperature for one hour after which the layers were separated and the water layer was extracted further with dichloromethane (2 x 150 mL). The combined organic extracts were concentrated on a rotary evaporator to a yellow liquid which was taken up in water (200 mL) and the resultant mixture was extracted with ether (400 mL). The organic layer was washed with a 2 M solution of NH4OH (2 x 200mL), a 2 M solution of NaOH (200 mL), and brine (200 mL). The organic layer was dried over sodium sulphate, filtered, and concentrated on a rotary evaporator to a brown liquid which was distilled through a vigreux column to give 17.32 g (79%) of the desired anisole (bp 110 - 118 "C/35 Torr). 'H-NMR (CDCl,, 300 MHz): 6 = 2.33 (s, 3 H), 3.88 (s, 3 H), 6.70 (d, 1 H, J = 8.0), 6.74 (s, 1 H), 7.22 (d, 1 H, J = 8.7). 13C-NMR(CDC13, 75 MHz): 6 = 21.4, 56.0, 113.0, 119.2, 121.9, 129.7, 137.9, 154.6. IR (neat): v = 3055, 3005, 2962, 2863, 1597, 1584, 1491, 1464, 1405, 1286, 1258, 1176, 1067,1037,804,722,653. Anal. calc. for C8H90Cl: C 61.36, H 5.79; found: C 61.31, H 5.75. exact mass calc. for Cg%OCl: 156.0342; found: 156.0336.

182

3.

3.5b

Aromatic Compounds

6-(2'-Methoxy-4'-methylphenyl)-2-methyl-2-heptene[31

156.6

3.)Li, NH,

232.4

An oven-dried flask fitted with an oven-dned cold finger condenser and gas inlet was flushed with nitrogen. The apparatus was charged with anhydrous diethyl ether (100 mL) and lithium wire (5.5 g, 790 mmol) that had been washed with xylene and cut into small pieces. 2-Chloro-5-methylanisole(2.2mL, neat) was added rapidly to the reaction with vigorous stirring. After 10 min the remaining 2-chloro-5-methylanisole (total 11.2 mL, -75 mmol) in ether (200mL) was added to the cloudy reaction mixture and the reaction was stirred for 3.5h. 6-Methyl-5-hepten-2-one (6.33g, 50.1mmol) in ether (50 mL) was added dropwise over 30 min to the reaction and stirred for 1.3h. The flask was cooled to -78OC and ammonia (-400 mL, predried by refluxing over lithium-ammonia solution) was condensed into the reaction over a period of 3.7 h. The resulting deep blue metalammonia solution was warmed to reflux and then quenched with solid NH4Cl until the solution turned white. After evaporation of the ammonia the residue was taken up in brine (400mL) and extracted with ether (400mL). The organic layer was dried over MgS04 and the solvent was removed on a rotary evaporator to give a yellow oil. Pure 6-(2'-rnethoxy-4'-methylphenyl)-2-methyl-2-heptene (8.58 g, 74%) was obtained by distillation at bp 85 - 108 "U0.27Torr, or alternatively, by flash chromatography through silica gel with 5% toluene in hexanes.

lH-NMR (CDCl3, 300 MHz): 6 = 1.17(d, 3 H, J = 7.0), 1.42- 1.70(bm, 2 H), 1.53 (s, 3-H),1.66(s, 3 H), 1.90(m, 2 H),2.33(s, 3 H), 3.13 (p, 1 H,J = 7.1),3.80 (s, 3 H), 5.11(t, 1 H, J = 1.4),6.67(s, 1 H), 6.73(d, 1 H,J = 7.7),7.04(d, 1 H, J = 7.6). 13C-NMR (CDC13, 75 MHz): 6 = 17.6,21.1,21.4,25.7,26.3,31.4,37.2,55.3,111.5, 121.1,124.9,126.5,131.1,132.8,136.2,156.9. IFt (neat): v = 3025,2964,2923,2910, 1610,1580,1503,1456,1410,1282,1256,1041, 810. UV (cyclohexane): h = 282.0 (log E = 3.28), 275.7(3.29),218 (shoulder, 3.87), 206.4 (4.22). Anal. calc. for C I ~ H ~ C~ 82.70, O : H 10.41; found: C 82.79,H 10.57. exact mass calc. for C16H24O: 232.1827;found: 232.1827.

3.

183

Aromatic Compounds

3.5

Photoreaction

hv, pentane

c

232.4

Vycor filter

OMe

232.4

Me0

6-(2'-Methoxy-4'-methylphenyl)-2-methyl-2-heptene (1.009 g, 4.344 mmol) and deoxygenated (nitrogen was bubbled through the solvent for 30 min) pentane (100 mL) were combined in a Vycor test tube (ammonium hydroxide washed and oven-dried). Nitrogen was bubbled through the solution for 10 min and the tube sealed and maintained under nitrogen. The solution was irradiated with a 450 W medium-pressure mercury arc lamp (Hanovia) for 20 h. The solution was concentrated to a yellow oil (1.01 g). Flash chromatography (silica gel, 20% toluene in hexanes) provided the linear isomer (0.268 g, 26.5%) and the angular isomer (0.336 g, 33.3%) as pale yellow liquids. Linear Product: 'H-NMR (CDC13,300 MHz): 6 = 0.89 (d, 3 H, J = 7.5),0.89 (s, 3 H), 1.00 (s, 3 H), 1.40 1.52 (bm, 3 H), 1.57 (s, 1 H), 1.60 - 1.75 (bm, 1 H), 1.77 (s, 3 H, J = 0.8), 1.80 - 2.10 (bm, 2 H), 2.54 (s, 1 H), 3.32 (s, 3 H), 5.37 (m, 1 H). 13C-NMR (CDC13,75 MHz): 6 = 17.5, 18.9,22.6,23.1,25.0,31.6,35.5, 36.4, 50.6, 53.7, 56.9,58.2,67.3,94.7, 124.2, 140.7. IR (neat): v = 3036,2953,2868, 1473,1448,1398,1374,1326,1266,1114,1008,820. Anal. calc. for C16H24O: C 82.70, H 10.41; found: C 82.61, H 10.56. exact mass calc. for C16H24O: 232.1827; found: 232.1826. Angular Product: 'H-NMR (CDC13, 300 MHz): 6 = 1.00 ( s , 6 H), 1.03 (d, 3 H, J = 7.1), 1.32 ( s , 3 H), 1.30 1.50 (m, 1 H), 1.45 - 1.60 (m, 2 H), 1.60 (d, 1 H, J = 16.2), 1.86 (dd, 1 H, J = 11.2, 7 4 , 2.04 (m, 1 H), 2.41 (m, 1 H), 3.35 (s, 3 H), 5.54 (d, 1 H, J = 5.7), 5.57 (d, 1 H, J = 5.5). 13C-NMR (CDC13,75 MHz): 6 = 17.1, 18.5,28.3,28.9,32.4,37.6,40.6,42.5, 55.9,57.5, 68.4,72.7,94.7, 131.5, 134.3. IR (neat): v = 3046,2951,2868, 1446, 1375,1351, 1216, 1131, 1038. Anal. calc. for C16H24O: C 82.70, H 10.41; found: C 82.69, H 10.49. exact mass calc. for C16H240: 232.1827; found: 232.1827.

184

3.5d

3.

Aromatic Compounds

Cedren-11-one

b

OMe

1.) Br,, CH,CI, 2.) Bu,SnH

Me0

H@,$ \

218.3

232.4

A soldtion of photoadducts (0.181 g, 0.788 mmol) in 3 mL of dry dichloromethane was placed into an oven-dried, nitrogen purged flask. The flask was cooled to 0 "C and a solution of bromine (0.044 mL, 0.856 mmol) in dichloromethane (11.0 mL) was added with stirring over 9 min. After 3 min at 0 "C the reaction was warmed to room temperature for 15 min. The solvent was then distilled away under vacuum to give a dark green oil. The vacuum was vented with nitrogen. Tributyltin hydride (0.46 mL, 1.7 mmol) was added and the reaction was stirred for 23 h. The resulting brown oil was stirred with hexane (5 mL) and a 1 M sodium hydroxide solution (5 mL) for 5 h. The layers were separated and the aqueous layer extracted twice with dichloromethane. The hexane and dichloromethane layers were combined and concentrated to a brown oil. Flash chromatography (silica gel, 29% dichloromethane in hexanes) gave the desired cedren-11-one (0.101 g, 58.7%) as a pale yellow oil.

'H-NMR (CDCl3, 300 MHz): 6 = 0.85 (d, 3 H, J = 7.4), 0.87 (s, 3 H), 1.16 (s, 3 H), 1.32 (m, 1 H), 1.48 (m, 1 H), 1.62 (m, 2 H), 1.73 (9, 3 H, J = 1.7), 2.08 (s, 1 H), 2.21 (m, 1 H), 2.35 (m, 2 H), 2.51 (m, 1 H), 5.37 (m, 1 H). 13C-NMR (CDC13,75MHz): 6 = 14.9,24.1,24.5,25.8,33.6, 36.0,41.7,42.1,57.0, 60.0, 65.6, 120.4, 138.1, 219.2. IR (neat): v = 3021,2957,2873, 1747, 1468, 1450, 1386, 1365, 1243, 1147,797. Anal. calc. for C15H220: C 82.52, H 10.16; found C 82.46, H 10.20. exact mass calc. for C15H220:218.1671; found: 218.1671.

3.5e

(f)-a-Cedrene[4-6] 1.) KOH, H,NNH,,

diethylene glycol

2.)A 218.3

t

204.4

3.

Aromatic Compounds

185

A 25-mL flask was fitted with a Claisen head that was fitted with a thermometer and a short path distillation apparatus. The apparatus was flushed with nitrogen and the flask was charged with cedren-11-one (0.053 g, 0.243 mmol) in diethylene glycol (1.5 mL). Potassium hydroxide (0.137 g, 2.44 mrnol) and 95% hydrazine (0.101 g, 3.15 mmol) were then added and the reaction was heated to 124 - 128 "C for 15 h (temperature measured internally). The temperature was raised to 215 - 217 "Cfor 3.3 h. The reaction was cooled to room temperature and hexane (5 mL) and saturated sodium ( 5 mL) bicarbonate solution were added. The layers were separated and the organic phase was washed with 1 M hydrochloric acid (5 mL) and brine (5 mL). The aqueous phases were combined and extracted with hexane ( 5 mL). The combined organic layers were concentrated to a yellow oil which after flash filtration through silica gel with hexanes gave (f)-a-cedrene (0.029 g, 58%) as a clear and colorless oil.

'H-NMR (CDC13, 300 MHz): 6 = 0.84 (d, 3 H, J = 7.1), 0.95 (s, 3 H), 1.02 (s, 3 H), 1.38 (m, 3 H), 1.50 - 1.92 (bm, 6 H), 1.67 (q, 3 H, J = 1.7), 1.75 (d, 1 H, J = 3.9), 2.17 (at, 1 H, J = 16.7,2.4), 5.22 (m, 1 H). I3C-NMR (CDC13,75 MHz): 6 = 15.4,24.7,25.6,27.6, 36.1, 38.8,40.6,41.4,48.1, 53.8, 54.8, 58.9, 119.2, 140.6. IR (neat): v = 3019, 2942, 2899, 2870, 1467, 1451, 1374, 1362, 1156, 1034, 998, 910, 814,800. Anal. calc. for c15H24: C 88.16, H 11.84; found: C 88.09, H 12.01. exact mass calc. for C15H24: 204.1880; found: 218.1878.

[l] [2] [3] [4] [5]

[6]

P. A. Wender, J. J. Howbert, J. Am. Chem. Soc. 1981,103,688 - 690. A. McKillop, J.-C. Fiaud, R. P. Hug, Tetrahedron 1974,30, 1379 - 1382. S. S. Hall, F. J. McEnroe, J. Org. Chem. 1975, 40, 271 - 275, and references cited therein. L. F. Fieser, M. Fieser, Reagents for Organic Synthesis; J. Wiley and Sons: New York, 1967; Vol. 1, pp 435 - 438. D. H. R. Barton, D. A. J. Ives, B. R. Thomas, J. Chem. Soc. 1955,2056. Huang-Minlon, J. Am. Chem. Soc. 1946,68,2487 - 2488.

186

3.

Aromatic Compounds

reZ-(1R,4R)-l-Acetyl-l,4-dihydro-l,4-ethanonaphthalene-9-onel21

3.6

submitted by

3.6a

D. Dopp, J. Bredehorn, H.-R. Memarian, B. Miihlbacher and J. Weber

a-Morpholinoacrylonitrile"]

CI-CH,-CH(OCH&

1.) HCI / HO , 2.) MorpholineeHCI 3.) NaCN / H+ 4.) NaOH / HO ,

124.6

H,C*

CN 138.2

This preparation must be carried out in a well ventilated fume hood. To a well cooled mixture of 25 mL. of water and 12.0 mL of 37% hydrochloric acid (150 mmol) 13.1 g (149 mmol) of morpholine were added slowly with vigorous stirring. The cooled solution was set aside. In a 250 mL three-necked flask a mixture of 16.2 g (130 mmol) of chloroacetaldehyde, dimethyl acetal and 20 mL of 0.75 N hydrochloric acid was heated to gentle reflux until a homogenous solution resulted (approx. 20 min required). To this hot solution, the previously prepared morpholine hydrochloride solution was added dropwise and thereafter the mixture was cooled to 5 - 10 "C. With rigorous stirring and while maintaining a temperature below 10 "C, a solution of 7.5 g (0.15 mol) of sodium cyanide in 25 mL of water was added very slowly over a period of 90 min by means of a tapered polyethylene tube attached to the outlet of a dropping funnel and with its open end immersed well below the surface of the stirred solution. After completion of addition, stirring was continued for 1 h. Thereafter, a cooled solution of 6 g (0.15 mol) of sodium hydroxide in 15 mL, of water was added through the funnel and the mixture stirred for another 90 min. After cooling to 0°C the crystalline precipitate was collected and washed several times with ice water. Filtrate and washings were disposed of by introducing them into an excess of a freshly prepared solution of 10% (w/w) of technical grade FeS04.7 H 2 0 in water. The crystals were taken up in warm pentane, and the supernatant solution was decanted, filtered and thoroughly chilled to yield 3.45 g (19%) of mp 60 - 63 "C,lid1] 62.5 - 63.5 "C.The material must be kept dry and refrigerated.

3.

187

Aromatic Compounds

lH-NMR (CDC13,300 MHz): 6 = 2.95 - 2.98 (m, 4 H, C_H2-N-C_H2),3.71 - 3.74 (m, 4 H, CI&O-CF&), 4.61 and 4.82 (2 d, J = 2.09 each, C=CH2). 13C-NMR (CDC13, 75 MHz): 6 = 47.93 (-CH2-N-cH2-), 65.84 (-CH2-O-_CH2-),101.23 (C=CH2), 115.45 (CN), 130.03 (C-2). IR (KBr): v = 2230 (CN), 1590,1255,1120,990,820.

3.6b

re&(1R,4R,9R)-1-Acetyl-1,4-dihydr0-9-morpholino1,4ethanonaphthalene-9-carbonitrile [21

170.2

138.2

308.4

A solution of 1.702 g (10 mmol) of 1-acetonaphthone and 1.382 g (10 mmol) of 3.6a in 100 mL of dry cyclohexane was irradiated with a 150 W high-pressure mercury vapour burner through a water cooled immersion well made of Duran glass ( h 2 280 nm) under continuous purging with dry argon or nitrogen for 2 h, during which time usually 26% of starting materials were converted and 698 mg of crystals, mp 152 - 156 "C, precipitated (irradiations may be extended to 60% conversion but byproducts tend to accumulate). Crystallization from ethyl acetatehexane gave 558 mg (70% based on converted starting material) of mp 157 - 159 "C. The photolysis solution on concentration gave 2.29 g of a 1:1 mixture of starting materials as analyzed by IH-NMR.

lH-NMR (CDC13, 300 MHz): 6 = 2.21 (A) and 1.92 (B) (AB-system, 2Jm = 12.5, 10-H2), 2.53 (s, CH,); 2.56 and 2.74 (m, C&-N-CH ), 6.93 (m, C€&-O-C_H ), 6.93 (A, 2-H), 6.77 (B, 3-H), 4.45 (X, 4-H) (ABX-system,-? J m = 7.8, 4JAx = 1.1,5JBx = 6.4), 6.98 (m,1 aromatic H), 7.17 - 7.27 (m, 3 aromatic H). 13C-NMR (CDCl3, 75 MHZ): 6 = 28.87 (q, CH3), 42.30 (t, C-lo), 45.49 (d, C-4), 48.74 (t. CH2N), 59.12 (s, C-l), 66.35 (s, C-9, and t, CHZO), 118.85 (s, CN), 120.88, 125.41, 126.26, 126.61 (C-5,-6,-7,-8), 134.24 (d, C-2), 137.50 (d, C-3), 136.81 and 141.89 (two s, C-4a, C-ga), 207.41 (CO). IR (KBr): v = 2225 (CN), 1705 (CO).

188

3.

'OCH3

308.4

Aromatic Compounds

CuSO,* 5H,O Na,HPO,* 12H,O

212.2

A suspension of 0.664 g (2.7 mmol) of CuSO4.5 H20 and 190 mg of Na2HFQ4.12 H20 in 10 mL of water, 15 mL of methanol and 15 mL of acetone was stirred for 10 min at RT, after which time 540 mg (1.75 mmol) of 3.6b were added, the mixture stirred for 6 h and treated with a further 130 mg of Na2HP0412 H20. After stirring at RT for 72 h, the solution was gently concentrated to one half of its original volume in vucuo at RT and the organic material was extracted with a total of 60 mL of chloroform. The extract was dried over MgS04 and concentrated. Crystallization of the solid residue from hexane gave 261 mg (70%)of mp 84 - 85 "C.

IH-NMR (CMJ13, 80 MHz): 6 = 2.33 (broad, 1O-H2), 2.54 (s, CH3), 6.91 (A, 2-H), 6.79 (B, 3-H), and 4.51 (X, 4-H) (ABX-system, 3Jm= 7.6, 4JAx = 1.4, 3JBx = 6.3), 7.01 7.43 (m, 4 aromatic H). IR (KBr): v = 1725 and 1705 (CO).

[l]

[2] [3]

S. C. J. Temin, Org. Chem. 1957,22, 1714- 1715. D. Dopp, H.-R. Memarian, Chem. Ber. 1990,123,315 - 319. G. Buchi, P. H. Liang, H. Wuest, Tetrahedron Left 1978,2763 - 2764.

3.

189

Aromatic Compounds

3.7

.-

Undecacyclo[ll.9.0.01'6.O 2,14.O 2,20.O 3,s.O 7,12.O 9,14.O 13,17 0'59'9.0'8922]d~~~~lO-ene-4-anti,5-anti-dicarboxylic anhydride[I]

The o,o'-benzohenzo [6+6]-photocycloaddition reaction is the key step in the synthesis of [2.2.1.llpagodane 3.7,a precursor for [ l . l . l . l ] p a g ~ d a n e s [and ~ ~ ~dodecahedrane~.[~I ] submitted by

3.7a

M. Wollenweber and H. Prinzbach

(la,2p ,3a,6a,7P ,Sa,,9p ,lop)-1,8,9,10,11,11-Hexachloro27 ' .O ' ldodec-44,5-(tetrachlorobenzo)tetracyclo[6.2.1.1 36

ene"]

364.9

253.9

554.8 A solution of isodrd4] (10.0 g, 27.4 mmol)in carbon tetrachloride (100 mL)was refluxed with tetrachlorothiophene l,l-dio~ide[~] (7.4 g, 29.1 mmol) under nitrogen for 2 h during which sulfur dioxide was evolved and a microcrystalline solid deposited. Ethanol (200mL) was added and, after concentration to 50mL, the precipitate was isolated by suction filtration. Washing with cold ethanol and drying in vucuo provided 15.2 g (100%) of colorless crystals, mp 295 "C.

190

3.

Aromatic Compounds

IH-NMR (CDC13, 250 MHz): 6 = 1.97 (dt, 12a-H), 2.25 (dt, 12s-H), 3.65 (m, 2-, 7-H), 3.76 (s, 9-, 10-H), 3.91 (m, 3-, 6-H). 13C-NMR (CDC13, 20.2 MHz): 6 = 46.0 (C-3, -6), 52.5 (C-2, -7), 57.5 (C-12), 58.4 (C-9, -lo), 75.3 (C-1, -8), 100.4 (C-11), 128.2 (C-3', -4,-5', -6 ), 143.0 (C-4, -5), 132.1. IR (KBr): v = 3045,2975,2940,2880, 1370, 1345,1275, 1215,1020,915,875,745,700.

3.7b

(1a,2~,3a,6a,7(3,8a)-4,5-Benzotetra-cyclo[6.2.1.13,6.O 2,71dodeca-4,9-diene@]

c 1 4 b c , 6

Li

554.8

s-. '

12

7

3

2

8 1

11

208.3

To a hot, vigorously stirred mixture of 3.7a (30.0 g, 0.054 mol), tert-butyl alcohol (100 g, 1.35 mol), and dry tetrahydrofuran (200 mL) under a nitrogen atmosphere was added granular lithium (1 1.0 g, 1.59 mmol) in 0.5 g portions such that the reaction mixture remained at gentle reflux. The mixture was refluxed for additional 15 h, cooled to room temperature, diluted with petroleum ether (80 mL), and poured on crushed ice (ca. 200 g). The organic phase was washed with water several times and dried (MgS04). Concentration and distillation (92 - 95 "C at 0.1 mm) of the resulting yellowish oil furnished pure 3.7b (10.5 g, 93%) (intense characteristic odor). The colorless viscous oil solidified on cooling to -20 "C.

lH-NMR (CDC13, 250 MHz): 6 = 1.40 (dm, lla-H), 1.48 (dm, 11s-H), 1.93 (unresolved AB, 12a-, 12s-H), 2.52 (m, 1-, 8-H), 2.96 (m, 2-, 7-H), 3.07 (m, 3-, 6-H), 4.70 (m, 9-, 10-H), 6.98 and 6.91 (2 AA'BB', 3'-, 4'-, 5'-, 6-H). 13C-NMR (CDC13, 20.2 MHz): 6 = 44.1 (C-1, -8), 46.1 (C-3, -6), 47.8 (C-2, -7), 56.3 (Cell), 56.7 (C-12), 122.0 (C-3', -6'), 125.7 (C-4', -5'), 128.9 (C-9, -lo), 146.2 (C-4, -5).

IR (KBr): v = 3060,1930,1885,1770,765,750.

3.

191

Aromatic Compounds

3.7~

(la,2~,3a,6a,7~,8~9~,14a)-4,5-Benzo-lO,ll,l2,13-tetra2 7 914 chloropentacyclo[6.6.1.1 36 ' .O ' .O ' ]hexadecad,lO,l2triene"]

208.3

253.9

398.2

A solution of 3.7b (3.6 g, 17.3 mmol) and tetrachlorothiophene 1,l-dioxide (4.8 g, 18.9 mmol) in toluene (15 mL) was heated at reflux for 1 h under a slow stream of nitrogen. Methanol (50 mL) was added and the mixture cooled to -20 "C for 2 h. The precipitate was seperated by suction filtration, washed with cold methanol, and dried in vacuo to yield colorless crystals of 3 . 7 ~6.4 g (92%), mp 169 - 170 "C.

lH-NMR (CDC13, 250 MHz): 6 = 1.64 (dm, 15s-H), 1.81 (dm, 15a-H), 1.97 (dm, 16a-H), 2.10 (dm, 16s-H),2.40 (d, 9-, 14-H),2.70 (m, 1-, 8-H), 2.82 (m, 2-, 7-H), 3.33 (m, 3-, 6-H), 7.20 and 7.11 (2 AA'BB', 3'-, 4'-, 5'-, 6'-H). 13C-NMR (CDC13,20.2 MHz): 6 = 42.3 (C-15), 45.5,46.3,47.2, 48.4 (C-1, -2, -3, -6, -7, -8, -9, -14), 60.4 (C-16), 122.7, 132.1 (C-10, -11, -12, -13) 123.4, 126.0 (C-3', -4', -5', - 6 ) , 146.5 (C-4, -5). IR (KBr): v = 3050, 3030, 3005, 2955, 2880, 2865, 1605, 1450, 1200, 1075, 805, 770, 755,650.

3.7d

(~)-(la,2~,3a,6a,7~,8a,9a,l4a)-4,5-Benzopentacyclo2 7 914 [6.6.1.13' .O ' .O ' ]hexadeca-4,1O-diene[11

398.2

262.4

To a boiling tetrahydrofuran solution (100 mL) of 3.7~(3.0 g, 8.2 mmol) and tert-butyl alcohol (6.2 g, 83.6mmol) was added granular lithium (0.7 g, 100.9 mmol) in small portions with vigorous stirring over 1 h, and heating was continued for additional 12 h. The mixture was poured into ice water (300 mL) and extracted with petroleum ether. The

192

3.

Aromatic Compounds

organic phase was washed with water, dried (MgS04) and concentrated in vacuo. Chromatography on silica gel (ca. 20 g, petroleum ether, Rf = 0.48) gave a colorless oil which was crystallized from ethanol to yield 1.9 g (88%) of 3.7d, mp 89 - 90 "C.

IH-NMR (CDC13, 250 MHz): 6 = 0.70 (m, 14-H), 1.45 - 1.15 (overlapping m, 12-, 12'-, 13-, 13'-, 15'-H), 1.58 (dm, 15-H), 1.70 (m, 9-H), 1.99 - 1.88 (m,l-, 8-, 16'-H), 2.03 (dm, 16-H), 2.69 (m, 2-, 7-H), 3.22 (m, 3-, 6-H), 5.62 (m, 11-H), 5.25 (m, 10-H), 7.10 and 6.98 (2 m, 3'-, 4'-, 5'-, 6'-H). IR (KBr): v = 3055, 3030, 3005, 2920, 2860, 2820, 1460, 1450, 1265, 1165, 745, 695, 620.

3.7e

(1a,2~,3a,6a,7~,8a)-4,5;9,1O-Dibenzotetracyclo[6.2.1.1 3'6.O 2'7]dodeca-4,9-diene[l]and

3.7f

(la,2~,3a,6a,7~,8a,9a,14a)-4,S-BenzopentacycloC6.6.1.1 3'6.O 2'7.O ''4]hexadec-4-ene[ll

-

14

Pd/C

12

262.4

+ 2

258.4

2

12

15

264.4

An intimate mixture of 3.7d (4.0 g, 15.3 mmol) with 10% palladium on charcoal (76.0 g) was placed into a thickwalled ampoule (3 x 25 cm) which was sealed and lowered for 30 min into a preheated oil bath maintained at 250 "C. After cooling to room temperature, the ampoule was carefully opened, and the content extracted with ethyl acetate overnight by using a Soxhlet apparatus. Evaporation of the extract left a dark green oil. Chromatographical purification on silica gel (5013 cm, petroleum ether) provided pure 3.7e (2.4 - 2.9 g, 61 - 74%, colorless needles, mp 181 - 182 "C (n-hexane), R f = 0.34) and 3.7f (0.9 - 1.3 g, 22 - 32%, colorless crystals, mp 92 - 93 "C (ethanol), Rf = 0.65). The ratio of 3.7e and 3.7f varies from run to run.

3.7e: IH-NMR (CDC13, 250 MHz): 6 = 1.79 (d, lla-, 12a-H), 1.99 (d, 11s-, 12s-H), 3.15 (m, 1-, 3-, 6-, 8-H), 3.17 (2-, 7-H), 6.54 (s, 3'-, 3"-, 4'-, 4"-, 5'-, 5"-, 6'-, 6"-H). 13C-NMR (CDC13,20.2 MHz): 6 = 45.9 (C-2, -7), 46.6 (C-1, -3, -6, -8), 58.6 (C-11, -12), 123.5 (C-3', -3", -6', -6"), 125.3 (C-4'. -4", -5, -5'7, 144.4 (C-4, -5, -9, -10). IR (KBr): v = 3010,2930,2850, 1455, 1445, 1265,750,732,715. UV (isooctane): A,,,= = 227 ( E = 4270), 250 (sh, 1220), 258 (1270), 265 (1650), 284 (390).

3.

Aromatic Compounds

193

3.7t lH-NMR (CDC13, 250 MHz): 6 = 0.70 - 0.82 (m, lo-, lo'-, 11-, 11'-, 12-, 12'-, 13-, 13'-H), 1.31 (m, 9-, 14-, 15a-H), 1.77 (dm, 15s-H), 1.85 (m, 1-, 8-H), 1.92 (dm, 16a-H), 2.02 (dm, 16s-H), 2.66 (m, 2-, 7-H), 3.19 (m, 3-, 6-H), 6.99 and 7.13 (2 AA'BB', 3'-, 4'-, 5'-, 6-H). 13C-NMR (CDC13, 20.2 MHz): 6 = 19.3 (C-11, -12), 23.3 (C-10, -13), 35.8 (C-9, -14), 41.2 (C-15), 46.5 (C-1, -8), 46.6 (C-3, -6), 48.1 (C-2, -7), 60.4 (C-16), 122.9 (C-3', -67, 124.6 (C-4', -57, 148.0 (C-4, -5). IR (KBr): v = 2960,2920,2890,2860,1465,755,625.

3.7g

813 816 1720 Octacyclo[l2.5.1.02,7.O 2,13.O 718 ' .O ' .O ' .O ' Ieicosa3,5,9,1 l-tetraene"]

258.4

'

258.4

A solution of 3.7e (15.0 g, 58.1 mmol) in cyclohexane (1.1 1) was divided into six quartz tubes (3 x 50 cm) and deoxygenated with nitrogen for 15 min. After being capped, the tubes were placed in a Rayonet apparatus and irradiated with 254 nm light for 16 h. The slightly yellow solution was filtered through silica gel (10 g) to remove colored impurities and the solvent distilled off under reduced pressure at a bath temperature of 60 "C. According to the lH-NMR spectrum, the colorless crystalline residue (14.8 g, 98.7%) contained ca. 25 - 30% of the photoproduct 3.7g, the remainder being unreacted 3.7e. In order to avoid the rather laborious purification of 3.7g, the mixture was used for the following experiment. For isolation of 3.7g, 2.00 g of the photolysis mixture was chromatographed on desactivated silica gel (800 g, petroleum ether/l% triethylamine) to give recovered 3.7e (1.46 g, 73%, Rf = 0.34), after isolation of pure 3.7g (520 mg, 26%, Rf = 0.40) which was recrystallized from ethanol, mp 184 - 185 "C.

lH-NMR (CDC13, 250 MHz): 6 = 1.76 (dm, 15s-, 19s-H), 1.85 (dm, 15a-, 19a-H), 2.28 (m, 1-, 14-, 16-, 18-H), 2.59 (m, 17-, 20-H), 5.30 (AA'BB', 3-, 6-, 9-, 12-H), 5.73 (AA'BB', 4-, 5-, lo-, 11-H). 13C-NMR (CDC13, 20.2 MHz): 6 = 37.9 (C-15, -19), 54.9 (C-1, -14, -16, -It?), 55.0 ((2-17, -20), 63.1 (C-2, -7, -8, -13), 123.3 (C-3, -6, -9, -12), 126.0 (C-4, -5, -10, -1 1). IR (KBr): v = 3050,3010,2990,2950,2930,2850, 1570,1445, 1280,835,740,685,675, 490. UV (isooctane): A,, = 258 (E = 2020), 268 (2030), 286 (2130).

194

3.

3.7h

Aromatic Compounds

.-

Undecacyclo[ 11.9.0.01'6.O 2,14.O 2,20 .O 3,8.O 7,12.O 9,14 .O 13J7 .O 15,19 018'22]docos-l0-ene-4-anti,5-anti-dicarboxylicanhydride"]

+ 258.4

benzene

O

e

0

98.1

/

356.4

[1 .l .l .1 Ipagodane To a solution of a 3.7d3.7g photoequilibrium mixture (14.8 g, 2575 by IH-NMR; 14.3 mmol of 3.7g) in dry benzene (10 mL) was added freshly sublimed maleic anhydride (3.10 g, 31.6 mmol), and the mixture was stirred at 80 "C for 12 h. After evaporation of the solvent, the residue was taken up in carbon tetrachloride (100 mL) and chromatographed on silica gel (3 x 25 cm). Elution with carbon tetrachloride (750 mL) gave the starting dibenzo compound 3.7e (11.1 g, 100%) which was recycled. Continued elution with methylene chloride (400mL) yielded the adduct 3.7 and unreacted maleic anhydride which was removed by sublimation. The crude adduct 3.7 was crystallized from methanol as colorless, fine needles (3.63 g, 98%), mp 183 - 184 "C.

IH-NMR (CDC13, 250 MHz): 6 = 1.27 (dm, 16s-H), 1.41 (dm, 21s-H), 1.44 (dm, 16a-H), 1.75 (dm, 21a-H), 2.00 (m, 7-, 8-H), 2.21 (m, 1 5 , 17-H), 2.32 (m, 20-, 22-H), 2.43 (3-, 6-H), 2.73 (m, 18-, 19-H), 2.77 (m, 9-, 12-H), 2.99 (4-, 5-H), 6.06 (m, lo-, 11-H). 13C-NMR (CDC13, 20.2 MHz): 6 = 33.3, 38.4, 38.5 (C-3, -4, -5, -6, -9, -12), 40.1, 41.7 ((2-16, -21), 41.9,43.9,44.6 (C-7, -8, -15, -17, -20, -22), 55.9,60.1 (C-1, -2, -13, -14), 59.9 (C-18, -19), 129.6 (C-10, -ll), 174.0 (C=O). IR (KBr): v = 3040,2940,2925,2855, 1860, 1770, 1230,1220,1020,900.

3.

Aromatic Compounds

195

W.-D. Fessner, G. Sedelmeier, P. R. Spurr, G. Rihs, H. Prinzbach, J. Am. Chem. SOC. 1987,109,4626- 4642. For scope and limitations of the [6+6]-photocycloaddition reactions s. M. Wollenweber, D. Hunkler, M. Keller, L. Knothe, H. Prinzbach, Bull. SOC. Chim. France 1993, I30, 32 - 57; R. Thiergardt, M. Keller, M. Wollenweber, H. Prinzbach, Tetrahedron Lett., in press. J.-P. Melder, R. Pinkos, H. Fritz, J. Worth, H. Prinzbach, J. Am. Chem. SOC.1992, 114, 10213- 10231;G.Lutz, R. Pinkos, B. A. R. C. Murty, P. R. Spurr, W.-D. Fessner, J. Worth, H. Fritz, L. Knothe, H. Prinzbach, Chem. Ber. 1992,125, 1741 -

1751. A. M. Soloway, A. M. Damiana, J. W. Sims, H. Bluestone, R. E. Lidov, J. Am. Chem. SOC.1960,82,5377- 5385. M. S.Raasch, J. Org. Chem. 1980,45,856- 867. K. Mackenzie, J. Chem. SOC.1965,4646- 4653.

196

3.8

3.

Aromatic Compounds

l-Allyl-4-cyanobenzene~~l submitted by

K. Mizuno

hv

CH,CN CN 128.1

114.3

143.2

A solution of 1,4-dicyanobenzene (p-DCB) (1.0 g, 7.8 mmol) and allyltrimethylsilane (3 mL, 18.9 mmol) in 50 mL of acetonitrile was placed in a Pyrex tube and irradiated with a 300 W high-pressure mercury lamp under argon atmosphere. The photoreaction was monitored by GLC (OV-17, 5%) and the irradiation was continued until most of the p-DCB was consumed (> 95%). The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (Merck Kieselgel 60). From hexane eluant 1.02 g of l-allyl-4-cyanobenzene (91 %, colorless oil) was obtained, and from hexane/ benzene ( 1:1) eluant unreacted p-DCB (90 mg) was recovered.

'H-NMR (CDCl,, 270 MHz): 6 = 3.44 (d, 2 H, J = 6, CH2), 5.07 (dd, 1 H, J = 1.6, 22, =CH2), 5.13 (dd, 1 H, J = 1.5,3.3, =CH2), 5.93 (ddt, 1 H, J = 6.6, 10, 16.8, CH=), 7.44 (ABq, 4 H, Av = 78 and J = 7.8, ArH). 13C-NMR (CDC13,67 MHz): 6 = 40.6 (CH2), 110.5 (=C), 117.7 (C=), 119.5 (CN), 129.9, 132.7, 136.1, 146.2 (Ar). IR (neat): v = 2900,2220,1640,1600, 1500. MS (70 eV): m/z = 143 (M+), 128, 116, 103,89.

[l]

K. Mizuno, K. Nakanishi, Y. Otsuji, Chem. Lett. 1988,1833 - 1836; K. Mizuno, M. Ikeda, Y. Otsuji, Tetrahedron Lett. 1985,26,461 - 464.

3.

197

Aromatic Compounds

3.9

3,6-Dicyano-4,5-benzotricyclo[4.2.1.03~8]-4-nonene~~-~~ submitted by

K. Mizuno

CN

@

+YSiMe,

CN

178.2

114.3

hv

CHsCN/MeOH phenanthrene

NC

193.3 11

220.3

A solution of 1,4-di~yanonaphthalene[~I (500mg, 2.8 mmol), allyltrimethylsilane (4 mL, 25 mmol), and phenanthrene (500mg, 2.8 mmol) in acetonitrile/methanol (4: 1, 250 mL) was placed in a doughnut-type vessel and irradiated through a Pyrex filter with a highpressure mercury lamp under argon atmosphere. The photoreaction was monitored by GLC (SE-30,5%, 1 m). The solution was removed under reduced pressure and the residue was purified by column chromatography on silica gel (Merck Kieselgel 60). Elution with hexane gave 490 mg of phenanthrene, elution with hexanehnzene (7:3) 104 mg (19%) of l-allyl-4-cyanonaphthalene,mp 59 - 60 "C, and elution with hexanehenzene (4:6)446 mg (72%) of 3.9, mp 152 - 153 OC.

1-Allyl-4-cyanonaphthalene: lH-NMR (CDC13,270 MHz): 6 = 3.88 (d, 2 H, J = 6, CH2), 5.06 - 5.20 (m, 2 H, C=CH2), 6.00 - 6.15 (m,1 H, CH=C), 7.38 - 8.29 (m, 6 H). 13C-NMR (CDCl3, 67 MHz): 6 = 37.5, 109.0, 117.5, 118.1, 125.5, 126.0, 127.5, 128.2, 131.7, 132.5, 132.7, 135.5, 142.7. IR (neat): v = 3020,2880,2200, 1650. MS (70 eV): m/z = 193 (M+, vw), 178,165. Anal. calc.: C 86.92, H 5.73, N 7.19; found C 87.01, H 5.74, N 7.25.

3,6-Dicyano-4,5-benzotricyclo[4.2.1 .O3l8]-4-nonene: 'H-NMR (CDC13,270 MHz): 6 = 1.72 (d, 1 H, J = 11.6, CH), 2.03 (d, 1 H, J = 12.2, CH), 2.20 (d, 1 H, J = 14.0, CH), 2.35 (dd, 1 H, J = 4.3, 12.2, CH), 2.54 (ad, 1 H, J = 9.7, 1 3 . 4 ) , 2 . 9 4 - 3 . 0 3 ( m , l H , J = 8 . 5 , 9 . 6 , 15.8),3.11-3.18(m,lH,J=9.1,11.0),3.78 (dd, 1 H, J = 4.3,6.1), 7.37 - 7.76 (m, 4 H). 13C-NMR (CDC13, 67 MHz): 6 = 35.1, 37.0, 40.2, 41.4, 44.7, 45.4, 45.6, 120.9, 121.1, 125.2, 126.1, 128.1, 129.2, 133.4, 137.3. IR (neat): v = 2950,2910,2220. MS (70 eV): m/z = 220 (M+, vw), 179,178, 152. Anal. calc.: C 81.56, H 5.33, N 12.67; found: C 81.79, H 5.49, N 12.72.

198

[l]

[2] [3] [4]

3. Aromatic Compounds

K. Mizuno, K. Terasaka, M. Ikeda, Y. Otsuji, Tetrahedron Lett. 1985, 26, 5819 5822. K. Mizuno, T. Nishiyama, K. Terasaka, M. Yasuda, K. Shima, Y. Otsuji, Tetrahedron 1992,48,9673 - 9686. M. Mella, E. Fasani, A. Albini, J. Org. Chem. 1992,57,6210 - 6216. L. Heiss, E. F. Paulus, H. Rehling, Liebiegs Ann. Chem. 1980, 1583 - 1596.

3.

199

Aromatic Compounds

3.10

6,7-Dimethoxycoumarin submitted by

trans-3,4-Dimethoxycinnamicacid"]

3.10a

Me0

G. Pandey

0cy

CH,(COOH),

\

166.2

-M Pyridine

Piperidine

104.1

\

Me0

208.2

15 g (90.3 mmol) of 3,4-dimethoxybenzaldehydeand 20.4 g (196 mmol) of malonic acid were dissolved in a mixture of dry pyridine (45mL) containing 0.5 mL of piperidine and the whole mixture was refluxed on a water bath using a condenser and a CaC12 guard tube for 2 h. After cooling to room temperature the mixture was poured into 200 mL of ice-cold water containing 60mL of conc. HCl. The crude cinnamic acid was filtered off at the pump, washed three times (3 x 20 mL) with water, dried and recrystallized from an ethanovwater mixture to give 16.5 g (80%) of trans-3,4-dimethoxycinnamic acid, mp 185 "C.

lH-NMR (acetone-%, 90 MHz): 6 = 3.85 (s, 6 H, O&), 6.39 (d, 1 H,J = 18, =CH-COO), 7.03 - 7.34 (m, 3 H, arom.), 7.61 (d, 1 H, J = 18, =CHJ. IR (KBr): v = 3000 - 2400, 1680, 1620, 1590, 1510, 1450, 1400, 1330, 1250, 1140,930, 830. MS: m/z = 208.

MeO

3.10b

6,7-Dimethoxycoumarin[21

DCN/CH,CN

Me0

\

208.2

hu

Me0

206.2

A mixture containing 0.582 g (2.79 mmol) of trans-3,4-dimethoxycinnamic acid and 30 mg (0.168 mmol) of 1,4-dicyanonapthalenein 500 mL of aqueous acetonitrile (1:4) was irradiated for 4 h with Pyrex filtered light (5 > 280 nm) using a 125 W mercury lamp

200

3.

Aromatic Compounds

under a slow stream of oxygen. After removal of the solvent residue the mixture was treated with 25 mL of saturated aqueous NaHC03 solution and extracted with ether (2 x 30 mL). The combined extracts were washed successively with water and saturated brine and finally dried over anhydrous sodium sulfate. Evaporation of the solvent gave a crude product which upon crystallization from hot water gave 6,7-dimethoxycoumarin (SO%), mp 136.6 "C.

'H-NMR (acetone-dg, 90 MHz): 6 = 3.84 (s, 6 H, Om), 6.41 (d, 1 H, J = 9.52, =CHCOO), 7.20 (s, 1 H, arom.), 7.22 (s, 1 H, arom.), 7.93 (d, lH, J = 9.52). IR (KBr): v = 3020,1700,1570,1560, 1490, 1450, 1270,1180,1110,1040,870,800. MS: m/z = 206.

[l] [2]

Vogel's Text Book of Practical Organic Chemistry, A. I. Vogel, B. S. Furniss, A. J. Hannaford, V. Rogers, P. W. G. Smith, A. R. Tatchell (Eds.), 1984, ELBS, London, 82. G. Pandey, A. Krishna, J. M. Rao, Tetrahedron Lett. 1986,27,4075 - 4076.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

Alkenes, Arylalkenes and Cycloalkenes

4

Formation of the lowest excited singlet state of simple alkenes arises from an allowed (R,K*)transition and generally requires light of short wavelengths extending to about 200 210 nm. In addition, there are energetically close transitions leading to (R, 3s) Rydberg and (n,a*) excited states. Because of the absorption of the solvents commonly used in homogenous reactions and the lack of suitable light sources photoreactions starting from the S1-state of simple alkenes are of little synthetic value. However, things are quite different for substituted alkenes or conjugated alkenes as dienes and arylalkenes of which the absorption bands are shifted to longer wavelengths. Another solution to circumvent the problems concerned with absorption at short wavelengths is to perform photoreactions by sensitization. By selecting an appropriate sensitizer various processes can be carried out via the triplet state of the alkene (triplet sensitization) or via radical ions (electron transfer sensitization). So far mostly the radical cation chemistry of alkenes has been investigated (eq. 2). Triplet sensitization (A: sensitizer):

3A* + B + A

+ 3B*

(1)

Electron transfer sensitization (A: sensitizer):

A* + B -+A-

+ B+*

(oxidative)

(2)

A* + B + A+* + B-•

(reductive)

(3)

In general, beside the energetics the efficiency of the intersystem crossing forming the triplet state of the sensitizer controls the outcome of the sensitization process (l), cf. General Features, e). With respect to the second type of sensitization the free enthalpy of electron transfer can be taken as the controlling factor. Only if AG is negative (exergonic process) an electron can be transferred from the donor to the acceptor molecule. Note that in general the reaction can be performed via the excited acceptor (eq. 2) or the excited donor (eq. 3). Regardless of the type of activation either by direct irradiation into the (x,R*) absorption band or by sensitization, the double bond of an alkene is changed in its bond order which has a strong impact on its reactivity. As a consequence, generally six types of reactions are possible: (9 (ii) (iii) (iv) (v) (Vi)

Z,E-Isomerizations Sigmatropic shifts Di-n-methane rearrangements Electrocyclic reactions Acyclic additions Dimerizations and cycloadditions

202

4.

Alkenes, Atylalkenes and Cycloalkenes

In addition, there are other processes caused by excitation into a Rydberg state which readily undergo nucleophilic addition. The interested reader is recommended to look for details in the references given below.

2,E-Isomerizations Z,E-homerizations of 1,Zdisubstituted alkenes are well documented and can occur either by direct irradiation via the singlet state or via the triplet by sensitization. Examples of electron transfer activation have also been reported and mainly involve radical cations of alkenes. For the reasons discussed above, in general, the sensitization is the method of choice. There are numerous examples collected in the textbooks and the reviews. The Z,E-isomerization of cyclooctenes presented by Y. Inoue belong to rare examples of a singlet sensitization. The advantage of such a process is that the reaction probably involve exciplex intermediates. By choosing a chiral sensitizer an asymmetric Z,E-isomerization is possible with an enantiomeric excess up to 53% (at -85 "C).

(ii)

Sigmatropic shifts

These rearrangements involve a migration of a o-bond across an adjacent n-system. The type of activation (thermal or photochemical) and the stereochemistry are often controlled by the Woodward-Hoffmann rules. In photochemical reactions stepwise processes involving biradical intermediates may also operate depending on the nature of the reactive excited state. The examples presented here may only formally fit into this category since the overall processes probably are non-concerted. The vinylcyclopropane-cyclopentene rearrangement of (+)-A2-carene leads to the racemic bicyclo[3.2.0]hept-2-ene derivative despite a direct irradiation as shown by H. R. Sonawane. Since triplet sensitization give the same result a mechanism involving a biradical intermediate is assumed. The photoproduct is an important building block in several natural product syntheses. An unusual photochemical rearrangement is shown by T. Miyashi. Irradiation of an p-isopropylstyrene derivative at 254 nm leads to a cyclopropane in excellent yield. The authors assume a [1,2] H-shift leading to a 1,3-biradical followed by ring closure. Ionic intermediates are excluded due to the lack of a solvent dependence.

(iii)

Di-n-methane rearrangements

This unique rearrangement was discovered by Zimmerman in the late sixties and generally belongs to sigmatropic rearrangements of the type [1,2]. Since it is not limited to 1,4-dienes but may also applied to oxa, aza and other analogues and since it has got a strong impact on synthetic chemistry often a single textbook chapter is devoted to this process. The numerous examples presented here still reflect the topicality of the di-nmethane rearrangement which allows the synthesis of enantiomeric pure compounds due to its stereospecificity. Whereas acyclic 1,4-diene systems often require direct irradiation in order to avoid Z,E-isomerization via triplet formation, constrained 1,4-dienes can also be triplet sensitized and thus, this procedure often leads to higher product yields.

4.

Alkenes, Atylalkenes and Cycloalkenes

203

To start with, the classic reactions developed by H. E. Zimmerman show the main features such as the regio- and the stereoselectivity of the di-wmethane rearrangement. The tetraphenyl-1,Cdiene dicarboxylic acid ester may count as an exception of the above mentioned limitation concerning the excited state behaviour. In excellent yields this acyclic diene regioselectively forms a vinyl cyclopropane by triplet sensitization. In the diphenyl-1,3-heptadiene one double bond of the benzene ring is involved in the rearrangement process leading to one single vinyl cyclopropane derivative. A similar rationalization counts for di(p-anisyl)-2,5-dimethylhexene.The 1,Cdienes discussed so far were disubstituted at the central carbon. The final example of the Madison group shows that this quaternary sp3-carbon may be replaced by a sp2-center. The I-diphenylmethylene-4,4-diphenyl-2,5-cyclohexadiene rearranges almost quantitatively to a bicyclic vinyl cyclopropane. Note that the analogous cyclohexandienone shows the same reaction (cf. chapter 1.2). Interesting applications to organic synthesis start from bicyclic 1,6dienes or P,y-enones (oxadi-rc-methanerearrangement, cf. chapter 1.2). Another striking example submitted by J. R. Scheffer is given in chapter 7. In homogeneous solution the dibenzo barrelene undergoes a very efficient rearrangement to a "sernibulvalene" derivative. (Note that analogous barrelenes have been investigated by M. Demuth using both artificial light sources and sun light.) The same starting material when crystallized in a chiral modification gives the photoproduct in >95% enantiomeric excess (cf. chapter 7). Another example of a constrained IP-diene is presented by T. Miyashi. Upon direct irradiation 5-dicyanomethylenebicyclo[2.2.2]oct-2-ene rearranges to a tricyclic compound in good yield.

(iv)

Electrocyclic reactions

Electrocyclic reactions belong to classic pencyclic reactions which generally can be rationalized on the basis of the Woodward-Hoffmann rules. Cyclobutene ring opening and hexatriene ring closure belong to the most frequently investigated isomerizations. Both processes have been utilized by A. Gilbert in the one-pot synthesis of a tricyclic tetrahydrofuran derivative (cf. chapter 3). In a somewhat similar way G. Kaupp first uses a [2+2] cycloaddition to build up a bicyclic cyclobutene which opens in a disrotatory way to a 1,Cdioxocine derivative. A seven-membered heterocycle (2-phenyl- 1,3-0xazepine) is synthesized by T. Miyashi starting from the corresponding bicyclic[3.2.0]ring system. Bridged Dewar benzenes are accessible according to a procedure presented by R. Gleiter. In elegant combinations of various reaction steps, annelated benzenes and prismanes are synthesized starting from 1,9-~ycIotetradecadiyne. The most striking application of the photochemical 1,3-~yclohexadienering opening is found in the synthesis of the phenanthrene unit. There is no doubt that the majority of examples reported so far come from W. H. Laarhoven. Starting from stilbenes various types of higher aromatic compounds bearing a phenanthrene unit are accessible. One of the most interesting example concerns the synthesis of hexahelicene. H. Meier also made use of this procedure in his synthesis of triphenanthreno-annelated [ 18lannulenes which form liquid crystals. They are also of great importance in material science.

204

(v)

4.

Alkenes, Arylalkenes and Cycloalkenes

Acyclic additions

The additions of free radicals to alkenes initiated by a photochemical process are often used in synthetic organic chemistry. For example, in chapter 2 some typical processes are shown generally involving H-abstraction as the first step. In these reactions the alkene acts as the partner in the electronical ground state. The alternative by photoactivation of the alkene is also possible, but then its reactivity is changed from a nucleophile to an electrophile. For example, irradiation of 1-methylcyclohexene leads to the formation of a highly strained "E-isomer" which readily can be trapped by an alcohol to form the Markovnikov adduct. Similar products can be obtained via the excited Rydberg states of the alkenes. A further type of activation involves an electron transfer. In general, two processes are possible, i.e. oxidation to a radical cation or reduction to a radical anion (eq. 4). Applications have been pioneered by Arnold (see refs. on electron transfer photochemistry).

The majority of examples reported so far involve oxidative pathways. Here only one synthetic application is presented by J. Mattay. The oxidation of an enol silyl ether bearing an unsaturated side chain cyclisizes via the radical cation to a bicyclic ketone. It has been shown for 6-hexenyl systems that this radical cationic reaction preferentially proceeds via a 6-end0 rather than a 5-exo mode as observed for free radical processes.

(vi)

Dimerizations and cycloadditions

The dimerization of alkenes and cycloaddition of one alkene to another one generally lead to cyclobutanes. Only in case of conjugated dienes other types of cycloaddition modes are observable, e.g. [4+2], [4+4] etc. However, these processes require special conditions such as the utilization of template effects with transition metals and have only frequently been applied (cf. chapter 5). As a consequence the examples summarized here are mainly concerned with [2+2] cycloadditions. The mechanisms involved are diverse and strongly depend on the conditions and the alkenes which are used as starting materials. For the reasons mentioned above most of the cycloadditions are performed under the conditions of sensitization either via the triplet excited state or via radical cations of the alkenes. Those carried out upon direct irradiation are generally concerned with substituted alkenes or conjugated dienes absorbing at longer wavelengths. One typical example is given by G. Kaupp with the [2+2] cycloaddition of diphenylacetylene to 1,4-dioxene leading to a bicyclic cyclobutene in good yield (cf. iv of this chapter). Another example is presented by T. Miyashi starting from naphthoquinonorbornadiene. In an intramolecular reaction a quadricyclane derivative is quantitatively formed upon irradiation at h > 400 nm. It is assumed that this process involves the diketonorbornadiene in its triplet state. Although the spin multiplicity of intermediates have not

4.

Alkenes, Arylalkenes and Cycloalkenes

205

been assigned a two-step mechanism via biradicals is also proposed in the former case (cf. chapter 1.2). The valence isomerization of cyclooctatetraene to semibullvalene developed by H. E. Zimmerman may be rationalized in terms of an intramolecular cycloaddition. Direct formation of C-C bonds between C1-C5 and C4-C6 of a hexatriene unit seems to be the most probable reaction pathway. It should be noted that this photoreaction belongs to the rare examples of a gas phase photolysis useful for synthetic purposes. The dimerization of vinyl acetylene presented by H. Hopf requires the presence of benzophenone as triplet sensitizer. Either by irradiation in sealed glass tubes or by using a low temperature immersion well apparatus 1,2-diethynylcyclobutaneis formed in good yields. Note that the analogous dimerization of 1,3-butadiene yields similar products beside vinylcyclohexane and cyclooctadiene depending on the triplet energy of the sensitizer. Stilbene and its derivatives have often been used in photochemical [2+2] cycloadditions. The intermolecular dimerization presented by H. Meier of 2,3-bis(2-phenylethenyl)naphthalene directly leads to cyclophane via two [2+2] cycloadditions in one step. The yield is surprisingly very high and comparable with those of intramolecular reactions presented by W. H. Laarhoven. Various examples of vinylstilbenes are photolyzed to form cyclobutanes via a "crossed" addition. Even [20+27c] cycloadditions and rearrangements involving H-transfer are utilized to construct unusual bicyclic or tricyclic compounds. Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizuno various bisenolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyanoanthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization of the silane-bridged bis-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-~yclohexadiene.He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed by Bauld and which may be called "hole catalyzed Diels-Alder reaction".

Recommend further reading General: A. Gilbert, J. Baggott in Essentials of Molecular Photochemistry 1991, Blackwell Scientific Publications, Oxford, p. 229 - 285; W. H. Horspool, D. Armesto in Organic Photochemistry 1992, Ellis Horwood, PTR F'rentice Hall, New York, p. 19 - 52; N. J. Turro in Modern Molecular Photochemistry 1978, The Benjamin/ Cummings Publ. Co., Menlo Park, Cal., chapter 10 - 12; P. J. Kropp in Organic Photochemistry, Vol. 4 , A. Padwa (Ed.) 1979, Marcel Dekker, New York, p. 1 142. Photoinduced electron transfer: G. J. Kavarnos, Fundamentals in Photoinduced Electron Transfer 1993, VCH, New York; K. Mizuno, Y. Otsuji, Topics in Current Chemistry 1994, 169, 301 - 346; G. Pandey, Topics in Current Chemistry 1993, 169, 175 - 221; F. Muller, J. Mattay, Chem. Rev. 1993, 93, 99 - 117; F. D. Lewis in

206

4.

Alkenes, Arylalkenes and Cycloalkenes

Photoinduced Electron Transfer, Part C, M. A. Fox, M. Chanon (Eds.), 1988, Elsevier, Amsterdam, p. 1 - 69; P. S. Mariano in Synthetic Organic Photochemistry, W. H. Horspool (Ed.), 1984, Plenum Press, New York, p. 145 - 257; S. L. Mattes, S. Farid in Organic Photochemistry, Vol. 6, A. Padwa (Ed.), 1983, Marcel Dekker, New York, p. 233 - 326. 2,E-Isomerization: J. Saltiel, J. L. Charlton in Rearrangements in Ground and Excited States, Vol. 3, P. de Mayo (Ed.), 1980, Academic Press, New York, p. 25 - 89. Sigmatropic shift and di-7c-methane rearrangement: general references (see above); H. E. Zimmerman in Organic Photochemistry, Vol. 11, A. Padwa (Ed.), 1991, Marcel Dekker, New York, p. 1 - 36; M. Demuth in Organic Photochemistry, Vol. 11, A. Padwa (Ed.), 1991, Marcel Dekker, New York, p. 37 - 109. Electrocyclic reactions: W. H. Laarhoven in Organic Photochemistry, Vol. 9, A. Padwa (Ed.), 1987, Marcel Dekker, New York, p. 129 - 224; W. H. Laarhoven in Organic Photochemistry, Vol. 10, A. Padwa (Ed.), 1989, Marcel Dekker, New York, p. 163 308. Acyclic addition: general references and photoinduced electron transfer (see above). Dimerization and cycloaddition: F. Muller, J. Mattay, Chem. Rev. 1993, 93, 99 - 117; W. H. Laarhoven in Organic Photochemistry, Vol. 9 , A. Padwa (Ed.), 1987, Marcel Dekker, New York, p. 129 - 224; N. L. Bauld in Advances in Electron Transfer Chemistry, Vol. 2, P. S. Mariano (Ed.), 1992, JAI Press Inc., Greenwich, Conn., p. 1 - 66; general references.

4.

207

Alkenes, Arylalkenes and Cycloalkenes

4.1

(E)-Cyclooctene[1-3] submitted by

4.la

Y. Inoue, H. Tsuneishi, T. Hakushi and A. Tai

o=EF

Racemic (E)-cyclooctene[21 hv

110.2

110.2

A cyclohexane solution (300 mL) of 13.2 g (0.12 mol) of (2)-cyclooctene and 2.0g (7.3 mmol) of methyl 3,5-bis(trifluoromethyl)benzoate placed in a donut-shaped annular quartz vessel (40 mm i.d. and 160 mm high) was irradiated at 254 nm under an argon atmosphere in a water bath at 25 "C. The irradiation using a 30 W mercury resonance lamp (Eikosha Co.), fitted with a Vycor filter and placed at the center of the vessel, was continued for 72 h without stirring until the EIZ ratio, determined by the gas chromatograpic analysis (over a 3 m packed column of 40% P,P'-oxydipropionitrile at 70 "C), no longer changed. The ultimate EIZ ratio obtained after 72 h irradiation was 0.46. The irradiated solution was extracted with three 25 mL portions of 20% aqueous silver nitrate solution at c 5 "C.The aqueous extracts were combined, washed with two 10 mL portions of pentane at < 5 "C, and then added dropwise into a stirred concentrated aqueous ammonia solution (100 mL) at 0 "C. The resulting mixture was extracted with three 25 mL portions of pentane. The combined pentane extracts were washed with water, dried over magnesium sulfate, and concentrated at a reduced pressure (50 - 100 Tom) to give an almost pure product, which was finally trap-to-trap distilled in vacuo to afford (E)-cyclooctene of > 99.5% purity (2.8 g, 21% yield). The use of dimethyl isophthalate as an alternative sensitizer gave a somewhat lower isolated yield (18%) under comparable conditions. '€I-NMR (CDC13, 400 MHz): 6 = 0.75 - 0.84 (m, 2 H),1.38 - 1.56 (m, 2 H),1.79 - 1.84 (m, 2 H), 1.91 - 2.00 (m, 4 H),2.35 - 2.39 (m, 2 H),5.48 - 5.52 (m, 2 H,CH=). 13C-NMR (CDC13, 100 MHz): 6 = 29.26 (t), 35.72 (t), 35.84 (t), 133.99 (d, CH=). IR (thin film): v = 3020,2925 (s), 2810 (s), 1655, 1450 (s), 1320, 1200,985 (s), 935,845, 815,790,700.

208

4.

4.lb

(-)-Tetrabornyl 1,2,4,5-benzenetetracarboxylateas a chiral sensitizer

+

cIoc~cocI

Alkenes, Arylalkenes and Cycloalkenes

Pyridine

a

R*02C

C0,R'

R'02C

C02R*

____1)

ClOC

COCl

327.9

OH (R'OH)

154.3

799.1

To a stirred pyridine solution (30 mL) of benzenetetracarbonyl tetrachloride (5.5 g, 17 mmol), prepared from benzenetetracarboxylic anhydride and phosphorous pentachloride, was added portionwise (-)-borne01 (10.3 g, 67 mmol) at 0 "C, and stirring was continued for 18 h under a nitrogen atmosphere. The reaction mixture was then poured into a mixture of 6% aqueous hydrogen chloride (150 mL) at 5 "C (ice bath) and extracted with three portions of ether (200 mL). The combined organic extracts were washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and then evaporated to dryness under a reduced pressure. The crude product obtained was purified by repeated recrystallization from methanol and then twice from hexane to yield pure (-)-tetrabornyl 1,2,4,5-benzenetetracarboxylate (8.0 g, 60%), mp 239.5 - 241.0 "C, [aID2O = -59.5" (0.9, benzene).

'H-NMR (CDC13, 400 MHz): 6 = 0.90 (s, 12 H), 0.91 (s, 12 H), 0.95 (s, 12 H), 1.21 (dd, 4 H, J = 14.1, 3.7), 1.26 - 1.55 (m,8 H), 1.73 - 1.80 (m, 8 H), 1.93 - 2.00 (m, 4 H), 2.47 (m, 4 H), 5.13 (m, 4 H), 8.06 (s, 2 H). IR (KBr): v = 2970,2890,1735,1460, 1395,1310,1280,1260,1135, 1105,1020,980.

4.1c

(-)-Hexakis((1R)-1-methylheptyl) benzenehexacarboxylate as a chiral sensitizer

c l o c ~ o c '

KH

ClOC

THF

COCl COCl

327.9

130.2

R*O&

799.1

(-)-2-Octanol (5.0 g, 38 mmol) was added to a tetrahydrofuran suspension (20 mL) of potassium hydride (5.7 g of 35 wt% dispersion in mineral oil, 40 mmol), which was washed with dry hexane (5 mL) prior to use, and the solution was stirred overnight. To the

4.

209

Alkenes, Arylalkenes and Cycloalkenes

stirred solution was added benzenehexacarbonylhexachloride (2.42g, 5.5 mmol) at 0 "C, and the mixture was continuously stirred for another 12 h. The resultant solution was diluted with 6% aqueous hydrogen chloride (100 mL), and then extracted with five portions of ether (50 mL each). The combined extracts were washed with saturated aqueous sodium bicarbonate and with brine, dried over sodium sulfate, and then evaporated under a reduced pressure. The crude product obtained was purified by column chromatography over silica gel with hexane/ethyl acetate (94:6) eluant to yield (-)hexakis((1R)-l-methylheptyl) benzenehexacarboxylate (3.5 g, 65%), mp 46.0- 47.0 "C, [aID2O = -166.6"(1.00,benzene).

IH-NMR (CDC13, 400 MHz): 6 = 0.88 (m, 18 H), 1.20 - 1.43 (m, 66 H),1.53 (m, 6 H), 1.66 (m, 6 H), 5.01 (m, 6 H,J = 6.3). IR (thin film): v = 2925,2855, 1745, 1730, 1465, 1425, 1380, 1335, 1220, 1175, 1120, 1035.

4.ld

Optically active (E)-cyclooctene[3] hu

Sens* 110.2

110.2

A pentane solution (300 mL) containing 6.6g (0.06mol) of (9-cyclooctene and 1.0g (1.3 mmol) of (-)-tetrabornyl 1,2,4,5-benzenetetracarboxylate4.lb as an optically active sensitizer was irradiated in a thermostated methanol bath maintained at -88"C by using an immersion cooler, Cryocool CC-10011 (NESLAB). The irradiation at the low temperature was continued for 72 h without stirring. The irradiated solution was treated as described above to afford (-)-(@-4,ld (0.4g, 6% yield) of > 99.5% chemical purity; the sample showed a specific rotation ([a],25) of -172.7"(2.3,CH~CIZ), which corresponds to the optical purity (op)I4] of 40.6% on the basis of the [a],20value of -426"(CH2C12) reported for the optically pure (-)-4.ld[S]. Irradiation at room temperature gave the same enantiomer (-)-4.ld in a lower op. of 11.5%[6]. Naturally, the use of (+)-tetrabomyl 1,2,4,5-benzenetetracarboxylateas an alternative sensitizer afforded the antipodal (+)-4.ld of comparable op. (-)-Hexakis( 1 -methylheptyl) benzenehexacarb~xylate[~~] 4.lc as chiral sensitizer gave better results, affording (-)-4.ld of 53% op in 3 - 4% yield at -85 "C. The optically active 4.ld gave the same IR and NMR spectra as shown above.

[I] 121

A. C. Cope, R, D. Bach, Org. Synth. Coll. Vol. 5 1973,315. N. Yamasaki, Y.Inoue, T. Yokoyama, A. Tai, J. Photochem. Photobiol. A 1989,48,

465.

210 [3] [4]

[5] [6]

4.

Alkenes, Arylalkenes and Cycloalkenes

Y. Inoue, T. Yokoyama, N. Yamasaki, A. Tai, J. Am. Chem. SOC. 1989, 111, 6480 6482; Y. Inoue, N. Yamasaki, T. Yokoyama, A. Tai, J. Org. Chem. 1992,57, 1332 1345. op. is defined by dividing the observed specific optical rotation [a]D (obsd) by that reported for the optically pure authentic specimen [a]D (pure). A. C. Cope, C. R. Ganellin, H. W. Johnson jr., T. V. Van Auken, J. S. Winkler, J. Am. Chem. SOC.1963,85,3216- 3219. However, this is not always the case. Since the temperature dependence of the product's op. is quite tricky in these enantiodifferentiating photoisomerization sensitized by optically active polyalkyl benzenepolycarboxylates, one should use special caution in changing irradiation temperature. For instance, (-)-tetramenthy1 1,2,4,5benzenetetracarboxylate gives (-)-4.ld of 9.6%op. at 25 "C,but produces the antipode (+)-4.ld of 28.5% op at -90 "C. Thus, the product chirality is often switched by the irradiation temperature; see referenceL3I for full detail.

4.

21 1

Alkenes, Arylalkenes and Cycloalkenes

4.2

(E)-1-Methylcyclooctene submitted by

4.2a

(Z)-l-Methylcyclooctene[ll

H. Tsuneishi, Y. Inoue, T. Hakushi and A. Tai

TA\3

W

W

126.2

142.2

124.2

An ether solution (200 mL) containing 52.4 g (0.415 mol) of cyclooctanone was added dropwise over 1 h at room temperature to a stirred ethereal solution (400 mL) of methylmagnesium iodide prepared from 30.1 g (1.24 mol) of magnesium turnings and 176 g (1.24 mol) of methyl iodide. The resulting mixture was slowly poured into a saturated aqueous ammonium chloride solution, and the whole solution was extracted with two 150 mL portions of ether. The combined ether extracts were dried over magnesium sulfate and evaporated in vacua to give a crude sample of 1-methylcyclooctanol. The crude 1-methylcyclooctanol obtained was spontaneously dehydrated upon distillation to give a distillate of a wide temperature range (100 - 165 "C), which was dried over magnesium sulfate and fractionally distilled to afford (a-1-methylcyclooctene (40.0 g, 0.323 mol) in 77.6% yield, bp 160 - 164 "C.

lH-NMR (CDCl3, 400 MHz): 6 = 1.45 (br. s, 2 H), 1.51 (br. s, 6 H), 1.68 (d, 3 H, C_H3), 2.05 (br. s, 2 H), 2.13 (dd, 2 H, J = 5.6,6.4), 5.34 (tq, 1 H, J = 1.2, 8.1, CH=). I3C-NMR (CDC13, 100 MHz): 6 = 23.45, 26.21, 26.52, 26.65, 28.00, 30.22, 30.34, 124.11 KH=), 136.94 (MeC=). IR (thin film): v = 3040,2930 (s), 2855 (s), 1470 (m), 1450 (m), 1380,905,895,835,820 (m), 745,595,590.

212

4.2b

4.

Alkenes, Arylalkenes and Cycloalkenes

(E)-l-Methylcyclooctene[z]

124.2

124.2

A pentane solution (300 mL) of 7.45 g (60 mmol) of (Z)-1-methylcyclooctene 4.2a and 0.41 g (3 mmol) of methyl benzoate placed in a donut-shaped annular quartz vessel (40 mm i.d. and 160 mm high) was irradiated at 254 nm under an argon atmosphere in a water bath at 25 "C. The irradiation using a 30 W mercury resonance lamp (Eikosha Co.), fitted with a Vycor filter and placed at the center of the vessel, was continued for 25 h without stirring until the EIZ ratio, determined by gas chromatograpic analysis (over a 3 m packed column of 20% polyethylene glycol-300 at 65 "C), no longer changed. The ultimate EIZ ratio obtained after 25 h irradiation was 0.20. The irradiated solution was extracted at < 5 "C with three 60 mL portions of 10% silver nitrate solution in methanol/ water (3:4). The combined methanol/water extracts were diluted with 175 mL of water, washed with two 25 mL portions of pentane, and then added dropwise into a stirred concentrated aqueous ammonia solution (100 mL) at 0 "C. The resulting mixture was extracted with three 25 mL portions of pentane. The combined pentane extracts were washed with water, dried over magnesium sulfate, and concentrated at a reduced pressure (50 - 100 Torr) to give an almost pure product, which was finally trap-to-trap distilled in vucuo to afford (0-1-methylcyclooctene 4.2b of > 99% purity (0.53 g, 7.1% yield).

'H-NMR (CDC13, 400 MHz): 6 = 0.65 (dt, 1 H, J = 6.1, 13), 0.90 (dt, 1 H, J = 5.9, 13), 1.42 (dq, 1 H, J = 5.4, 12.2), 1.57 - 1.70 (m, 3 H), 1.74 (d, 3 H, J = 1.2, CH3), 1.84 (br. d, 1 H, J = 12.2), 1.89 - 1.97 (m, 1 H), 2.06 (dt,l H, J = 4.6, 11.9), 2.13 - 2.31 (m, 3 H), 5.38 (dd, 1 H, J = 1.2, 11.5, CH=). 13C-NMR (CDC13, 100 MHz): 6 = 18.19, 27.90, 30.25, 30.98, 33.48, 36.75, 41.69, 127.19 (CH=), 137.69. (MeC=). IR (thin film): v = 3040,2910 (s), 2850 (s), 1450 (s), 1380, 1200 (m), 990,980, 925, 875 (m), 845,810,750,700,560,525.

[I] [2]

H. C. Brown, M. Borkowski, J. Am. Chem. Soc. 1952, 74, 1894 - 1902. H. Tsuneishi, Y. Inoue, T. Hakushi, A. Tai, J. Chem. Soc., Perkin Trans. 2, in press.

4.

213

Alkenes, Arylalkenes and Cycloalkenes

4.3

1,4,4-Trimethyl-cis-bicyclo[3.2.0]heptan-3-one~~~ submitted by

4.3a

H. R. Sonawane, B. S. Nanjundiah and D. G. Kulkarni

1,4,4-Trimethyl-cis-bicyclo[3.2.0]hept-2-ene

136.2

136.2

A solution of 4.80 g (30 mmol) of A*-carene ([a],25 = +10.2", 0.60 CHC13) in 500 mL of petroleum ether (40 - 60 "C) containing 3.1 mL of toluene was irradiated with a 450 W Hanovia immersion-type lamp through a Vycor filter for 50 h. The solvent was slowly distilled out using a vigreux fractionating column and the residue was distilled, bp 130 140 "C. The distillate was further purified by preparative GLC to yield 3.04 g (75%) of product.

'H-NMR (CDC13, 90 MHz): 6 = 0.94 (s, 3 H, CH3), 0.97 (s, 3 H, C&), 1.16 (s, 3 H, C_H3), 1.56 - 1.87 (m, 4 H, -C_H2C&-), 1.8 - 2.1 (m, 1 H, -C_H),5.38 (s, 2 H, C_H=C_H). IR (neat): v = 1600.

4.3b

Epoxidation of 4.3a

@ 136.2

mCPBA

* O x i I 152.2

A solution of 1.03 g (6.0 mmol) of mCPBA in 10 mL of chloroform was slowly added at room temperature to a stirred solution of 0.546 g (4.0 mmol) of 4.3a in 5 mL of chloroform. After 3 h, the reaction mixture was diluted with chloroform, washed with dilute

214

4.

Alkenes, Arylalkenes and Cycloalkenes

sodium carbonate and concentrated to yield 0.511 g (80%) of a 70:30 diastereomeric mixture of epoxides.

'H-NMR (CDC13, 90 MHz): 6 = 0.80, 0.96, 1.07 (3 s, 3 H each, signals of high intensity), 1.00 and 1.18 (2 s, 9 H, signals of low intensity), 2.80 - 3.16 (m, 4 H). IR (neat): v = 3003, 2976, 2874, 1470, 1455, 1400, 1360, 1265, 1100, 1020, 890, 840, 760.

O P

4 . 3 ~ Lithium aluminium hydride reduction of the mixture of epoxides LAH

-

+ isomer

Ho%

152.2

154.3

A solution of 456 mg (3.0 mmol) of the mixture of epoxides in 3 mL of anhydrous THF was added under a nitrogen atmosphere to a well-stirred slurry of 570 mg (15.0 mmol) of LAH in 10 mL of THF. The reaction mixture was refluxed for 16 h after whch it was quenched with water and extracted with ether. Rota-evaporation of the solvent afforded 393 mg (80%)of a 7030 mixture of alcohols.

'H-NMR (CDC13,90 MHz): 6 = 0.78,0.98, 1.15 (3 s, 3 H each, signals of high intensity), 0.74,0.90, 1.20 (3 s, 3 H, signals of low intensity), 3.64 - 4.2 (m, 2 H). IR (neat): v = 3378.

4.3d

1,4,4-Trimethyl-cis-bicyclo[3.2.O]heptan-3-one PCC Ho* 154.3

-

O* 152.2

A solution of 309 mg (2.0 mmol) of the mixture of alcohols in 3 mL of methylene chloride was added dropwise to a suspension of 860 mg (4 mmol) of PCC and 54 mg (0.6 mmol) of sodium acetate in 10 mL of dry CH2CI2. After stirring for 1 h at room temperature, the reaction mixture was diluted with n-hexane and passed through a short column of silica

4.

Alkenes, Arylalkenes and Cycloalkenes

215

gel. Rota-evaporation of the solvent and column chromatography afforded 201 mg (70%) of the title compound and 87 mg (30%) of its regioisomer.

'H-NMR (CDC13, 90 MHz): 6 = 0.90 (s, 3 H, CH3), 0.95 (s, 3 H, C&), 1.33 (s, 3 H, C_H3),2.31 (q, 2 H, J = 19, C&CO). IR (neat): v = 1735.

Discussion Vinylcyclopropane-cyclopentene rearrangement (VCP-CP) reaction under thermal conditions is a useful transformation and has been extensively utilized in the synthesis of number of cyclopentanoid natural products.[2] However, cis-alkyl-vinylcyclopropanes pose a serious problem since the retro-ene reaction, a lower energy pathway occurs readily instead. To obviate this problem, we sought to explore the excited state chemistry of cis-alkyl-vinylcyclopropanes.[3] Thus, sensitized photolysis of (+)-A2-,,,,, readily afforded the VCP-CP product exclusively in a preparative yield. The obtention of a racemic product can be rationalized by involving a diradical intermediate.[l] However, the same transformation when applied to substrates habing a substituent at C,, offered products in moderate to good diastereoselectivity, thus leading to chiral bicyclo[3.2.0]hept-2-enes, important building blocks in organic synthesis. Their utility was demonstrated by the formal synthesis of both the enantiomers of A9(12)-capnellene.[1]

[l]

[2] [3]

H. R. Sonawane, V. G. Naik, N. S. Bellur, V. G. Shah, P. C. Purohit, M. U. Kumar, D. G. Kulkarni, J. R. Ahuja, Tetrahedron 1991,47,8259 - 8276. T. Hudlicky, T. M. Kutchan, S. M. Naqvi, Org. React. 1985,33,247 - 335. H. R. Sonawane, N. S. Bellur, D. G. Kulkami, J. R. Ahuja, Synletr 1993, 875 - 884.

216

4.4

4.

l-Cyano-l-phenyl-2,2-dimethylcyclopropane~~~ submitted by

4.4a

Alkenes, Arylalkenes and Cycloalkenes

T. Miyashi

2-Phenyl-4-methylpent-2-enenitrile

72.1

117.2

171.2

To a vigorously stirred solution of sodium ethylate, prepared from 35 mmol of sodium metal (808 mg) and 210 mL absolute ethanol, 100.0 g (0.845 mol) of phenylacetonitrile was added at -10 "C and then 90.9 g (1.241 mol) of isobutyraldehyde was slowly added at such a rate that the temperature did not rise above -5 "C (approximate 120 min). The resulted solution was allowed to stand in in the refrigerator for one night. The reaction mixture was extracted with ether (3 x 300 mL) after the dilution with 300 mL of water, washed with water ( 5 x 500 mL) and dried over sodium sulfate. Fractionation of the dried product gave 143.7 g (purity 98%, yield 96%) of the nitrile boiling at 68 - 69 "U0.3 Tom.

4.4b

1-Cyano-l-phenyl-2,2-dimethylcyclopropane[ 11

hu

171.2

cyclohexane

-

dr,, Ph 171.2

A solution of 117 mmol of 2-phenyl-4-methylpent-2-enenitrile[2] (10.0 g) in 500 mL of cyclohexane was irradiated (Rayonet photoreactor RPR, h = 254 nm) in a quartz vessel under a nitrogen atmosphere for 28 h at 20 "C. After rota-evaporation of the solvent the crude product was purified by column chromatography (Woelm silica gel 32 - 63 pm) with hexane/ethyl acetate (1OO:3) as eluant yielding 8.38 g (84%) of cyanophenylcyclopropane, mp 48 - 49 "C.

4.

Alkenes, Arylalkenes and Cycloalkenes

217

IH-NMR (CC14, 90 MHz): 6 = 0.80 (s, 3 H, C2-Me), 1.32 (d, J = 6.0, C3-Ha), 1.45 (d, J = 6.0, C3-Hb), 1.51 (s, 3 H, C2-Me), 7.28 (s, 5 H, Ar-H). MS (25 eV): m/z = 171 (60, M+), 170 (79), 156 (69), 129 (100). IR (KBr): v = 2980,2240, 1496, 1449, 1380, 1370. UV (CH3CN): h,, = 259 nm (E = 302).

[l] [2]

T. Kumagai, E. Segawa, Z. Endo, T. Mukai, Tetrahedron Lett. 1986, 27, 6225 6228. J. V. Murray, J. B. Cloke, J. Am. Chem. SOC.1936,58,2014 - 2018.

218

4.5

4.

Alkenes, Arylalkenes and Cycloalkenes

Sensitized photolysis of l,l-dicarbomethoxy-3,3,5,5tetraphenyl-1,4-pentadiene[ll

PhX C O O M e Ph COOMe 488.6

submirted by

H. E. Zimmerman

hv, sens.

-

benzene

Ph

Ph

488.6

A solution of 200 mg (0.41mmol) of l,l-dicarbomethoxy-3,3,5,5-tetraphenyl-l,4-pentadiene and 8.03 g (66.9mmol) of acetophenone in 200 mL of benzene was irradiated for 30 min through Pyrex using a 450 W Hanovia medium-pressure lamp and the standard immersion well. The solvent was removed under vacuum leaving a yellow oil. The acetophenone sensitizer was removed by bulb to bulb distillation at 0.015Torr and 30 "C with dry ice cooling of the receiving bulb. The residue consisted of 202 mg (98%) of colorless crystals whose N M R spectrum show complete conversion. Recrystallization from ether/ hexane afforded 161 mg of colorless crystals, mp 216 - 217 "C. Concentration and silica gel chromatography (5% etherhexane) of the residue afforded an additional 30 mg of the tetraphenyl cyclopropane, mp 217 - 218 "C.The total yield was 191 mg (95.6%).

[I]

H. E. Zimmerman, R. E. Factor, Tetrahedron 1981.37, Supplement 1, 125 - 141.

4.

4.6

219

Alkenes, Arylalkenes and Cycloalkenes

Direct photolysis of l,l-dicyano-5,5-diphenyl-3-isopropyl-6-methyl-1,3-heptadiene"] submitted b y

H. E. Zimmerman

hu

Ph

354.5

CH,CN

354.5

A solution of 49.5mg (0.14 mmol) of 1 ,l-dicyano-5,5-diphenyl-3-isopropyl-6-methyl-l,3heptadiene in 160 mL of acetonitrile was irradiated with a Pyrex filter in a 450 W Hanovia

immersion apparatus for 15 min. The solution was purged with nitrogen prior to and during photolysis. Concentration under vacuum and chromatography of the residue on a 20 x 20 cm preparative silica plate with elution using 5% etherhexane afforded a band (Rf = 0.6) which contained 40.9 mg (83%) of 2-(2,2-dicyanovinyl)-cis-1,3-diphenyl-cis1,2-diisopropylcyclopropane.This was recrystallized from hexane to afford 32.2 mg (65%) of crystalline photoproduct, mp 157 - 158 "C.

[I]

H. E. Zimmerman, H. E. and J. M. Cassel, J. Org. Chem. 1989,54,3800 - 3816.

220

4.7

4.

Alkenes, Arylalkenes and Cycloalkenes

Sensitized irradiation of (E)-2,5-di(p-anisyl)-2,5dimethylhexene"] submitted by

H. E. Zimmerman

hv 4

An 324.5

acetone 324.5

A solution of 2.5 g (7.72mmol) of (E)-2,5-di(p-anisyl)-2,5-dimethyl-3-hexenein 1 L of acetone was irradiated through Pyrex in an 450 W Hanovia apparatus for 20 h and concentrated under vacuum. The residual oil was separated by chromatography on a 148 x 27 cm silica gel column with hexane elution; 100 mL fractions were collected. Fraction 18 - 34 contained 2.23 g of cyclopropane product as a colorless oil and fractions 35 - 44 afforded a colorless oil weighing 320 mg (12.8%) and composed of reactant (E)- and (Z)-2,5-dianisyl-2,5-dimethylhexenes.The crude cyclopropane product from fractions 18 34 was recrystallized from pentane to give 2.01 g (6.2 mmol, 92.2% based on unrecovered reactant) of pure trans- 1-p-anisyl-2-p-methoxy-cumenyl-3,3-dimethylcyclopropane.

[l]

H. E. Zimmerman, A. P. Kamath, J. Am. Chem. Soc. 1988,110,900- 91 1.

4.

4.8

22 1

Alkenes, Arylalkenes and Cycloalkenes

Direct irradiation of l-diphenylmethylene-4,4diphenyl-2,5-cyclohexadiene[4] submitted by

396.5

H. E. Zimmerman

396.5

A solution of 252 mg (0.636 mmol) of I-diphenylmethylene-4,4-diphenyl-2,5-cyclohexadiene was irradiated in 250 mL of t-butyl alcohol for one hour under nitrogen. After concentration, NMR analysis indicated complete conversion to photoproduct. This residue was dissolved in ether and filtered through silica gel and then reconcentrated to afford 237 mg (93.5%) of colorless oil. Recrystallization from ethanol afforded 202 mg (79.7%) of 6,6-diphenyl-2-diphenylmethylenebicyclo[3.1 .O]hex-3-ene, mp 141 - 142 "C.

--________________ [4]

c

H. E. Zimmerman, D. R. Diehl, J. Am. Chem. Soc. 1979,101, 1841 - 1857.

222

4.9

4.

2,2-Dicyanotricyclo[4.2.l.O~~]non-7-ene~~~ submitted by

4.9a

Alkenes, Arylalkenes and Cycloalkenes

T. Miyashi

5-Dicyanomethylenebicyclo[2.2.2]oct-2-ene

122.2

66.1

170.2

A solution of 0.269 mol of bicyclo[2.2.0]octenone (32.9 g) and 0.435 mol of malononitrile (28.7g) in 650 mL of anhydrous pyridine was stirred at 70 "C under a nitrogen atmosphere for 48 h. 2 N Hydrochloric acid (450 mL) was added to the reaction mixture and extracted with ether (5 x 300 mL), washed with water, aqueous sodium bicarbonate, saturated sodium chloride solution, and dried over sodium sulfate. After rota-evaporation the crude product (mp 55 - 60 "C) was recrystallized from ethanol to give 31.6 g (69%) of pure material, mp 69 - 70 "C.

4.9b

2,2-Dicyanotricyclo[4.2.1.013]non-7-ene

170.2

pentane

170.2

A solution of 6.7 mmol5-dicyanomethylenebicyclo[2.2.2]oct-2-ene (1.14 g) in 500 mL of pentane was irradiated (Rayonet photoreactor RPR, h = 254 nm) in a quartz vessel under nitrogen atmosphere for 5 h at 10 "C. After rota-evaporation at 40 "C the crude product (mp 55 - 60 "C) was recrystallized from ethanol yielding 718 mg (63%) of colorless prisms, mp 62 - 63 "C.

lH-NMR (CCl,, 90 MHz): 6 = 1.10 (dd, J = 6.3, 6.0, 2-H), 1.7 - 2.0 (m, 4 H), 2.3 - 2.5 (m, 2 H), 2.65 (m, 6-H), 6.22 (dd, J = 5.9, 3.0,7-H), 6.33 (d, J = 5.9, 8-H).

4.

Alkenes, Arylalkenes and Cycloalkenes

223

13C-NMR (CDC13, 50 MHz): 6 = 12.69 (C-2), 19.87 and 20.87 (C-4 and C - 3 , 30.45 (C-3), 34.33 (C-6), 37.73 (C-9), 39.84 (C-I), 111.81 (CN), 113.90 (CN), 132.73 (C-7), 142.36 (C-8). MS (25 eV): m/z = 170 (M+, 2.5), 142 (loo), 115 (45). IR (KBr): v = 2960,2230, 1480, 1235. UV (Cyclohexane): Lax = 217 nm (E = 4460).

[l] E

T. Kumagai, K. Murakami, H. Hotta, T. Mukai, Tetrahedron Lett. 1982, 23, 4705 4708.

224

4.

4.10

6,7-Diphenyl-2,3-dihydro-1,4-dioxocine~~~ submitted by

4.10a

Alkenes, Arylalkenes and Cycloalkenes

G. Kaupp

1,4-Dioxene[21

(O 01

+

88.1

CI,

70.9

-4

0

0

x

CI

CI

157.0

86.1

180 g (2.54 mol) of chlorine gas were introduced into a spiral type washing bottle fitted with a reflux condenser at the end, filled with 200 mL (2.35 mol) of peroxide-free 1,4-dioxane containing 1 g of iodine and heated to 90 "C in such a way that virtually no chlorine escaped through the condenser. Then a stream of air was passed through which expelled the hydrogen chloride formed. The liquid was fractionated in a vacuum to give 310 g (84%) of truns-2,3-dichloro-l,4-dioxane, bp 81 - 82 "C/14 Ton, mp 28 - 30 "C. In a 2 L 3-necked flask with stirrer, dropping funnel and reflux condenser were placed 1 L of anhydrous ether and 79 g (3.25 moles) of magnesium turnings. Then 94 g (0.37 mol) of iodine were added in small portions. These reacted with liberation of heat. After the mixture became colorless, 300 g (1.91 mol) of 2,3-dichloro-l,4-dioxanemixed with 200 mL of ether was added dropwise with vigorous stirring at such a rate that the liberated iodine could only form a light brown color. The colorless mixture was poured on ice, the ether layer was collected, dried and fractionally distilled to give 128 g (78%) of lA-dioxene, bp 93 - 95 "C.

4.10b

1,6-cis-7,8-Diphenyl-2,5-dioxa-bicyclo[4.2.O]~t-7-ene~~~

$"+

hv

Ph

178.2

0

86.1

Ph

264.3

A solution of 2.0 g (11.2 mmol) of diphenylacetylene in 90 g of 1,4-dioxene was irradiated for 3 d in a Rayonet reactor with 8 low-pressure mercury lamps at 30 - 35 "C. Excess

4.

225

Alkenes, Arylalkenes and Cycloalkenes

dioxene was recovered by distillation, the oily residue recrystallized from 50 mL of methanol at -20 "C giving 1.05 g product, mp 88 "C. A further crop of 860 mg (total yield 64%) in addition to 100 mg of 6,7-diphenyl-2,3-dihydro1,4-dioxocine was obtained by chromatography of the mother liquor over 300 g of silica gel with benzene.

IH-NMR (CC14,90 MHz): 6 = 3.5 - 4.0 (AA'BB', 4 H), 4.95 (s, 2 H, 1-, 6-H), 7.15 - 7.75 (10 H, Ar-H). 13C-NMR (CDC13,25 MHz): 6 = 61.51,71.05, 127.15, 128.65, 128.85, 133.40, 143.00. UV (CH3CN): A, = 225 (Ig E = 4.35), 229 (sh, 4.31), 294 (4.22), 299 (sh, 4.22), 318 (sh, 3.97); (etherlethano1= 1:2, 83 K): hax = 284 (sh, Ere, = 0.55), 296 (0.85), 309 (1.00), 320 (horiz., 0.64). Fluorescence (cyclohexane/N2): = 383 nm, $fl= 0.32; (ethedethanol = 1:2, (Qrel) = 355 (sh, 0.77), 369 (1.OO), 385 (sh, 0.85). 77 K): (hcorr)max

264.3

264.3

1.0 g (3.8 mmol) of the adduct from 4.10b were irradiated in 500 mL of benzene for 1 h with a high-pressure mercury lamp (Hanau TQ 150) through a Pyrex filter under NF After concentration of the solution and cooling to -20 OC, 850 mg of product crystallized out, mp 114 "C (methanol). The mother liquor contained another 30 mg (total yield 88%) of product.

'H-NMR (CCI4, 90 MHz): 6 = 4.02 (br.s, Av112 = 2, 2-CH2, 3-CH2), 6.50 (s, 5-H, 8-H), 6.9 - 7.2 (10 H). W (CH3CN): Lax = 227 (sh, lg E = 4.20), 244 (4.26), 279 (sh, 3.72). photolysis: At 253.7 nm irradiation in CH3CN a 56/44-stationary mixture with the precursor from 4.10b is obtained.

[I] 121

G. Kaupp, M. Stark, Chem. Ber. 1978,111,3608 - 3623. R. I. Meltzer, A. D. Lewis, A. Fischman, J. Org. Chem. 1959,24, 1763 - 1766.

226

4.

4.11

Alkenes, Arylalkenes and Cycloalkenes

2-Phenyl-1,3-oxazepine[ll submitted by

T. Miyashi

Ph

hv 0

171.2

hexane 171.2

A solution of 1.2 mmol of 4-phenyl-2-oxa-3-azabicyclo[3.2.0]hepta-3,6-diene~2~ (193 mg) in 300 mL of hexane was irradiated (Rayonet photoreactor RPR,h = 254 nm) in a quartz vessel under nitrogen atmosphere for 4 h at 30 "C. After rota-evaporation of the solvent the crude product was purified by preparative thin-layer chromatography (Merck silica gel 60 PF254)using benzene yielding 141 mg (73%) of oxazepine as light yellow oil.

]€I-NMR (CDC13, 90 MHz): 6 = 5.75 - 6.05 (m, 3 H, 4-H, 5-H, and 6-H), 7.02 (dt, J = 7.2, 1.3,7-H), 7.2 - 7.5 (m, 2 H, Ar-H), 7.9 - 8.1 (m, 2 H, Ar-H). I3C-NMR (CDC13, 15 MHz): 6 = 117.6 (C-5 and C-6), 127.9 (Ph), 129.0 (Ph), 130.6 (Ph), 131.4 (Ph), 138.2 (C-4), 140.0 (C-7), 144.8 (C-2). IR (thin film): v = 3050, 1630, 1610, 1578, 1490, 1450, 1356. UV (EtOH): Lax = 238 nm ( E = 14450), 323 (4570).

[l] [2]

T. Kumagai, M. Sawaura, C. Kabuto, T. Mukai, Nippon Kagaku Kasishi 1984, 158 - 164; T. Mukai, H. Sukawa, Tetrahedron Lett. 1973, 1835 - 1838. G. Bianchi, R. Gandolfi, P. Griinanger, Tetrahedron 1970,26, 51 13 - 5122.

4.

227

Alkenes, Arylalkenes and Cycloalkenes

4.12

Hexacyclo[9.5.0.0 1,3.O 2,lO.O 3'9.O 9'11Ihexadeca-2,lOdimethyldicarboxylate[ll submitted by

120.2

323.9

R. Gleiter

188.3

A solution of 5 g (42 mmol) of 1,8-n0nadiyne[~Iin 1 L of dry tetrahydrofuran (THF) was cooled to -20 "C and 34 mL of 2.5 M n-butyllithium in hexane was added via a syringe with stirring over 10 min. A slightly yellow precipitate was obtained. The mixture was allowed to warm to room temperature, stirring was continued for another 15 min and finally 14.5 g (45 mmol) of 1,5-dii0dopentane[~]was added. The resulting mixture was refluxed for 3 - 7 d until the precipitate had disappeared. The reaction was terminated as soon as gaschromatographic analysis showed that all the 1,g-nonadiyne had reacted. After cooling, the solution was poured into a mixture of 150 mL of petroleum ether and 200 mL of 2 N HCl. The organic layer was separated and the aqueous layer washed two times with 50 mL of petroleum ether. The combined organic extracts were neutralized with saturated NaHC03 solution, dried with Na2S04 and the solution concentrated on a rotatory evaporator. The raw material was filtered through silica gel (CCl4, 10 cm, 50 mm) and recrystallized from 40 mL of ethanol at -15 "C. This afforded 5 to 6 g (64- 77%) of white crystals of 1,8-cyclotetradecadiynewith a characteristic odor, mp 98 OC12].

lH-NMR (CDC13, 200 MHz): 6 = 1.2 - 1.4 (m, 8 H, CH2), 1.4 - 2.0 (m, 4 H, C€12), 2.4 (m, 8 H, C&). 13C-NMR (CDC13,50.32 MHz): 6 = 18.4 (CH2). 26.7,28.0, 80.7 (S).

2.0 -

228

4.

4.12b

Alkenes, Arylalkenes and Cycloalkenes

Tetracyclo[7.5.2.0.02~*]hexadeca-2(8),15-diene-l5,l6dimethyldicarboxylate and

4 . 1 2 ~ Tetracyclor12.2.0.01'7.O 8'1 4]hexadeca-7(8),15-diene-l5,16dimethylcarboxylate[ 11 1 .) AICI, CH,CI, 188.3

'E

330.4

The following reaction was carried out under argon in dry CH2C12. A slurry of 2.7 g (20 mmol) of A1Cl3 (sublimed) and 20 mL of CH2C12 was cooled to -40 OC and a solution of 3.8 g (20 mmol) of 1,8-~yclotetradecadiynein 20 mL of CH2C12 was added slowly. The color of the solution turned to red, as the AlC13 is dissolved. The solution was allowed to warm to room temperature, stirred for 30 min and cooled to -20 "C. A solution of 5.7 g (40 mmol) of dimethyl acetylenedicarboxylate (DMAD) in 10 mL of CH2C12 and 10 mL of dimethyl sulfoxide in 40mL of CH2C12 were added successively. The mixture was poured onto 150 mL of ice water and 150 mL of pentane, separated, the aqueous layer extracted twice with 50 mL of pentane, and the organic layer dried over Na2S04 and concentrated on a rotary evaporator. The crude products (Rf= 0.25 - 0.35) were separated from the side products (Rf = 0.7 - 0.8) and DMAD (Rf = 0.5) by column cromatography (silica gel, CHzC12, 35 cm, 60 mm) affording 4 g (60%) of a mixture of 4.12b and 4 . 1 2 ~ in a ratio of 70:30. 4.12b: lH-NMR (CDC13,200 MHz): 6 = 1.1 - 2.3 (m, 20 H, C&), 3.76 (s, 6 H, OCI-13). 13C-NMR (CDC13, 50.32MHz): 6 = 26.5, 27.6, 28.4, 28.5, 29.2 and 33.2 (CH2), 51.5 (OCH3), 61.1 (C), 147.7 and 151.2 (=C), 162.8 EOO). IR (CDC13): v = 2834,1704,1618, 1307, 1202. W (acetonitrile): 3Lmm = 240 sh (lg E = 3.84), 190 sh (4.41). 4.12~: %NMR (CDC13,200 MHz): 6 = 1.2 - 2.4 (m, 20 H, C€J2), 3.77 (s, 6 H, OC_H3). 13C-NMR (CD2C12, 50.32MHz): 6 = 27.2, 28.1,28.3, 28.6 and 31.1 (CH2), 51.6 (OCH3), 60.4 (C), 146.5 and 150.3 (=Q, 163.5 EOO). IR (CDC13): v = 2930, 2878, 2844, 1734, 1720, 1709, 1695, 1691, 1430, 1306, 1234, 1190. UVNIS (CH3CN): hax = 244 sh (lg E = 3.05), 196 (4.08).

4.

229

Alkenes, Arylalkenes and Cycloalkenes

4.12d

Photochemical separation of 4.12b and 4 . 1 2 ~

hu

330.4

330.4

The isomeric Dewar benzenes 4.12b and 4.12~could be separated by photolysis: 800 mg (2.4mmol) of the Dewar benzene mixture was dissolved in 500 mL diethyl ether and irradiated (A 2 320 nm, 125 W high-pressure mercury lamp) for 2 to 3 h under an argon atmosphere at about 10 "C. While Dewar benzene 4.12b remained unchanged the second isomere 4.12~rearranged quantitatively into a twofold bridged phthalic ester derivative 4.12d. Separation by column chromatography (silica gel, petroleum ethedether 4: 1, 25 cm, 50 mm) afforded 500 mg of 4.12b (Rf = 0.23) and 270 mg of phthalic ester derivative 4.12d (Rf= 0.16).

lH-NMR (CDC13, 300 MHz): 6 = 1.5 - 1.8 (m, 12 H, Cl&), 2.78 - 2.82 (m, 4 H, C I 3 , 2.87 - 2.91 (m, 4 H, CH2), 3.84 (s, 6 H, OCH3). 13C-NMR (CDC13,75.47 MHz): 6 = 26.6,27.2, 29.4,30.8 and 31.4 (C_H2), 52.2 (OCH?), 128.9 and 139.0 (=C),143.3, 169.9 (COO). IR (CDC13): v = 2920,2828, 1725,1435, 1300, 1210, 1174. W (CH3CN): Lax = 285 (lg E = 3.15), 240 sh (3.8), 213 (4.45).

4.12e

Hexacyclo[9.5.0.0 1'3.O 2,lO.O 3,9.O 9,11]hexadeca-2,10-dimethyldicarboxylate [*341 and

4.12f

l-(l-Ethoxyethyl)-4-pentyl-6,7,8,9-tetrahydro-5~benzocycloheptane-2,3-dimethyldkarboxylate

404.6

330.4

330.4

230

4.

Alkenes, Arylalkenes and Cycloalkenes

500 mg of Dewar benzene 4.12b was dissolved in 500 mL of dry diethyl ether and irradiated for 48 to 60 h (A 2 320 nm, 125 W high-pressure mercury lamp). After removal of the solvent the crude mixture was separated by column chromatography (neutral alumina 111, petroleum ethedether 4:1, 28 cm, 50 mm) affording 225 mg of 4.12b (Rf= 0.23171), 195 mg of 4.12f (Rf= 0.15[71)and 115 mg of 4.12e (Rf= 0.10[7]). Prismane 4.12e is a clear oil which can be crystallized from pentane, its yield depends on the purity of starting material 4.12b.

Note: The existence of 4.12f

can be accounted for by formation of a [5]paracyclophane intermediate, cleavage of the para bridge and insertion of diethyl ether which serves as a solventPI.

4.12e: 'H-NMR (CDCl,, 300 MHz): 6 = 1.73 (s, br, 20 H, CEJ2), 3.66 (s, 6 H, OC_H3). 13C-NMR (CDC13, 75.46 MHz): 6 = 24.5, 30.8 and 32.2 (CH2), 42.2 (C),51.0 (OCH3), 57.0 (C),169.7 (COO). IR (CDC13): v = 2928,2842, 1688, 1431, 1304, 1194. UV (CH3CN): hax = 248 sh (Ig E = 3.34), 208 (3.95). 4.12f: lH-NMR (CDC13 300 MHz): 6 = 0.9 (m, 3 H, CH3), 1.1 (t. 3 H, 3J(H,H) = 7.0, C_H3), 1.2 - 1.4 (m, 4 H, C€&), 1.57 (d, 3 H, 3J(H,H) = 6.7, C&), 1.4 - 1.7 (m, 6 H, C_H2), 1.7 - 1.8 (m, 2 H, C&), 2.4 - 2.7 (m, 2 H, C_H2),2.8 - 3.0 (m, 4 H, C&), 3.1 - 3.4 (m, 2 H, C&O), 3.82 (s, 3 H, OC_H3), 3.84 (s, 3 H, OC_H3), 4.64 (q, 1 H, 3J(H,H) = 6.7,

a).

13C-NMR (50.32MHz, CDC13): 6 = 13.9, 14.9 and 22.3 cH3), 22.4, 26.7, 26.9, 28.5, 28.8, 30.8, 30.9, 31.3 and 32.1 (CHz), 52.0 and 52.2 (OCH3), 65.1 (OCHz), 75.8 169.7 and 170.3 coo). (OCH), 129.2, 130.5, 136.0, 136.4, 144.0 and 144.7 (-S), IR (CDC13): v = 2920,2848,1733,1719,1305,1280,1199,1176. UV (ether): hax = 245 sh (lg E = 3.72), 212 (4.44).

R. Gleiter, B. Treptow, Angew. Chem. 1990, 102, 1452 - 1454; Angew. Chem. Znt. Ed. Engl. 1990,29, 1427 - 1429. J. Dale, A. J. Hubert, G. S. D. King, J. Chem. Soc. 1963,73 - 86. R. Gleiter, R. Merger, G. Pflasterer, B. Treptow, W. Wittwer, Synthesis 1993, in press. Houben-Weyl, Vol. V/2a, 497; Houben-Weyl, Vol. V/2a, 355; 0. F. Beumel, R. F. Harris, J. Org. Chem. 1963,28,2775 - 2779. l,5-Diiodopentane: To a saturated solution of 225 g NaI (1.5 mol) in acetone is added 115 g (0.5 mol) of 1,5-dibr0mopentane[~].The solution is stirred under exclusion of light at room temperature for 24 h. In this time a white voluminous precipitate of NaCl is formed. After the reaction is complete (controlled by GC) 1 L of water is added. The solution is extracted four times with 200 mL of CH2C12. The combined organic layers are dried over MgS04 and the solvent is removed in vucuo.

4.

[6]

[7] [8]

Alkenes, Arylalkenes and Cycloalkenes

23 1

The crude product is purified by distillation under reduced pressure (bp 101 102 "C/3mbar). Yield 146 g (90%) of 1,5-diiodpentane. 1,5-D)ibromopentane:To 50 g (47 mol) of cooled (0 "C) neat 1S-pentanediol is added dropwise 47 g of conc. H2S04 and subsequently 244 g of aqueous HBr (48%). After refluxing for 6 h the phases are separated and the aqueous phase is extracted three times with 50 mL of CC14. The organic phase is washed two times with 5% NaHC03 solution and dried over MgSO,. After removal of the solvent the residue is distilled with a Vigreux column (bp 97 - 100 "C/20 mbar). Yield 77.2 g (71%) of 1,5-dibromopentane. Thin layer chromatography is carried out on silica gel plastic sheets. R. Gleiter, B. Treptow, J. Org. Chem., submitted.

232

4.

4.13

Alkenes, Arylalkenes and Cycloalkenes

Hexahelicener* A W. H. Laarhoven

submitted by

4.13a

2-(4-Methylstyryl)naphthalene CH,Br

PPh,

mcH2p /

221.1

483.4

262.3

CH3 120.2

0

483.4

244.3

A solution of 4.4 g (20 mmol) of 2-bromomethylnaphthalene and 5.2 g of triphenylphosphine in 400 mL of xylene was boiled for 5 h. After cooling the precipitate was filtered off and washed with hexane and cold dry ether. The salt (mp 247 - 248 "C)was used in a Wittig synthesis without further purification. To a solution of 9.66 g (20 mmol) of 2-naphthylmethyltriphenylphosphoniumbromide and 2.40 g (20 mmol) of p-tolualdehyde in methanol (80 mL) a solution of freshly prepared sodium methoxide (2.16 g, 40 mmol) in methanol (20 mL) was added with vigourous stirring which was continued overnight. The precipitated product was filtered off. The solvent of the filtrate was evaporated and the residue, after addition of water, was extracted with toluene. The extract was dried over MgS04, the solvent evaporated and the residue chromatographed over silica gel. After elution of some 2-methylnaphthalene with carbontetrachloride, the product mixture was eluted with toluene. The total yield was 3.45g (70%) of cis and trans 2-(4-methylstyryl)naphthalene. (trans, mp 186 "C).

4.

233

Alkenes, Arylalkenes and Cycloalkenes

4.13b

2-Methylbenzo[c]phenanthrene

'2

244.3

-

242.3

To a M solution of 2-(4-methylstyryl)naphthalene (one isomer or a mixture of both) in methanol was added about 25 mg of iodine. The solution was irradiated by a highpressure mercury lamp (Philips, HPK 125) which was surrounded by a Pyrex tube and immersed into the solution. After 16 h the solvent was evaporated. A small volume of CCl, was added to the residue and again evaporated. This procedure was repeated until the violet color of iodine was not present anymore in the distillate. The residue was purified by chromatography on silica gel and toluene. 2-methylbenzo[c]phenanthrene was isolated in 70% yield and melted at 82 - 83 "C.

IEI-NMR (CDC13): 6 = 2.60 ppm (s, 3 H, Me), 7.07 - 7.93 (m,11 H),8.70 (s, 1-H), 8.97 (m, 12-H).

4.13~ 2-Styrylbenzo[c]phenanthrene

\

\

0

0

242.3

178.0

____c

\

\

/

/

321.2

262.3

583.5

a solution of 485 mg (2 mmol) of 2-methylbenzo[c]phenanthrene in 10 mL of CC14 Ccvas added 356 mg (2 mmol) of freshly crystallized N-bromosuccinimide (NBS) and a few @gof benzoyl peroxyde. The mixture was irradiated with a tungsten lamp and refluxed 1the NBS was consumed. The reaction mixture was cooled to room temperature, dltered to remove the succinimide and concentrated under reduced pressure to give a light &OW oil of 2-bromomethylbenzo[c]phenanthrene, which crystallized on standing (mp .)- 96 "C). The bromide was dissolved in 20 mL of toluene, 524 mg (2 mmol) of dphenylphosphine was added and the solution stirred overnight. The precipitated 6 0

234

4.

Alkenes, Arylalkenes and Cycloalkenes

phosphonium salt (950 mg, 90% yield) was filtered off, washed with cold ether and dried, mp 320 - 321 "C.

583.5

106.1

330.4

The phosphonium salt was subjected to a Wittig reaction with a dimethylfonnamide solution of 212 mg (2mmol) of benzaldehyde and sodium methoxide as a base. The solution was heated at about 80 "C and stirred for 8 h. After cooling, water was added and the mixture extracted with toluene. The combined extracts were washed with water, dried over MgS04 and the solvent evaporated. After column chromatography of the residue on aluminium oxide with CC14 as the eluant the cis-isomer of 2-~tyryIbenzo[c]phenanthrenewas isolated, whereas the trans-isomer was obtained after elution with a mixture of hexane and toluene (15). The overall yield was 65% (mp cis: 142 - 144 "C,mp rrans: 224 - 226 "C).

cis-4.13c: 'H-NMR (CDC13): 6 = 6.72(ethylene), 7.0- 7.9(m, 14 H),8.40 (12-H),8.98 (1-H).

trans-4.13~: lH-NMR (CDC13): 6 = 7.23(ethylene), 9.08(1-H), 9.12(m,12-H).

4.13d

Hexahelicene

hu

@ ' '1

/

330.4

/

328.4

4.

Alkenes, Arylalkenes and Cycloalkenes

235

To a l o 3 M solution of 2-styrylbenzo[c]phenanthrene (one isomer or a mixture of both) in toluene was added about 25 mg of iodine. The solution was irradiated by a high-pressure mercury lamp (Philips, HPK IZS), which was surrounded by a pyrex tube and immersed into the solution. After 8 h the solvent was evaporated. A small volume of CC14 was added to the residue and again evaporated. This procedure was repeated until the violet color of iodine was not present anymore in the distillate. The residue was purified by chromatography on silica gel. Hexahelicene was isolated in 80% yield and melted at 240 - 242 "C after crystallization from ethyl acetate.

lH-NMR (CDC13): 6 = 6.65 (m, 2-H, 15-H), 7.18 (m, 3-H, 14-H), 7.58 (dd, 1-H, 16-H), 7.78 (dd, 4-H, 13-H), 7.87 (m, 5-H, 6-H, 11-H, 12-H), 7.92 (m, 7-H, 8-H, 9-H, 10-H). UV (CH30H): h,, = 407 (log E = 2.47), 387 (2.79), 345 (4.09), 323 (4.43), 312 (4.45), 300 (sh, 4.26), 287 (sh, 4.14), 260 (4.72), 253 (4.76), 247 (sh, 4.71), 228 (4.68).

[l] [2]

For a review about helicenes see: W. H. Laarhoven, W. J. C. Prinsen, Topics in Current Chemistry 1984,125,63 - 130. For reviews about photocyclizations of 1,Zdiarylethylenes see: W. H. Laarhoven, Recl. Trav. Chim. Pays Bas 1983, 102, 185 - 204 and 241 - 54; F. B. Mallory, C . W. Mallory, Org. Reactions 1984, 30, 1 - 456; W. H. Laarhoven, Org. Photochemistry 1989,10,163 - 308.

236

4.14

4.

Triphenanthro-anellated[181 Annulenes Liquid Crystals[ll submitted by

4.14a

Alkenes, Atylalkenes and Cycloalkenes

H. Meier, H. Kretzschmann

2,3-Bis(hexyloxy)toluene[~l H3c&oH

C,H,,Br / KOH (Aliquat 336)

124.1

165.1

-H3C6 OCIHl3

292.5

To a stirred solution of 12.40 g (0.1Omol) of 3-methyl-l,2-benzenediolin 40mL of 1,2dimethoxyethane was added slowly 14.00g (0.24mol) of powdered KOH and then 41.25 g (0.25 mol) of 1-bromohexane and 4.05 g (0.01 mol) of Aliquat 336. After 18 h refluxing the hot reaction mixture was filtered and the solvent rota-evaporated. The residue was purified by column chromatography (10 x 15 cm silica gel, dichloromethane). The yield of the analytically pure, oily compound amounted to 28.40 g (97%). IH-NMR (CDCl3, 400 MHz): 6 = 0.90 (t, 6 H, CH3), 1.33 (m, 8 H, CH2), 1.48 (m, 4 H, CH2), 1.78 (m, 4 H, CH2), 2.26 (s, 3 H, Ar-CH3), 3.92 (t, 2 H, OCH2), 3.94 (t, 2 H, OCH2), 6.72 (d, 1 H, 4-/5-/6-H), 6.73 (d, 1 H, 4-/5-/6-H), 6.89 (t, 1 H, 44.546-H). 13C-NMR (CDC13, 100 MHz): 6 = 14.0/14.0/16.0 (CH3), 22.6/22.6/25.8/25.9/29.4/30.4/ 31.6131.8 (CH2), 68.6172.7 (OCH2), 111.2 (C-4), 122.6/123.2 (C-5, C-6), 132.1 (C-l), 146.9 (C-2), 152.3 (C-3). IR (thin film): v = 3040, 3000,2960,2900, 1590, 1500, 1480, 1390, 1320, 1280, 1230, 1100,780,750.

4.

237

Alkenes, Arylalkenes and Cycloalkenes

4.14b

3,4-Bis(hexyloxy)-2-methylbenzaldehyde~~~ (Rieche Formylation)

H3c613 OCBH,,

292.5

H&-O-CHCIZ

H,C$

(SnCI,)

OHC

115.0

H,,

320.5

A solution of 27.10 g (92.8 mmol) of 4.14a in 30 mL of dichloromethane was cooled to 0 "C and 36.25 g (139.0 mmol) of SnC14 was added slowly. After stirring for 1 h at 0 "C 16.00 g (139.0 mmol) of dichloromethyl methyl ether was added dropwise. The reaction mixture was kept for 1 h at 0 'C, an additional 1 h at room temperature and then poured on 200 g of crushed ice. The organic layer was separated and the neutralized water phase extracted with 3 x 50 mL, of ether. The combined organic layers were washed with water, a saturated solution of NaHC03 and again with water, dried and rota-evaporated. The purification by column chromatography (10 x 40 cm silica gel, petroleum ether (40 - 70 OC)/ ether 10:1) afforded 1.56 g (5%) of 2,3-bis(hexyloxy)-4-methylbenzaldehyde,2.20 g (7%) of 3,4-bis(hexyloxy)-5-methylbenzaldehyde and 20.82 g (70%) of 3,4-bis(hexyloxy)-2methylbenzaldehyde4.14b as colorless liquids.

'H-NMR (CDC13, 200 MHz): 6 = 0.88 (t, 6 H, CH3), 1.32 (m, 8 H, CH2), 1.45 (m, 4 H, CH,), 1.78 (m, 4 H , CH2), 2.55 (s, 3 H, Ar-CH3), 3.86 (t, 2H, OCH2), 4.00 (t, 2 H , OCH2), 6.81 (d, 1 H, Ar-H), 7.50 (d, 1 H, Ar-H), 10.05 (s, 1 H, CHO). 13C-NMR (CDC13, 100 MHz): 6 = 11.3/13.9/14.0 (CH3), 22.5/22.6/25.7/25.7/29.1/30.2/ 31.5131.7 (CH2), 68373.0 (OCH2), 109.8 (C-5), 128.2 (C-6), 129.7 (C-l), 134.9 (C-2), 146.8 (C-3), 157.0 (C-4), 191.4 (CHO). IR (thin film): v = 2940 , 2840, 2710, 1670, 1575, 1555, 1480, 1450, 1435, 1370, 1260, 1240,1230, 1060,800.

238

4.

Alkenes, Arylalkenes and Cycloalkenes

4.14~ (E)- and (Z)-l-[3,4-Bis(hexyloxy)-2-methylphenyl]-2phenylethene[1 1

(WittigReaction)

320.5

388.9

394.6

A solution of 0.87 g (37.5 mmol) of sodium in 30 mL of dry ethanol was dropped quickly under nitrogen into a stirred solution of 14.57 g (37.5 mmol) of benzyltriphenylphosphonium chloride in 150 mL of dry ethanol. The reaction mixture became turbid and pale yellow within 10 min at room temperature After having slowly added 12.00 g (37.5 mmol) of 4.14b in 50 mL of absolute ethanol the mixture was stirred for an additional 3 h. It turned colorless but was still turbid. Rota-evaporation afforded a residue which was heated for 10 min under reflux in 200 mL of hexane. Triphenylphosphane oxide was filtered off and the solvent removed from the filtrate. The remaining brown oil was purified by column chromatography (10 x 15 cm silica gel, petroleum ether (40 70 "C)/ether 1O:l). Principally the stereoisomers could be separated by a second column chromatography. However, the ZIE mixture (Colorless oil, yield 12.40 g (84%)) was used in the following reaction step. @)-isomer: lH-NMR (CDC13, 400 MHz): 6 = 0.91 (t, 6 H, CH3), 1.35 (m, 8 H, CH2), 1.50 (m, 4 H, CHz), 1.80 (m, 4 H, CH2), 2.34 (s, 3 H, Ar-CH3), 3.90 (t, 2 H, OCH,), 3.98 (t, 2 H, OCH& 6.76 (d, 1 H, Ar-H), 6.8717.27 (AB, 3J = 16.1, 2 H, olefinic H), 7.23 (t, 1 H, H , phenyl), 7.29 (d, 1 H, Ar-H), 7.34 (t, 2 H, H,, phenyl), 7.49 (d, 2 H, H,, phenyl). l3C&MR (CDC13, 50 MHz): 6 = 12.2/14.0/14.0 (CH3), 22.6/22.7/25.8/25.8/29.4/30.4/ 31.6131.8 (CH3), 68.6172.9 (OCH2), 110.9 (C-5), 120.9 (C-6), 126.3 (0-C, phenyl), 126.8/127.2/128.5 (CH), 128.6 (m-C, phenyl), 130.1/130.4/138.0/146.7/15 1.9 (Cq). IR (thin film): v = 3020., 2940, 2900, 2840, 1590, 1480, 1455, 1370, 1280, 1260, 1200, 1060,955,795,740,690.

(3-' isomer:

lH-NMR (CDC13, 400 MHz): 6 = 0.90 (t, 6 H, CH3), 1.33 (m, 8 H, CH2), 1.49 (m, 4 H, CH2), 1.78 (m, 4 H, CH2), 2.17 (s, 3 H, Ar-CH3), 3.92 (m, 4 H, OCH,), 6.5U6.59 (AB,3 J = 12.3, 2 H, olefinic H), 6.59 (d, 1 H, Ar-H), 6.81 (d, 1 H, Ar-H), 7.11 (m, 5 H, H,,,,p. phenyl).

4.

239

Alkenes, Arylalkenes and Cycloalkenes

13C-NMR (CDCl3, 100 MHz): 6 = 12.9/14.0/14.1 (CH3), 22.6/22.7/25.9/25.9/29.5/30.4/ 31.6/31.8 (CH2), 68.4172.8 (OCH3), 110.7 (C-5), 124.1 (C-6), 126.8 (CH), 128.0A28.9 (0-C, m-C, phenyl), 1 2 9 3130.0 (CH), 130.4/ 130.6/137.3/146.8/ 151.4 (Cq). IR (thin film): v = 3020 , 2940, 2900, 2840, 1590, 1480, 1460, 1440, 1370, 1290, 1260, 1210,1070,800,780,690.

4.14d

2,3-Bis(hexy1oxy)-1-methy1phenanthrene[ 11 C6H130,

394.6

253.8

392.6

A solution of 6.00 g (15.2 mmol) of 4 . 1 4 ~and 2.60 g (10.2 mmol) of iodine in 2 L of dry cyclohexane was irradiated for 42 h with a Hanovia 450 W mercury vapor lamp equipped with a Vycor filter (Alternatively, an equimolar amount of I2 with an excess of methyloxirane can be usedL2I). The reaction mixture was treated with an aqueous solution of Na2S203 in order to reduce the excess iodine, dried over Na2S04 and rota-evaporated. The residue was purified twice by column chromatography (10 x 5 cm alumina, ether and 10 x 15 cm silica gel, dichloromethane) yielding 4.47 g (75%) of an analytically pure, colorless oil.

lH-NMR (CDC13, 400 MHz): 6 = 0.93 (t, 6 H, CH3), 1.40 (m, 8 H, CH2), 1.55 (m, 4 H, CH2), 1.85 (m, 2H, CH2), 1.94 (m, 2H, CH2), 2.65 (s, 3 H, 1-CH3), 4.02 (t, 2 H , 2-OCH2), 4.21 (t, 2 H , 3-OCH2), 7.53 (m, 1 H, 7-H), 7.59 (m, 1 H, 6-H), 7.65 (d, 1 H, 9-H), 7.86 (m, 2 H, 8-H, 10-H), 7.94 (s, 1 H, 4-H), 8.55 (d, 1 H, 5-H). 13C-NMR (CDC13, 100 MHz): 6 = 11.8/14.0/14.0 (CH3), 22.7/22.7/25.9/26.0/29.4/30.4/ 31.6131.8 (CH2), 68.5 (3-OCH2), 73.4 (2-OCH2), 102.8 (C-4), 122.6 (C-5), 122.9 (C-lo), 124.5 (C-9), 125.81126.0 (C-6, C-7), 126.3/127,3/127.3 (C-1, C-4a, C-lOa), 128.5 (C-8), 130.0 (C-8a), 131.6 (C-4b), 146.7 (C-2), 152.0 (C-3). IR (thin film): v = 3040, 2950, 2920, 2860, 1590, 1460, 1380, 1270, 1230, 1200, 1070, 810, 750.

240

4.

4.14e

Alkenes, Arylalkenes and Cycloalkenes

2,3-Bis(hexyloxy)-l-methylphenanthrene-9-~rbaldehyde~~~ (Rieche Formylation)

C6H130

C6Hl,0 H3C

392.6

115.0

420.6

CHO

Into a solution of 2.00 g (5.1 mmol) of 4.14d in 15 mL of dichloromethane 1.82 g (7.0mmol) of SnC14 was dropped at 0 "C. After 1 h stimng 0.81 g (7.0mmol) of dichloromethyl methyl ether was added slowly while cooling. HCl gas evolved and the reaction mixture turned red. It was warmed up to room temperature and poured onto 50 g of crushed ice. The water phase was extracted with dichloromethane (3 x 30 mL) and the extract combined with the organic layer. After washing with water, aqueous solution of NaHCO3 and again water, the solution was dried over Na2S04 and rota-evaporated. Column chromatography (3 x 80 cm silica gel, dichloromethane) yields 1.67 g (78%) of a colorless oil.

lH-NMR (CDC13, 200 MHz): 6 = 0.93 (t, 6 H, CH3), 1.38 (m, 8 H, CH2), 1.55 (m, 4 H, CH2), 1.89 (m, 4 H , CH2). 2.67 (s, 3 H, l-CH3), 4.00 (t, 2 H , OCH2), 4.19 (t, 2 H , OCH2), 7.63 (m, 2 H , 6-H, 7-H), 7.81 (s, 1 H, 4-H), 8.26 (s, 1 H, 10-H), 8.48 (m, 1 H, 5-H), 9.33 (m, 1 H, 8-H), 10.27 (s, 1 H, CHO). 13C-NMR (CDC13, 100 MHz): 6 = 11.7/14.0/14.1 (CH3), 22.6/22.6/25.8/25.9/29.2/30.3/ 31.6/31.7 (CH2), 68.4173.4 (OCHZ), 102.4 (C-4), 122.6 (C-5), 124.3 (Cq), 125.W 126.91127.5 (CH), 127.9/129.3/130.1/130.9 (Cq), 137.6 (CH), 146.8 (C-2), 154.9 (C-3), 193.6 (CHO). IR (thin film): v = 2940, 2840, 2720, 1665, 1590, 1450, 1380, 1270, 1230, 1180, 1070, 1050,745.

4.

24 1

Alkenes, Arylalkenes and Cycloalkenes

4.14f

(E)-N-Phenyl-2~-bis(hexyloxy)-l-methylphenanthrene-9carbaldimine[l]

CGH5NH* 420.6

CHO

93.1

*

495.7

"1

C-H

\

C6H!5

An equimolar mixture of 1.53 g (3.6 mmol) of 4.M and 0.34 g (3.6 mmol) of aniline was stirred for 6 h at 60 "C. Several times the water generated in the reaction was removed by reducing the pressure. Finally the slightly green oil began to crystallize and 1.80 g (100%) of 4.14f could be obtained; mp 60 "C.

'H-NMR (CDCl3, 400 MHz): 6 = 0.95 (t, 6 H, CH3), 1.41 (m, 8 H, CH2), 1.57 (m, 4 H, (3321, 1.86 (m, 2H, (3421, 1.96 (m, 2H, CHz), 2.72 (s, 3 H, l-CH3), 4.03 (t. 2H, 2-OCH2), 4.22 (t, 2 H, 3-OCH2), 7.27 (t, 1 H, Hp, phenyl), 7.33 (d, 2 H, H,, phenyl), 7.45 (t, 2 H, b,phenyl), 7.65 (m, 2 H, 6-H, 7-H), 7.91 (s, 1 H, 4-H), 8.41 (s, 1 H, 10-H), 8.59 (d, 1 H, 5-H), 9.05 (s, 1 H, CHN), 9.28 (m, 1 H, 8-H). 13C-NMR (CDC13, 100 MHz): 6 = 11.8/14.0/14.0 (CH3), 22.6/22.6/25.8/25.9/29.3/30.4/ 31.6/31.8 (CH2), 68.4173.4 (OCH2), 102.6 (C-4), 120.9 (o-C, phenyl), 122.9/125.5/ 125.6/126.4/126.7 (CH), 125.2/127.8/128.6 (Cq), 129.1 (m-C, phenyl, 129.3A29.3 (Cq), 129.4 (CH), 130.4 (Cq), 146.8 (C-2), 153.0A53.6 (C-3 and C,, phenyl), 161.3 (CHN). IR (KBr): v = 3080,3050, 2920,2850, 1620, 1580, 1480, 1450, 1370, 1270, 1080, 750, 690.

242

4.14g

4.

Alkenes, Arylalkenes and Cycloalkenes

(SE,17E,26E)-6,7,15,16,24,25-Hexakis( hexyloxy)t riphenanthro[S,9,1O-abc:S,9,10-ghi:8,9,10-mno]cyclooctadecenei 11 C6H130

495.7

N"C-H \

t

I

To a solution of 1.16 g (10.3 mmol) of KOQu in 100 mL of DMF (freshly distilled over CaH,) 1.70 g (3.4 mmol) of 4.14f in 120 mL of DMF was dropped slowly at 85 "C in a nitrogen atmosphere. After vigorous stirring for 2 h, the dark reaction mixture was cooled to 5 "C and 100 mL of water and 100 mL of 2 N HCl were added. The temperature was kept at 5 "C and a brown glutinous residue was separated. Standing overnight in methanol afforded a solid raw product, which was dried in vucuo at 30 "C. Column chromatography (3 x 100 cm silica gel, dichloromethane) furnished a first fraction that contained a green fluorescing compound which was recrystallized from acetone to yield 135 mg (10%) of yellow-green needles.

4.

Alkenes, Arylalkenes and Cycloalkenes

243

The system represents a discotic mesogen of an immense diameter (1.6 nm), with six flexible side chains. The crystalline phase is transformed at 115 "C to a broad nematic phase N, in which two discs have a parallel arrangement with an average distance of 0.43 nm. Finally, the isotropic melt is formed at 192 "C.

Figure 4: Texture of the highly mobile, photosensitive nematic phase ND of the title compound measured by polarization microscopy (scale 1:340).

k N M R (CDC13, 400 MHz): 6 = 0.89 (t, 9 H, CH3), 1.02 (t, 9 H, CH3), 1.28 (m, 12 H, CH2), 1.45 (m, 18H, CH2), 1.65 (m, 6H, CH2), 1.90 (m, 6H, CH2), 1.99 (m, 6H, CH2), 4.03 (t, 6 H, 7-OCH2, 16-OCH2, 25-OCH2), 4.19 (t, 6 H, 6-OCH2, 15-OCH2, 24-OCH2), 7.34 (d, 3J = 16.1, 3 H, 8-H, 17-H, 26-H), 7.52 (t, 3 H, 2-H, 11-H, 20-H), 7.60 (t, 3 H, 3-H, 12-H, 21-H), 7.94 (s, 3 H, 5-H, 14-H, 23-H), 8.1 1 (d, 3J = 16.1, 3 H, 9-H, 18-H, 27-H), 8.19 (s, 3 H, 28-H, 29-H, 30-H), 8.40 (d, 3 H, 1-H, 10-H, 19-H), 8.54 (d, 3 H, 4-H, 13-H, 22-H). 13C-NMR (CDC13, 100 MHz): 6 = 14.0/14.1 (CH3), 22.6/22.7/25.9/26.1/29.6/30.7/31.8/ 32.0 (CH2), 68.5173.4 (OCH2), 103.7 (C-5, C-14, C-23), 119.2 (C-28, C-29, C-30), 122.8 (C-4, C-13, C-22), 123.1 (C-8, C-17, C-26), 125.4 (C-1, C-10, C-19), 125.5 (C28a, C-29a, C-30a), 125.7 (C-2, C-11, C-20), 126.0 (C-3, C-12, C-21), 127.2 (C-4b, C13b, C-22b), 128.9 (C-7a, C-16a, C-25a), 129.8 (C-4a, C-l3a, C-22a), 130.6 (C-9b, C18b, C-27b), 132.9 (C-9a, C-l8a, C-27a). 135.9 (C-9, C-18, C-27), 146.8 (C-7, C-16, C-25), 152.1 (C-6, C-15, C-24). IR (KBr): v = 3060,2940,2900,2840, 1570, 1470, 1430, 1410, 1370, 1270, 1240, 1220, 1180,1070,970,830,770,740.

[ 11 [2]

H. Meier, H. Kretzschmann, H. Kolshorn, J. Org. Chem., in press 1993. L. Liu, B. Yang, T. J. Katz, M. K. Poindexter, J. Org. Chem. 1991,56, 3769 - 3775.

244

4.15

4.

-

Ethyl-S-oxo-4-isopropyl-bicyclo[ 3.2.lloctane-1 carboxylate submitted by

4.15a

Alkenes, Arylalkenes and Cycloulkenes

A. Heidbreder and J. Mattay

Ethyl-l-(4-methyl-3-pentenyl)-2-oxocyclopen~ne-lcarboxylate

156.2

163.1

'

238.3

24.2 g (0.15mol) of ethyl-2-oxocyclopentane-1-carboxylate were added dropwise to a stirred solution of 17.7 g (0.16mol) of potassium tert-butoxide in 600 mL of dry dimethyl were added sulfoxide. After 1 h, 26.9 g (0.16mol) of l-bromo-4-methyl-3-pntene[1] dropwise. After 40 h at ambient temperature the solution was diluted with water (600mL) and extracted with ethyl acetate (3 x 250 mL). The combined organic layers were washed with water and brine (250mL each), dried with magnesium sulfate and evaporated. The crude yellowish product was purified by column chromatography (silica gel, cyclohexand ethyl acetate 955) to yield 34.7 g (92%) of ethyl-l-(4-methyl-3-pentenyl)-2-oxocyclopentane-1 -carboxylate as a colorless liquid. *H-NMR (CDC13, 300 MHz): 6 = 1.25 (t, 3 H, J = 7.0,C02Et), 1.60 (s, 3 H), 1.65 (s, 3 H), 1.70- 2.10(m, 7 H), 2.20- 2.30 (m, 1 H), 2.30 - 2.50 (m, 1 H), 2.50 - 2.60 (m, 1 H), 4.15 (q, 2 H, J = 7.0, CO2Et), 5.05 (m, 1 H). 13C-NMR (CDC13, 75 MHz): 6 = 13.9 (CH3, CO,Et), 17.3 (CH3), 19.4 (CH2), 23.4 (CH2), 25.4 (CH3), 32.5 (CHZ), 33.7 (CHZ), 37.7 (CH2), 60.2 (C-l),61.1 (OCH2), 123.2(CH=), 132.1 (s, =C(CH3)2), 170.7 ( G O , C02Et), 214.3 (C=O, C-2). IR (neat): v = 3000,2950,1755 (s), 1725 (s), 1450,1370,1260,1220,1150,1025,825. MS (GC): m/z = 238 (1, M+), 165 (3, 157 (lo), 156 (lo), 110 (lo), 83 (75), 82 (18), 67 (14),55 (100).41 (25).

4.

245

Alkenes, Arylalkenes and Cycloalkenes

4.15b

Ethyl-l-(4-methyl-3-pentenyl)-2-trimethylsilylox~ cyclopent-2-enyl-1-carboxylate

(fy Me,Si

1.) LDA, THF, -78OC

*

C02Et

238.3

2.) Me,SiCI

COZEt

31 0.5

A solution of 8.4 mL (60mmol) of diisopropylamine in 125 mL of dry tetrahydrofuran (THF) was placed under an argon atmosphere into a flame-dried three-necked flask equipped with a septum cap. The solution was cooled to 0 "C and 33 mL (53 mmol) of a 1.6M solution of n-butyllithium in n-hexane were carefully added via a syringe. After stirring 30 min at 0 "C the solution was cooled to -78"C and a solution of 11.9g (50mmol) of ethyl-1 -(4-methyl-3-pentenyl)-2-oxocyclopentane1 -carboxylate 4.15a in 10 mL of dry THF was added dropwise over a period of 10 min. After 1 h at -78"C 1 1 mL (87mmol) of chlorotrimethylsilane were added, the solution was allowed to warm up, and stirred at room temperature for 1 h. The solvent was evaporated, the residue was suspended in 50 mL of dry pentane, and LiCl was removed by filtration. After evaporation of the solvent the crude product was distilled (96"C/0.05 mbar) to give 12.8 g (83%) of ethyl-l-(4-methyl-3-pentenyl)-2-trimethylsilyloxy-cyclo~nt-2-enyl-l-carboxylate as a colorless oil.

'H-NMR (CDC13, 300 MHz): 6 = 0.20 (s, 9 H, Si(CH3)3), 1.25 (t, 3 H,J = 7.0, C02Et), - 1.65 (m, 1 H), 1.60 (s, 3 H), 1.68 (s, 3 H), 1.75 - 2.00 (m, 3 H),2.10 - 2.30 (m, g 1.50 1 H), 2.30- 2.45 (m, 2 H), 4.15(9, 2 H, J = 7.0,C02Et), 4.65(s, 1 H), 5.15 (m, 1 H). 1 13C-NMR (CDC13, 75 MHz): 6 = -0.4(Si(CH3)3), 14.1 (CH3, C02Et), 17.3 (CH3), 23.2 (CH2), 25.5 (CH3), 26.3 (CH2), 31.8 (CHz), 34.6 (CH2), 57.9 (C-3), 60.0 (CH2, C02Et), 102.3 (CH=, C-l), 124.4(CH=), 131.1 (=C(CH3)2, 153.3 (=COSiMe3, C-2), 174.9 ((20, C02Et). IR (neat): v = 3000,2950,1730 (s), 1650,1450,1330,1220,1160,1060,1030,865,845. (m):m/z = 310 (12,M'), 267 (14),239 (20),237 (25),228 (53), 213 (72), 185 (58), 182 (44),169 (30),167 (30). 110 (34),109 (34),83 (38).82 (36),75 (66),73 (loo), 69 (76),67 (32),55 (70). (.

1 I

246

4.

31 0.5

Alkenes,Arylalkenes and Cycloalkenes

238.3

A solution of 1.4 g (4.5 mmol) of ethyl-l-(4-methyl-3-pentenyl)-2-trimethylsilyloxycyclopent-2-enyl-1-carboxylate4.15b and 103 mg (0.45 mmol) of 9,lO-dicyanoanthracene (DCA) in 1OOmL of dry acetonitrile was degassed by argon bubbling and distributed among 10 mL Duran glass tubes. After purging the tubes with argon for 1 min, they were sealed and irradiated for 100 h in a Rayonet reactor fitted with 450-nm lamps and a merry-go-round inset. The solvent was evaporated and purification by HPLC (20x 250 mm LiChrosorb Si 60-5, cyclohexandethyl acetate 97:3) lead to 0.5 g (47%) of ethyl8-oxo-4-isopropyl-bicyclo[3.2.l]octane-l-carboxylateand 0.18 g (17%) of 4.15a as a byproduct resulting from solvolysis of the intermediate radical cation.

'H-NMR (CDC13,3OO MHz): 6 = 0.58 (d, 3 H, J = 6.5, CH3), 0.61 (d, 3 H, J = 6.5, CH3), 0.80 - 1.00 (m, 1 H, 3-H), 1.05 (t, 3 H, J = 7.0, C02Et), 1.10 (m, 1 H, CH(CHCJ~), 1.20 - 1.40 (m, 4 H, 3-H, 4-H, 6-H,,, 6-He ), 1.50 (ddd, 1 H, J = 1.5, 5.0, 12.5, 7-H), 1.85 (ddd, 1 H, J = 1.5,6.0, 13.5,2-H), 2.12 (dddd, 1 H, J = 1.5, 5.5, 13.5, 13.5, 2-H), 2.30(d, 1 H, J=7.0,5-H),2.50(dddd, 1 H, J = 1.5,5.0, 12.5, 12.5,7-H),4.10(q, 2H, J = 7.0, C02Et). 13C-NMR (CDC13, 75 MHz): 6 = 13.9 (CH3, C02Et), 17.3 (CH2, C-6), 20.7 (2 x CH3), 22.7 (CH2, C-3), 27.2 (CH2, C-7), 30.3 (CH, CH(CH3)2), 36.6 (CH2, C-2), 48.0 (CH, C-5), 57.1 (C-l), 60.7 (CH2, C02Et), 171.2 (C=O, C02Et), 215.2 (C=O, C-8). IR (neat): v = 3000,2800, 1750 (s), 1730 (s), 1450, 1390, 1370, 1350, 1300, 1250, 1175, 1080,1025,850. MS (GC): m/z = 238 (35, M+). 210 (90), 167 (70), 136 (36), 121 (50), 95 (3d6), 93 (loo), 81 (45),79 (32), 67 (30), 55 (50),43 (35),41 (52).

[ 13

[2]

L.-F. Tietze, Th. Eicher in Reaktionen und Synthesen im organisch-chemischen Praktikum, 1981, Thieme, Stuttgart, 224. A. Heidbreder, J. Mattay, Tetrahedron Left. 1992,33, 1973 - 1976.

4.

247

Alkenes, Arylalkenes and Cycloalkenes

4.16

An example of a gas phase photolysis: Semibullvalene from cyclooctatetraene"] submitted by H. E. Zimmerman

104.2

104.2

Three 100 mL, one-necked flasks with 24/40 ground glass joints and a 4 L beaker (25 cm high and 18 cm in diameter) are employed for the photolysis together with a Hanovia 450 W medium-pressure mercury lamp and immersion well apparatus. A Pyrex filter cylinder is used. Into each flask is added 100 mg (0.96 mmol) of cyclooctatetraene. Each flask is sealed under vacuum by first being cooled in a dry icelacetone bath followed by subsequent application of 0.05 mm vacuum. The lamp well is immersed in the center of the beaker filled with water maintained at 70 "C. The beaker is surrounded by aluminum foil which serves as a reflector. The flasks containing the cyclooctatetraene are placed in the water in proximity to the lamp well and irradiated at 70 "Cfor 60 h. At the end of the photolysis, the product is distilled to each flask bottom and removed by pipette. The total crude material weighs 0.26 g and is determined by NMR and IR to consist of > 98% semibullvalene with traces of cyclooctatetraene and benzene (< 1% each). Alternatively, the photolysis can be carried out in a Rayonet apparatus equipped with 12 RPR 350 nm lamps. A cylindrical Pyrex vessel, 25 cm long and 11 cm in diameter, also having a 10 mm cold finger at the bottom and a glass joint at the other end, is employed for the photolysis. A charge of 0.27 g (2.6 mmol) of cyclooctatetraene is added to the cold finger and cooled with dry ice/acetone while the vessel is sealed under vacuum (0.05 mm). With the vessel at the center of the Rayonet apparatus, the sample is irradiated for 60 h with the Rayonet wrapped with aluminum foil. The temperature generated by the lamps is about 70°C. At the end of the run, the product is condensed in the cold finger and removed and weighs 0.24 g. NMR analysis show this to consist, again, of > 98% semibullvalene with traces of benzene and and cyclooctatetraene.

[l]

N. J. Turro, J. Liu, H. E. Zimmerman, R. E. Factor, J. Org. Chem., 1980, 45, 351 1 3512.

248

4.17

4.

cis - and trans-1,2-Diethinylcyclobutane submitted by

4.17a

Alkenes, Arylalkenes and Cycloalkenes

H. Hopf and D. Kolassa

Vinylacetylene from 3,4-dichloro-l-butene C

CI

I

125.0

A

KOH

* 52.1

400 g of potassium hydroxide and 500 mL of ethylene glycol are placed in a 2 L threenecked flask, and 100 mL of ethylene glycol mono-n-butylether are added under intensive stirring. While the flask is slowly heated to a temperature of 165 - 170 "C by means of an oil bath a vigorous stream of nitrogen is passed through the apparatus. The gas stream is reduced when the addition of 125 g (1 mol, 105 mL) of 3,4-dichloro-l-butene begins. The formation of 4.17a is accompanied by strong splashing and decrepitation. With a rate of roughly 2 drops per second the addition of 3,4-dichloro-l-butene takes about 1 h. The gaseous elimination mixture is swept through a reflux condenser (1 = 60 cm) kept at 10 "C, passes a CaC12 drying tube, and is condensed in a methanoudry ice trap. The water clear condensate (36.8 g, 71%) consists mainly of 4.17a, small amounts (2 - 6%) of 2-chloro- 1,3-butadiene (chloroprene) being formed as well. Vinylacetylene has a characteristic odor and may be kept safely over calcium chloride at -30 "C for months. The raw eliminate may be used directly for the subsequent photodimerization, superior results (less formation of polymeric films on the immersion well, see below) are obtained though if it is first distilled (bp 5 "C).

4.17b

Photodimerization of 4.17a to cis- and truns-diethinylcyclobutane

52.1

104.2

\

A falling-film photoreactor is carefully purged with purified nitrogen for 1 h, and charged with 27 g (0.15 mol) of recrystallized benzophenone. The reactor is cooled to -18 "C by a

4.

Alkenes, Arylalkenes and Cycloalkenes

249

cryomat and, after additional purging to remove traces of air, 125 g (2.4 mol) of degassed 4.17a is transferrred to the apparatus from a cold trap. Magnetic stirring is started and when a homogenous solution has been achieved the immersion lamp (Hanau TQ 718, 500 W) is started. The dimerization is monitored by removing small aliquots and analyzing them by IH-NMR spectroscopy. A polymer film which forms on the cooling tube is removed occasionally, and after ca. 9 d during which the mixture turns yellow and more viscous no more changes in product composition are detectable (NMR analysis). A reduction of the volume by about 15% may also be discerned towards the end of the dimerization. The photolysate is transferred to a distillation apparatus and non-reacted 4.17a is removed by applying aspirator vacuum at -78 "C. The photodimer 4.17b (57.5 g, 46%) is finally separated from the sensitizer and polymeric products by vacuum transfer at Torr and room temperature. -

~

~~

trans-isomer: lH-NMR (CDCl,, 60 MHz): 6 = 1.90 - 2.40 (m, 4 H, -CH2CH2-, truns-3), 2.50 (d, 2 H, J = 2.0, =C-H, truns-3), 2.85 - 3.25 (m, 2 H, -CH-, trans-3). IR (CDC13): v = 3310,2958,2878,2120 (tr~ns-3).

cis-isomer: lH-NMR (CDC13, 60 MHz): 6 = 2.10 - 2.45 (m, 6 H, =CH and -CH2CH2-, cis-3), 3.05 3.40 (m, 2 H, -CH-, cis-3). JR (CDC13): v = 3304,2996, 2950,2870,2115, 1250 (cis-3).

250

4.18

4.

Alkenes, Arylalkenes and Cycloalkenes

3,4,17,18-Tetraphenylheptacyclo[18.8.0.02'5.O 6'15.O 8,13.016,19.022~710Ctacosa1(28),6,8( 13),9,11,14,20,22(27),23,25-decaene[ll (Cyclophane Synthesis by Photocycloaddition) submitted by

4.18a

H. Meier

2,3-Bi~(2-phenylethenyl)naphthalene[19~1

mCH3 C,H,-N=CH-C,H,

CH3

156.2

(KOC(CH,), / DMF) 181.2

332.4 \Ph

A solution of 3.84 g (24.6 mmol) of 2,3-dimethylnaphthalene (Fluka) and 11.2 g (100mmol) of KO% in 150mL of dry DMF was stirred and heated to 80°C. In a nitrogen atmosphere 9.40 g (52.0 mmol) of benzylideneaniline in 50 mL of DMF was added dropwise. After 1 h at 90-95 "C the reaction mixture was cooled to 10 "C and 150mL of water was added. The deep red solution turned orange after the addition of 150 mL of 10% HCl. A yellow precipitate was formed which was washed with water and treated twice with 100 mL of methanol. Column chromatography (60 x 3 cm silica gel, petroleum ether (50 - 80 "C)/toluene 1:3) afforded the raw product that was recrystallized from ethanol; yield 4.16 g (51%), mp 158 "C.

1H-NMR (CDC13,400 MHz): 6 = 7.1317.53 (AB, 3J = 16.0, 2 H, olefinic H), 7.30 (t, 2 H, Hp, phenyl), 7.39 (t, 4H, H, phenyl), 7.46 (m, 2 H , 6-H, 7-H), 7.57 (d, 4H, Q, phenyl), 7.84 (m, 2 H, 5-H, 8-H), 8.01 (s, 2 H, 1-H, 4-H). 13C-NMR (CDC13, 100 MHz): 6 = 126.7A28.7 (0-,m-CH, phenyl), 125.4/126.1/127.1/ 127.7/127.8/131.8 (CH), 131.1/134.9/137.6(Cq). IR (KBr): v = 3000 - 3060,1590, 1485,955,745. UV (hexane): A,, = 285.6, ha= 6.2 x lo5.

4.

25 1

Alkenes, Arylalkenes and Cycloalkenes

4.18b

3,4,17,18-Tetraphenylhe tacyclo[18.8.0.02'5.O 6'15.O 8'13.O 16,18.O 22,27loctacosa1(28),6,8(13),9,11,14,20,22(27),23,25-decaene~~1 Ph hu

332.4

664.9

An oxygen-free solution (N2 or freeze and pump technique) of 333 mg (1.0 mmol) of 4.18a in 190 mL of dry benzene was irradiated with a Hanovia 450 W mercury vapor lamp equipped with a Pyrex filter (h2 290 nm). Nitrogen was passed through the solution during the irradiation period of 30 min. The solvent was rota-evaporated and the residue purified on a column (20 x 2.5 cm silica gel, petroleum ether (40 - 70 "C)/toluene 1:l). A twofold recrystallization from ethanol afforded 225 mg (72%) of the cyclophane as colorless crystals, mp 296 "C.

IH-NMR (CDC13, 400 MHz): 6 = 4.90 (s, 8 H, 2-H, 3-H, 4-H, 5-H, 16-H, 17-H, 18-H, , phenyl), 7.35 (m, 4 H, 10-H, 11-H, 19-H), 7.19 (t, 4 H, H , phenyl), 7.28 (t, 8 H, H 24-H, 25-H), 7.37 (d, H, &, phenyl), 7.71 (m, 4 H, 9-H, 12-H, 23-H, 26-H), 7.76 (s, 4 H, 7-H, 14-H, 21-H, 28-H). I3C-NMR (CDCI3, 100 MHz): 6 = 45.3146.2 (CH, 4-membered rings), 128.2D28.3 (0-C, m-C, phenyl), 124.3/125.3/126.1/127.3(CH), 132.2/137.6/140.7(Cq). IR (KBr): v = 3030,2930,1595,1490,1450,880,780,750,720,695.

8

[ll [2]

H. Meier, E. PraB, R. Zertani, H.-L. Eckes, Chem. Ber. 1989,122,2139 - 2146. A. E. Siegrist, P. Liechti, H. R. Meyer, K. Weber, Helv. Chim. Acra 1969, 52, 2521 - 2554.

252

4.

4.19

Cyclobuta-12-crown-4 ether[ll21 submitted by

4.19a

Alkenes. Arylalkenes and Cycloalkenes

K. Mizuno

1,2-Bis(2-ethenyloxyethoxy)ethane~3]

A HO 0,

202.3

reflux

+

72.1

n

202.3

A solution of 3 g of H ~ ( O A Cin) ~30 g of 22-(ethy1enedioxy)diethanol(200 mmol) and 200 mL, of ethyl vinyl ether was refluxed for 48 h. 20 g of anhydrous potassium carbonate were then added to the cooled reaction mixture and excess of ethyl vinyl ether and ethanol were distilled off. Distillation of the residue gave 5.6 g (28 mmol, 14%) of crude product 4.19a, bp 148 - 149 "C/40 Torr.

lH-NMR (CC14, 60 MHz): 6 = 3.42 (s, 4 H, CH2), 3.64 (s, 8 H, CH2), 3.63 - 4.14 (m, 4 H, C=CH2), 6.01 - 6.45(dd, 2 H, J = 7, 14, CH=C). IR (neat): v = 2910,2860,1615, 1205, 1130. MS:m/z = 202 (M+, VW),159. '

4.19b

Cyclobuta-12-crown-4ether

do

A

+ 202.3

202.3

"to

0 O)

202.3

A solution of the divinyloxy compound 4.19a (1.01 g, 5 mmol) and 1,4-dicyanonaphthalene[4] (90 mg, 0.5 mmol) in 100 mL of toluene was placed in a doughnut-type Pyrex

4.

Alkenes, Arylalkenes and Cycloalkenes

25 3

vessel and irradiated with a 300 W high-pressure mercury lamp (h > 280 nm) under an argon atmosphere. The progress of the photoreaction was monitored by GLC (SE-30, 10 %, 1 m) and the irradiation was continued until most of the starting compound (> 90 %) was consumed. The solution was evaporated and the residue separated by column chromatography on silica gel (Merck Kieselgel 60) with benzene/ether (9: 1) eluant. Distillation of the crude product using a Kugelrohr apparatus gave a mixture of trans- and cis-cyclobuta-12-crown-4 ethers (bp 110 - 120 "U0.5 Torr, 0.8 g, 80 %, colorless oil) in a 3:2 ratio. The ratio was determined by IH-NMR. trans-4.19b: IH-NMR (CC14, 100 MHz): 6 = 1.1 - 1.3 (m, 2 H, CH2), 1.7 - 1.9 (m, 2 H, CH2), 3.3 3.7 (m, 12 H, CH2), 3.7 - 3.9 (m, 2 H, CH). IR (neat): v = 2840, 1130. MS (70 eV): m/z = 202 (M+), 174. cis-4.19b: lH-NMR (CC14, 100 MHz): 6 = 1.8 - 2.0 (m, 4 H, CH2), 3.4 - 3.8 (m, 12 H, CH2), 3.9 4.0 (m, 2 H, CH). IR (neat): v = 2840, 1130. MS (70 eV): m/z = 202 (M+), 174.

K. Mizuno, T. Hashizume, Y. Otsuji, J. Chem. Suc., Chem. Cummun. 1983, 772 773 and 977 - 978. K. Mizuno, Y. Otsuji, Chem. Lett. 1986,683 - 686. [2] W. H. Watanabe, L. E. Conlon, J. Am. Chem. SUC. 1957, 79,2828 - 2830. [3] L. Heiss, E. F. Paulus, H. Rehling, Liebigs Ann. Chem. 1980, 1583 - 1596 [4] [l]

254

4.

4.20

Cyclobuta-1,4-dioxa-[4.5]-p-cyclophane[* *21 submitted by

4.20a

Alkenes, Arylalkenes and Cycloalkenes

K. Mizuno

1,5-Bis(4-ethenyloxyphenyl)pentane[3~41

256.3

284.4

A solution of 1,5-bis(4-methoxyphenyl)pentane ( 14.3 g, 50 mmol), trimethylsilyl chloride (10.8 g, 0.1 rnol), sodium iodide (15 g, 0.1 mol) in 40 mL of acetonitrile was refluxed for 12 h.L3] The mixture was cooled and taken up in benzene and water. The organic layer was washed with brine and the solvent was evaporated to give 12.7 g of crude 1,5-bis-

(4-hydroxypheny1)pentane.

CICH,CH,CI (CH2)5

H

O

256.3

W

20'o

a

CICH2CH20

aq Nao'ClCH,CH20

(CH2)5

381.3

To a stirred suspended solution of 12.8 g of 1,5-bis(4-hydroxyphenyl)pentane (50mmol) in 1,2-dichloroethane (150 mL) was added a 20% aqueous solution of sodium hydroxide (50 mL). The resulting mixture was vigorously refluxed for 24 h. The organic layer was washed with 20% aqueous solution of sodium hydroxide for three times and concentrated under reduced pressure to give 12.4 g of crude 1,5-(4-(2-chloroethoxy)phenyl)pentane (63%).

4.

255

Alkenes, Arylalkenes and Cycloalkenes

381.3

31 8.5

To a stirred solution of 12.2 g of crude 1,5-(4-(2-~hloroethoxy)phenyl)pentane(32 mmol) in toluene/ether (1:l) (150 mL) was added a 50% aqueous solution of sodium hydroxide (100 mL) and tetra-n-butylammonium hydrogen sulfate[5] (24 g, 70 m m ~ l ) . [ ~The ] resulting mixture was stirred for 12 h at room temperature, and the organic layer was separated, washed with water, dried with sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on silica gel. Elution with benzenehexane (1:l) gave a pure sample of 4.20a (7.8 g, 79%) as an oil.

IH-NMR (CCl,, 60 MHz): 6 = 1.20 - 1.85 (m, 6 H, CH2), 2.52 (t, 4 H, J = 7, CH2), 4.22 (d, 2 H, J = 6, C=CH2), 4.55 (d, 2 H, J = 14, CSH,), 6.46 (dd, 2 H, J = 6, 14, CH=C), 6.70 (d, 4 H, J = 10, aromatic H), 6.92 (d, 4 H, J = 10, aromatic H). IR (neat): v = 1640, 1240. MS (70 eV): m/z = 308 (M+), 137,107.

4.20b

Cyclobuta-l,4-dioxa-[4.5]-p-cyclophane

A solution of 1,5-bis(4-ethenyloxyphenyl)pentane (200 mg, 0.5 mmol) and 9,lO-dicyanomthracene (10 mg) in 200 mL of acetonitrile was placed in a doughnut-type Pyrex vessel and irradiated with a 300 W high-pressure mercury lamp under argon atmosphere. The progress of the photoreaction was monitored by GLC (SE-30,2%,1 m) and the irradiation

25 6

4.

Alkenes, Arylalkenes and Cycloalkenes

was continued until 60 - 70 % of the starting compound was consumed. The solvent was evaporated and the residue separated by column chromatography on silica gel (Merck Kieselgel 60). Elution with benzenehexane (2: 1) gave the trans-cyclobutane derivative (64 mg, 32%). Recrystallization from hexane gave a pure sample as a colorless cyrstal, mp 125 - 127 "C. Similar irradiation in toluene gave the cis-cyclobutane derivative (105 mg, 53%). Recrystallizations from hexane gave a pure sample as a colorless crystal, mp 132 - 133 "C. The product ratios were determined by 'H-NMR.

trans-4.20a: IH-NMR (CDC13, 100 MHz): 6 = 0.65 - 1.00 (m, 2 H, CH2), 1.20 - 1.60 (m, 4 H, CH2), 1.60 - 2.00 (m, 2 H, CH2), 2.00 - 2.65 (m, 6 H, CH2), 4.45 - 4.85 (m, 2 H, CH), 6.10 6.90 (m, 8 H, aromatic H). IR (neat): v = 1605, 1505, 1240, 1055.

cis-4.2Oa: IH-NMR (CDC13, 100 MHz): 6 = 0.55 - 0.95 (m, 2 H, CH2), 1.20 - 1.50 (m, 4 H, CH& 2.15 - 2.50 (m, 8 H, CH2), 4.70 - 4.90 (m, 2 H, CH), 6.22 - 6.60 (m, 8 H,aromatic H). IR (neat): v = 1610, 1510, 1245.

[l] [2] [3] [4] [5]

K. Mizuno, H. Kagano, Y. Otsuji, Tetrahedron Lett. 1983, 24, 3849 - 3850; K. Mizuno, Y. Otsuji, Chem. Lett. 1986,683 - 686. S. L. Mattes, H. R. Luss, S. Farid, J. Phys. Chem. 1983,87,4779. T. Morita, Y. Okamoto, H. Sakurai, J. Chem. SOC., Chem. Commun. 1978, 874 875. K. Mizuno, Y. Kimura, Y. Otsuji, Synthesis 1979,688. Supplied from Tokyo Chemical Industry Co. Ltd.

4.

257

Alkenes, Arylalkenes and Cycloalkenes

4.21

2,2-Dimethyl-2-sila-1',2'-cyclobuta-[2.31 -p-cyclophane"] submitted by

4.21a

K. Mizuno

Dimethylbis(4-vinylphenyImethy1)silane Mg

Me2SiC,I

Me

Et20

152.6

372.3

To a stirred solution of magnesium (3.4 g, 0.14 mol) in dry ether (30 mL) was added a dry ether solution (60 mL) of 4-vinylphenylmethylchloride(17.1 g, 0.112 mol). The mixture was stirred for 1 h, and dry ether solution (40 mL) of dichlorodimethylsilane (5.8 g, 45 mmol) was added and the mixtures was refluxed overnight. After work-up with aqueous solution of ammonium chloride, the ether solution was separated and dried with sodium sulfate. The solvent was evaporated under reduced pressure and the residue was separated by column chromatography on silica gel. From hexane elution, dimethylbis(4-vinylphenylmethy1)silane (9.8 g, 74%) was obtained as an oil.

lH-NMR (CDC13, 270 MHz): 6 = -0.01 (s, 6 H, Me), 2.14 (s, 4 H, CH2), 5.45 (dd, 2 H, J = 1, 11, C=CH2), 5.71 (dd, 2 H, J = 1, 16, C=CH2), 6.72 (dd, 2 H, J = 11, 16, CH=C), 7.15(ABq, 8 H, Av = 86, J = 8, aromatic H). 13C-NMR (CDCl3,67 MHz): 6 = -3.8,25.1, 112.2, 126.2, 128.3, 133.7, 136.8, 139.7. IR (neat): v = 2960,1630,1607,1510,1249,990,903,849. MS (70 eV): m/z = 292 (M+), 277,145,91,59,43.

258

4.

4.21b

Alkenes. Arylalkenes and Cycloalkenes

2,2-Dimethyl-2-sila-1',2'-cyclobuta-[2.3]-p-cyclophane hu C6H6

292.5

292.5

A solution of 250 mg (0.86 mmol) dimethyl-bis(4-vinylphenylmathy1)silane 4.21a in 75 mL toluene was placed in a Pyrex tube and irradiated with a 300 W high-pressure mercury lamp under argon atmosphere. The solvent was evaporated and the residue was chromatographed on silica gel. Elution with hexane gave 162 mg (65 %) of the cyclophane 4.21b. Recrystallization from ethanol gave a pure sample as colorless crystalls, mp 100 - 102 "C.

lH-NMR (CDCI,, 270 MHz): 6 = 0.26 (s, 3 H, CH3), 0.28 (s, 3 H, CH3), 2.44 - 2.52 (m, 4 H, CH& 4.04 - 4.08 (m, 2 H, CH), 6.33 (ABq, 4 H, Av = 62, J = 8, aromatic H), 6.58 (ABq, 4 H, Av = 14, aromatic H). 13C-NMR (CDC13,67 MHz): 6 = -0.33,25.8,29.7,47.1, 128.1, 131.1, 136.6, 137.5. MS (70 eV): m/z = 292 (M+). Anal. calc.: C 82.12, H 8.27; found: C 82.3, H 8.4.

[l]

K. Nakanishi, K. Mizuno, Y. Otsuji, J. Chem. Soc., Perkin Trans. I 1990, 3362 3363.

4.

259

Alkenes, Arylalkenes and Cycloalkenes

(-)-(lS,2R,4R)-4,9-Diacetyl-2-isopropyl1,2,3,4-

4.22

tetrahydrocarbazole-1-carbaldehyde submitted by

4.22a

0. Wiest, A. Gieseler and E. Steckhan

(10R)-9-Acetyl-lO-isopropyl-3-methyl-1,4,4a,9a-tetrahydro-1,4-ethanocarbazole[1~

+ \

AcCI, hv

\

117.2

H

136.2

78.5

\

295.4

Ac

234 mg (2 mmol) of indole, 544 mg (4 mrnol) of (R)-5-isopropyl-2-methyl-l,3-cyclohexadiene (Merck), 40 mg (5 mol%) of triphenylpyrylium tetrafluoroborate (Aldrich), 157 mg (2 mmol) of acetyl chloride, and 350 mg of NaHC03 were dissolved in methylene chloride. The mixture was transfered to a 50 mL Schlenck tube and purged of oxygen with argon for 15 min. The closed Schlenck tube was placed in a water bath (15 "C) and irridiated (Xenon or Halogen lamp 3L > 345 nm) for 8 h. The organic phase was washed with water and dried. Evaporation of the solvent and purification by column chromatography (silica gel 30-60 pm, cyclohexandethyl acetate 102) 336 mg (57%) of 4.22a together with minor amounts of the exo-isomer as a yellowish oil.

IH N M R (CDCI3, 400 MHz): 6 = 7.1 and 7.17 (2 d, 1 H, J = 7.25, 5-H, two rotamers),

6.92 (dd, 1 H, J = 7.5, 7.25, 6-H), 7.075 (dd, 1 H, J = 7.5, 8.2, 7-H), 8.075 and 6.97 (2 d, 1 H, J = 8.25, 8-H, two rotamers), 4.285 and 4.54 (2 dd, 1 H, J = 9,2.5,9a-H, two rotamers), 3.625 and 3.4852 (2 dd, 1 H, J = 9, 3, 4a-H, two rotamers), 2.95 - 3.0 (m, 1 H, 1-H), 2.66-2.71 (m, 1 H, 4-H), 5.42 - 5.5 (m, 1 H, 2-H), 2.28 and 2.63 (2 s, 3 H, amid CH3, two rotamers), 1.25 - 1.4 (m, 1 H, 10-H), 1.77-1.89 (m, 1 H, 11-H), 0.96 1.1 (m, 1 H, 11-H), 1.335 and 1.305 (2 s, 3 H, methyl CH3, two rotamers), 1.1 - 1.25 (m, 1 H, 15-H), 0.89 and 0.79 (2 d, 3 H, J = 6.5, isopropyl C&, two rotamers), 0.825 and 0.77 (2 d, 1 H, J = 6.5, isopropyl CH3, two rotamers). 13C N M R (CDC13, 100 MHz, all signals are doubled because of two amide rotamers): 6 = 169.08 and 168.72 (C-12), 144.81 and 143.59 (C-8a or C-4b), 143.07 and 141.75

260

4.

Alkenes, Arylalkenes and Cycloalkenes

(C-8a or C-4b), 133.92 and 136.21 (C-3), 119.29 and 120.77 (C-2), 127.34 and 127.12 (C-7), 123.32 and 122.66 (C-6), 123.32 and 124.81 (C-5), 116.79 and 113.45 (C-8), 65.67 and 64.91 (C-9a), 45.63 and 43.91 (C-4a), 43.56 and 43.00 (C-lo), 41.05 and 41.43 (C-4), 37.84 and 35.29 (C-I), 32.62 and 32.95 (isopropyl CH), 30.46 and 29.73 (C-11), 23.62 and 25.50 (amid CH3), 21.32 and 21.25 (methyl CH3), 21.18 (isopropyl CH3), 20.46 (isopropyl CH3). IR kBr): v = 3000,2910,1680, 1610,1495, 1410,770.

4.2213

(-)-(lS,2R,4R)-4,9-Diacetyl-2-isopropyl-1,2,3,4-tetrahydrocarbazole-1-carbaldehyde

295.4

325.4

295 mg (1 mmol) of 4.22a were dissolved in 25 mL of methylene chloride and cooled to -78 "C. A stream of ozone (10 vol% 03,2 Wmin) was bubbled through the solution until the blue color of unreacted ozone appears (10 min). The solution was stirred at -78 "C for an additional 15 min, then 0.2 mL (2.5 mmol) of dimethyl sulfide was added. After stirring for l h at -60 "C, l h at 0 "C and 1 h at room temperature, the solvent was evaporated and the product was purified by column chromatography (silica gel 30-60 pm) with pentanelmethylene chloride/diethyl ether 5:l:l to give 191 mg (59%) of 4.22b as a = -53,7" (0.67, CHZC12). yellow oil, [a],,

'H-NMR (CDC13,400 MHz): d = 10.1 (d, 1 H, J = 1, CHO), 7.62 (ddd, 1 H, J = 8.2, 1.2, 0.8,5-H), 7.3 (m, 2 H, 6-H and 7-H), 7.23 (ddd, 1 H, J = 8, 1, 0.8, 8-H), 4.84 (m, 1 H, 1-H), 3.72 (m, I H;4-H), 2.78 (s, 3 H, amide CH3), 2.13 - 2.18 (m, 1 H, 2-H), 2.05 (s, 3 H, acetyl CH3), 1.7 - 1.8 (m, 3 H, 3-H and isopropyl CHJ 1.23 and 1.03 (d, 6 H, J = 6.2, isopropyl W3). 13C-NMR (CDC13, 100 MHz): 6 = 21 1.1 (acetyl CO), 201.2 (aldehyde CO), 169.9 (amide CO), 135.3 and 129 (3 C, C-9a, C-8a, C-4b), 124.7, 123.6, 119.2 (3 C, C-5, C-6, C-7), 118.0 (C-4a), 114.2 (C-8), 49.7 (C-4), 49.1 (C-1), 46.2 (C-2), 29.8 (isopropyl CH), 27.5 (amide CH3), 25.6 (C-3), 25.1 (acetyl CH3), 21.9 and 21.6 (2 C, isopropyl CH3). IR (CC14lNaCl):v = 2950,1720,1705, 1695, 1460, 1370, 1310, 1215,795,745.

[ll

A. Gieseler, E. Steckhan, 0. Wiest, F. Knoch, J. Org. Chern. 1991,56, 1405 - 1411.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

5

Organometallic Compounds

Although the photochemical reactivity of organometallic compounds has been known for a long time, applications to organic synthesis are rare. Obviously one reason is that there are only specialists for single areas of research like coordination complexes and organometallics on the one hand and synthetic organic chemistry one the other hand. The special features of photochemistry may even increase this lack of exchange of information. However, it is clear from the contributions to this chapter that the development of organometallic photochemistry is moving in the direction of synthetic applications as pioneered for example by Hegedus. As the various disciplines approach each other and grow together new types or reaction will be discovered and applied to the synthesis of organic compounds. The high synthetic potential of chromium-carbene complexes often linked to the Dotzreaction has recently been dramatically increased by the beautiful work of L. S. Hegedus and his group. They found that metal-coordinated ketenes are formed from Fischer-type carbene complexes upon photolysis. These species undergo similar cycloadditions as free ketenes, however, generally at room temperature allowing reactions even with partners which are sensitive to higher temperature. In a series of papers Hegedus and coworkers have applied their method to the synthesis of lactames, cyclobutanones, amino acids, dipeptides etc., all as optically pure compounds. From this catalogue one example is presented here, i.e. the synthesis of an enantiomerically pure lactone via the formation of a corresponding cyclobutanone as the photochemical key step. In a similar way a bicyclic thioalkylcyclobutanone was synthesized by J. Mattay starting from readily available thioalkyl-substituted chromium carbene complexes and cyclopentadiene. If the intermediately formed ketene is trapped by a hexatriene unit, a phenol derivative is formed. C. A. Merlic made use of this procedure in a benzannulation reaction leading to orthosubstituted phenols. Note that the photochemical method perfectly complements the Dotzreaction which gives p-alkoxyphenols from chromium carbene complexes and alkynes. Higher order cycloaddition reactions of the type [6n;+4n;], [4n;+4n;] and [6n;+2n;] typically proceed with high stereoselectivity but with relatively low efficiency. Starting from the pioneering work of Kreiter the group of J. H. Rigby developed a procedure for synthesizing medium-size carbocycles. The idea is that an appropriate metal form a precomplex both for the 6n; and the 4n; reaction partners. This was realized for cyclic trienechromium complexes and dienes. Two examples are presented here which illustrate the high potential for the synthesis of decane rings either monocyclic or bicyclic ones. Finally, in order to overcome the problems of short wavelength excitation, energy wasting by Z,E-isomerisation and unfavorable entropy effects, the intramolecular [2+2] cycloaddition of 1,6-dienes can be efficiently catalyzed by means of copper(1)triflate. J. Mattay made use of this procedure for the synthesis of the pheromone grandisol (cf. chapter 1.2). The photochemical key step is the excitation of the preformed copper (I) complex with the 1,6-hexadieneacting as a bidentate ligand.

262

5.

OrganometallicCompounds

Recommended further reading General: G. J. Ferraudi in Elements of Inorganic Photochemistry 1988, Wiley, New York; Photochemistry and Photophysics of Coordination Compounds, H. Yersin, A. Vogler (Eds.), 1987, Springer, Berlin; H. Hennig, D. Rehorek in Photochemische und photokatalytische Reaktionen von Koordinationsverbindungen 1988, Teubner, Stuttgart. Chromium carbene complexes: L. S. Hegedus, Pure Appl. Chem. 1990,62,691. Transition metal promoted higher-order cycloadditions: J. H. Rigby, Acc. Chem. Res.

1993,26,579.

Homogeneous metal-catalysis: R. G. Salomon, Tetrahedron 1983, 39, 485.

5.

263

Organometallic Compounds

5.1

Synthesis of Optically Active Cyclobutanones and y-Lactones from Chromium Carbene Complexes[ll submitted by

5.1a

M. Miller, L. S. Hegedus

(S)-Phenyl glycinol H2N Y O H Ph" 0 151.2

H2Nu

NaBH, t

BF,

OH

$'

Ph

Et,O

137.2

NaBH4 (7.5 g, 98 mmol) and THF (200 mL) were placed into a 3-neck round-bottom flask equipped with an addition funnel (under argon). The mixture was cooled to 0 "C, and BF3Et20 (50 mL, 387 mmol) was added via the addition funnel to the mixture at 0 "C. After the addition was complete, (S)-phenyl glycine (15.0 g, 99 mmol) was added in several portions to the white slurry at 0 "C. The mixture was warmed to 25 "C and stirred at that temperature (15 h). MeOH was added to quench the excess NaBH4. The solution was concentrated under reduced pressure to remove the THF, and the resulting white slurry was stirred at 25 "C (10 h) with 20% NaOH (400 mL). The aqueous solution was extracted with CHC13 (5 x 100 mL), and the combined CHC13 layers were washed with brine and dried over MgSOk Filtration and concentration under reduced pressure gave 11.O g (8 1%) of (9-phenyl glycinol as a white solid. Spectroscopic data was identical with reported values[2].

'H-NMR (300 MHz, CDC13): 6 = 2.17 (s, 3 H, NH2, OH), 3.55 (dd, 1 H, J = 8.3, 10.7), 3.74 (dd, 1 H, J = 4.3, 10.7), 4.04 (dd, 1 H, J = 4.4, 8.3), 7.26 - 7.35 (m, 5 H, Ar).

5.lb

[(Ethoxy)(methyl)carbene]pentacarbonyl chromium (0) 1.) MeLi

WCO), 220.1

2.) Et30BF,

-

OCH2CH3 (C0)5Cr=( 264.2

CH3

264

5.

Organometallic Compounds

Cr(C0)6 (2.2 g, 10 mmol) in Et2O (50 mL) was placed into a dry 100 mL airless flask. The flask was placed into a 25 "C water bath, and MeLi (8.5 mL, 1.4 M in Et20, 12 mmol) was added to the flask. The resulting dark brown solution was stirred at 25 OC (20 h). H20 (30 mL) was added to the mixture, and then Et30BF4 (2.09 g, 11 mrnol) was added to the biphasic mixture. The orange mixture was stirred for 0.5 h. The aqueous layer was extracted with Et20, and the combined Et20 layers were washed with brine and dned over MgS04 Filtration and concentration under reduced pressure gave an orange oil. Purification via flash chromatography (hexane, Si02) gave 2.06 g (78%) of the carbene complex as an orange oil.

lH-NMR (300 MHz, CDCl3): 6 = 1.62 (t, 3 H, J = 7.1, W 3 ) , 2.92 (s, 3 H, OCH$ 5.00 (bs, 2 H, CH2).

OCH,CH, (CO),cr=( 264.2

H,N

CH3

+

OH

?--/

Ph'

137.2

1.) DMF

2.)NaH / (PhO),C=O

w

"u"i $

Ph

189.2

The procedure previously reported was modified to accommodate the scale-up of this reactionf3]. [(Ethoxy)(methyl)carbene]pentacarbonyl chromium(0) 5.lb (1.95 g, 7.36 mmol) and (3-phenyl glycinol5.la (1.0 g, 7.36 mmol) in DMF (30 mL) were placed into a 100 mL round bottom flask, and the mixture was stirred at 25 "C under argon (3 h). The reaction mixture was partitioned between Et20 (50 mL) and H20 (50 mL). The aqueous layer was extracted with Et2O (2 x 50 mL). The combined Et20 layers were washed with H20 (2 x 50 mL) and brine (50 mL) and dried over MgS04. Filtration (silica gel) and concentration under reduced pressure gave the amino carbene complex as a thick yellow oil. Two 100 mL airless flasks were flame dried and filled with argon. NaWoil dispersion (50 wt%) (353 mg each, 14.7 mmol) was added to each flask. The oil was washed away with hexane (3 x 5 mL). Diphenyl carbonate (1.58 g, 7.36 mmol) and THF (10 mL) were placed into one flask, and THF (10 mL) was placed into the other flask. The amino carbene complex was taken up in THF (20 mL) and added to the flask containing NaH/THF via a cannula at 25 "C. After H2 (g) evolution ceased (10 min), the faint red solution was added to the diphenyl carbonate/THF/NaH mixture via a cannula at 25 "C. The resulting deep red mixture was stirred at 25 "C (13.5 h). Air was bubbled through the mixture upon

5.

265

Organometallic Compounds

which time the mixture became green. The green mixture was concentrated under reduced pressure to remove the THF. The green residue was taken up in hexane/ EtOAc (1: 1, 100 mL), and the solution was filtered through silica gel to afford a yellow solution. The solution was washed with 2 N NaOH (2 x 50 mL), H20 (50 mL), and brine (50 mL). The organic layer was dried over MgS04. The organic layer was filtered and diluted to 350 mL hexaneEtOAc (1: 1). The solution was saturated with air and was oxidized in a light box equipped with six 20 W Vitalite fluorescent lamps (24 h). Every 6 - 8 h, the solution was filtered to remove the brown precipitate. The solvent was removed to give a clear oil. Purification via flash chromatography (1 :1 hexane/EtOAc, SiO2) gave 1.08 g (78%, from the alkoxy carbene complex) of the ene-carbamate as a white solid. Spectroscopic data was identical with reported values[3].

'€I-NMR (300 MHz, CDC13): 6 = 4.07 (dd, 1 H, J = 1.3, 16.1,Z-HC=CN), 4.1 1 (dd, 1 H, J = 5.3, 8.7, CHzO), 4.29 (dd, 1 H, J = 1.2, 9.2, E-€JC=CN), 4.71 (t, J = 8.8, CHzO), 5.01 (dd, 1 H, J = 5.3, 9.1, C w h ) , 6.81 (dd, 1 H, J = 9.2, 16.1, NC&C), 7.22 - 7.38 (m, 5 H, ArH).

5.ld

(2R,3S)-3-[2-Methoxy-2-(4-rnethoxyphenyl)-3-0~0cyclobutyl]-4S-phenyl-oxazolidin-2-one OCH,

(CO),Cr=(

'

342.2

C6H4p-OCH3

+

p-CH30CeH4 OCH3 0 hv

CH,CI,

I

t

0&NAO

/ CO

,.z

Ph 367.4

i.

189.2 F

i

'

b !

Ph

The aryl carbene complex[4] (684 mg, 2 mmol) and the (S)-ene-carbamate 5.lc (189 mg, 1 mmol) in degassed CH2C12 (20 mL) were placed into an Ace pressure tube (# 15 thread). Glass beads were placed into the tube to effectively dilute the reaction mixture, and this facilitated the penentration of light into the reaction mixture. The tube was outfitted with a pressure head capable of maintaining 150 psi, and the vessel was pressurized to 80 psi with CO. The mixture was photolyzed at 25 "C (450 W ConradHanovia 7825 medium-pressure Hg lamp, Pyrex well) for 14.5 h. The solvent was removed under reduced pressure, and the Cr(C0)6 (370 mg, 84%) was removed via sublimation (0.1 Torr, 50 "C). Purification via flash chromatography gave 3 15 mg (86%) of the cyclobutanone as a white solid, mp 177 - 178 "C, [a],-,+156" = (0.25, CH2C12).

266

5.

Organometallic Compounds

'H-NMR (300 MHz, CDC13): 6 = 2.61 (dd, 1 H, J = 9.3, 18.5, C&C=O), 2.82 (dd, 1 H, J = 10.2, 18.5, C€&C=O), 3.25 (s, 3 H, OC_H3),3.63 (dd, 1 H, J = 3.6, 8.7), 3.81 (dd, 1 H, J = 3.7, 8.5), 3.86 (s, 3 H, ArOC_H3),4.00 (t, 1 H, J = 8.5), 4.84 (t, 1 H, J = 9.8, C m ) , 7.0 (m, 4 H, ArH), 7.3 (m, 5 H, ArH). 13C-NMR (75.5 MHz, CDC13): 6 = 44.97 (CH2C=O),51.14, 53.62, 55.32, 57.88, 70.52 (OCH2), 100.18 (C(OCH3)(CH2)), 114.53 (Ar), 124.74 (ipso-Ar), 125.65, 128.88, 129.12, 129.42 (Ar), 140.07 (ipso-Ar), 158.30, 160.51,206.08 (cyclobutanoneC=O). IR (film): v = 1784,1738 (C=O). An analytical sample was obtained via recrystallization (hexane/CH2C12). Anal. calc. for C21H21NO5: C 68.65, H 5.76, N 3.81; found: C 68.53, H 6.00, N 3.76.

5.le

(2S,3S)-3-[2-Methoxy-2-(4-methoxyphenyl)-S-oxotetrahydrofuran-3-yl]-4S-phenyl-oxazolidin-2-one

The cyclobutanone 5.ld (100 mg, 0.27 mmol), 80% m-CPBA (89 mg, 0.41 mmol), and Li2CO3 (6 mg, 0.089 mmol) in CH2C12 (15 mL) were stirred at 25 "C (24 h). The reaction mixture was washed with 10% Na2S203 (aq) and sat. NaHC03 (aq) and dried over MgS04. Filtration and concentration gave the crude lactone. Purification via flash chromatography (1:l hexaneEtOAc, SiOz) gave 97 mg (94%) of the lactone as a white solid, mp 154 - 155 "C, [a],=+94" (0.35, CH2C12). An analytical sample was obtained via recrystallization (hexane/CH2C1~).

'H-NMR (300 MHz, CDC13): 6 = 1.98 (d, 1 H, J = 18.4, C€&C=O), 2.93 (dd, 1 H, J = 8.6, 18.4, C&C=O), 3.07 (s, 3 H, OC_H3),3.55 (t, 1 H, J = 8.5), 3.79 (dd, 1 H, J = 3.2, 8.5), 3.84 (s, 3 H, ArOCH3), 4.17 (dd, 1 H, J = 3.2, 8.6), 5.05 (bd, 1 H, J = 7.9, C m ) , 7.00 (m, 2 H, ArH), 7.15 (m, 2 H, ArH), 7.35 (m, 3 H, ArH), 7.50 (m, 2 H, ArH). "C-NMR (75.5 MHz, CDC13): 6 = 32.42 (CH2C=O), 51.12, 55.28, 57.04, 58.85, 70.67 (OCH2), 112.35 (C(OCH$(CH2)), 114.04 (Ar), 124.84 (ipso-Ar), 126.36, 128.07, 129.37, 129.49 (Ar), 139.77 (ipso-Ar),157.86, 160.59, 173.80 (lactone C=O). IR (film): v = 1800, 1750 (C=O). Anal. calc. for C21H21N06: C 65.79, H 5.52, N 3.65; found: C 65.58, H 5.38, N 3.57.

5.

[l]

[2] [3] [4]

Organometallic Compounds

267

L. S. Hegedus, R. W. Bates, B. C. Siiderberg, J. Am. Chem. SOC.1991, 113, 923 927. R. Imwinkelried, L. S. Hegedus, Organometallics 1988, 7,702 - 706. J. Montgomery, G. M. Wieber, L. S. Hegedus, J. Am. Chem. SOC.1990, 112, 6255 6263. E. 0. Fischer, C. G . Kreiter, J. Kollmeier, J. Miiller, R. D. Fischer, J. Orgunomet. Chem. 1971,28,237 - 258.

268

5.2

5.

7-(Butylthio)-7-methylbicyclo[3.2.0]hept-2-en-6-one submitted by

5.2a

Organometallic Compounds

S. Kobbing and J. Mattay

Pentacarbonyl[(butylthio)(mehtyl)carbene]chromi~m(O)~~~

(co),c~< 264.2

OEt

+

CH3

BUSH 90.2

Na,CO,

MeOH / 0°C

*

SBu ( W 5 C 4 308.3

CH3

To a solution of 6.14 g (23 mmol) of pentacarbonyl[(ethoxy)(methyl)-carbenelchromium(0)[2] in 115 mL of methanol 2.44 g (23 mmol) of sodium carbonate and 4.20 g (46 mmol) of 1-butanethiol are added at 0 "C. The brown solution is stirred for 15 min, then 25 mL of water and 25 mL of petroleum ether are added. The organic layer is separated and the aqueous layer extracted with petroleum ether. The combined organic layers are dried with sodium carbonate, and the solvent is evaporated. Column chromatography of the residue (petroleum ether) yields 5.0 g (70%) of 5.2a as a dark red oil.

'H-NMR (c&j/Cs2, 300 MHz): 6 = 8.87 (t, 3 H, J = 7.2, CHZCH~),1.29 (sept, 2 H, J = 7.2, C&CH3), 1.42 (dt, 2 H, J = 7.4, 7.2, SCH2C&), 2.53 (t, 2 H, J = 7.4, SCH,), 3.26 (s, 3 H, CH3). 13C-NMR (c@dCs2,75 MHz): 6 = 13.8 (CH2GH3). 22.3 (CH2CH3), 29.2 (SCH2cH2), 42.4 (SCH,), 45.6 (CH3), 216.6 (4 Cq, cis-CO), 227.2 (trans-CO), 366.1 (carbene C). IR (neat): v = 2955 (CH), 2045 (trans-C=O), 1900 - 1980 (cis-C=O). MS (70 eV): m/z = 308 (8, M+), 280 (4, M+-CO), 252 (5, M+-2 CO), 224 (1 1, M+-3 CO), 196 (16, M+-4 CO), 168 (28, M+-5 CO). Anal. calc. for C1 1H12Cr05S:C 42.86, H 3.92; found: C 43.29, H 4.07.

5.

Organometallic Compounds

269

350 mg (5.30 mmol) of cyclopentadiene is added with a syringe to a solution of 330 mg (1.07 mmol) of the carbene complex 5.2a in 20 mL of diethyl ether in a 50 mL Duran pressure tube. The solution is saturated with CO (3 cycles to 5 bar of CO) and irradiated (Philips HPK 125 W high-pressure mercury lamp, Duran immersion well) under CO overnight using a filter solution for h > 400 nm[41. The colorless solution is removed by a pipet from precipitated Cr(C0)6 and the solvent is evaporated. Afterwards, 20 mL of methanol is added to separate the remainder of Cr(C0)6. The solvent is evaporated, the residue is put on a 15 x 2 cm silica gel column and eluted with petroleum etherlether (9: 1) to give 160 mg (71%) of a mixture of exo- and endo-5.2b (2:l) as a colorless oil. Both stereoisomers can be separated by chromatography. exo-isomer: 'H-NMR (CDC13, 300 MHz): 6 = 0.90 (t, 3 H, J = 7.3, CH2C_H3), 1.33 (s, 3 H, CH,), 1.40 (mc, 2 H, C_H2CH3), 1.53 (mc, 2 H, SCH2C_H2),2.44 (dddd, 1 H, J = 17.3, 9.4, 4.2, 2.0, CHz), 2.5 (mc, 3 H, CH2 and SCH2), 3.19 (ddd, 1 H, J = 9.2, 5.0, 2.3, CH), 4.30 (ddd, 1 H, J = 9.2, 7.1, 1.6, COCH), 5.73 (ddd, 1 H, J = 5.7,4.5, 2.3, CHC_H=), 5.92 (ddd, 1 H, J = 5.7,4.0,2.0, CH=C_HCH2). 13C-NMR (CDCl,, 75 MHz): 6 = 13.5 (CH2CH3), 15.6 (CH3), 21.9 (CHzCH-j), 29.0 (SCH2CH2), 31.3 (SCH2), 33.9 (CH, C-4), 50.2 (C-1), 58.7 (C-5), 67.7 (C-7), 129.2 (C-3), 135.0 (C-2), 208.5 (C-6). IR (neat): v = 3045 (=CH), 2950 (CH), 1764 (CO), 1690 (C=C). MS (GC): m/z = 210 (7, M'), 182 (3, M+-CO), 144 (21), 125 (22, M+-SBu), 66 (42), 57 (31). Anal. calc. for Cl2HI80S: C 68.53, H 8.63; found: C 68.46, H 9.01. endo-isomer: 'H-NMR (CDC13, 300 MHz): 6 = 0.90 (t, 3 H, J = 7.2, CH2C_H3), 1.40 (mc, 2 H, CH2CH3), 1.53 (mc, 2 H, SCH2C_H2), 1.66 (s, 3 H, CH3), 2.47 (dddd, 1 H, J = 17.2, 9.7, 3.7, 1.8, CH2), 2.62 (mc, 1 H, CH2), 2.73 (mc, 2 H, SCH2), 3.38 (ddd, 1 H, J = 9.4, 7.8, 2.3, CH), 3.96 (ddd, 1 H, J = 9.4, 8.0, 1.5, COCH), 5.84 (ddd, 1 H, J = 4.6, 4.1,2.3, CHCH=), 5.90 (ddd, 1 H, J = 4.6,3.7, 1.8, CH=C_HCH2). 13C-NMR (CDC13, 75 MHz): 6 = 13.6 (CH2CH3), 22.1 (CH2CH3), 23.3 (CH3), 28.8 (SCH2CH2), 31.9 (SCH2), 34.4 (C-4), 52.3 (C- I), 57.7 (C-5), 68.5 (C-7), 130.1 (C-3), 134.4 (C-2), 212.7 (C-6). IR (neat): v = 3043 (=CH), 2964 (CH), 1769 (CO). MS (GC): m/z = 210 (6, M'), 182 (5, M+-CO), 144 (46), 125 (36, M+-SBu), 66 (36), 57 (74). Anal. calc. for C12HlgOS: C 68.53, H 8.63; found: C 68.82, H 8.99.

[ll 121 131

S. Kobbing, J. Mattay, G. Raabe, Chem. Ber. 1993, 126, 1849 - 1858: 5.2a was synthesized according to a method reported by R. Aumann and J. Schroder for alkyl- and arylthiocarbene complexes in Chem. Ber. 1990,123,2053 - 2058. M. Miller, L. S. Hegedus, this issue. E. 0. Fischer, A. Maasbol, J. Organomet. Chem. 1968, 12, P15 - P17.

270 [4]

5.

Organometallic Compounds

Photolytic reactions of the thiocarbene complexes are conducted in a reation vessel surrounded by a filter solution for 3L > 400 nm. This solution is prepared by the addition of 54 mL of 30% aqueous ammonia to a solution of 4.5 g of copper sulfate in 6 mL of water. The solution is added to a second solution containing 22.5 g of sodium nitrite and 30 mL of water. Finally, the mixture is diluted with water to lo00 mL.

5.

27 1

Organometallic Compounds

5.3

2-Hydroxy-l-methoxy-furo[2,3-b]naphthalene~~~ submitted by

5.3a.

Craig A. Merlic

l-Bromo-2-(2'-furyl)benzene

0 0 68.1

1.) BuLi 2.) ZnCI,

t

aBr

3.) PdCI,(PPh&

282.9

223.1

I

Butyllithium (9.5 mL, 15 mmol, 1.6 M solution in hexane) was added to a solution of furan (1.1 mL, 15 mmol) in THF (15 mL) at 0 "C. After stirring at 0 "C for 1 h and room temperature for 1 h, the yellow solution was slowly transferred via cannula into a solution of zinc chloride (15 mL, 15 mmol, 1 M solution in Et20) at 0°C. The mixture was stirred for 1 h at 0 "C and then added to a solution of 1-bromo-2-iodobenzene(1.3 mL, 10 mmol) and bistriphenylphosphine palladium chloride (0.21 g, 0.3 -01) in THF (2 mL). After stirring for 12 h at room temperature, the reaction was added to 1M HCl aqueous solution (10 mL) and the product was extracted into ether and washed with saturated aqueous sodium bicarbonate solution. The ether solution was dried (MgSO4) and the solvent was removed in vucuo. The crude material was purified by flash chromatography (hexane) to give 2.10 g (95%) of the l-brom0-2-(2'-furyl)-benzene 5.3a as a colorless oil.

1H-NMR(CDC1~,360MH~):6=6.52(dd,1H,J=3.5,1.8),7.11(td,1H,J=7.8,1.7)

7.16(d,1H,J=3.5),7.35(td,1H,J=7.6,1.2),7.51(d,1H,J=1.6),7.64(dd,1H, J = 8.0, 1.2), 7.79 (dd, 1 H, J = 7.9, 1.7). 13C-NMR(CDC13,90 MHz): 6 = 110.6, 111.5, 119.7, 127.4, 128.5, 128.8, 131.3, 134.1, 142.3, 151.4. MS:m/z = 224 (99, M'), 222 (100, M'), 134 (1l), 115 (5 1). exact mass calc. for C10H781BrO: 223.9666; found: 233.9660. exact mass calc. for C1f1779BrO: 221.9681; found: 221.9673.

272

5.3b

5.

Organometallic Compounds

[(1-(2'-Furyl)phen-2-yl)methoxymethylene]pentacarbonylchromium

223.1

378.3

Tert-butyllithium (7.6 mL, 13 mmol, 1.7 M in pentane) was added to a solution of l-bromo-2-(2'-furyl)benzene (1.36 g, 6 mmol) in ether (50 mL) and the milky solution was stirred for 5 h at -78°C. The resulting solution was slowly transferred via cannula into a suspension of chromium hexacarbonyl (1.32 g, 6 mmol) in ether (70 mL) at 0 "C. The yellow-orange solution was stirred for 40 min after complete addition. Saturated aqueous sodium bicarbonate solution (0.5 mL) was added followed by rapid addition of methyl triflate (0.8 mL, 7 mmol). After stirring at room temperature (40 min), the reaction was quenched by addition of saturated aqueous sodium bicarbonate solution (20 mL). The organic layer was separated, dried (MgS04) and the solvents were removed in vucuo. The resulting red oil was purified via silica gel chromatography (hexane/ethyl acetate 90: 10) followed by recrystallization from hexane to provide 1.87 g (82%) of the carbene product as an orange-red solid.

'H-NMR (CDC13, 360 MHz): 6 = 4.09 (br.s, 3 H), 6.46 - 6.48 (m, 1 H), 6.60 (s, 1 H), 6.85 (br.s, 1 H), 7.30 - 7.39 (m, 2 H), 7.47 (s, 1 H), 7.64 (d, J = 7.3, 1 H). 13C-NMR (CDC13, 50 MHz): 6 = 65.7, 108.1, 111.9, 120.3 (br), 120.9, 126.4, 127.3, 128.1, 143.5, 1513,215.9, 224.3,354.8. IR (hexane): (CO only) v = 2065 (m), 1990 (vw), 1953 (vs). MS: m/z = 378 (8, M+), 322 (13, M+-CO), 294 (13, M+-2 CO), 266 (33, M+-3 CO), 238 (99, M+-4 CO), 208 (13), 195 (loo), 171 (21), 153 (ll), 127 (9), 115 (48), 101 (12). exact mass calc. for CI7Hl0CrO7: 377.9832; found: 377.9797.

5.

Organometallic Compounds

273

A solution of 0.177g (0.468mmol) [(2-(2'-furyl)phenyl)methoxymethylene]pentacarbonylchromium 5.3b in THF (150 mL) was photolyzed for 2 h with a 450 W mediumpressure mercury lamp with a Pyrex filter while slowly sparging with CO. The yellow solution was stirred overnight under 1 atm of CO to effect decomplexation of the product from its tricarbonylchromium complex. The resulting colorless solution was concentrated in vacuo and the residue was purified by flash chromatography on silica gel (hexane/ethyl acetate, 75:25)to yield 0.095g (95%) of 2-hydroxy-l-methoxy-furo[2,3-b]naphthalene as a white powder.

'H-NMR (CDCl3, 360 MHz): 6 = 3.94( s , 3 H), 6.39(s, 1 H), 7.04(d, 1 H, J = 2.0),7.44 (td, 1 H, J = 7.5,1.3), 7.50(td, 1 H, J = 7.6,1.4),7.69(d, 1 H, J = 2.0),8.00(d, 1 H, J = 8.0),8.23(d, J = 7.7). 13C-NMR (CDC13, 90 MHz): 6 = 61.9,105.2,115.6, 117.3,120.5,121.0,123.8,125.6

(2C),135.0,139.8,144.0,148.4. IR (CDC13): v = 3530 (OH), 3060,3001,2942,2840,1636,1590,1510, 1469,1441, 1418,1390,1359,1327,1270,1253,1118,1041. MS: m/z = 214 (79,M+), 199 (loo), 171 (64),143 (15), 126 (15), 115 (71). exact mass calc. for C13H1003: 214.0630;found: 214.0646. Anal. calc. for C13H1003: C 72.89,H 4.70;found: C 72.85,H 4.90.

[l]

C. A., Merlic, D. Xu, J. Am. Chem. Soc. 1991,113,7418- 7420.

274

5.

5.4

7-Hydroxy-l,3,5,8-decatetraene[ll submitted by

5.4a

Organometallic Compounds

J. H. Rigby and A. Ch. Krueger

Thiepin-1,l-dioxide[2] 1.) hv, then SO2

2.)Br2 / CH2CIz 80.1

t

3.) Et,N / CH,C12

142.2

A solution of 1,3-cyclohexadiene (2.0 g, 25.0 mmol) in diethyl ether (350 mL) was placed into an oven-dried photochemical reaction vessel, equipped with a quartz immersion-well. Irradiation was carried out by means of a Canrad-Hanovia 450 W medium-pressure mercury lamp. Irradiation and nitrogen bubbling were maintained for 40 min. The solution was then concentrated in vacuo to 20 mL and placed in a 100 mL capacity pressure tube. The tube and contents were cooled to -78 "C, sulfur dioxide (20 g, 312 mmol) and 50 mg hydroquinone (50 mg, 0.45 mmol) were added, the tube was sealed and heated to 70 "C for 48 h. The tube was then recooled to -78 "C, opened and the contents were concentrated in vacuo to a black oil which was purified by column chromatography on silica gel using hexane/ethyl acetate (2: 1) as eluant yielding 540 mg of a white solid. This solid was then dissolved in dichloromethane (20 mL) and bromine (0.19 mL, 4.0 mmol) mixed with dichloromethane (5 mL) was added dropwise over 1 h. The solution was allowed to stir at room temperature for a total of 5 h and then the solvent was removed in vucuo leaving a viscous oil. This oil was dissolved in dichloromethane (10 mL) and triethylamine (5 mL, 35.9 mmol) was added dropwise over 15 min. After stirring for 1 h, the solid was removed and water (50 mL) was added to the solution. The aqueous layer was extracted with dichloromethane (6 x 30 mL), the organic extracts were combined and dried over anhydrous MgSO,, then concentrated and purified by column chromatography on silica gel using hexane/ethyl acetate (1: 1) as eluant. The solid was then recrystallized from hexane/ethyl acetate to yield 320 mg (9%) of 5.4a as a white solid, mp 116 - 117 "C.

lH-NMR (CDC13, 300 MHz): 6 = 6.70 (d, 2 H , J = 10.6, S02CH), 7.02 (m, 2H,

S02CHC_H),7.14 (m, 2 H, S02CHCHCH). 13C-NMR (CDC1-+75 MHz): 6 = 132.5, 133.2, 134.4. IR (nujol): v = 1116, 1290, 1371, 1458, 1520,3024.

5.

275

Organometallic Compounds

5.4b

(q6-Thiepin-l,l-dioxide)tricarbonylchromium (0) THF -

(MeCN),Cr(CO), 142.2

259.1

278.2

Freshly distilled acetonitrile (50 mL) was added to solid chromium hexacarbonyl (2.05 g, 9.28 mmol), a water cooled condenser attached and the solution refluxed for 12 h. The chromium hexacarbonyl that sublimes into the condenser during heating should be scraped back into the refluxing solution over the first few hours. The orange solution was then allowed to cool to room temperature and the acetonitrile was removed in vacuo through the condenser leaving the yellow solid trisacetonitriletricarbonylchr~miurn[~~~] which is then covered with a blanket of nitrogen or argon gas. 5.4a (0.67 g, 4.64 mmol) in dry tetrahydrofuran (75 mL) was added to the trisacetonitriletricarbonylchromiumand the solution was stirred at room temperature for 12 h. The solvent was evaporated in vacuo, and the residue purified by column chromatography on silica gel using hexane/ethyl acetate (1: 1) as eluant to afford 1.11 g (86%) of 5.4b as a red solid, mp 173 - 174 "C.

'H-NMR (CDC13, 300 MHz): 6 = 4.99 (d, 2 H, J = 8.4, S02C_H), 5.66 (m, 2 H, S02CHC_H),6.00 (m, 2 H, S02CHCHC14). 13C-NMR (CDC13,75 MHz): 6 = 77.8,93.2,99.9,226.0 (Cr-c0). IR (nujol): v = 1122, 1142, 1302, 1946, 1986,2017,3041,3074.

5.4~

7a-Acetoxy-(1H~,6H~)-1l-thiabicyclo[4.4.l]undeca2,4,6-trien-11,1l-dioxide

278.2

112.1

254.3

A solution of 5.4b (150 mg, 0.54 mmol) in a mixture of dichloromethane (150 mL) and hexane (200 mL) was placed into an oven-dried photochemical reaction vessel, equipped with a Pyrex immersion-well and a uranium glass filter. To this solution was added

276

5.

Organometallic Compounds

1-acetoxy- 1,3-butadiene (Aldrich) (0.64 mL, 5.40 mmol) and the solution deoxygenated by nitrogen bubbling. Irradiation was carried out by means of a Canrad-Hanovia 450 W medium-pressure mercury vapor lamp. Irradiation and nitrogen bubbling were maintained for 50 min. The solvent was then removed in vucuo, diethyl ether (100 mL) was added to the residue, and the solution was stirred for 24 h under an oxygen atmosphere to effect decomplexation. The solvent was removed in vucuo and the residue purified by column chromatography on silica gel using hexanelethyl acetate (2:l) as eluant. The solid was then recrystallized from hexane/ethyl acetate to yield 108 mg (78%) of 5 . 4 ~as a white solid, mp 151 - 152 "C.

'H-NMR (CDCl3,300 MHz): 6 = 2.12 (s, 3 H, 0CQ-j). 2.68 (m, 1 H, C&CHp), 2.98 (m, 1 H, CH,CHp), 3.84 (m, 1 H, S02CHCH2), 4.06 (m, 1 H, S02CHCOAc), 5.56 (m, 3 H), 5.74 (m, 1 H), 5.99 (m, 3 H). 13C-NMR (CDC13, 75 MHz): 6 = 20.9 (OCH3), 26.3 (CH2), 64.5 (CHOAc), 68.7 (SO2CHCH9, 70.1 (SO~CHCOAC),120.3, 123.2, 126.2, 127.9, 129.4, 135.1, 169.4 (C=O). IR (nujol): v = 1113, 1219, 1292, 1645, 1725, 3049.

5.4d

7-Hydroxy-l,3,5,8-decatetraene

254.3

148.2

A solution of 5 . 4 ~(75 mg, 0.295 mmol) in a mixture of dichloromethane (150 mL) and hexane (200 mL) was placed into an oven-dried photochemical reaction vessel, equipped with a quartz immersion-well. Irradiation was carried out by means of a Canrad-Hanovia 450 W medium-pressure mercury lamp. Irradiation and nitrogen bubbling were maintained for 13 min. The solution was then concentrated in vucuo and the residue dissolved in methanol (3 mL). Potassium carbonate (50 mg, 0.362 mmol) was added and the solution was stirred for 4.5 h. Water (5 mL) was then added, the mixture extracted with diethyl ether (3 x 10 mL), and dried over anhydrous magnesium sulfate. The solvent was removed in vucuo and the residue was purified by column chromatography using hexanelether (4:l) as eluant. The solid was recrystallized from hexane/ether to yield 20 mg (47%) of 5.4d as a white solid, mp 62 - 63 "C.

lH-NMR (CDC13,300 MHz): 6 = 2.43 (m, 1 H, C€12), 3.44 (m, 1 H, C€J2), 5.47 (m, 3 H), 5.56 (m, 2 H), 5.72 (m, 1 H), 5.83 (m, 1 H), 5.99 (m, 2 H).

5.

Organometallic Compounds

277

13C-NMR (75 MHz, CDC13): 6 = 28.9 (CHz), 66.6 (CHOH), 125.8, 126.6, 126.8, 127.4, 129.0, 130.6, 132.2, 132.9. IR (nujol): v = 1 1 10, 1588, 3005, 3348.

[l] [2] [3] [4]

J. H. Rigby, H. S. Ateeq, A. C. Krueger, Tetrahedron Lett. 1992,33, 5873 - 5876. W. L. Mock, J. Am. Chem. Soc. 1967,89, 1281 - 1283; W. L. Mock,J. H. McCausland, J. Org. Chem. 1976,41,242 - 247. D. P. Tate, W. R. Knipple, J. M. Augl, Inorg. Chem. 1962, 1,433 - 434. Caution should be used when working with trisacetonitriletricarbonylchromium,as it is a pyrophoric compound.

278

5.5

5.

7a-Trimethylsilyloxy-(1HP,6HP)bicyclo[4.4.l]undeca-2,4,8- triene submitted by

5.5a

Organometallic Compounds

J. H. Rigby and H. S. Ateeq

(q6-Cy1oheptatriene)tricarbonylchromium (0)

To a solution of cycloheptatriene (15.0 mL, 12.0 g, 130 mmol) and freshly distilled diglyme (60 mL) was added Cr(C0)6 (1 1.1 g, 50.4 mmol), and the reaction mixture was heated at reflux for 4 h. The Cr(C0)6, that sublimed into the condenser, was periodically scraped back into the reaction flask. The reaction mixture was allowed to cool to room temperature and most of the diglyme was removed by distillation at reduced pressure (water-aspirator). Purification of the resultant viscous material via flash-chromatography (silica gel; hexane/ether 1O:l) afforded 7.48 g (65%) of 5.5a as a red solid, mp 129 130 "C.

k N M R (C&, 300 MHz): 6 = 0.93 (dm, 1 H, J = 14, C m ) , 1.99 (dt, 1 H, J = 14, 9, C W ) , 2.51 (ddd, 2 H, J = 3, 9, 12, CHzCH), 4.03 (m, 2 H, CH2CH=C€I), 5.08 (dd, 2 H, J = 5,3). 13<=NMR (CgDg, 75 MHz): 6 = 23.7,56.3, 98.0, 100.7. IR (CCld): v = 1896, 1922, 1988.

5.

279

Organometallic Compounds

5.5b

7a-Trimethylsilyloxy-(~~,6H~)-bicyclo[AAl]undeca2,4,8- triene

Q Q

1.) hexane, hv +

-0TMs

Cr(CO),

228.2

142.3

2.) CO, hexane

3.)P(OMe),

- H

234.4

A solution of 1.36 mmol (q6-cyc1oheptatriene)tricarbonyl chromium (0) (309.7 mg, 1.36 mmol) in hexane (350 mL) was placed into an oven-dried photochemical reaction vessel, equipped with a pyrex immersion-well. This solution was deoxygenated by nitrogen bubbling. 1-Trimethylsilyloxy-1,3-butadiene (Aldrich) (1.2 1 g, 8.50 mmol) was added and irradiation was carried out by means of a Canrad-Hanovia 450 W medium-pressure mercury vapor lamp. Irradiation and nitrogen bubbling were maintained for 30 min. The reaction mixture was immediately vacuum-filtered into a 500 mL round-bottomed flask, purged with CO and allowed to stir under a positive pressure of CO for 15 h. The reaction mixture was then concentrated to approx. 15 mL and treated with P(OMe)3 (15 mL) for 6 h. The reaction mixture was concentrated in vucuo and then purified by flash chromatography on silica gel using hexane/ethyl acetate (19: 1) as eluant to provide 272.6 mg (86%) of 5.5b as a colorless oil. lH-NMR (CDC13, 300 MHz): 6 = 0.16 (s, 9 H, Si(C_H3)3), 2.13 - 2.49 (m, 4 H, C€-I$, 2.72 (br.s, 1 H, CHJ, 2.82 (br.s, 1 H, C@, 4.67 (m,1 H, CHOTMS), 5.55 (m, 2H, 2 =C@, 5.84 (m, 3 H, 3 =C@, 6.05 (m, 1 H, =CkI). 13C-NMR (CDCl3, 75 MHz): 6 = 0.1 (SicH3)3), 31.8, 33.4, 37.5, 46.8, 75.1 CHOTMS), 125.2, 126.2, 126.7, 134.7, 137.3, 141.1. IR (neat): v = 1083, 1199, 3010, 3022,3069.

280

5.6

5.

1-Methylbicyclo[3.2.01 heptan-4-one submitted by

5.6a

Organometallic Compounds

K. Langer and J. Mattay

l-Brom-3-methyl-3-butene[~l PPh, / NBS

v

86.1

149.0

At room temperature, 92.2 g (520 mmol) of N-bromosuccinimide are added portionwise to a mechanically stirred solution of 136.8 g (520 mmol) of triphenylphophine and 43.0 g (500 mmol) of 3-methyl-3-buten-1-01in 480 mL of dry dichloromethane. After stirring for 12 h, the dichloromethane is removed at a pressure of about 100 Torr. Then, the pressure is reduced to 0.01 TOIT and the product is distilled out of the mixture into a cooled (-78 "C) receiving flask. The crude product is redistilled to give 43.5 g (58%) of a colorless liquid (bp 48 "C/50 TOIT).

IH-NMR (CDC13, 300 MHz): 6 = 1.75 (s, 3 H, CH3), 2.57 (t, 2 H, J = 7.4, 2-H), 3.45 (t, 2 H, J = 7.4, 1-H), 4.75 (s, 1 H, 4-H), 4.85 (s, 1 H, 4-H). '3C-NMR (CDC13, 75 MHz): 6 = 21.8 (q, CH3), 30.5 (t, C-l), 40.8 (t, C-2), 112.5 (t, C-4), 142.2 (s, C-3). IR (neat): v = 3050,2950,2920, 1640, 1440, 1370, 1305,1250,1200,880. MS (GC): m/z = 150 (6, M'). 148 (6, M+>,69 (89), 53 (13), 44 ( l l ) , 43 (33), 41 (loo), 40 (88), 39 (37).

5.6b

6-Methyl-l,6-heptadien-3-01[21 1.) Mg, ether 2.) acrolein 149.0

126.2

In an atmosphere of argon, a solution of 19.4 g (130 mmol) of 5.6a in 70 mL of dry diethyl ether is added slowly to 3.4 g (140 mmol) of magnesium turnings in 35 mL of dry diethyl ether. The mixture is cooled to -20 "C, and a solution of 7.84 g (140 mmol) of

5.

28 1

Organometallic Compounds

freshly distilled acrolein in 60 mL of dry diethyl ether is added. The solution is stirred for an additional hour and poured into saturated aqueous ammonium chloride solution. After neutralizing with 2 M hydrochloric acid, the mixture is extracted with diethyl ether. The organic layer is washed with saturated ammonium chloride solution and brine, dried with magnesium sulfate and concentrated in vucuo to give 13.6 g of a colorless oil with a purity of 88% (by GLC). As a distillation causes decreasing yields, the product is irradiated without purification.

'H-NMR (CDC13, 300 MHz): 6 = 1.57 (m, 2 H, 4-H) 1.68 (s, 3 H, CH3), 2.05 (dd, 2 H, J = 7.2, 7.8, 5-H), 2.28 (s, 1 H, OH), 4.05 (dd, 1 H, J = 6.2, 6.7, 3-H), 4.67 (m, 2 H, 7-H), 5.06 (dt, 1 H, J = 1.3, 10.4, 1-H), 5.18 (dt, 1 H, J = 1.4, 17.2, 1-H), 5.82 (ddd, 1 H, J = 17.2, 10.4,6.2, 2-H). 13C-NMR (CDCl,, 75 MHz): 6 = 22.3 (q, CH,), 33.3 (t, C-4/5), 34.7(t, C-4/5), 52.6 (d, C-3), 109.7 (t, C-7), 114.4 (t, C-1), 141.0 (d, C-2), 145.3 (s, C-6). IR (neat): v = 3300,3050, 2950, 2900, 1640, 1430, 1370, 1310, 1270, 1110, 1050, 980, 910, 870. MS (GC): m/z = 126 (1, M+), 108 (23), 93 (82), 91 (22), 80 (23), 79 (44), 77 (21), 70 (loo), 69, (28), 57 (82), 55 (56), 43 (26), 41 (58), 40 (82), 39 (24).

-

-

5 . 6 ~ endo and ex0 1-Methylbicyclo[3.2.0] heptan-4-01[~?~1

! 1

$ 126.2

CuOTf, hv

-

HO H

++H& CH3

126.2

CH3

In an atmosphere of argon, a solution of 13.5 g (88%, 94 mmol) of 5.6b and 300 mg (1 1 mmol) of copper (I) trifluoromethanesulfonate benzene complex (CuOTf) in 120 mL of dry diethyl ether is irradiated in a Pyrex photoreactor with a water cooled quartz immersion well by a high-pressure mercury lamp (HPK 125 W, Fa. Philips). After the reaction is complete (monitored by GLC), the mixture is concentrated in vucuo and purified by column chromatography (cyclohexanelethyl acetate 2:3) to give 10.5 g (64% from 5.6a) of a colorless oil containing the two diastereoisomers in an enddexo-product ratio of 6.8. They can be separated for characterization by HPLC (cyclohexane/ethyl acetate 85: 15). em- l-Methylbicyclo[3.2.0]heptan-4-ol: 'H-NMR (CDCl,, 300 MHz): 6 = 1.14 - 1.35 (m, 2 H), 1.24 (s, 3 H, CH3), 1.46 (dd, 1 H, J = 5.2, 7.3), 1.55 - 1.77 (m, 3 H), 1.83 (dd, 1 H, J = 6.8, 13.7), 1.95 - 2.20 (m, 3 H),

282

5.

Organometallic Compounds

13C-NMR (CDC13, 75 MHz): 6 = 16.9 (t, C-6), 27.3 (q, CH$, 29.7 (t, C-7), 34.3 (t, C-2/3), 38.0 (t, C-2/3), 44.6 (s, C-I), 52.0 (d, C-5), 79.3 (d, C-4). IR (neat): v = 3300,2900,2840,1445,1370, 1330,1260,1195,1155,1105,1010,990. MS (GC): m / z = 108 (38), 93 (7% 83 (loo), 79 (47), 70 (48), 67 (28), 57 (52), 55 (45), 43 (33), 41 (70). endo- l-Methylbicyclo[3.2.0]heptan-4-ol: 'H-NMR (CDC13, 300 MHz): 6 = 1.11 (s, 3 H, CH3), 1.25 (ddd, 1 H, J = 5.0, 7.0, 12.5), 1.40 (dd, 1 H, J = 6.0, 6.3, 1.67 (m, 1 H), 1.71 - 1.85 (m, 3 H), 1.86 - 2.00 (rn, 2 H), 2.23 (m, 1 H), 2.33 (s, 1 H, OH), 4.16 (dt, 1 H, J = 7.0,9.9, H-4). 13C-NMR (CDC13): 6 = 12.1 (t, C-6), 27.1 (CH3), 31.3 (t, C-7), 33.1 (t, C-2/3), 37.2 (t, C-2/3), 43.4 (s, C-l), 46.0 (d, C-5),74.5 (d, C-4). IR (neat): v = 3300,2900,2820, 1440, 1370, 1330, 1300, 1280, 1260, 1200, 1160, 1120, 1060,930, 870. MS (GC): m / z = 108 (23), 93 (41), 83 (loo), 79 (28), 70 (28), 57 (27), 55 (25), 41 (36), 40 (23).

5.6d

l-Methylbicyclo[3.2.0]heptan-4-one~2]

HO H

O H CrO, / H,SO,

CH,

CH, 126.2

CH,

124.2

A solution of 10.0 g (100 mmol) of chromium trioxide in 28 rnL of water and 9 mL of concentrated sulfuric acid is added at 0 - 5 "C to a solution of 12.6 g (100 mmol) of a mixture of endo- and exo-5.6~in 65 mL of acetone. The mixture is stirred for 1.5 h at 0 "C, 120 mL water are added and the mixture is extracted with diethyl ether. The organic layer is washed with saturated sodium hydrogen carbonate solution and brine, dried with magnesium sulfate and concentrated in vucuo to give 10.1 g (80%) of a yellow oil.

'H-NMR (CDCl3, 300 MHz): 6 = 1.22 (s, 3 H, CH3), 1.54 - 1.74 (m, 2 H), 1.76 - 1.91

(m,2 H), 1.98 (ddd, 1 H, J = 7.1, 9.4, 12.0), 2.15 - 2.40 (m, 3 H), 2.63 (ddd, 1 H, J = 9.2, 10.8, 18.3, H-5). 13C-NMR (CDC13): 6 = 18.5 (t, C-6), 25.6 (CH3), 30.5 (t, C-7), 35.3 (t, C-2/3), 38.1 (t. C-2/3), 42.3 (s, C-l), 50.0 (d, C-5), 222.0 (s, C-4). IR (neat): v = 2920,2840,1730, 1445, 1405, 1370, 1265, 1155, 1090, 1025. MS (GC): d z = 124 (23), 96 (71), 95 (19), 81 (52), 69 (32), 68 (34), 67 (52), 55 (loo), 53 (33), 41 (66), 39 (72).

5.

[l] [2]

[3]

Organometallic Compounds

283

G. Pattenden, S . J. Teague, J. Chern. Sac. Perkin Trans. I , 1988, 1077 - 1083. K. Langer, J. Mattay, A. Heidbreder, M. Moller, Liebigs Ann. Chem., 1992, 257 260. R. G. Salomon, D. J. Coughlin, S . Ghosh, M. G. Zagorski, J. Am. Chern. Soc., 1982, 104,998 - 1007.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

6

Photooxygenation and Photoreduction

The first excited state of molecular oxygen, the lAg state, is 22.3 kcal/mol higher in energy than the ground state, 3Zu. In the case of such a remarkably low energy gap a multitude of sensitizers can be used to transfer their energy to triplet oxygen and transform it into its singlet state. For this reason, this type of photooxygenation using excited "singlet oxygen" was developed as one of the most powerful methods for the photochemical oxyfunctionalization of organic compounds. The simplicity of these reactions is striking: singlet oxygen can be produced in all solvents (with lifetimes between 2 ps and several ms) with a broad variety of sensitizers. The reaction of organic compounds with singlet oxygen can lead to reactive molecules such as hydroperoxides, 1,2-dioxetanes, and endoperoxides. These compounds can then be transformed into a multitude of products by means of reduction or rearrangement reactions. An important synthetic application of the "ene-reaction"of singlet oxygen with acyclic alkenes is described by W. Adam. The starting material is derived from mesityl oxide and in two steps it can be transformed into a mixture of epoxy alcohols with a remarkably high diastereomeric excess. Here the key reaction is a titanium (IV) catalyzed intramolecular oxygen transfer which resembles the key step in the famous Sharpless epoxidation. In this reaction sequence singlet oxygen is generated via a tetraphenylporphyrine (TPP) sensitized energy transfer. Other dyestuffs can also be used for this reaction (bengal rose, methylene blue). A remarkable example for an ene-reaction which does not use an allylic C-H group in the abstraction step is reported by K. Mizuno. Reaction of a phenyl substituted tetrahydroindole with singlet oxygen (generated by a methylene blue sensitized energy transfer) leads to the formation of an allylic hydroperoxide. This is an example of a vinylic version of the ene-reaction with an activated N-H group. The hydroperoxide is reduced using dimethyl sulfide and the resulting hydroxy 2H-pyrrol derivative is isomerized to a spirobicyclic product. The importance of electron-transfer reactions in photochemistry is widely recognized. Many photooxygenations also involve photochemically initiated electron-transfer steps. In most cases the sensitizer serves as an electron acceptor and generates a radical cation from an appropriate electron donor. Subsequently triplet oxygen can react with the electrophilic radical cation or a superoxide anion can be generated via second electron transfer step. Singlet oxygen photooxygenation and electron transfer photooxygenation, although involving different intermediates can sometimes lead to the same products. As described by B. Pandey photooxygenation of 1,3-dithiolanes gives 1,3-dithiolane-1-oxides in good yields irrespective of the sensitizer. Both rose bengal (a typical singlet oxygen sensitizer) and 1-cyanonaphthalene (an electron transfer sensitizer which produces sulfide radical cations) can be used in methanol and aqueous acetonitrile, respectively. Oxidation of the second thioether group was not observed in either reaction types. This fact indicates a strong deactivating effect of the sulfoxide group. Compared with photooxygenation, i.e. the photochemical activation of oxygen, the definition of photoreduction is more difficult. Many photochemical processes involve redox reactions where one part of the substrate (in intramolecular reactions) or a second molecule (in intermolecular reactions) is reduced and the original substrate is oxidized (or

286

6.

Photooxygenation and Photoreduction

vice versa). These reactions are not normally described as photoreductions. Whenever a reducing reagent is used that only reacts with electronically excited substrates, the reaction can be defined as a photoreduction. The electron-transfer initiated reduction of weak (e.g. strained) C-C single bonds is such an example. Trialkylamines serve as electron and as hydrogen donors. One example of this type has already been described in Chapter 1.2. The photoreduction of an unsaturated bicyclo-[4.1.O]heptan-5-one as submitted by J. Mattay is another one (cf. chapter 1.2). A similar process is the very useful transformation of semibullvalene derivatives into bicyclo[3.3.0]octanes via a PET mediated reduction of the cyclopropane ring, developed by B. Pandey, which is also described in this chapter. An alternate reducing agent is tributyltin hydride which is used by T. Hasegawa for comparable transformations. Applying the corresponding allyltin reagent results in the formation of an a-allylated P-hydroxy ketone. In both cases cleavage of an oxirane C - 0 single bond follows the intermolecular hydrogen (or tributyltin) abstraction.

Recommended further reading General: Singlet Oxygen H. H. Wasserman, R. W. Murray, (Eds.), 1979, Academic Press, New York; Singlet 0 2 A. A. Frimer (Ed.), 1984, CRC Press, Boca Raton, Fl.; Organic Peroxides W. Ando (Ed.), 1992, Wiley, New York. Reviews on singlet oxygen and on photo electron transfer oxygenations: K. H. Pfortner in Photochemistry in Organic Synthesis J . D. Coyle (Ed.), 1986, The Royal Society of Chemistry, London; C. S . Foote, Acc. Chem. Res. 1968, I , 104; D. R. Kearns, Chem. Rev. 1971, 71, 395; R. W. Denny, A. Nickon, Organic Reactions 1973, 20, 133; L. Lopez, Top. Curr. Chem. 1990,156, 117.

6.

287

Photooxygenation and Photoreduction

6.1

4,5-Epoxy-4-methylpentan-2,3-diol[~~ submitted by

6.la

W. Adam and B. Nestler

4-Methyl-3-penten-2-0Pl 0

OH

LIAIH, Et,O

98.2

38.0

100.2

To a suspension of 1.00 g (26.4 mmol) of lithium aluminium hydride in 15 mL of dry ether was added under stirring a solution of 5.00 g (50.9 mmol) of freshly distilled mesityl oxide in 10 mL of ether at a rate to keep the mixture at gentle reflux. Stirring was continued for 30 min, then 1 mL of water, 1 mL of 15% aqueous sodium hydroxide and 3.5 mL of water were introduced slowly (caution! vigorous evolution of hydrogen gas). The precipitate was removed by filtration and the solution dried over sodium carbonate. Distillation afforded 4.23 g (83%) of a colorless liquid with bp 87 - 89 "C/90 Torr. '€I-NMR (CDC13,250 MHz): 6 = 1.20 (d, 3 H, J = 6.2, CHOHCH3), 1.60 (d, 1 H, J = 3.3, Om, 1.66 (d, 3 H, J = 1.2, CH3), 1.68 (d, 3 H, J = 1.1, CH3), 4.53 (ddq, 1 H, J = 8.6,

6.2,3.3,CI-JOH),5.18(dqq,lH,J=8.6,1.2,l.l,C=C€I).

13C-NMR (CDC13, 63 MHz): 6 = 118.4 (q, CHOHCH3), 24.0 (q, CH3), 26.0 (9, CH3), 66.2 (d, CHOH), 129.8 (d, C=CH), 134.4 (s, (CH3)2c=CH). IR (CC14): V = 3620,2980, 1670, 1450,1380,1070, 1030.

6.lb

2

3-Hydroperoxy-4-methyl-3-penten-2-ol[~l

100.2

O,,TPP, hv

HOOJ

+

HOO$

132.2

A solution of 501 mg (5.00 mmol) of 6.la and ca. 5 mg of tetraphenylporphin in 80 mL of methylene chloride was irradiated with two external Philips G/98/2 SON 150 W sodium lamps at 0 "C while passing continously a stream of dry oxygen through the solution. The

288

6.

Photooxygenationand Photoreduction

course of the reaction was monitored by means of TLC (silica, petroleum ether/ether (4:l), detection: the TLC plates were sprayed with a solution of 10% of phosphomolybdic acid in ethanol and then heated. 6.lb can also be detected with an aqueous solution of KI); after approximately 4 h all starting material had been consumed. The obtained solution contains (S,S)- and (S$)-6.lb in a 90:lO ratio, it may be stored in a refrigerator for weeks without decomposition.

6.lc

4,5-Epoxy-4-methylpentan-2,3-diol~~l

Ho3?Ti(OiPr),

132.2

284.3

132.2

After addition of ca. 2 g of molecular sieves (4A) to the solution of 6.lb the mixture was cooled to -25 "C. At this temperature 75 mL (5 mol%) of titaniumtetraisopropylate were injected with a micro syringe (TLC control!). After 5 min the reaction was quenched by addition of 50 mL of ether and 0.5 mL of water under vigorous stirring. Stimng was continued for 30 min, then the solvent was removed under reduced pressure and the residue at once purified by column chromatography (ca. 50 g of silica gel 60-230 mesh) eluting with ether, yielding 456 mg (69% based on 6.la) of colorless plates, mp 7 1 - 72 "C. The isolated product is a 9 5 5 mixture of (2S,3R,4S)- and (2S,3R,4R)-6.lc. (2S,3R,4S)-6.1~: 'H-NMR (CDC13, 250 MHz): 6 = 1.28 (d, 3 H, J = 6.5, CHOHC_H3), 1.37 (s, 3 H, CH3), 2.65 (d, 1 H, J = 4.5, COClrl,), 2.91 (d, 1 H, J = 4.5, COC€&), 3.34 (d, 1 H, J = 3.7, CI-JOH), 3.50 (s, 2 H, OH), 3.88 (dq, 1 H, J = 6.5,3.7, CHOH). 13C-NMR (CDC13,63 MHz): 6 = 17.6 (9, CH3), 19.8 (q, CH3), 51.5 (t, COCH2), 57.5 (s, COCH2), 67.5 (d,CHOH),76.3 (d,CHOH). (2S,3R94R)-6.1c: 'H-NMR (CDC13,250 MHz): 6 = 1.18 (d, 3 H, J = 6.4, CHOHC€&), 1.32 (s, 3 H, CH,), 2.67 (d, 1 H, J = 4.6, COC&), 2.83 (d, 1 H, J = 4.6, COCfJ2), 3.08 (d, 1 H, J = 6.2, CHOH), 3.50 (s, 2 H, OH), 3.80 (quin, 1 H, J = 6.3, CHOH). 13C-NMR (CDCl3,63 WZ): 6 = 16.0 (q, CH3), 18.8 (q, CH3), 52.4 (t, COCH2), 58.3 (s,

COCH2),67.9(d,CHOH),79.l(d,CHOH).

lR kC14): v = 3580,2980,1390,1150,1082, 1010,910. [I] [2]

W. Adam, B. Nestler, J. Am. Chem. SOC.1992,114,6549 - 6550. M. E. Cain, J. Chem. SOC.1964,3532 - 3535.

6.

289

Photooxygenation and Photoreduction

4-Phenyl-A4-pyrrolin-2-one-3-spiro-l’-cyclopen~ne~~~

6.2

submitted by

6.2a

K. Mizuno

2-Phenyl-4,5,6,7-tetrahydroindole[2Jl

P h y B , N. OH

+

214.1

Q,L o 167.3

WPh “I

0

Toluene RT

Lr

wPh “I

0

300.4

Fe,(CO) 12 8OoC

300.4

\

H

197.3

A toluene solution (20 mL) of 1.1 g of a-bromoacetophenone oxime ( 5 mmol) was added to a solution of 1.7 g of N-cyclohexenylmorpholine (10 mmol) in toluene (50 mL). The mixture was stirred at room temperature for 3 h. Then, 3.8 g of Fe3(CO),, (7.5 mmol) were added to the solution and stirred under argon at 80 “C for 3 h and filtered. The solvent was removed, and the residue was chromatographed on silica gel with hexanelbenzene (1:l) to give 0.66 g of 6.2a (68%). Recrystallization from petroleum etherholuene gave a pure sample as colorless crystals, mp 112 - 113 “C.

‘H-NMR (CDCI3, 60 MHz): 6 = 1.65 - 1.95 (m, 4 H, CH2), 2.36 - 2.75 (m, 4 H, CH2), 6.18 (d, 1 H, J = 2, pyrrole ring H), 7.03 - 7.47 (m, 5 H, Ar-H), 7.50 - 8.00 (m, 1 H, NH). IR (KBr): v = 3400. MS: m/z = 197 (M+), 169, 141, 128,77.

290

6.2b

6.

Photooaygenation and Photoreduction

2-Phenyl-7a-hydroperoxy-4,5,6,7,7a-pen~hydroindolenine

197.3

229.3

A solution of 2-phenyl-4,5,6,7-tetrahydroindole(200 mg, 1.02 mmol) and methylene blue (2 mg) in 200 mL methanol was placed in a doughnut-type vessel with a 300 W halogen lamp for 20 min under a stream of oxygen. After evaporation of methanol below 30 OC, the residue was dissolved in benzenehexane (1:1). Insoluble methylene blue was filtered off. Evaporation of the solvent below 30 "C gave 210 mg (quantitative yield) of 6.2b, mp 126 - 128 "C (dec.).

IH-NMR (CDC13, 60 MHz): 6 = 0.80 - 3.05 (m, 8 H, CH2), 6.40 (s, 1 H, CH=C), 7.00 7.60 (m, 5 H, phenyl), 12.0 (br s, 1 H, -0OH). IR (KBr): v = 3040,2840,2740 (OOH-N), 1640 (C=N), 1600. MS (70 eV): m/z = 213 (M+-16). UV (MeOH): hax = 252 (E = 14000).

W

P

h

O.O'H

229.3

Me,S

*

W

P

h

OH

213.3

0.3 mL, of dimethylsulfide was added to a stirred solution of 108 mg (0.5 mmol) of 6.2b in 20 mL of methanol and the mixture was stirred further for 12 h. The solvent was removed under reduced pressure to yield 100 mg (quantitative yield) of 6 . 2 ~as a colorless solid, mp 154 - 155 "C (dec.).

IR (KBr): v = 3080 (OH), 1635 (C=N). MS (70 eV): m/z = 213 (M+). W (MeOH): Am, = 252 (E = 17200).

6.

29 1

Photooxygenation and Photoreduction

6.2d

4-Phenyl-A4-pyrrolin-2-one-3-spiro-1'-cyclopentane

213.3

213.3

H

Heating 98 mg (0.46 mmol) of 6 . 2 ~under argon atmosphere at 180 "C for 3 min yields 95 mg (98%)of 6.2d, mp 181 - 182 "C. 'H-NMR (CDC13, 60 MHz): 6 = 1.40 - 2.10 (m, 8 H, CH2), 5.65 (d, 1 H, J = 2, CH=C), 7.20 - 7.60 (m, 5 H, phenyl), 9.45 (br s, 1 H, -NH). 13C-NMR(CDC13): 6=26.1,36.5,57.4,111.6, 124.7, 128.6, 128.8, 130.3, 138.0, 187.0. IR (KBr): v = 3040,2840,2740 (OOH-N), 1640 (C=N), 1600. MS (70 eV): m/z = 213 (M+). UV (MeOH): A,,= = 252 (E = 14000).

[l] [2] [3]

K. Mizuno, N. Ohmura, S. Nakanishi, Y. Otsuji, J. Chem. Soc., Chem Cumnun. 1983,355 - 356. S. Nakanishi, Y. Otsuji, K. Itoh, N. Hayashi, Bull. Chem. SOC.Jpn. 1990,63, 3595 3600. K. Takagi, N. Kobayashi, T. Ueda, Bull. SOC. Chim. Fr. 1973,2807 - 2809.

292

6.3

6.

Photooxygenationand Photoreduction

1,4-Dithiaspiro[4.4lnonane-l-oxide"] submitted by

"0" n

160.3

hu, CNN

B. Pandey

n

CH,CN : HO , 0,-satd

176.3

A solution of 1,4-dithiaspiro[4.4]nonane (0.16 g, 1 mmol) and 1-cyanonaphthalene 76.5 mg (CNN, 0.5 mmol) in CH$N/H20 (3:l) in a Pyrex vessel was bubbled with 0 2 for 15 min and irradiated (Rayonet photoreactor, RPR, h = 350 nm) for 8 - 10 h under an oxygen atmosphere. Oxygen bubbling was repeated intermittently during photolysis. Progress of the reaction was monitored by TLC and/or GLC ensuring that 90% of dithiolane was consumed. Acetonitrile was removed under vacuum, 10 mL of water were added and the aqueous layer was extracted with 3 x 10 mL of dichloromethane. Drying of organic extracts over anhydrous sodium sulphate, removal of solvent with a rotary evaporator and column chromatography with silica gel (60- 120 mesh) using prtroleum ether/ acetone (9: 1) as eluant afforded 140 mg (80%) of S-oxide, bp 118 - 120 "C/0.05 mm.

lH-NMR (CDC13, 90 MHz): 6 = 1.8 - 2.0 (m, 7 H, CH2), 2.6 (m, 1 H, CH), 3.1 - 3.8 (m, 4 H, S-CH2-CH2-S). IR (thin film): v = 3000, 1250, 1040. -----------------[l]

B. Pandey, S. Y. Bal, U. R. Khire, Tetrahedron Let?. 1989,30,4007 - 4008.

6.

6.4

293

Photooxygenation and Photoreduction

1,4-Dithiaspiro[4.5ldecane-1-oxide B. Pandey

submitted by

8 n

174.3

n

lo2,MeOH =-

"0"-" 190.3

A solution of 1,4-Dithiaspir0[4S]decane[~l(l74 mg, 1 mmol) in 25 mL of methanol with photosensitizer (either Rose Bengal or Methylene Blue, 5 x lo4 mmol) was saturated with oxygen for 20 - 30 min. The solution was irradiated in a Pyrex vessel with a 200 W Hanovia lamp for 4 - 5 h under continuous oxygen agitation. The ambient temperature was maintained (k2 "C) by continuous water circulation. The progress of the reaction was monitored by either GLC or IH-NMR. Removal of the solvent and purification of the residue by column chromatography on silica gel (60-120mesh) with hexane/acetone (5: 1) furnished 142 mg (75%) of 6.4, mp 87 "C.

-

lH-NMR (CDC13): 6 = 1.6- 2.1 (m, 10 H, CH2), 3.1 3.6(m, 4 H, S-CH2-CH2-S). IR (nujol): v = 2910,1440,1220,1040.

[l]

B. Pandey, S. Y.Bal, U.R. Khire, A. T. Rao, J. Chern. Soc. Perkin Trans. I 1990, 3217 - 3218.

294

6.

6.5

Bicyclo[3.3.0]octan-3-one~1~

Photooxygenationand Photoreduction

submitted by

B. Pandey

hv

= 122.2

0 3 - O 124.2

A solution of tricycl0[3.3.@*~]octan-3-one (2.24 g, 18 mmol) 1.2.ld (see M. Demuth chap. 1.2)was dissolved in 1 L of 20% triethylamine/ethanol (by volume) and was purged with a slow stream of nitrogen for 10 min. The closed vessel under nitrogen atmosphere was irradiated in a Srinivasan Rayonet photochemical reactor at 300 nm in a pyrex tube for 6 h. The progress of the reaction was monitored by GC/TLC. The solvent and TEA were evaporated under reduced pressure and the residue was chromatographed on silica gel (60-120mesh) using petroleum ethedacetone (99:l) as eluant to afford 1.8 g (79%) of 6.5 as a liquid.

lH-NMR (CDC13,90 MHz): 6 = 1.25- 2.45 (m,10 H),2.88(m, 2 H, 1-Hand 5-H). 13C-NMR (CDC13, 80 MHz): 6 = 25.20(t, 1 C),33.17(t, 2 C),39.54(t, 2 C), 44.36 (d, 2 C), 220.00(s, C=O). IR (thin film): v = 2930,1740,1400.

[ 1I

B. Pandey, A. T. Rao, P. V. Dalvi, P. Kumar, Tetrahedron 1994,543843- 3848.

6.

295

Photooxygenationand Photoreduction

1,2-tralzs-Epoxy-5-hydroxy-1,5-diphenylpentan-3-one~~~

6.6

submitted by

6.6a

E. Hasegawa

trans,trans-l,2,4,5-Diepoxy-l,5-diphenylpentan-3-one 0

Ph*Ph

234.3

H202,NaOH MeOH

-

PhA 0

P

h

266.3

To a well stirred solution of 10.0 g (0.043 mol) of trans,trans-dibenzylideneacetone[2] in 170 mL of methanol cooled in an ice-water bath a mixture of 25 mL (0.25 mol) of 31% H202 and 25 mL (0.050 mol) of 2 N NaOH was added slowly. The mixture was stirred for 10 min and then poured into 800 mL of water. The mixture was allowed to stand in a refrigerator overnight. The precipitate formed was filtered and washed with water and cold methanol to give 3.5 g (31%) of a colorless solid. This solid was recrystallized from ethanol, mp 118 - 118.5 'Ci3].

lH-NMR (CDC13,90 MHz): 6 = 3.80 (d, 2 H, J = 1.9), 4.09 (d, 2 H, J = 1.9), 7.1 - 7.4 (m,

10 H). 13C-NMR (CDCl3, 22.49 MHz): 6 = 58.9 (d), 61.0 (d), 125.8 (d), 128.8 (d), 129.2 (d), 134.8 (s), 199.0 (s, C=O). IR (KBr): v = 3016,1720, 1428, 1098,890,732,698.

6.6b

1,2-trans-Epoxy-5-hydroxy-1,5-diphenylpen~-3-one~~~ hv, Bu,SnH

Ph&Ph 0

266.3

C6H6

0 +Ph Ph 0

OH

268.3

A solution of 262 mg (0.98 mmol) of trans,trans-dibenzylideneacetonediepoxide 6.6a and 0.33 mL (1.18 mmol) of tributyltin hydride in 20 mL of benzene placed in a Pyrex tube was purged with nitrogen for 10 min and then irradiated with a Riko 400 W high-pressure

296

6. Photooxygenation and Photoreduction

mercury lamp for 60min. The photolysate was concentrated and subjected to a short column on silica gel using n-hexane as eluant to remove tin-containing compounds. The part obtained by subsequent elution with acetone was subjected to a column on silica gel using a mixed solvent of ethyl acetatdn-hexane (1 :2) as eluant to give 199 mg (75%) of a colorless solid. This was recrystallized from methylene chlorideln-hexane, mp 85 86 "C14]. 'H-NMR (CDC13,90 MHz): 6 = 2.84 - 3.10 (m, 2 H, CH2), 3.01 (broad s, 1 H, OH), 3.51 (d, 1 H, J = 1.8), 3.86 (d, 1 H, J = 1.8), 5.17 - 5.31 (m, 1 H, CHOH), 7.10 - 7.40 (m, 10 H). 13C-NMR (CDC13, 22.49 MHz): 6 = 46.6 (t, CH2), 58.0 (d), 63.3 (d), 70.0 (d, CHOH), 125.8 (d), 127.9 (d) 128.7 (d), 129.1 (d), 135.0 (s), 142.9 (s), 205.3 (s, C=O). IR (KBr): v = 3444,3020, 1712, 1344,1074,762,700,548.

[l] [2] [3] [4]

E. Hasegawa, K. Ishiyama, T. Kato, T. Horaguchi, T. Shimizu, S. Tanaka, Y.Yamashita, J. Org. Chem. 1992,57,5352 - 5359. Organikum, 16. Aufl., VEB Deutscher Verlag der Wissenschaften, Berlin, 1986, 452 - 453. A single diastereomer was obtained by recrystallization of the crude diastereomenc mixture and this was used for the photoreaction. Even when excess amount of tributyltin hydride (5 equiv.) was used, 1.5-dihydroxy1,5-diphenyl-pentan-3-onewas not obtained.[lI

6.

297

Photooxygenation and Photoreduction

6.7

2-Hydroxymethyl-1-phenylpent-4-en-1-one[1>21 submitted by

6.7a

E. Hasegawa

3-Epoxy-1-phenylpropan-1-one[31 H,02, NaOH

Ph

134.2

MeOH

-

Ph

0 150.2

To a well-stirred solution of 6.0 g (43 mmol) of a~rylophenone[~] in 110 mL ice-cooled methanol a mixture of 11 mL (0.1 1 mol) of 31% H202 and 11 mL (22 mmol) of 2 N NaOH was added slowly. Then this was poured into 200 mL of water and extracted with ether. The organic layer was washed with saturated NaCl solution and water, then dried over Na2SO4 and conentrated. The oily residue was allowed to stand in a refrigerator overnight to become solid. The solid was filtered and washed with cold n-hexane to give 2.9 g (46%) of a colorless solid. This solid was purified by sublimation, mp 49 - 50 "C.

'H-NMR (CDC13, 90 MHz): 6 = 2.97 (dd, 1 H, J = 5.9, 2.6, CHz), 3.13 (dd, 1 H, J = 5.9, 4.4, CH2),4.25 (dd, 1 H, J = 4.4,2.6, CH), 7.30 - 7.72 (m,3 H), 7.80 - 8.12 (m, 2 H). 13C-NMR (CDCl3, 22.49 MHz): 6 = 47.5 (t, CH2), 51.0 (d, CH), 128.3 (d), 128.8 (d), 133.9 (d), 135.5 (s), 194.7 ( s , C=O). IR (KBr): v = 1686,1230,708.

6.7b

2-Hydroxymethyl-1-pheny1pentl4-en-1-one[1921

150.2

191.3

A solution of 89 mg (0.6 mmol) of acrylophenone epoxide and 0.39 mL (1.2 mmol) of allyltributyltin in 2.6 mL of benzene placed in a Pyrex tube was purged with nitrogen for 10 min and then irradiated with an Ushio 500 W xenon-mercury lamp for 4 h. The

298

6. Photooxygenationand Photoreduction

photolysate was concentrated and subjected to a short column on silica gel using n-hexane as eluant to remove tin-containing compounds. The part obtained by subsequent elution with acetone was subjected to TLC on silica gel using methylene chloride as a developing solvent to give 96 mg (85%) of a colorless oil.

lH-NMR (CDC13, 90 MHz): 6 = 2.25 - 2.58 (m, 2 H, CH2), 2.91 (broad s, 1 H, OH), 3.50-4.05 (m, 3 H, CH and CH,OH), 4.85 - 5.15 (m, 2 H , =CH2), 5.50- 5.95 (m, 1 H, =CH), 7.25 - 7.65 (m, 3 H), 7.75 - 8.00 (m, 2 H). 13C-NMR (CDCI,, 22.49 MHz): 6 = 33.5 (t, CH2), 48.8 (d, CH), 63.2 (t, CH20H), 117.0 (t, =CH2), 128.5 (d), 128.7 (d), 133.1 (d), 135.3 (d), 137.7 (s), 203.2 (s, C=O). IR (neat): v = 3428, 1678, 1446, 1242, 1208.

[I] [2] [3] [4]

E. Hasegawa, K. Ishiyama, T. Horaguchi, T. Shimizu, Tetrahedron Lett. 1991, 32, 2029 - 2032. E. Hasegawa, K. Ishiyama, T. Kato, T. Horaguchi, T. Shimizu, S. Tanaka, Y. Yamashita, J. Org. Chem. in press 1992. E. Hasegawa, K. Ishiyama, T. Horaguchi, T. Shimizu, J. Org. Chem. 1991, 56, 1631 - 1635. Acrylophenone (bp 42 - 44 "C/0.044 Torr, 40%) was obtained by steam distillation of 3-DimethylaminopropiophenoneHydrochloride: C.E. Maxwell, Org. Synth. Coll. Vol. I l l 1955, 305).

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

7

Photochemistry in Organized Media

Ever since chemists made use of light in a scientific way, the control of distance, geometry, diffusion etc. remain the main challenges. Therefore it is not surprising that over the last one to two decades photochemistry partly migrated to an area which is linked to a discipline often referred to as "photochemistry in organized and constrained media". The main aim in this field has been the discovery or development of 'reaction cavities' that can be utilized by chemists to make molecules behave (chemically and physically) in the way chemists would like them to. There is a wealth of information on this subject and the interested reader is recommended to refer to V. Ramamurthy's monograph which comprehensively covers all photophysical and photochemical aspects up to 1991. However, applications to modem organic synthesis are still very seldom and therefore the editors are very grateful to the two authors who contributed examples to this book. From a geometric point of view the counterpart of a chemical reaction in the gas phase or in solution is a reaction in the solid state. The highest degree of control is achieved in the medium of a well-organized crystal. In general two types of reactions are possible, unimolecular and bimolecular. Classic examples of the latter type are the long-known dimerization of cinnamic acid in its a- or P-modification leading to truxillic acid or truxinic acid, respectively. However, the geometric requirements are very strict since the size of the reaction centers must not exceed certain values (for cinnamic acid < about 400pm). Therefore many photoreactions in the solid state are concerned with rearrangements. The two examples presented here are di-n-methane rearrangements. At a first glance this does not seem to be very exciting since the corresponding photoreactions in solution are known to proceed with high selectivity (cf. chapter 1.2 and 4). The exceptional feature is that these rearrangements proceed in the environment of chiral crystals. J. R. Scheffer who certainly is an expert in the field of solid state photochemistry used a single crystal of the chiral modification of a dibenzobarrelene derivative and irradiates it at 337 nm to obtain the rearranged product in more than 95% optical purity. In the di-n-methane rearrangement example presented by M. Demuth the normal equipment of preparative laboratories is used, i.e. the suspension of chiral crystals are irradiated in a Rayonet reactor leading to two isomers both in optically pure form. These examples illustrate the high synthetic potential of photochemistry in organized media. Future developments will certainly lead to more applications utilizing the special features of other microenvironments such as host-guest complexes, molecules absorbed on silica, alumina and other surfaces, molecules as inclusion complexes in zeolites, porous materials, liquid crystals, micelles, vesicles, and even in biological media. The following recommended reading list may also stimulate future applications.

Recommended further reuding: General: Photochemistry in Organized and Constrained Media V. Ramamurthy (Ed.), 1991, VCH, New York; K. Kalyanasundaram in Photochemistry in Microheterogeneous Systems, 1987, Academic Press, Orlando; V. Balzani, F. Scandola in Supramolecular Photochemistry, 1991, Ellis-Horwood, New York.

300

7.1

7 . Photochemistry in Organized Media

Racemic and Optically Active Diisopropyl4b,8b,8c,8d-tetrahydro-dibenzo[aflcyclopropa[c,d]pentalene8b,8c-dicarboxylate[l,*I J. R. Scheffer

submitted by

7.la

Dimethyl 9,10-dihydro-9,10-ethenoanthracene-11,12dicarboxylate[3] MeOOC

TOMe

A ____c

COOMe 178.2

142.1

320.3

A mixture of 5.0 g (28.1 mmol) of anthracene and 4.3 g (30 mmol) of dimethyl acetylenedicarboxylate was heated at 190 "C for 1 h. After cooling to room temperature, the resulting brown polycrystalline mass was dissolved in 30 mL of hot chloroform, 50 mL of ethanol were added and crystallization induced by scratching with a glass rod. The resulting pale yellow solid was collected by filtration and recrystallized twice from chlorofodethanol to afford 8.1 g (90% yield) of colorless crystals, mp 160 - 161 "C (lid3] 160 - 161 "C).

lH-NMR (CDCl,, 80 MHz): 6 = 3.8 (s, 6 H, CH3), 5.5 (s, 2 H, bridgehead CH), 6.9 - 7.5 (m, 8 H, Ar-H). IR (KBr): v = 1720,1713,1632,1275.

7.

30 1

Photochemistry in Organized Media

7.1b

Diisopropyl9,10-dihydro-9,10-ethenoanthracene-l1,12dicarboxylate

'& MeOOC

-

iPrOOC

H+

-

-

(CH,),CHOH

320.3

376.4

A solution of 5.0 g (15.6 mmol) of 7.la in 200 mL of anhydrous 2-propanol containing 2 m L of conc. H2S04 was refluxed for 10 d. The 2-propanol was removed by rotary evaporation, the residue dissolved in 100mL of ether and the ether solution washed successively with water (2 x 50 mL), 5% sodium bicarbonate solution (2 x 50 mL), water again (2 x 50 mL) and dried over sodium sulfate. Removal of ether in vacuo followed by flash chromatography on silica gel by using low boiling petroleum etherlethyl acetate (96:4) as eluant afforded 4.9 g (84% yield) of crystalline 7.lb. Recrystallization from cyclohexane afforded visually indistinguishable crystals (large prisms) in two dimorphic modifications, Pbca and P212121, which had identical melting points (145 - 146 "C) but different solid state IR spectra.

lH-NMR (CDC13, 300 MHz): 6 = 1.28 (d, 3J = 6, 12 H, CH3), 5.1 (hept, 3J = 6, 2 H, C_HMe2), 5.7 (s, 2 H, bndghead CH), 6.9 - 7.4 (m,8 H, Ar-H). IR (KBr, Pbca): v = 1720,1640,1262. IR (KBr, F'212121): v = 1724,1704, 1636,1270. Structure of both dimorphs confirmed by X-ray crystallography.[l]

7.lc

Racemic Diisopropyl4b,8b,8~,8d-tetrahedrodibenzo [a~cyclopropa[c,d]pentalene-8b,8c-dicarbo~ylate~~~ iPrOOC

376.4

iPrOOC

acetone

376.4

COOiPr

(racemic)

A solution of 1.O g (2.7 mmol) of 7.lb in 250 mL of spectral grade acetone was irradiated (immersion well apparatus, Pyrex filter sleeve, Hanovia 450 W medium-pressure mercury lamp) under a nitrogen atmosphere until capillary gas chromatography indicated little

302

7.

Photochemistry in Organized Media

remaining starting material (ca. 1 h). Removal of acetone in vucuu followed by silica gel flash chromatography of the residue (dichloromethane eluant) afforded 0.94 g (94% yield) of racemic photoproduct 7.lc, mp 111 - 112 "C (ether/ethanol).

'€I-NMR (CDC13): 6 = 1.2- 1.5 (m, 1 2 H , CH3), 4.45 (s, 1 H, 8d-H), 5.0 (m, I H, C m e 2 at 8c), 5.0 (s, 1 H, 4b-H), 5.2 (m, 1 H, C W e 2 at Sb), 7.0 - 7.4 (m, 8 H, Ar-H). IR (KBr): v = 1728, 1712, 1256, 1236. Structure confirmed by X-ray crystallography.[2]

7.ld

Optically Active Diisopropyl4b,Sb,Sc,Sd-tetrahydrodibenzo[a~cyclopropa[c,dJpentalene-8b,8cdicarboxylate"921

376.4

crystal

376.4

(>95% ee)

A large single crystal of the chiral P212121 modification of 7.lb weighing 31.8 mg was grown by slow evaporation of a cyclohexane solution previously seeded with a small crystal known from infrared spectroscopy to be in this space group. The crystal was sealed under nitrogen in a Pyrex tube and irradiated for 20 min with the unfocused output from a Molectron UV-22 nitrogen laser (337 nm, 330 mW average power). The sample was dissolved in a known volume of chloroform and its rotation measured at the sodium D line. From the percent conversion (20.9%, determined by capillary gas chromatography) plus the weight of the original crystal, the specific rotation of 7.ld could be estimated as -24.5' (0.007, CHC13). The unreacted starting material contributes nothing to the rotation because it is achiral in solution. The enantiomeric excess of product 7.ld in the experiment described above was estimated to be 95% by 300 MHz NMR spectroscopic analysis of the photolysis mixture using the chiral shift reagent Eu(hfc)3. The melting point of the optically pure material was 124 - 125 "C, and anomalous dispersion X-ray crystallographic analysis showed that (-)-7.ld has the (S)-4b, (S)-8b, (S)-8c, (S)-8c absolute configuration.[2] By way of contrast, irradiation of crystals of the achiral Pbca dimorph gave only racemic photoproduct. A simpler method to obtain optically active photoproduct 7.ld was to place the starting diester 7.lb (mixture of dimorphs) in open Pyrex glass ampoules, heat the samples to 20 "C above the mp of 145 "C for 20 min and then allow the molten liquid to solidify. The resulting polycrystalline samples were photolyzed within the same vials by exposing them to the nitrogen laser beam (30 min for 100 mg samples, ca. 8% conversion). Analysis by

7.

Photochemistry in Organized Media

303

GC and polarimetry as above indicated optical purities comparable to those obtained from the single crystal runs. In most of the runs, (-)-7.ld was obtained. In order to eliminate bias by adventitious seeding, the following experiment was designed: Known Pbca single crystals were placed in ampoules, the ampoules sealed and the crystals melted as before. Upon cooling, these samples formed supercooled glasses. Attempts to induce crystallization by touching the vials with a piece of Dry Ice were unsuccessful. Crystallization could be induced, however, by opening the ampoules and pricking the liquid with a clean stainless steel needle. The samples were then photolyzed and analyzed as before. Optical purities were high, and of eight separate runs, four gave (+)-7.ld and four gave (-)-7.ld.

[l]

[2] [3]

S. V. Evans, M. Garcia-Garibay, N. Omkaram, J. R. Scheffer, J. Trotter, F. Wireko, J. Am. Chem. SOC.1986,108,5648 - 5650. M. Garcia-Garibay, J. R. Scheffer, J. Trotter, F. Wireko, J. Am. Chem. SOC. 1989, 111,4985 - 4986. 0. Diels, K. Alder, Justus Liebigs Ann. Chem. 1931,486, 191 - 202.

304

7.

Photochemistry in Organized Media

Di-n-Methane Type Solid State Photorearrangements. Asymmetric Induction in Chiral Crystals of an Achiral Compound

7.2

submitted by

A. L. Roughton and M.Demuth

74Cyclohex-l-en-1-yl)-7-(cyclopent-8-en-8-yl)methanedicarbonitrile

7.2a

Q

NC

+

O O B r

CN

146.2

THF/DMF

161.0

-

0C $N

CN

226.3

(a) Preparation: A dry THF (160mL) solution of 3-bromo-2-cyclopenten-l-one[1] (25.0g, 155.3mmol) was added dropwise to a THF/DMF (50 mW300 mL) solution of the NaH-derived (6.78g, about 155.3mmol of a 55% oil dispersion) dienazate anion of cyclohexylidenemalononitrile[2] (22.7g, 155.3mmol) under argon at 0 "C. The dark mixture was warmed to room temperature and stirred for 10h under aluminium foil cover. Water (500 mL) was added and the mixture's pH brought from about 12 to about 3 with 10% HC1 solution. Dilution with diethyl ether and extractive work-up afforded a dark oil from which 7.2a (28.4g of off-white solid, 81%) was chromatographically isolated on silica gel with n-hexanelethyl acetate 4:1 as eluant. (b) Crystallization:Generally, solid 7.2a was fully dissolved in a warm (about 30 - 35 "C) mixture of CHzC12/diethyl etherln-hexane (1:20:5),filtered over glass frit into a Pyrex vessel and set, loosely capped, to crystallize without agitation at ambient temperature (1826 "C) to afford colorless crystals, mp 87 - 90"C.L3]

lH-NMR (CDC13, 270 MHz):6 = 1.50- 1.75(m, 4H), 1.90- 1.97(m, 2 H),2.10- 2.25 (m, 2H),2.52- 2.56(m, 2H), 2.61 - 2.64(m, 2H), 6.33- 6.36(m, 1 H),6.45- 6.46 (m, 1 H). "C-NMR (CDC13, 67.9 MHz):d = 20.79,21.92,24.06,25.23,26.64,35.58,46.06,

11 1.64x 2,126.08,131.62,134.35,165.65,205.36.

MS: m/z = 226 (M+), 81 (loo), 53,27.

7.

305

Photochemistry in Organized Media

IR (KBr): v = 2932 - 2862,2249, 1713, 1674, 1617, 1444, 1429, 1312, 1276, 1233, 1179, 1144, 1122. UV (CH3CN):,,,A = 216 (E = 16477), 328 (49). Anal. calc. for C14H14N20: C 74.31, H 6.24, N 12.38; found: C 74.29, H 6.26, N 12.35.

7.2b

7,7-Dicarbonitrile-l-(cyclopent-8-en-lO-on-~-yl)-bicyclo[dl.O]heptane and

7.2~ 6,6 Dicarbonitrile-5-(cyclohex-7-en-7-yl)-bicyclo[3.1.0]hexan-2-one[3]

hv

0 CN 226.3

acetonitrile

NC

CN

7.2b 0

226.3

7.2~ 0

(a) Preparation from homogeneous solution of 7.2a: Argon was bubbled through a stirred 0.1 M CH3CN solution of 7.2a (7.2 g, 31.7 mmol) in a pyrex vessel which was then sealed with a cooling finger (€I20 coolant, ca. 18 "C) and irradiated in a Rayonet RPR-100 reactor equipped with 350 nm lamps for 32 h. The solution was concentrated to a yellow oil from which 7.2b (4.6 g of white/yellow solid) and 7 . 2 ~(1.43 g of off-white solid) were chromatographically isolated on silica gel with n-hexanelethyl acetate 3:2 as eluant [260 mg, 4 %, white solid, of intramolecular [2+2] photoproduct and 249 mg of an unidentified solid were also isolated]. (b) Preparation from suspension of 7.2a in H20: Crystalline 7.2a (6 g, 26.4 -01) was ground to a fine powder and poured into a pyrex vessel mounted in a Rayonet reactor with 350 nm lamps containing vigorously stirred H20 (300 mL, distilled). A cooling finger (H20 coolant, about 11 "C) was lowered into the mixture and the vessel was irradiated for 90 h. The turbid lightly orange mix was poured into a separatory funnel and the remaining orange and yellow solidmelt was washed from the vessel with CH2C12 (300 mL). Extractive work-up afforded a dark reddish orange oil from which 7.2a (2.93 g, 49%), 7.2b (1.36 g, 23%) and 7 . 2 ~(1.68 g, 28%) were chromatographically isolated as in (a). Physical data for 7.2b: colorless crystals, mp 125 - 127 "C for 1 97% optically pure (+)-7.2b and 96 - 98 "C for racemate; [a],20=+63.5" optically pure (extrapolated, 0.99, CHC13).

306

7 . Photochemistry in Organized Media

lH-NMR (CDC13, 270 MHz): 6 = 1.64 - 1.28 (m, 4 H), 1.97 - 1.84 (m, 1 H), 2.16 - 2.09 (m,ZH),2.30-2.19(m, lH),2.48-2.43(m,3H),2.6O(dddd, lH,J=18.3,5.5,3.9, 1.Q 2.77 (dddd, 1 H, J = 18.3, 5.7, 3.9, I&, 6.02 (t, 1 H, J = 1.8). 13C-NMR (CDC13, 67.9 MHz): 6 = 15.63, 18.99, 19.50, 19.84, 24.55, 28.28, 33.72, 35.14, 38.58, 112.47, 113.62, 131.95, 175.28,207.80. MS: m/z = 226 (M', C I ~ H ~ ~ N209, ~ O 197, ) , 183, 169, 155, 135, 115, 107 (loo), 91, 53, 39,27. IR (KBr): v = 2953 - 2869,2239, 1707, 1675, 1599, 1437,1401, 1331, 1259. UV (CH3CN): h,, = 228 (E = 16584), 324 (49). Anal. calc. for C14H14N20: C 74.31, H 6.24, N 12.38; found: C 74.35, H 6.24, N 12.36.

Physical data for 7.2~:colorless crystals, mp 82 - 83 "C for 2 99% optically pure (+)-7.2c and 73 - 75" for racemate; [a],20+159.90 optically pure (extrapolated, 0.24, CHC13). lH-NMR (CDC13, 270 MHz): 6 = 1.52 - 1.62 (m, 2 H), 1.65 - 1.74 (m, 2H), 2.01 - 2.23 (m, 4 H), 2.32 - 2.60 (m, 4 H), 2.96 (s, 1 H),5.69 - 5.73 (m, 1 H). 13C-NMR (CDC13, 67.9 MHz): 6 = 15.36, 21.37, 21.92, 24.62, 26.00, 26.17, 34.97, 45.03,53.28, 111.27, 111.55, 128.90, 130.33,204.57. MS: m/z = 226 (M', C I ~ H ~ ~ N208, ~ O 183,169 ), (loo), 155, 135,115,91,51,39. IR (KBr): v = 3058 - 2833,2240,1745,1448,1403, 1241,1159, 1041. UV (CH3CN):,,,A = 224 (E = 2208), 291 (37). Anal. calc. for C14H14N20: C 74.31, H 6.24, N 12.38; found: C 74.33, H 6.22, N 12.33. X-ray data: structures 7.2b and 7 . 2 ~were crystallographically s e c ~ r e d [ ~ . ~ I .

[l] [2] [3] [4]

E. Piers, J. R. Grierson, C. K. Lau, I. Nagakura, Can. J. Chern. 1982,60,210 - 223. H. Hart, Y. C. Kim,J. Org. Chem. 1966,31,2784 - 2789. A. L. Roughton, Ph. D. Thesis, Max-Planck-Institut fur StrahlenchemieKJniversity of Essen, 1992. A. L. Roughton, M. Muneer, I. Klopp, C. Kruger, M. Demuth, J. Am. Chem. SOC. 1993,115,2085 - 2087.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

8

Photochromic Compounds

Photochromism is a term that characterizes reversible reactions in which one or both directions can be triggered photochemically. The absorption spectrum of the substrate and the photoproduct differ with respect to the wavelength and extinction, i.e. a color change caused by the absorption of radiation. In principle this is one of the easiest ways to store information reversibly. It can be erased in a second step either thermally or photochemically by irradiation at another wavelength. Obviously, no irreversible chemical reactions must occur during such a photochromic cycle. Using the terminology of information storage, an irreversible change such as the elimination of a smaller molecule, formation of a strong bond, skeletal rearrangements, etc. leads to an irreversible storage of information. Photochromic systems can also be used to transform photon energy into heat and therefore they may serve as photostabilizers. Further, photochromic systems can be used to measure the amount of light that is absorbed by a compound and thus be used as a chemical actinometer. Many classes of photochromic compounds are known and described in the literature. A highly aesthetic example comes from H. Bows-Laurent: an intramolecular anthracene-dimerization. Using the output of a high-pressure mercury lamp and a Pyrex filter, the bis-anthracene compound can be converted quantitatively into the [4+4] photocycloisomer. By heating this compound, the starting material is regenerated. Alternatively irradiation at wavelengths < 300 nm where the photocycloisomer starts to absorb regenerates the substrate. This cycle of photocyclodimerization and regeneration works several times. More complex examples can be found in the literature. Many examples of photochromic compounds involve charge separation, for instance, the classical isomerization of a spiropyran in a highly colored merocyanine dye.

Similar examples are described by H.Durr. A variety of beautifully colored zwitterions are generated by a photochemical ring-opening of spirocyclic compounds. Without any doubt these examples are very impressive and constitute an appropriate completion of this collection.

Recommendedfirther reading General: G. H. Brbwn, Photochromism, 1971, Wiley, New York; Photochromism, Molecules and Systems H. Diirr, H. Bouas-Laurent (Eds.), 1990, Elsevier, Amsterdam; Frontiers in Supramolecular Organic Chemistry and Photochemistry H.-J. Schneider, H. Diirr (Eds.), 1990,VCH,Weinheim, New York.

308

8.

Photochromic Compounds

Photodimerization of Arenes

8.1

submitted by

H. Bouas-Laurent and J.-P. Desvergne

Anthracene photodimerization has been known for more than a century[lI anc it was shown that the photodimer can revert to the monomer on heating or by irradiation.[l] A great number of anthracene derivatives undergo this photochromic reactionI2I which is accompanied by a large reversible change of the absorption spectrum.[2] Bichromophores consisting of two photoreactive sub-units linked by an inert chain undergo intramolecular processes which are more efficient. One of these systems, bis(9-anthrylo~y)methane[~Iis described as follows:

&la: preparation of bis(9-anthry1oxy)methane 8.lb: photocycloisomerization of bis(9-anthry1oxy)methane 8 . 1 ~photochromic : behaviour of bis(9-anthry1oxy)methane

Bis(9-anthry1oxy)methane

8.l a

0 0

+ CH,CI,

H

H

194.2

84.9

-

0

/

@ , J J

KOH,RT Et4NHS04

/

/

CH*

\0

J ( k J J

/

0

/

/

400.5

A mixture of anthrone (9.7 g, 0.05 mol), KOH (5 g, 0.09 mol), and tetraethylammonium hydrogensulfate (1.1 g, 0.0048 mol) in dichloromethane (dried on neutral alumina) (150 mL,) was stirred in the darkness (aluminum foil) at RT for 15 h under nitrogen in a three-necked round-bottomed flask. The yellow precipitate was washed with water up to neutrality. The powder was chromatographed on silica gel (eluant: toluene) to obtain 8.la as a pale yellow powder (yield: 4.8 g, 48%); mp 208 - 210 "C.

'H-NMR (CDC13): 6 = 6.0 (2 H, s, OC_H20).7.1 - 8.7 (18 H, m, aromatic).

8.

309

Photochromic Compounds

IR (KBr): v = 3030, 2940, 1615, 1445, 1340, 1270, 1165, 1155, 1145, 1040, 945, 860, 720. UV (cyclohexane): Lax = 387.5 (lg E = 4.31), 367 (4.28), 348 (4.05), 333 (3.74), 317 (3.36), 256 (5.60), 247 (5.30).

8.1b

Photocycloisomer of bis(9-anthry1oxy)methane

/

C"2

\ hv

0

Et,O

400.5

400.5

A degassed (by freeze and thaw cyclesa solution of 8.la (200 mg, 0.5 mmol) in 750 mL diethyl etherb (6.3 x lo4 MC was placed in a Pyrex flask and irradiated using a highpressure mercury lamp for 2 h. After the solution was concentrated, the photoproduct precipitated as white crystals which were collected, washed, and dried in vucuu (yield: 150 mg, 75%); mp > 260 "C (dec.).

lH-NMR (CDC13): 6 = 4.6 (2 H, s, OCH20), 6.7 - 7.5 (16 H, m, aromatic). IR (KBr): v = 3030,2900,2840,1465,1450,1375,1365,1320,1085,1015,735. MS: m/z = 400 (20, M+), 207 (loo), 194 (66). W (diethyl ether): hmax= 280 (lg E = 2.89), 270 (3.04), 260 (3.25), 253 (3.44).

a

b

The photocycloisomer can also be obtained if one bubbles argon into the solution for a few minutes but is it better to get rid of traces of 0, owing to the liability of anthracene to oxidation. Other solvents such as hydrocarbons, alcohol or acetonitrile can be used. The photocycloisomerisation quantum yield were found to be 0.38 (cyclohexane) 0.54 (methanol) and 0.43 (acetonitrile). High dilution conditions are necessary for exclusive intramolecular reactivity.

3 10

8.lc

8.

Photochromic Compounds

Photochromic behaviour of bis(9-anthry1oxy)methane

-

Slnm

A

-

0

400.5

400.5

300

hu

400

Fig. 5a: UV absorption spectra in cyclohexane of 8.la (--) and 8.lb (-) conc. = M. The absorbance decreasesat300chc400nm(l,2,3)byirradiation through Pyrex whereas 8.lb is generated (spectrum 4).

n(cycles) Fig. 5b: Photocycles of 8.la in degassed M). The solucyclohexane (conc, = tion was first irradiated at 366 nm until A387 is = 0 and then heated to reach again A387max.

The UV spectrum of 8.la in cyclohexane" between 200 and 500 nm shows two absorption regions: I 300 - 400 nm (3.3 c log E c 4.4); I1 200 - 300 nm (3.3 c log E c 5.6). The photochemical cyclization of 8.la can be followed by recording the UV spectra vs time until complete disappearance of band I (Fig. 1). The absorption of the photocycloisomer (8.lb) is that of four orthoxylene units which exhibit maxima at 270 and 280 nm. Heating

"

A quarz UV cell with a stopper can be used and the solution is degassed by gentle N2 bubbling for a few minutes. The photocycloisomerizationis conducted using a Pyrex glass filter.

8.

Photochromic Compounds

31 1

the cell with a commercial hair dryer for 10 - 15 min regenerates 8.la from 8.lb as observed by recording O.D. at 387 nm. Photochemical closure and thermal reopening can be performed several times under these experimental conditions. Photodissociation occurs when the W cell is irradiated without filter with a low-pressure mercury lamp (
[l] [2]

131 [4]

I. Fritzsche, J. Prakt. Chem. 1867, 101, 333 - 343; ibid. 1869, 106,274 - 293. H. Bouas-Laurent, J-P. Desvergne, [4+4/ cycloaddition reactions between unsaturated conjugated systems in Photochromism, Molecules and Systems H. Diirr and H. Bouas-Laurent (Eds.), 1990, Elsevier, Amsterdam, pp. 561 - 630. J-P. Desvergne, H. Bouas-Laurent, F. Lahmani, J. Sepiol, J. Phys. Chem. 1992, 96, 10616 - 10622. J-P. Desvergne, H. Bouas-Laurent, A. Deffieux, Mof. Cryst. Liq. Cryst. 1994, 246, 111 - 118.

3 12

8.2

8.

Photochromic Compounds

Spirocyclopropenes submitted by A. A. Abdel-Wahab, H. Diirr

CO2CH3

+

I

ether

C02CH3

192.2

142.1

334.3

A mixture of 1.90 g (9.89 mmol) of 9-dia~ofluorene[~~] and 1.70 g (1 1.96 mmol) of dimethyl acetylenedicarboxylatewas dissolved in 10 mL of dry ether. After standing for 24 h, the precipitated yellow crystals were separated in almost quantitative yield, mp 110 "C (methanol).

Anal. calc. for CI9Hl4N2O4: N 8.38; found: N 8.65.

8.2b

1,2-Dicarbomethoxycyclopropene-(3-spiro-9)-fluorene~~-~~

334.3

306.3

Irradiation of 1.00 g (2.98 mmol) of 8.2a in 150 mL of tetrahydrofuran (high-pressure mercury lamp, Hanau Q 81) at 30 "C gave a quantitative amount of nitrogen and 0.64 g (70%) of the product 8.2b. Crystallization from methanol or ethedpetrolether afforded colorless crystals, mp 146 "C (yield 70%).

IH-NMR (CDC13, 60 MHz): 6 = 3.1 (s), 7.2 - 7.1 (m).

8.

313

Photochromic Compounds

UV (CHC13): h,, = 266 (lg E = 4.45). Anal. calc. for C19H1404:C 74.5, H 4.61; found: C 74.29, H 4.78.

A

306.3

79.1

385.4

A mixture of 0.63 g (2.07 mmol) of 8.2b in 60 mL of ether and 0.22 g (2.76 mmol) of pyridine was stirred for one hour in the dark. Cooling of the deep-green solution with icewater gave 0.38 g (47%) of a yellow powder, mp 135 "C. Distillation of ether at normal pressure followed by column chromatography on silica gel using methylene chloride as eluant gave the product (63%) after removal of solvent and recrystallization from ether/ pentane.

'H-NMR (CDC13): 6 = 3.26 (s, 3 H, CH3), 3.99 (s, 3 H, CH3), 4.46 (d, J = 10, 8-H), 5.18 7.23 - 7.77 (t, J = 7,6-H), 5.49 (s, 1 H, 8-H), 5.68 (mc, 1 H, 7-H), 6.42 (d, J = 7, 5-H), (m, 8 H, Ar-H). 13C-NMR (CDC13): 6 = 50.76 and 53.04 (q, CH3), 64.54 (s, C-H), 69.74 (d, C-ga), 104.56 - 147.53 (Ar-C and olefinicc), 162.10 and 163.72 (s, 2 C=O). MS: m/z = 385 (10, M'), 384 (34), 326 (5), 284 (46), 189 (100). IR (KBr): v = 2945, 1702, 1740, 1645, 1624,1584, 1550,1462, 1224,752,742,712. W (CHC13): &ax = 384 (log E = 4.02). Anal. calc. for C24H19N04: C 74.79, H 4.97, N 3.63; found C 74.60, H 4.95, N 3.60.

314

8.

8.2d

Photochromic Compounds

l-(1,2-Dicarbomethoxy-2-fluorene-9-yl-ethenyl)pyridinium[4]

Betaine: green

yellow

A solution of 8 . 2 ~in chloroform m o m ) was purged with argon, placed in a 13 cm cuvet and exposed to light (tungsten lamp or h = 366 ndmonochromator; Philips HPK 125 W Hg high-pressure lamp; C-W-filter). The yellow solution turned green due to the formation of the betaine form 8.M. The green solution of the colored betaine fades with a half life of t1/2 = 14.2 s.

Color of 8.2d: green. UV (CHC13): hax = 586, hax ( hax Of 8.2d - &ax k = 0.00488 s-l for reaction 8.2d to 8 . k . t1/2 at 22 "C = 14.2 s.

8.2e

Of 8.2~)= 202.

1'H-2'~'-Dicarbomethoxy-spiro[fluorene-9,l'-py~olo[1,2-b]pyridazhe][41

b02CH b ,

306.3

80.1

386.4

To a solution of 1.20g (3.85 mmol) of 8.2b in 75 mL of ether was added 0.31 g (3.85 mmol) of pyridazine while stimng in the dark at room temperature. Evaporation of ether, treatment of the residue with methanol afforded 1.10 g (74%) of 8.2e as yellow crystals, mp 146 "C.

8.

315

Photochromic Compounds

'H-NMR (CDCl3, 90 MHz): 6 = 3.28 (s, E), 4.97 (mc, J7,6 = 9.8, J7,5 = 1.5, J7,7a = 1.5, 7-H), 5.28 (t, J7a,7 = 1.5, J7a,6 = 2.0,7-H), 5.65 (mC, 56.7 = 9.8, J6,7a = 2.0, J6,5 = 3.5, 6-H), 6.93 (dd, J s , ~= 1.5,5-H), 7.3 - 7.9 (m, 8 H, Ar-H). MS: m/z = 386 (73, M+), 327 (48), 286 (24), 247 (100). IR (KBr): v = 2945,1746, 1682, 1595,1530,1440,1420, 1230,1195,1145. Anal. calc. for C23H18N204: C 7 1.49, H 4.70, N 7.25; found C 7 1.30, H 4.63, N 6.50.

8.2f

l-(1,2-Dicarbomethoxy-2-fluorene-9-yl-ethenyl)pyridazinium[4]

yellow

Betaine: red-violet

The yellow solution of spiro-fluorene-pyrrolo-pyridazine8.2e in chloroform was irradiated (see procedure for 8.2d),after flushing with argon, in a 13 cm cuvet. The solution turned red-violet with the formation of the betaine form 8.2f. The color of the betaine 8.2f faded with a half life of t1,2 = 4.95 s. Color: red-violet UV (CHC13): hX = 505, h-(h, of 8.2f - Lax of 8.2e) = 116. k = 0.014 s-l for reaction betaine 8.2f to 8.2e. at 22 "C = 4.95 s.

8.2g

1'H-2',3'-Dicarbomethoxy-5',8'-dimethyl-spiro-[fluorene9,l'-pyrrolo[ 1,2-b]pyrida~inel[~]

306.3

108.1

414.5

316

8.

Photochromic Compounds

0.80 g (7.4 mmol) of 3,6-dimethylpyrida~ine[~I was added to a solution of 1.40 g (4.6 mmol) of spirocyclopropene 8.2b while stirring at room temperature in the dark. The deep green reaction solution was stirred for 24 h. The precipitated yellow product was separated and chromatographed on neutral alumina with ether eluant. Crystallization of the product with a small amount of cold ether gave 1.30 g (68%) of yellow crystals, mp 214 "C of 8.2g.

'H-NMR (CDC13, 90 MHz,): 6 = 1.45 (s, 3 H, CH3), 2.00 (s, 3 H, CH$, 3.35 (s, 3 H, C02CH3), 4.06 (s, 3 H, C02CH3), 5.05 (d, J = 10, 1 H, 7-H), 5.55 (d, J = 10, 1 H, 6-H), 7.2 - 7.98 (m, 8 H, Ar-H). MS: m/z 415 (21, M++l), 296 (14), 247 (58), 109 (17). IR (KBr): v = 3040,2980,1730,1675, 1560,1425,1380. UV (CH2C12): A,, = 405 (Ig E = 4.02). Anal. calc. for C25H22N204: C 72.44, H 5.35, N 6.76; found C 72.45, H 5.42, N 6.64.

8.2h

l-(1,2-Dicarbomethoxy-2-fluorene-9-yl-ethenyl)-3,6dimethylpyridazinium[51

yellow

Betaine: green

Exposure of the methylene chloride solution of the pyridazine 8.2g to normal visible light (tungsten lamp) or to monochromatic light (Bausch and Lomb monochromator) gave a green colored solution characteristic for the betaine 8.2h. This betaine 8.2h faded with a half life of t112 = 14.4 min to the starting material. Color: green. W (CH2C12): Lax = 446,639. t1/2 at 20 "C = 14.4 min.

8.

317

Photochromic Compounds

8.2i

1-(1,2-Dicyano-2-fluorene-9-yl-ethenyl)py~dazinium~~~

268.3

80.1

320.4 Betaine: deep red

A pale-yellow solution of 0.50 g (1.86 mmol) of the 4,5-dicyano-3H-pyrazole-(3-spiro-9)flu~rene[~l in 200 mL of dry ether and 2 mL of pyridazine was flushed with nitrogen and irradiated. (HPK 125 Phillips, 125WI Pyrex filter). The solution turned to a deep color after one minute. After nitrogen evolution had ceased (about one hour) the solvent was evaporated and the dark residue chromatographed using silica gel/CH2C12. Yield 0.29 g (46.8%), deep red, mp 106 "C (from ethedpentane).

W (CH2C12): hmax= 535 (Ig E = 4.51), 335 (94.45).

8.2j

1'H-2'~'-Dicyano-spiro[fluorene-9,1'-pyrrolo~l,2-b]pyridazine][61 R

320.4

320.4

A suspension of 0.590 g (1.84 mmol) of the betaine 8.2i in ether/petroleum ether was stirred in the absence of light at room temperature for 24 h. The reaction product was separated on a silica ger column with methylene chloride as eluant. Yellowish-green needles precipitated from ethedpentane in a dry ice mixture. Yield 0.195g (33.3%), mp 188 OC. The decolorization of the betaine 8.2i solution can also be brought about by irradiation (monochromator, h = 535 nm).

'H-NMR (CDCI,, 90 MHz): 6 = 5.27(dt, 1 H, J = 10, 2, 8-H), 5.39 (t, J = 2, 8a-Hh 5.71 (dt, 1 H,J = 10,3,7-H),7.08 (dd, 1 H, J = 3,2,6-H), 7.34 - 7.88 (m,8 H, Ar-H).

318

8.

Photochromic Compounds

MS: m/z = 320 (100, M'), 319 (68), 294 (78), 268 (25), 240 (80), 239 (78), 214 (45). IR (KBr): v = 3080,3040,2240,2220,1580,1520,1440,750. Anal. calc. for C21H12Nq: C 78.74, H 3.77, N 17.49; found: C 78.93, H 3.68, N 17.28.

[71

J. van Alphen, Rec. Trav. Chim. Pays-Bas 1943,62,491 - 496. L. Schrader, Thesis, Saarbrucken 1969; H. Diirr, L. Schrader, Z. Narutj6orsch. 1969, 24 B, 536 - 538. A. Schonberg, W.J. Awad, N. Latif, J. Chem. SOC. 1951, 1368 - 1369. G. Ege, Tetrahedron Letters 1963, 1667 - 1669. G. Hauck, Thesis, Saarbriicken 1980; G. Hauck, H. Durr, Angew. Chem. 1979, 91, 1010 - 1011; Znr. Ed. Engl. 1W9,18,945; H.Durr, G. Hauck, DOS 1980,2906193. J. Mosbach, Thesis, Saarbriicken 1984. H. GroB, Thesis, Saarbriicken 1982; H. GroB, H. Durr, Angew. Chem. 1982, 94, 204; Int. Ed. Engl. 1982,21,216; Angew. Chem. Suppl. 1982,559 -565. J. Levisalles, Bull. SOC.Chim. France, 1957,997 - 1003.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

Graphical Index 1.l.lj

p.20

1.l.lk

p.20

1.l.ln

p.23

h v I -CO h’

I

+-+ 1.1.2b

p.26

1.1.3c

p.29

320

Graphical Index

1.1.4d

p.33

1.1.5b

p.35

1.1.6~

p.39

0

NA COOEt Ts

Ph

hu ether

-

COOEt

Ts

1.1.6d

p.40

0

Ph+NACOORZ R'

Acyl

hv cyclohexane / benzene (80/20)

H Ph

COOP

1.1.7c+ 1.1.7d

p.43

1.1.8b

p.47 hu

0

OR' major diastereorner

1.1.9b

p.52

1.1.1oc

p.54

32 1

Graphical Index

l.l.llb

p.57 hu

benzene

OMe

pc'

p.59

1.1.12b

* p ' C O O H

hu

/

aq. acetone

1. l .139

p.64

OoMe hv, NEt3

0

CH,CN

'0

0

p.66

1.1.14 hu

CH,CN I NEb

0

p.68

1.1.15~ hv

NEb / CH,CN

1.2.ld

p.74

Q"

hv

acetone

1.2.2

p.77

&god+god \

o

*

hu

n-hexane, -50 C n --N

OH

.*

322

Graphical Index

1.2.3d

p.79

fOEt

hu

Ph

L

Ph

1,2-dimethylimidazole

1.2.4a

p.81

1.2.4~

DH O

O

p.83

HO

' " O F

OH

+ .A

hu

acetone

p.87

1.2.5~ Ph

0 4

0

N-Ph

Ph-Ph

hu ether

-

P h Z N OAPh

1.2.6d + 1.2.6e

p.90 hv

acetone

COOCH,

COOCH,

kOOCH,

1.2.7~+ 1.2.7d

p.94

1.2.8~

p.99

+

FH2 CH2

acetone, -25OC

-

+

"QHO+-

323

Graphical Index

1.2.9~ & H2 +

6'

p.106 hu

benzene

0

p.106

1.2.9d hv

&.HZ

0

0

1.2.10

p.107

K 7 hv

&OH+

0

go

1.2.11c

hv

-

CH,CN/acetone (9/1)

1.2.12b hu

benzene

0

x

p.109

H

p.112

-

&-&

1.2.13

p.114

CH2CI, hv

0

0

p.116

1.2.14~ hu

0

benzene

324

Graphical Index

1.2.16 hv, sens. Ph

benzene / MeOH

Ph

2.le

11.118

&Ph Ph

p.123

Ph hu

PhCOON

Ar Ar = p-CIC,H,

*

CH,CI,

CI

2.2c

p.126 hv /CH,CI,

“OCOPh

2.3b

p.129 hu ICH,CIZ

acetophenone

Ph

I

Ts

p. 130

2.4a

-

2.4~

p.132

hv

hu’, A

Ph

p. 135

2.5~

k+J N

\

+

EtOOC-N=N-COOEt

hv DME

*

A

325

Graphical Index

2.6~

2.8f

p.139

p.146

,

2.9~

r hu

H

1

p.149

2.10a

p.151

2.10b

p.152

326

Graphical Index

2.1 oc

p.152

I

p. 155

2.109 hu

i

__L

2.10h

p.159

2.1 l e hu L

I

0'

2.12c

p.161 hu c

0-

NO2

p.164

2.13b hu

327

Graphical Index

~~~

p.166

2.1%

0.. OPh ~

3.la D O M e

+

fCN

Me0

-

~.173

hu

MeO

C6H12

p. 176

3.2b

CN

CN

NC

NC

3.3

p.177

0.

hu

0

EtOH, EbN

3.4b

HO

H ..

hv (254nm)

cyclohexane

-

p. 178

H

@ $ls b 6

8

H

5

3.5c

p. 183

3.6b

Me0

vycor filter

/

p.187

COCH, CN

328

Graphical Index

3.79

p.193 hv

6

12

3.8

p.196 hv

+

-SiMe,

CH,CN

CN

3.9

p.197

CN

@ CN

hv

+YSiMe,

CH,CN/MeOH,, phenanthrene

NC

3.10b

p.199

~

~

~

~

DCNICH3CN c o hv

4.1a

o=

-o

H

Me0

p.207

hv

4.1d

1x209

hv

Sens'

p.212

4.2b

4.3a

,

p.213

329

Graphical Index

4.4b hu cyclohexane

Ph

4.5 hv, sens. COOMe Ph COOMe

4.6

b

-

benzene

p.216

Ph CN

p.218

-

p.219

,

"+

4.7

6

4-a Ph

Ph

Ph

Ph

An

hu acetone

An

p.220

An

p.221

t-butylhvalcohol

*

'&Ph

Ph

p.224

4.10b

[,9 0

+

Ph

Ph

p.225

330

Graphical Index

4.1 1

p.226 hu

hexane

0

4.12d

p.229

-

E

p.229

hu

dCHa '8 Et,O

AOEt

p.233

4.13b

hu

/

___)

',

'*

\

\

\

/

4.13d

p.234

___)

4.14d

p.239

C6H130 c

6

H

C6H130 1

3

0

hu

w

H3c ~~~~~

'2 ~

4.15c

& C02Et

DCA, hv CH,CN

~

eH '-13'

"3C

& C02Et

p.246

33 1

Graphical Index

p.247

4.16

p.248

p.255

4.20b

hv

t

DCA

4.21b

%

,Me

hv

w s i . M e

c&

@ &

p.258

,Me

"*Me

4.22a

p.259 AcCI. NaHCO, CH2CI2, hv

Ac

332

Graphical Index

5.3c

5.4a

0

p.272

1.) hv, then SO,

2.)Br,ICH,Clz

3.) EkN ICH,CI,

p.274

-

5.4c

p.275 1.) hu, > 350 nm

2.) 0, I Et,O

8

5.4d

H

H \ / OAc

L

H

p.276 1.) hv, c 220 nrn

2.)K2C03,MeOH

D

p.279

5.5b 1.) hexanes, hv

2.)CO, hexanes 3.)P(OMe),

333

Graphical Index

p.287

~~

p.290

6.2b

6.3

n

hu, CNN

CH,CN: H,O 0,-satd

6.4

p.292

- 6

n

n s,, s-0

p.293

n

hv

’O,, MeOH

5-o

6.5

p.294

6.6b

p.295

6.7b

p.297

P

h 0L

hv. Ou,Snw C6H6

-

Ph+ OH

334

Graphical Index

7.lc iPlOOC hv /

\

-\

acetone

-

fi IPrOOC

COOiPr

\ I

-

p.301

(racemic)

7.ld

p.302

(>95% ee)

crystal

0

p.309

8.lb

&m

ICH2\,

/

/

/

/

/

/

hv -

EGO

8.2b

p.312

8.2d

p.313

yellow

Betaine: green

335

Graphical Index

8.2f

p.315 hu

CO,CH, yellow

Betaine: red-violet

8.2h

p.316

yellow

8.2j

E

Betaine: green

p.317

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

INDEX: PHOTOCHEMICAL KEY STEPS Exp.

Lamp(s)

1.l.lj 1.l.lk 1.l.ln 1.1.2b 1.1.3~ 1.1.4d 1.1.5b 1.1.6~ 1.1.6d 1.1.7cd 1.1.8b 1.1.9b 1.1.1oc l.l.llb 1.1.12b 1.1.13g 1.1.14 1.1.15c 1.2.ld 1.2.2 1.2.3d 1.2.4a 1.2.4~ 1.2.5c 1.2.6e 1.2.7d 1.2.8~ 1.2.9~ 1.2.9d 1.2.10 1.2.11c 1.2.12b 1.2.13 1.2.14~ 1.2.15 1.2.16 2.le 2.2c 2.3b 2.4a 2.4~

MPMTQ718 LPM LPM LPM 500W HPM 125W HPM HPM HPM HPM 450 W MPM 125W HPM 450W MPM RUL 300 nm 200W Han. RUL 300 nm RUL 254 nm RUL 254 nm RUL 300 nm RUL 300 nm LPM 254 nm 450W MPM MPM TQ 150 HPM HPK15O HPM 125W HPM 250W MPM HPK- 150 500W HPM 500W HPM 500W HPM 450W MPM 450W MPM 150W HPM RUL 350 nm 450W MPH lOOOW HPH 400W MPM 400W MPM 400W MPM 500W HPM HPM

Filter VesseUReactor Sens. Cond.+Comments P V V V P D P P P V P

Q P P P

Q Q D

Q Q

P G P P P

Q Q

P P P P PIC G U P FS P P P S B

Vycor-reactor Vycor-reactor Vycor-reactor Vycor-reactor immersion external external external external immersion immersion immersion Rayonet Immersion Rayonet external Rayonet Rayonet Rayonet external immersion immersion immersion external immersion immersion Immersion immersion immersion immersion immersion external immersion Rayonet immersion immersion immersion immersion immersion immersion immersion

A

A

A Fu3 A

A

A

AP

AP AP

N/N5 "C N/MC/RT N/RS/- 196 "C N/RS/-196 "C AdMeOWO "C N/THF/RT N/E/RT N/E/RT N/CH-PhHRT A r l P W 8 "C N/Tol/RT N/E/RT N/AN/13 OC NIPWRT N/A/RT NIAN-TEA/RT NIAN-TEART Arl AN-TENRT ArlAlRT ArfHI-50 "C NIPhHIRT O/MeOWRT N/A/RT N/E/RT N/A/RT ArlANl10 "C Ethylenel-25 "C N/PhwRT NIPhwRT NINRT NIAN-A/O "C N/PhH/RT N/MC/RT ArIPhWRT N/EtOWRT N/PhwRT NIMCIRT N/MC/RT N/MC/RT N/PhH/RT NIMCIRT

Page 20 20 23 26 29 33 35 39 40 43 47 52 54

57 59 64 66 68 74 77 79 81 83 87 90 94 99 106 106 107 109 112 114 116 117 118 123 126 129 130 132

337

INDEX: Photochemical Key Steps

2.5c 2.6~ 2.7d 2.8f 2.9~ 2.1Oa 2.10b 2.10c 2.10g 2.10h 2.11e 2.12c 2.13b 2.13e 3.la 3.2b 3.3 3.4b 3.5c 3.6b 3.7g 3.8 3.9 3.10b 4.la 4.ld 4.2b 4.3a 4.4b 4.5 4.6 4.7 4.8 4.9b 4.10b 4.10~ 4.11 4.12d 4.12e 4.13b 4.13d 4.14d 4.15~ 4.16 4.17b 4.18b

LPM 257 nm LPM 257 nm TQl5OW HPM 450W MPH 450W HPM 450W HPM 450W HPM 450W HPM 450W HPM 450W HPM 125W MPM 125W HPM 450W MPM 450W MPM 90W LPM 90W LPM RUL 300 nm RUL 254 nm 450W MPM 150W HPM RUL 254 nm 300W HPM 300W HPM 125W HPM 254 nm 254 nm 254 nm 450W HPM RUL 254 nm 450W MPH 450W MPH 450W MPH 450W MF'H RUL 254 nm RUL 254 nm 150W HPM RUL 254 nm 125W HPM 125W HPM 125W HPM 125W HPM 450W MPH RUL 450 nm 450W MPH 500W HPM 450W MPH

Q Q

P V U V V V V V P P P P Si

Q P

Q V D

Q P P P

Q Q Q V

Q P P P P

Q Q P

Q

P P P P V D P

Q P

immersion immersion immersion immersion immersion external external external external external immersion immersion immersion immersion external external Rayonet Rayonet immersion immersion Rayonet external external immersion immersion immersion immersion immersion Rayonet immersion immersion immersion immersion Rayonet Rayonet immersion Rayonet immersion immersion immersion immersion immersion Rayonet immersion FF-reactor immersion

DCB

P DCN B C,D MB To1

A

DCA BP

-

Ar/DME/RT Ar/DME/RT ArIPhWRT N/MCIRT Ar/MC/RT N/S/RT N/S/RT N/S/RT N/S/RT N/S/RT N/CH/RT NPhHRT NPhHIRT N/PhH/RT N/CH/RT NICWRT NEtOH-TEA/RT Ar/CH/RT NPIRT N/CH/RT N/CH/RT Ar/AN/RT Ar/AN/RT O/AN/RT Ar/CHlRT Arm/-88 "C ArPlRT N/PIYRT N/CWRT NPhWRT N/AN/RT N/A/RT N/tBuOH/RT N/P/lO "C "35 "C N/PhH/RT NfH/RT Ar/E/10 "C NEIRT N/MeOH/RT N/ToVRT N/CH/RT AdANIRT N/GP/70 "C N/S/-18 "C NIPhHlRT

135 139 142 146 149 151 152 152 155 155 159 161 164 166 173 176 177 178 183 187 193 196 197 199 207 209 212 213 216 218 219 220 22 1 222 224 225 226 229 229 233 234 239 246 247 248 25 1

338 4.19b 4.20b 4.21b 4.22a 5.ld 5.2b 5.3c 5.4a 5.4c 5.4d

5.5b 5.6~ 6.lb 6.2b 6.3 6.4 6.5 6.6b 6.7b 7.lc 7.ld 7.2~ 8.lb 8.2b 8.2d 8.2f 8.2h 8.2j

INDEX: Photochemical Key Steps

300W HPM 300W HPM 300W HPM Xenon>345 nm 450W MPH 125W HPM 450W MPM 450W MPH 450W MPH 450W MPH 450W MPH 125W HPM 150W Na 300W Hal RUL 350 nm 200W Han. RUL 300 nm 400W HPM 500W Xe-Hg 450W MPM N-Laser 337nm RUL 350 nm HPM HIJM 125W HPM 125W HPM w lamp 125W HPM

P P P G P D P

Q U

Q

P P G P P P P P P P P P P P P P G P

external external external immersion immersion immersion immersion immersion immersion immersion immersion immersion external external Rayonet Immersion Rayonet immersion immersion immersion external Rayonet immersion immersion external external external immersion

DCN DCA

ArIToVRT Ar/AN/RT Ar/Tol/RT TPT Ar/MC/RT CO/MC/70"C CO/E/RT CO/THF/RT N/E/RT N/MC-H/RT N/MC-H/RT N/WRT CuOTf N/E/RT TPP O/MC/O"C MB O/MeOWRT CNN O/AN/RT MB/R OIMeOHRT N/EtOH-TEA/RT N/PhWRT N/PlWRT A N/A/RT N/S/RT - Ar/AN/18 "C Ar/E/RT N/THF/30°C Ar/C/RT Ar/C/RT - N/MC/RT - N/E/RT

252 255 258 259 265 268 272 274 275 276 279 28 1 285 290 292 293 294 295 297 301 302 305 309 312 314 315 316 317

LAMPS: HPM = high-pressure mercury lamp; MPM = medium-pressure mercury lamp; LPM = low-pressure mercury lamp; RUL = Rayonet lamps. SENSITIZERS: AP = acetophenone; BP = benzophenone; A = acetone; B = methyl 33bis(trifluoromethy1)benzoate; C = (-)-tetrabornyl 1,2,4,5-benzenetetracarboxylate; D = (-)-hexakis( 1-methylheptyl) benzenehexacarboxylate;MB = methyl benzoate; P = phenanthrene; CNN = 1-cyanonaphthalene;DCA = 9,lO-dicyanoanthracene;DCB = 1,4-dicyanobenzene; DCN = 1,4-dicyanonaphthaIene; CuOTf = copper(1) trifluoromethanesulfonate benzene complex; TPT = tetraphenylpyrylium tetrafluoroborat. SOLVENTS: C = chloroform; CH = cyclohexane; PhH = benzene, E = diethyl ether; THF = tetrahydrofuran; AN = acetonitrile; A = acetone; MC = methylene chloride; To1 = toluene; H = hexane; P = pentane; PE = petroleum ether; TEA = triethylamine; RS = Rigisolve (Merck); S = substrate, GP = gas phase. ATMOSPHERE: Ar = argon, N = nitrogen, 0 = oxygen, CO = carbon monoxide. FILTER GLASS: P = Pyrex; Q = quartz; V = vycor; D = duran; S = solidex; Si = silica; C = Corning filter plate; G = glass (A > 400nm); U = uranium filter, FS = filter solution; B = bandpass filter.

Photochentical Key Steps in Organic Synthesis Edited by Jochen Mattay and Axel G. Griesbeck copyright 0 VCH Verlagsgesellschaft mbH,1994

SUBJECT INDEX Absolute asymmetric synthesis 302,305 absorption spectra 4 , 3 10 acetal carbohydrate 6 1 chiral75 - 6 from B-keto ester 92 cleavage 63 formation 82 from B-keto ester 109 via Paternb-Biichi reaction 43 acetonaphthone 187 acetophenone triplet energy acetylallene 5 1 acetylene dicarboxylate as dienophile 300 as dipolarophile 3 12 reaction with cyclobutadiene 228 acrylonitrile as dienophile 73 a-morpholino I86 ortho-photocycloaddition173, 176 acylation of tert-alcohol78 of amines 134, 137 of arenes 58 of a-aminoesters 38 of aniline 161 ofenamines 86 of indole 163 alcohols photoaddition 83 photooxygenation 287 aldehyde y,&unsaturated photochemical 29 Paternb-Biichi reaction 43 aldimine 241 alkene alcohol photoaddition 83 EIZ isomerization 87, 132 hydroboration 102 synthesis

dehalogenation 224 dehydrohalogenation 186

alkylation a-deprotonation S-keto ester 108, 244 see also amine alkyne multistep transformation 18 photocycloaddition 20,224 synthesis 227,248 terminal, Grignard reagent 18 ally1 bromide 1 15 allylic cation 32 allylic hydroperoxides 287,290 allyltrimethylsilane 196 - 7 aluminum chloride acylation reaction 58 amidation 35, 134, 137 with phthalic anhydride 53 tosylamide 38 benzamide 38 amine oxidation 158 a-amino acid glycine 37 isodehydrovaline 55 phenyl glycine 263 proline 40 valine 53 amino carbene complex intermediate 264 aminoethanol, N,N-dimethyl as hydrogen donor 77 aniline as nucleophile in SNAr 160 benzylidene in olefination 250 aldimine formation 241 anthracene Diels-Alder reaction 300 photodimerization 309 anthrone 308 arabinose 61 arenes lithiation 272 ortho-photocycloaddition 173

340

Subject Index

intramolecular 176 meta-photocycloaddition intramolecular 178, 183 photodimerization 308 asymmetric induction in carbene addition 265 in photocycloaddition 47,99 in photoisomerization of amino acid 55 ofa,B-unsat. ester 77 in photooxygenation 287 in solid state reactions 302, 305 2H-azirine 135, 138 azomethine h i d e photochemical generation 141 azomethine ylide photochemical generation 135, 139 Baeyer-Villiger rearrangement 266 Barton-decarboxylation 110 benzaldehyde W h i g reaction 234 benzoate methyl(o-methoxymethyl) 56 benzocyclobutene 173 benzoxazepine synthesis, photochem. 159 p-benzoquinone 112 benzothiazole 2-methylthio 130 benzoylation ofoxime 123, 126 of amines 38 benzylamine 86 benzylic position bromination 233 betaine photochromic 313,315 7 bicycle[ 3.2.0lheptan 2-oxa 116 bicyclo[3.2.0]heptan-4-one I-methyl268 bicyclo[4.1.O]heptan-5-one I-(3-butenyl) 68 bicyclo[3.2.0]hept-2-ene 213,268 bicyclo[3.1.O]hexan-2-one 117 - 8 bicyclo[3.1.O)hex-Zene

-

3-alkylidene 22 1 bicyclo[4.2.0]octane cisltrans-isomerization 9 1 bicyclo[3.3.0]octane 3-one 294 bicyclo[3.2. lloctane 246 bicyclo[2.2.2]octene 5-acetyl-6-methylene 5 1 bicyclo[2.2.2]octenone 222 bicyclo[3.2.l]oct-6-en-8-one179 trans-bicyclo[5.3. I]undecane 110 biradical 1,3cyclization 35,216 1,4amino trapping 106 hydrgen migration 54 hydroxy trapping 107 13cyclization 40, 57 bis-(9-anthryloxy)methane 308 borneol208 boron tribromide elimination 173 bromine addition to ketone 3 1 addition to enolate 15 bromination 184 a-carbonyl 15,31 cyclopentadienone20 - 22 hexauiene-S02-adduct 274 Wohl-Ziegler 144 brominatioddehydrobromination 16,21 see also N-bromosuccinimide 4-bromobut-1-ene ether synthesis 175, 178 3-bromo-2-cyclopentenone304 1-bromohexane 236 1-bromo-3-methyl-3-butene280 1-bromo-4-methyl-3-pentene244 N-bromosuccinimide (NBS) benzylic bromination 233 bromination of alcohol 280 Wohl-Ziegler bromination 144 1,3-butadiene l-acetoxy 275 1-tnmethylsilyloxy 279

Subject Index

l-butanethiol 268 butenolide hydroxy 8 1,97 tert-butyloxycarbonyl = BOC Cage compounds 1 12 carbene formation, photochem. 151 - 2, 155 addition to alkenes 151 - 2, 155 carbinol dehydration 21 1 carbon monoxide insertion 265 carboxamindes 134, 137 carbazole deriv. photochemical 106,260 carbene complexes chromium 263,272 carbohydrate photochem. modification 64 carboxyl group activation 35 A2-carene 2 13 catechol 3-methyl236 cedrene 184 cedren- 11-one 184 cheletrope reaction cycloaddition of SO2 274 chiral auxiliar glucofuranose 77 menthol 82,98 menthone 92,95 phenylglycine 263 8-phenylmenthol46 tartrate, diethy175 chiral sensitizer from borne01 208 from (R)-2-octanol208 chiral space group 302 chlorination dichloride from ketone, by PCl5 17 a-nitrile, by PCl5 73 of propargyl alcohol 19 of quinoline 157 radical 224

34 1 meta chloroperbenzoic acid 2 13, 266 chromium hexacarbonyl263,272,275,278 pentacarbonyl butylthio methyl carbene 268 ethoxy methyl carbene 263, 268 anisyl methoxy carbene 265 trioxide oxidation of sec-ROH 282 trisacetonitriltricarbonyl275 cinnamic acid derivative, photochem. 199 Claisen rearrangement 115 cleavage reaction of acetals 63 B-cleavage (photochem.) of epoxy ketone 64 condensation to phenylacetonitrile 216 copper (I), OTf complex catalysis, photochem. 281 coupling biaryl photochemical 149 coumarin 6,7-dimethoxy, photochemical 199 crown ether synthesis, photochemical 252 crystallization separation of diastereomers 99 formation of chiral crystals 305 1-cyanonaphthalene 292 cycloaddition, via allylic cation 32 cycloaddition, I ,3-dipoIar photochemically induced intermolecular 135, 139 intramolecular 142 thermal intermolecular 3 12 cyclobutadiene 0-complex 228 tetra-tert-butyl23, 26 cyclobutane chiral, by photocycloaddition 94 1,2-diethinyl248

342 by ortho-photocycloaddition173 by PET-photocyclization 252,255 cyclobutanol Norrish typ I1 product 33 cyclobutanone synthesis, photochem. 268 optically active 265 cyclobutene annulated, photochemial90 synthesis, photochemical 224 ring opening, photochemical 225 cyclodehalogenation of as’-dibromoketones 32 cyclohexadiene, 1,3 cycloaddition 5 1,73 chiral, PET-catalyzed 259 photochemical ring opening 274 cyclohexadiene, 2,5 1-alkylidene 22 1 cyclohexa-2,5-diene-1-one 4,4-diphenyl 118 cyclohexanone a-alkylation 108 spiroannulated photochemical 68 cyclohex-2-ene-1-one 4,4-diphenyl 117 3-(3-butenyl) 67 3-ethoxy 67 cycloheptatriene chromium complex 278 decomplexation 279 cyclohexylamine 28 cyclooctadecene triphenanthro liquid crystal 242 cyclooctatetraene = COT photolysis 247 cyclooctene cisltrans isomerization 207 1-methyl 2 11 cyclopentadiene 177 cyclopentadienone tetra-rerr-butyl22 tri-rerr-butyl 20 cyclopentanone 28 cyclopentene

Subject Index

as 2rc component 94, 164 cyclophane synthesis by photocycloadd. 25 1 cyclopropane by cyclization, photochemical 35, 39,216 from enone 68 PET- induced hydrogenation 294 ring opening of reductive 68, 184,294 acid catalyzed 179 vinyl di-n-methane rearrangement 218 - 9 cyclopropene from pyrazole photochem. 3 12 ring opening pyridazine addition 314 - 6 pyridine addition 3 13 cyclopropenyliumtetrafluoroborate tri-terr-butyl 25 1,9-~yclotetradecadiyne 227 Debromination thiepin- 1,l -dioxide 274 decarboxylation Barton method 110 decatetraene 1,3,5,8,-7-hydroxy 276 dechlorination with lithium metal 190 - 1 decomplexation chromium complex 279 dehydrogenation Pd-catalyzed I92 deoxybenzoin 121

1,8-diazabicyclo[5.4.O]undec-7-ene DBU, in dehydrobromintion 145

diazoalkanes as 1,3-dipols 3 12 as carbene precursors 151 - 2,155 9-diazo-4,5-diazafluorene155 synthesis 154 2-diazodimedone 66 diazofluorene 312 a-diazoketone

343

Subject Index

synthesis 148 via tosylhydrazone 25 a-lithio 25 photolysis 149 diazomethane for synthesis of a-diazoketone 148 diazothioxanthene-S,S-dioxide151 - 2 dibenzobmelene 301 - 2 dibenzoylmethane 86 benzoyl peroxide in polymerization 145 in Wohl-Ziegler bromination 144 dibenzylamine 35 dibenzylideneacetone295 dichloromethyl methyl ether in Rieche formylation 240 9,lO-dicyanoanthracene = DCA see sensitizer 1,4-dicyanobenzene photosubstitution with 196 1,4-dicyanonaphthaline= DCN see sensitizer photosubstitution with 197 Diels-Alder reaction allene/diene 5 1 anthracenekdkyne 300 butadiene equivalent 189 cyclobutadiene 228 e m selectivity 177 ketene equivalent 73, 186 maleic anhydride 194 quinonekiene 112 diethyl azodicarboxylate as dipolarophile 135 diiodopentane 227 diketene 95 2,7-dioxabicyclo[3.2.0]hept-3-ene from Paternb-Buchi rct. 43 1,3-dioxin-4-0ne synthesis 109 photocycloaddition 109 1,3-dioxol 2,2-dimethyl47 diphenylcarbamate as phosgene equivalent 264 1,3-dipolar cycloaddition photochemical

intermolecular 135, 139 intramolecular 142 thermal 3 12 di-n-methane rearrangement 2 18 - 22 1 asymmetric induction in solid state 302, 305 aza version of 1-aza- 1,4-diene 126 of bicyclo[4.2.0]octatriene from COT 247 1,4-cyclohexadiene 3-alkylidene 221 cyclohexadienone 118 cyclohexenone 117 dibenzobarrelene in solution 301 in solid state 302 1,l-dicyanoalka-1,4-diene 222 1,3-heptadiene 55diphenyl219 oxa version bicyclo[2.2.2loctenone 74 nonracemic substrate 76 1,Cpentadiene 3,3,5,5-tetraphenyl 218 1,4-dimethoxybenzene 173 Nfl-dimethylaminopyridineDMAP 42, 103 dimethyl sulfide ozonolysis workup 42,44, 260 dodecahedrane precursor 194 Electrocyclic reaction ring opening photochemical 225 thermal 176 of dewar benzene 229 ring formation photochemical 176 elimination of B-acetoxy ester 79 of a-bromo ketone 16 of 1,l-dihalide 18 enamine synthesis 86, 186 from cyclopentanone 28

344 a-alkylation 28 ene carbamate 264 ene reaction 285, 287 enol ether synthesis from ketones 105 0-silyl245 photocycloaddition 106 enones photoreaction with alcohols 83 enyne synthesis 248 epoxidation 213, 295, 297 epoxides see oxiranes epoxy ketones photochemistry 295,297 erythrose, deriv. 49 ether synthesis 103 phenol/RX 175, 178 cleavage 179 ester a,Bunsaturated from B-keto ester 92,95 esterification acid catalyzed 53,301 with isobutene 15 with oxalyl chloride 46 with propionyl chloride 42 chiral senstizer 208 etherification 98, 103 of anomeric OH group 61 of butenolide 82 of 13-hydroxyfuran 115 of phenols 140,175, 178,236 ethylene in photocycloaddition 99 Filter solution 268 Fischer carbene complex photolysis 268,272 photochemical reaction with ene carbamate 265 thermal reaction with amino alcohol 264 formylation

Subject Index

Rieche formylation 237 Friedel-Crafts acylation 58 furan alkylation 27 1 in [4+3] cycloaddition 32 photocycloaddition 43 furan-2-one 97 furan-3(2H)-one 115 G a s phase photolysis of COT 247 glyoxylic acid 97 grandisol 103 precursors 282 Grignard reaction addition to acrolein 280 addition to ene- 1,4-dione 15 addition to ketone 18,211 substitution, propargyl chloride 19 Hemiacetal cleavage 84 Huang-Minlon reaction 184 hexahelicene 234 3-hexene 2,5-dimethyl,2,5-dianisyl photolysis 220 hydrazones B,y-unsaturated photocyclization 129 conversion to diazoalkanes 154 hydroboration 102 hydrogen abstraction benzylic position 57 y-position 33 from amino acids 54 13-position 35, 39 &position 40 hydrogenation catalytic 33 hydroxy ketones from epoxy ketones 295,297 2-hydroxyquinoline 157 Ibuprofen 59 indene 56

345

Subject Index

indole cycloaddition 259 indole derivatives synthesis photochemical 106 photooxygenation 289 indolizine deriv. 3 13 iodine in oxidative photocyclization 233 4,239 isodrin 189 isomaltol 115 isomerization photochemical EIZ 87, 132 isopropanol photochem. addition 83 Ketene equivalent synthesis 186, 268 deprotection 74, 188 generation, photochemical 149 trapping, intramolecular 149 B-ketoamide photocyclization 66 ketone LLchloro 121 photocycloaddition 52 synthesis lithiumalkyl+ester 56 a,B-unsaturated from B-chloro ketone 121 Knoevenagel condensation with malodinitrile 222 with malonic acid 199 Lactones y-butyro-, optically active 266 light sources properties 9 liquid crystals 242 - 3 literature, photochemical 2 - 3 lithium ammonia reduction of alcohols 182 butyl

metalation of arenes 272 NWdeprotonation 108 tert-butyl substitution of vinylhalide 22 diisopropylamide56, 103 syn. of enolphosphates 135, 138 a-imine alkylation 28 syn. of silyl enol ether 245 metal arylation 182 dechlorination 190 - 1 methyl addition to ester 100 Maleic acid esterification with isobutene 15 - anhydride, terr-butyl 17 malodinitrile cyclohexylidene 304 derivative 304 Mannich reaction with aryl alkyl ketones 37 menthol 82,98 menthone 31,92,95 2-mercaptopyridine,N-oxide in decarboxylation rct. 110 mesityl oxide 287 rneta cycloaddition see photocycloaddition metalation aryllithium 182 2-methylallyl chloride 140 methylation with dimethylsulfate 181 3-methyl-2-buten-l-ol substrate for esterification 42 3-methyl-3-buten- l-ol substrate for bromination 280 2-methylfuran substrate for [2+2]-addition 43 methyl oxalyl chloride 44 Michael addition 304 Naphthalene 2,3-dimethy1250 2-bromomethyl232 2-(4-methylstyryl) 232

346 naphthofuran derivatives photochemical 107 naphthopyrane derivative photochemical 149 naphthoquinone 177 cycloadduct 114 %-amino105 nitrile a,B-unsaturated 216

2,4-dinitrochlorobenzene

substrate for SNAr 160 nitrocinnamic acid cyclization 157 1,8-nonadiyne 227 norbornadiene conversion to quadricyclane 114 Nomsh typ I reaction of cyclopentanone 29 Nomsh typ I1 photocyclization 33 Optical resolution of bicyclo[2.2.2]octenone 75 organized media 302, 305 organometallic compounds (see corresponding metals) photochemistry with 265,268,272, 275,279 ortho cycloaddition see photocycloaddition oxalyl chloride 4 6 , H oxazepine 1,3-, 2-phenyl photochemically 226 oxaziridine as intermediate 159. oxazole 2S-dihydro 139 oxetanes from a-keto ester 47 oxidation 2" alcohol Swern-oxdn. 64 with PCC 55 quinoline 158 oxidoallyl cations cycloadditions 32 oxime

Subject index

from aldehyde 125 from enone 122 from ketone addition to enamines 289 oxirane from 1,2-diol 63 from alkenehydrogen peroxide 295, 297 from alkendm-CPBA 213 reductive ring opening 214 2-oxocyclopentane-1-carboxylate a-alkylation 244 oxosulfonium ylide trimethyl 68 OXYYW

singlet 287,290,293 ozonolysis dimethyl sulfide - workup 42,260 of furan cycloadducts 44

Pagodane, [1.1.1.1] 194 palladium bistriphenylphosphine chloride 148, 27 1 catalyst for dehydrogenation 192 [5]-Paracyclophane intermediate 229 Paternb-Buchi reaction a-keto ester 47 aldehyde - furan 43 intramolecular 52 PCC: pyridinium chlorochromate pentacyclo[5.4.0' 93.02@05 77]undecane 114 1,Cpentadiene 3,3,5,5-tetraphenyl di-n-methane rearrangement 218 peroxy maleic anhydride 158 phase transfer catalysis alkylation 181 phenanthrene 2-methylbenzo[c]by photocyclization 233 phenanthrolene 153 phenazine-10-oxide synthesis, photochem. 161

347

Subject Index

phenol 4-cyano 175 ether 140, 175, 178 phenyl diazonium chloride 141 phenyl glycinol 263 phenyl glyoxylic acid 46 8-phenylmenthol46 phosphine for bromination of alcohol 280 phosphonium benzyltriphenyl238 photoaddition of alcohols 83 of allyltributyl tin to epoxy ketones 297 of carbene complex to ene carbamate 265 photochemical induced 1,2-aryl shift 59 cleavage of cyclopentanone 29 1,Zhydrogen migration 216 ring opening cyclobutene 225,226 2H-azirine 135, 139 tetrazole 142 VCP-CP-rearrangement 2 13 photochemical di-n-methane rearrangement see di-n-methane rearrangement photochemistry in organized media 302,305 photochromism anthracene dimer 310 pyridazinium-fluorenyl betaine 315 - 7 pyridinium-fluorenyl betaine 313 photocrosslinking 146 photocycloaddition 1,3-dipolar 135, 139, 142 ene-enone 90 intramolecular 116 asymmetric 99 intramolecular ene-enone 109 [6+61 pagodane-route 193 164-41

chromium complex 275,279 [6+21

retro- 276 [4+2] 177 enamine 187 naphthalene 187 PET-catalyzed 259 [2+21 alkyne 20, 224 asymmetric 94 criss-cross 23 enyne-enyne 248 indole 164 intramolecular 112,114, 116 intramol., Cu-catalyzed 281 PET-initiated 252,255 to prismane 229 styrene deriv. 25 1 trapping 106, 107 meta addition intramolecular 178, 183 ortho addition 173 intramolecular 176 Paternb-Buchi a-keto ester 47 aldehyde-furan 43 intramolecular 52 photocyclization 1-azadiene 123 carbene compound 272 cyclooctatetraene247 cyclooctatriene 176 cyclopropanes 35,39 to hexahelicene 234 hydrazones B,y-unsaturated 128 o-nitroanilines 160 Nomsh typ I1 33 oxidative with iodine 233 - 4,239 via radical cation 246 PET induced 66, 196, 197,252,255 proline dervative 40 retro of dewar benzene 229 spiro product 57 photocycloisomer 309

348 photodecarbonylation tricycle[ 1.1.0.02.51pentan2-one 23 photodecarboxylation with cyclobutene ring opening 20 photodenitrogenation of diazoalkanes 151 - 155 of a-diazoketone 66, 149 of tetrazole 142 of thiadiazole 146 of pyrazole 3 12 photodimerization of N-acylindole 166 photo electron transfer carbonyl-amine 177,294 cycloaddition intermolecular 259 intramolecular 252,255 photohalogenation chlorination 224 photoisomerization of amino acid 54 of 1,3-~yclohexadiene274 of cyclooctatetraene247 EIZ 87,132 EJZ cyclooctene 207,212 of heteroaromatic N-oxide 159 of tetrahedrane 23 of unsaturated ester 77,79 photolysis gas phase 247 photooxygenation allylic alcohols 287 furans 81 indole, tetrahydro 290 thioether 292 - 3 photoreduction 294 of cyclopropane PET-initiated 294 of epoxyketone 64 with tributyl tin hydride 295 photostationary state207,212 photosubstitution aromatic 196 - 7 phthalic anhydride for imide synthesis 53 N-phthaloyl valine 53

Subject Index

polymerization radical of thiadiazole 145 prismane synthesis, photochem. 229 proline deriv. synthesis, photochem. 40 propargylamine 66 propionyloxyacetaldehyde via ozonolysis 42 ProPYne 3-phenoxy, coupling 148 pyrazoline photochemical 129 pyridazine addition to cyclopropene 314 - 6 pyridine addition to cyclopropene 313 2,3-dihydro-4( 1H)-on photocycloaddition 90 pyridin N-oxide 4-nitro 88 4-methoxy 88 pyridinium chlorochromate oxdn. of sec. alcohols 55,214 pyrrolopyridazine 3 14-5 Quadric yclane from norbornadiene 114 quantum yields for ISC 6 quinoline synthesis 157 chlorination 157 N-oxide 158 Rearrangement see di-%-methane radical reaction photochemically induced 295,297 reduction dimethylsulfide allylic hydroperoxides 290 ozonides 42,44 lithium aluminnum hydride, rct. with epoxide 2 14

Subject Index

ester 49 a,B-unsat. ketone 287 sodium borohydride carboxylic acid 263 pyridine 89 sodium borohydride on A1203 of aldehydes 44 zinc pyridine N-oxide 89 Reformatsky reaction 78 Rieche formylation 237 ring contraction of benzothiazepine thermal 131 acid-catalyzed 132 of phenanthrolene oxidative 153 of pyrazole photochemical 312 ring enlargement photochemical of benzothiazol 130 salicylic aldehyde 140 saponification of acetate 276 of carbamate 165 of 1,3-dioxan-4-0ne 110 of ketene equivalent 74, 188 semibullvalene dihydro, annulated 178 rearrangement 179 tetrahydro, ketone 74 from COT, by photolysis 247 sensitizer acetophenone 74, 118, 126, 129, 218 acetone 74,220 benzophenone 248 chiral from borne01208 from (R)-2-octanol208 methyl benzoate 2 12 methylene blue 290, 293 for photo electron transfer: 1-CNN 292 9,lO-DCA 246,255

349 1,4-DCN 199,252 TPT 259 rose bengale 81,293 tetraphenylporphine 287 Sharpless reaction 285 single crystal irradiation 302 singlet oxygen 285,287,290,293 silyl enol ether synthesis 245 radical cation 246 singlet energies 6 solid state photochemistry 302, 305 solvent parameters 5 spirocyclization 57 trans-stilbene 130 stilbene synthesis 232,238 Stille coupling 27 1 styrene carbene addition, to 151, 152, 155 substitution alkyne anion 227 nucleophilic, aromatic 88, 158, 160 sulfoxide 292,293 sulfur dioxide reaction with hexatriene 274 cleavage, photochem. 276 sulfur ylide for cyclopropanation 68 suspension photoreaction in 305 Swern oxidation 64

Tandem reaction photolthermolphoto 176 tartrate, diethyl chiral auxiliar 75 terebic acid 84 tetracyclo[4.4. 1.02,7.02*10]undecane 178 tetrahedrane, tetra-rert-butyl23, 26 tetrazole synthesis 141 photolysis 142 thermolysis of pentahydroindolenine 29 1 thiadiazole from tosyl hydrazone 143 thiepin- 1,l -dioxide 274

350 thioether 292,293 thionyl chloride 143 tin hydride cyclopropane opening 184 tin tetrachloride in Rieche formylation 237 titanium tetrakis(2-propanolate) epoxyhydroxylation 288 TMS-chloride for O-silylation 245 tolane photocycloaddition 224 tosyl hydrazone substrate for photolysis 128 substrate for thiadiazole syn. 143 reaction with diazonium chloride 141 tosylation of 2" OH 62 of amines 38 TPT = triphenylpyrylium-tetrafluoroborat see sensitizers transacetalization of oxetane 48 trapping reaction of 1,Cbiradicals by amines 106 by alcohols 107 tricyc10[4.2.1.01*3]non-7-ene 222 tricycl0[3.2.1.0396]octan-2-one 116 tricyclo[4.3.1. 12J]undecane 33 triethylamine as electronlhydrogen donor 64,66, 294 triflate methyl 272 trifluoroacetate, methyl trapping reagent 1,3-dipolar cycloadd. 139 trifluoroacetic acid 109 trifluoroacetic anhydride 109 trimethylsilyl = TMS triplet energies 6 triquinanes 184 - 5 tosylation 103

Subject Index

U

a,Bunsaturated amino acids synthesis, photochemically 54

VCP-CP rearrangement 2 13

(vinylcyclopropyl-cyclopentene-r.) vinylacetylene 248

Wittig olefination of hemiacetals 101 stilbene synthesis 232 - 4,238 Wohl-Ziegler bromination 144 Wolff rearrangement amide synthesis 66 ketene trapping, intramol. 149 Zinc metal, for Reformatsky rct. 78