SYNTHETIC APPLICATIONS OF 1,3-DIPOLAR CYCLOADDITION CHEMISTRY TOWARD HETEROCYCLES AND NATURAL PRODUCTS This is the fifty-ninth volume in the series THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS The Chemistry of Heterocyclic Compounds, Volume 59: Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Edited by Albert Padwa and William H. Pearson. Copyright # 2002 John Wiley & Sons, Inc. ISBN: 0-471-38726-6 THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS A SERIES OF MONOGRAPHS EDWARD C. TAYLOR AND PETER WIPF, Editors ARNOLD WEISSBERGER, Founding Editor SYNTHETIC APPLICATIONS OF 1,3-DIPOLAR CYCLOADDITION CHEMISTRY TOWARD HETEROCYCLES AND NATURAL PRODUCTS Edited by Albert Padwa Department of Chemistry Emory University William H. Pearson Department of Chemistry University of Michigan AN INTERSCIENCE 1 PUBLICATION JOHN WILEY & SONS, INC. Designations used by companies to distinguish their products are often claimed as trademarks. In all instances where John Wiley & Sons, Inc., is aware of a claim, the product names appear in initial capital or ALL CAPITAL LETTERS. Readers, however, should contact the appropriate companies for more complete information regarding trademarks and registration. Copyright # 2002 by John Wiley & Sons, Inc., New York. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic or mechanical, including uploading, downloading, printing, decompiling, recording or otherwise, except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act, without the prior written permission of the Publisher. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, (212) 850-6011, fax (212) 850-6008, E-Mail: PERMREQ @ WILEY.COM. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold with the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional person should be sought. ISBN 0-471-22190-2 This title is also available in print as ISBN 0-471-38726-6. For more information about Wiley products, visit our web site at www.Wiley.com. The Chemistry of Heterocyclic Compounds Introduction to the Series The chemistry of heterocyclic compounds is one of the most complex and intriguing branches of organic chemistry, of equal interest for its theoretical implications, for the diversity of its synthetic procedures, and for the physiological and industrial significance of heterocycles. The Chemistry of Heterocyclic Compounds has been published since 1950 under the initial editorship of Arnold Weissberger, and later, until his death in 1984, under the joint editorship of Arnold Weissberger and Edward C. Taylor. In 1997, Peter Wipf joined Prof. Taylor as editor. This series attempts to make the extraordinarily complex and diverse field of heterocyclic chemistry as organized and readily accessible as possible. Each volume has traditionally dealt with syntheses, reactions, properties, structure, physical chemistry, and utility of com- pounds belonging to a specific ring system or class (e.g., pyridines, thiophenes, pyrimidines, three-membered ring systems). This series has become the basic reference collection for information on heterocyclic compounds. Many broader aspects of heterocyclic chemistry are recognized as disciplines of general significance that impinge on almost all aspects of modern organic chemistry, medicinal chemistry, and biochemistry, and for this reason we initiated several years ago a parallel series entitled General Heterocyclic Chemistry, which treated such topics as nuclear magnetic resonance, mass spectra, and photoche- mistry of heterocyclic compounds, the utility of heterocycles in organic synthesis, and the synthesis of heterocycles by means of 1,3-dipolar cycloaddition reactions. These volumes were intended to be of interest to all organic, medicinal, and biochemically oriented chemists, as well as to those whose particular concern is heterocyclic chemistry. It has, however, become increasingly clear that the above distinction between the two series was unnecessary and somewhat confusing, and we have therefore elected to discontinue General Heterocyclic Chemistry and to publish all forthcoming volumes in this general area in The Chemistry of Hetero- cyclic Compounds series. It is a major challenge to keep our coverage of this immense field up to date. One strategy is to publish Supplements or new Parts when merited by the amount of new material, as has been done, inter alia, with pyridines, purines, pyrimidines, quinazolines, isoxazoles, pyridazines and pyrazines. The chemistry and applica- tions to synthesis of 1,3-dipolar cycloaddition reactions in the broad context of organic chemistry were first covered in a widely cited two-volume treatise edited by Prof. Albert Padwa that appeared in 1984. Since so much has been published on this fascinating and broadly useful subject in the intervening years, we felt that a Supplement would be welcomed by the international chemistry community, and we are immensely grateful to Prof. Padwa and Prof. Pearson for tackling this arduous task. The result is another outstanding contribution to the organic and heterocyclic chemistry literature that we are delighted to publish within The Chemistry of Heterocyclic Compounds series. E DWARD C. TAYLOR Department of Chemistry Princeton University Princeton, New Jersey PETER WIPF Department of Chemistry University of Pittsburgh Pittsburgh, Pennsylvania vi The Chemistry of Heterocyclic Compounds: Introduction to the Series Preface Cycloaddition reactions figure prominently in both synthetic and mechanistic organic chemistry. The current understanding of the underlying principles in this area has grown from a fruitful interplay between theory and experiment. The monu- mental work of Rolf Huisgen and co-workers in the early 1960s led to the general concept of 1,3-dipolar cycloaddition. Few reactions rival this process in the number of bonds that undergo transformation during the reaction, producing products considerably more complex than the reactants. Over the years, this reaction has developed into a generally useful method for five-membered heterocyclic ring synthesis, since many 1,3-dipolar species are readily available and react with a wide variety of dipolarophiles. The last comprehensive survey of this area dates back to 1984, when the two- volume set edited by Padwa, ‘‘1,3-Dipolar Cycloaddition Chemistry,’’ appeared. Since then, substantial gains in the synthetic aspects of this chemistry have dominated the area, including both methodology development and a body of creative and conceptually new applications of these [3 þ 2]-cycloadditions in organic synthesis. The focus of this volume centers on the utility of this cycloaddition reaction in synthesis, and deals primarily with information that has appeared in the literature since 1984. Consequently, only a selected number of dipoles are reviewed, with a major emphasis on synthetic applications. Both carbonyl ylides and nitronates, important members of the 1,3-dipole family that were not reviewed previously, are now included. Discussion of the theoretical, mechanistic, and kinetic aspects of the dipolar-cycloaddition reaction have been kept to a minimum, but references to important new work in these areas are given throughout the 12 chapters. Beyond the ability of the 1,3-dipolar cycloaddition reaction to produce hetero- cycles, its importance extends to two other areas of organic synthesis, both of which are included in the current volume. First, the heteroatom-containing cycloadducts may be transformed into a variety of other functionalized organic molecules, whether cyclic or acyclic. Second, many 1,3-dipolar cycloadditions have the ability to generate rings (and functionality derived from transformations of such rings) containing several contiguous stereocenters in one synthetic operation. The con- figurations of these new stereocenters arise from the geometry of the dipole and dipolarophile as well as the topography (endo or exo) of the cycloaddition. An additional stereochemical feature arises when the reactive p faces of either of the cycloaddends are diastereotopic. Relative stereocontrol in 1,3-dipolar cycloaddi- tions is dealt with in some detail, and asymmetric versions of these dipolar cycloadditions represent an entirely new aspect of the current reference work. In recent years, numerous natural and unnatural products have been prepared by synthetic routes that have a 1,3-dipolar cycloaddition as a crucial step in their synthesis. Consequently, this reaction has become recognized as an extremely important transformation in the repertoire of the synthetic organic chemist. A LBERT PADWA Department of Chemistry Emory University Atlanta, Georgia WILLIAM H. PEARSON Department of Chemistry University of Michigan Ann Arbor, Michigan viii Preface Contents 1 NITRONES 1 Raymond C. F. Jones 2 NITRONATES 83 Scott E. Denmark and Jeromy J. Cottell 3 AZOMETHINE YLIDES 169 L. M. Harwood and R. J. Vickers 4 CARBONYL YLIDES 253 Mark C. McMills and Dennis Wright 5 THIOCARBONYL YLIDES 315 Grzegorz Mloston and Heinz Heimgartner 6 NITRILE OXIDES 361 Volker Jager and Pedro A. Colinas 7 NITRILE YLIDES AND NITRILE IMINES 473 John T. Sharp 8 DIAZOALKANES 539 Gerhard Maas 9 AZIDES 623 Chin-Kang Sha and A. K. Mohanakrishnan 10 MESOIONIC RING SYSTEMS 681 Gordon W. Gribble 11 EFFECT OF EXTERNAL REAGENTS 755 Shuji Kanemasa 12 ASYMMETRIC REACTIONS 817 Kurt Vesterager Gothelf and Karl Anker Jorgensen INDEX 901 SYNTHETIC APPLICATIONS OF 1,3-DIPOLAR CYCLOADDITION CHEMISTRY TOWARD HETEROCYCLES AND NATURAL PRODUCTS This is the fifty-ninth volume in the series THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS [...]...The Chemistry of Heterocyclic Compounds, Volume 59: Synthetic Applications of 1,3- Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products Edited by Albert Padwa and William H Pearson Copyright # 2002 John Wiley & Sons, Inc ISBN: 0-471-38726-6 CHAPTER 1 Nitrones Raymond C F Jones and Jason N Martin Department of Chemistry, Loughborough University, Loughborough,... 3-Hydroxy-4-methylproline (96) is a common structural feature of the echinocandins and mulundocandins, which exhibit specific fungicidal activities, and as such this moiety has been retained in a number of synthetic antifungal agents Langlois and Rakotondradany (80) have prepared the natural (2S,3S,4S) form of 96 by the 1,3- dipolar cycloaddition of (1-ethoxy)ethoxymethyl protected a,b-unsaturated g-lactam... effect of catalysis on the rate and selectivity of the nitrone cycloaddition reaction has been examined from which impressive results have begun to emerge Thus, nitrones represent a powerful tool in modern synthetic chemistry, whose limits are still being explored more than a century after their discovery 1.2 TOWARD NATURAL PRODUCTS THROUGH NITRONE CYCLOADDITIONS With a wealth of nitrone-derived cycloadditions... many volumes; instead, this chapter will focus upon the highlights of synthetic endeavor through 1,3- dipolar cycloaddition reactions of nitrones since 1984 1 2 Nitrones 1.1 NITRONES AND THE 1,3- DIPOLAR CYCLOADDITION REACTION Nitrones (or azomethine oxides) (1–7) were first prepared by Beckmann in 1890 (8,9) and named from a shortening of ‘‘nitrogen–ketones’’ by Pfeiffer in 1916 to emphasize their similarity... (36) and a synthetic precursor respectively, via intramolecular nitrone–alkene 1,3- dipolar cycloaddition reactions with complete diastereocontrol Alcaide et al (68,69) recently published their studies of the intramolecular 1, 3dipolar cycloaddition reactions of alkynyl-b-lactams in which they found that the desired cycloaddition was in competition with a reverse-Cope elimination The reaction of alkynyl... measure of stereoselectivity into intermediates of potent oligoamide renin inhibitors through the use of a homochiral alkenylamine dipolarophile (149) Peptide functionality may be prepared in a homochiral dipolarophile for subsequent cycloaddition reaction, as demonstrated in the synthesis of peptidomimetic isoxazolidine anatagonists of human neurokinin-A by Brandi and co-workers (150) (Scheme 1.23) The 1,3- dipolar. .. dipoles from a readily available chiral pool (155–162) or as off-the-shelf homochiral dipolarophiles (163–165), and also constitute important synthetic targets (166–168) The carbohydrate-derived nitrones of Vasella and co-workers (169) are among the earliest examples of homochiral cyclic nitrone 1,3- dipoles and applications include the addition of methyl methacrylate to the spirocyclic nitrone 123 (Scheme... Kibayashi and co-worker (102,103) reported two total syntheses of the indolizidine (þ)-monomorine I (57), both of which rely on the same cycloaddition reaction of an achiral methyl glyoxalate-derived nitrone and a homochiral allyl ether The resultant mixture of isoxazolidines was a 3:1 mixture in favor of the desired product in 76% combined yield The rare reports of quinolizidine formation by a nitrone cycloaddition. .. major structural component of the cell wall of most fungi (Scheme 1.2) Merino and co-workers (38,39) reported the total synthesis of (þ)-polyoxin J 1b and of the isoxazolidine analogue of thymine polyoxin C, by nucleophilic addition to chiral sugar nitrones By a 1,3- dipolar cycloaddition route, they have prepared polyoxin analogues 2 in which the furanose ring of the parent nucleoside is substituted by... glyoxal hydrate and benzylhydroxylamine but found it exerted incomplete stereocontrol in its cycloaddition to benzyl crotonate The major isolated products, a 1:1 mixture of isoxazolidines 31a and 31b, are rationalized as the consequence of endo or exo addition to the more reactive (E) form of nitrone (30), respectively Simultaneous O- and N-debenzylation and NÀ bond hydrogenolysis of 31b ÀO gave an . COMPOUNDS The Chemistry of Heterocyclic Compounds, Volume 59: Synthetic Applications of 1,3- Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Edited by Albert Padwa and William. 1984. The Chemistry of Heterocyclic Compounds, Volume 59: Synthetic Applications of 1,3- Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Edited by Albert Padwa and William. SYNTHETIC APPLICATIONS OF 1,3- DIPOLAR CYCLOADDITION CHEMISTRY TOWARD HETEROCYCLES AND NATURAL PRODUCTS This is the fifty-ninth volume in the series THE CHEMISTRY OF HETEROCYCLIC