Name Reactions Fourth Expanded Edition Jie Jack Li Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications Fourth Expanded Edition 123 Jie Jack Li, Ph.D. Discovery Chemistry Bristol-Myers Squibb Company 5 Research Parkway Wallingford, CT 06492 USA [email protected] ISBN 978-3-642-01052-1 e-ISBN 978-3-642-01053-8 DOI 10.1007/978-3-642-01053-8 Springer Dordrecht Heidelberg London New York Library of Congress Control Number: 2009931220 c Springer-Verlag Berlin Heidelberg 2009 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design:KunkelLopka¨ GmbH Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) To Vivien Foreword I don't have my name on anything that I don't really do. –Heidi Klum Can the organic chemists associated with so-called “Named Reactions” make the same claim as supermodel Heidi Klum? Many scholars of chemistry do not hesitate to point out that the names associated with “name reactions” are often not the actual inventors. For instance, the Arndt–Eistert reaction has nothing to do with either Arndt or Eistert, Pummerer did not discover the “Pummerer” rearrangement, and even the famous Birch reduction owes its initial discovery to someone named Charles Wooster (first reported in a DuPont patent). The list goes on and on… But does that mean we should ignore, boycott, or outlaw “named reactions”? Absolutely not. The above examples are merely exceptions to the rule. In fact, the chemists associated with name reactions are typically the original discoverers, contribute greatly to its general use, and/or are the first to popularize the transformation. Regardless of the controversial history underlying certain named reactions, it is the students of organic chemistry who benefit the most from the cataloging of reactions by name. Indeed, it is with education in mind that Dr. Jack Li has masterfully brought the chemical community the latest edition of Name Reactions. It is clear why this beautiful treatise has rapidly become a bestseller within the chemical community. The quintessence of hundreds of named reactions is encapsulated in a concise format that is ideal for students and seasoned chemists alike. Detailed mechanistic and occasionally even historical details are given for hundreds of reactions along with key references. This “must- have” book will undoubtedly find a place on the bookshelves of all serious practitioners and students of the art and science of synthesis. Phil S. Baran May 2009 La Jolla, California Preface The first three editions of this book have been warmly embraced by the organic chemistry community. Many readers have indicated that while they like the detailed mechanisms, they prefer to have more real case applications in synthesis. For this edition, we have revolutionized the format, which finally liberated more space to accomodate many more synthetic examples. As a consequence, the subtitle of the book has been changed to A Collection of Detailed Mechanisms and Synthetic Applications. When putting together the 4th edition, I also strived to cap- ture the latest references, up to 2009 whenever possible. Coincidentally, my daughter Vivien, a sophomore at the University of Michigan, will take soon Or- ganic Chemistry. I hope she finds this book useful in preparing for her exams. I am very much indebted to the readers who have kindly written to me with suggestions, which helped transform this book into a useful reference book for senior undergrate and graduate students around the world—the second edition was translated to both Chinese and Russian. I am grateful to my good friend Derek A. Pflum at Ash Stevens Inc. who kindly proofead the entire manuscript and provided many invaluable suggestions. Prof. Derrick L. J. Clive at University of Alberta also proofread the first half of the manuscript and offered helpful comments. I also wish to thank Prof. Phil S. Baran at Scripps Research Institute and his students, Tanja Gulder, Yoshi Ishihara, Chad A. Lewis, Jonathan Lockner, Jun Cindy Shi, and Ian B. Seiple for proofreading the final draft of the manuscript. Their knowledge and time have tremendously enhanced the quality of this book. Any remaining errors are, of course, solely my own responsibility. As always, I welcome your critique! Jie Jack Li May 2009 Killingworth, Connecticut Table of Contents Foreword............................................................................................................... VII Preface ................................................................................................................ IX.. Abbreviations .......................................................................................................XIX Alder ene reaction ..................................................................................................... 1 Aldol condensation.................................................................................................... 3 Algar–Flynn–Oyamada reaction............................................................................... 6 Allan–Robinson reaction........................................................................................... 8 Arndt–Eistert homologation.................................................................................... 10 Baeyer–Villiger oxidation....................................................................................... 12 Baker–Venkataraman rearrangement...................................................................... 14 Bamford–Stevens reaction ...................................................................................... 16 Barbier coupling reaction........................................................................................ 18 Bartoli indole synthesis ........................................................................................... 20 Barton radical decarboxylation ............................................................................... 22 Barton–McCombie deoxygenation ......................................................................... 24 Barton nitrite photolysis.......................................................................................... 26 Batcho–Leimgruber indole synthesis...................................................................... 28 Baylis–Hillman reaction.......................................................................................... 30 Beckmann rearrangement........................................................................................ 33 Abnormal Beckmann rearrangement............................................................ 34 Benzilic acid rearrangement.................................................................................... 36 Benzoin condensation.............................................................................................. 38 Bergman cyclization................................................................................................ 40 Biginelli pyrimidone synthesis................................................................................ 42 Birch reduction ........................................................................................................ 44 Bischler–Möhlau indole synthesis .......................................................................... 46 Bischler–Napieralski reaction ................................................................................. 48 Blaise reaction ........................................................................................................ 50 Blum–Ittah aziridine synthesis ............................................................................... 52 Boekelheide reaction ............................................................................................... 54 Boger pyridine synthesis ......................................................................................... 56 Borch reductive amination ...................................................................................... 58 Borsche–Drechsel cyclization................................................................................. 60 Boulton–Katritzky rearrangement........................................................................... 62 Bouveault aldehyde synthesis ................................................................................. 64 Bouveault–Blanc reduction..................................................................................... 65 Bradsher reaction..................................................................................................... 66 Brook rearrangement............................................................................................... 68 Brown hydroboration .............................................................................................