THE NITRO GROUP IN ORGANIC SYNTHESIS The Nitro Group in Organic Synthesis. Noboru Ono Copyright © 2001 Wiley-VCH ISBNs: 0-471-31611-3 (Hardback); 0-471-22448-0 (Electronic) ORGANIC NITRO CHEMISTRY SERIES Managing Editor Dr. Henry Feuer Purdue University West Lafayette, Indiana 47907 USA EDITORIAL BOARD Hans H. Baer George Olah Ottawa, Canada Los Angeles, CA, USA Robert G. Coombes Noboru Ono London, England Matsuyama, Japan Leonid T. Eremenko C.N.R Rao Chernogolovka, Russia Bangalore, India Milton B. Frankel John H. Ridd Canoga Park, CA, USA London, England Philip C. Myhre Dieter Seebach Claremont, CA, USA Zurich, Switzerland Arnold T. Nielsen François Terrier China Lake, CA, USA Rouen, France Wayland E. Noland Heinz G. Viehe Minneapolis, MN, USA Louvain-la-Neuve, Belgium Also in the Series: Nitroazoles: The C-Nitro Derivatives of Five-Membered N- and N,O-Heterocycles by Joseph H. Boyer Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis: Novel Strategies in Synthesis by Kurt B.G. Torssell Nitro Compounds: Recent Advances in Synthesis and Chemistry Edited by Henry Feuer and Arnold T. Nielsen Nitration: Methods and Mechanisms by George A. Olah, Ripudaman Malhotra, and Sabhash C. Narong Nucleophilic Aromatic Displacement: The Influence of the Nitro Group by François Terrier Nitrocarbons by Arnold T. Nielsen THE NITRO GROUP IN ORGANIC SYNTHESIS Noboru Ono New York Chichester Weinheim Brisbane Singapore Toronto A JOHN WILEY & SONS, INC., PUBLICATION Designations used by companies to distinguish their products are often claimed as trademarks. In all in- stances 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 com- plete information regarding trademarks and registration. Copyright © 2001 by Wiley-VCH. 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, re- cording 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 profes- sional services. If professional advice or other expert assistance is required, the services of a competent professional person should be sought. ISBN 0-471-22448-0 This title is also available in print as ISBN 0-471-31611-3. For more information about Wiley products, visit our web site at www.Wiley.com. CONTENTS Series Foreword ix Preface xi Acknowledgments xiii Abbreviations xv 1. Introduction 1 2. Preparation of Nitro Compounds 3 2.1 Nitration of Hydrocarbons / 3 2.1.1 Aromatic Compounds / 3 2.1.2 Alkanes / 7 2.1.3 Activated C-H Compounds / 10 2.1.4 Alkenes / 11 2.1.5 Synthesis of = -Nitro Ketones / 16 2.1.6 Nitration of Alkyl Halides / 17 2.2 Synthesis of Nitro Compounds by Oxidation / 20 2.2.1 Oxidation of Amines / 20 2.2.2 Oxidation of Oximes / 21 3. The Nitro-Aldol (Henry) Reaction 30 3.1 Preparation of β -Nitro Alcohols / 31 3.2 Derivatives from β -Nitro Alcohols / 38 3.2.1 Nitroalkenes / 38 3.2.2 Nitroalkanes / 44 3.2.3 = -Nitro Ketones / 46 3.2.4 > -Amino Alcohols / 48 3.2.5 Nitro Sugars and Amino Sugars / 48 3.3 Stereoselective Henry Reactions and Applications to Organic Synthesis / 51 4. Michael Addition 70 4.1 Addition to Nitroalkenes / 70 v 4.1.1 Conjugate Addition of Heteroatom-Centered Nucleophiles / 70 4.1.2 Conjugate Addition of Heteroatom Nucleophiles and Subsequent Nef Reaction / 80 4.1.3 Conjugate Addition of Carbon-Centered Nucleophiles / 85 4.2 Addition and Elimination Reaction of β -Heterosubstituted Nitroalkenes / 100 4.3 Michael Addition of Nitroalkanes / 103 4.3.1 Intermolecular Addition / 103 4.3.2 Intramolecular Addition / 113 4.4 Asymmetric Michael Addition / 115 4.4.1 Chiral Alkenes and Chiral Nitro Compounds / 115 4.4.2 Chiral Catalysts / 118 5. Alkylation, Acylation, and Halogenation of Nitro Compounds 126 5.1 Alkylation of Nitro Compounds / 126 5.2 Acylation of Nitroalkanes / 128 5.3 Ring Cleavage of Cyclic α -Nitro Ketones (Retro-Acylation) / 131 5.4 Alkylation of Nitro Compounds via Alkyl Radicals / 133 5.5 Alkylation of Nitro Compounds Using Transition Metal Catalysis / 138 5.5.1 Butadiene Telomerization / 138 5.5.2 Pd-Catalyzed Allylic C-Alkylation of Nitro Compounds / 140 5.6 Arylation of Nitro Compounds / 147 5.7 Introduction of Heteroatoms to Nitroalkanes / 149 6 . Conversion of Nitro Compounds into Other Compounds 159 6.1 Nef Reaction (Aldehydes, Ketones, and Carboxylic Acids) / 159 6.1.1 Treatment With Acid (Classical Procedure) / 159 6.1.2 Oxidative Method / 160 6.1.3 Reductive Method / 164 6.1.4 Direct Conversion of Nitroalkenes to Carbonyl Compounds / 165 6.2 Nitrile Oxides and Nitriles / 167 6.3 Reduction of Nitro Compounds into Amines / 170 6.3.1 Ar-NH 2 From Ar-NO 2 / 170 6.3.2 R-NH 2 From R-NO 2 / 172 6.3.3 Oximes, Hydroxylamines, and Other Nitrogen Derivatives / 175 7. Substitution and Elimination of NO 2 in R–NO 2 182 7.1 R–Nu from R–NO 2 / 182 7.1.1 Radical Reactions (S RN 1) / 182 7.1.2 Ionic Process / 185 7.1.3 Intramolecular Nucleophilic Substitution Reaction / 191 7.1.4 Allylic Rearrangement / 192 7.2 R–H from R–NO 2 / 193 7.2.1 Radical Denitration / 193 7.2.2 Ionic Denitration / 211 7.3 Alkenes from R–NO 2 / 214 vi CONTENTS 7.3.1 Radical Elimination / 214 7.3.2 Ionic Elimination of Nitro Compounds / 218 8. Cycloaddition Chemistry of Nitro Compounds 231 8.1 Diels-Alder Reactions / 231 8.1.1 Nitroalkenes Using Dienophiles / 231 8.1.2 Asymmetric Diels-Alder Reaction / 243 8.2 1,3-Dipolar Cycloaddition / 249 8.2.1 Nitrones / 249 8.2.2 Nitrile Oxides / 258 8.2.3 Nitronates / 267 8.3 Nitroalkenes as Heterodienes in Tandem [4+2]/[3+2] Cycloaddition / 274 8.3.1 Nitroalkenes as Heterodienes / 275 8.3.2 Tandem [4+2]/[3+2] Cycloaddition of Nitroalkenes / 279 9. Nucleophilic Aromatic Displacement 302 9.1 S N Ar / 302 9.2 Nucleophilic Aromatic Substitution of Hydrogen (NASH) / 309 9.2.1 Carbon Nucleophiles / 310 9.2.2 Nitrogen and Other Heteroatom Nucleophiles / 316 9.2.3 Applications to Synthesis of Heterocyclic Compounds / 318 10. Synthesis of Heterocyclic Compounds 325 10.1 Pyrroles / 325 10.2 Synthesis of Indoles / 338 10.3 Synthesis of Other Nitrogen Heterocycles / 346 10.3.1 Three-Membered Ring / 346 10.3.2 Five- and Six-Membered Saturated Rings / 346 10.3.3 Miscellaneous / 355 Index 365 CONTENTS vii SERIES FOREWORD In the organic nitro chemistry era of the fifties and early sixties, a great emphasis of the research was directed toward the synthesis of new compounds that would be useful as potential ingredients in explosives and propellants. In recent years, the emphasis of research has been directed more and more toward utilizing nitro compounds as reactive intermediates in organic synthesis. The activating effect of the nitro group is exploited in carrying out many organic reactions, and its facile transformation into various functional groups has broadened the importance of nitro compounds in the synthesis of complex molecules. It is the purpose of the series to review the field of organic nitro chemistry in its broadest sense by including structurally related classes of compounds such as nitroamines, nitrates, nitrones, and nitrile oxides. It is intended that the contributors, who are active investigators in various facets of the field, will provide a concise presentation of recent advances that have generated a renaissance in nitro chemistry research. Henry Feuer Purdue University ix PREFACE The purpose of this book is to emphasize recent important advances in organic synthesis using nitro compounds. Historically, it was aromatic nitro compounds that were prominent in organic synthesis. In fact they have been extensively used as precursors of aromatic amines and their derivatives, and their great importance in industrial and laboratory applications has remained. This book is not intended to be a comprehensive review of established procedures, but it aims to emphasize new important methods of using nitro compounds in organic synthesis. The most important progress in the chemistry of nitro compounds is the improvement of their preparations; this is discussed in chapter 2. Environmentally friendly methods for nitration are emphasized here. In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters: Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the S N Ar reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). Noboru Ono Matsuyama, Ehime xi ACKNOWLEDGMENTS Mr. Satoshi Ito, a graduate student in my group, has drawn all figures. It would have been impossible to complete the task of writing this book without his assistance. I would like to dedicate this book to the late Dr. Nathan Kornblum whom I met 30 years ago at Purdue University. Since then I have been engaged in the chemistry of nitro compounds. It is a pleasure to express my gratitude to all persons who contributed directly or indirectly to the accomplishment of the task. Dr. Henry Feuer advised me to write this monograph and also provided many helpful suggestions, for which I thank him. Thanks to professors Node, Vasella, Ballini, Ohno and Ariga, who kindly sent me their papers. I also express my gratitude to Dr. H. Uno for his careful proofreading. Finally, thanks to my wife Yoshiko and daughter Hiroko for their constant encouragement. Professors Kornblum and Ono. xiii [...]... nitrating agents under ambient conditions Under forced conditions, they undergo cleavage of the C-C bond to give a complex set of oxidation products and lower nitroalkanes The nitration in the gas phase has been used in industry since the 1940s, producing nitromethane, nitroethane, 1-nitropropane, 2-nitropropane, 1-nitrobutane and 2-nitrobutane.1 Although this method is important for the preparation of nitroalkanes... 1,5-dinitropentane in 78% yield on treatment with acid In a similar way, 1,5-dinitropentane and 1,4-dinitrobutane are prepared in about 70% yield.40 Dianions derived from carboxylic acids are nitrated to give nitroalkanes in 45–68% yield (Eq 2.21).41 Arylnitromethanes are readily prepared by this method (Eq 2.22).42 This method is useful for the preparation of arylnitromethanes with electron-rich aryl groups,... single electron transfer reaction The Nitro Group in Organic Synthesis Noboru Ono Copyright © 2001 Wiley-VCH ISBNs: 0-471-31611-3 (Hardback); 0-471-22448-0 (Electronic) 1 INTRODUCTION The remarkable synthetic importance of nitro compounds has ensured long-standing studies of their utilization in organic synthesis Historically, nitro compounds, especially aromatic nitro compounds, are important for precursors... (1971) and vol E16D/1 (1992) 2 The Chemistry of the Nitro and Nitroso Group (parts 1 and 2), edited by H Feuer, Wiley Interscience, New York, 1969/1970 3 Seebach, D., E W Colvin, F Lehr, and T Weller Chimia, !!, 1 (1979) 4 Rosini, G., and R Ballini Synthesis, 833 (1988) 5 Barrett, A G M., and G G Graboski Chem Rev.,&$, 751 (1986) The Nitro Group in Organic Synthesis Noboru Ono Copyright © 2001 Wiley-VCH... reported in Collective Volume 6 in Organic Synthesis Methyl 3-nitroacrylate, which is a very important reagent for organic synthesis, is prepared by the reaction of methyl acrylate with N2O4 in the presence of iodine, which is followed by the subsequent treatment with sodium acetate (Eq 2.26).51 The reaction of alkenes with nitrogen oxides in the presence of oxygen gives a mixture of vicinal nitro nitrates... Interestingly, nitroalkylpyridine alkaloids, which have anti-macrofouling activity, are isolated from the Okinawan marine sponge Callyspongia sp The synthesis of such compounds has been done by the nitration of the corresponding bromide with silver nitrite (Eq 2.51) The biogenesis of nitroalkyl compounds is an interesting process, since nitroalkyl compounds are extremely rare metabolites of marine organisms.97... nitrates in the presence of bases provides a useful method for the preparation of nitro compounds As a typical example, cyclopentanone, cyclohexanone, and cyclooctanone react with amyl nitrate in the presence of potassium t-butoxide in THF at a low temperature (–30 °C) to give α,α-dinitrocycloalkanones in 35–72% yield The products are converted into α,ω-dinitroalkanes Thus, the potassium salt of 2,6-dinitrocyclohexanone... preparation of nitroalkenes, which is based on the reaction with NO, has been reported Treatment of alkenes at ambient pressure of nitrogen monoxide (NO) at room temperature gives the corresponding nitroalkenes in fairly good yields along with β-nitroalcohols in a ratio of about 8 to 2 The nitroalcohol by-products are converted into the desired nitroalkenes by dehydration with acidic alumina in high total... Scheme 1.2 Reaction of nitro compounds synthesis, synthesis in water or without solvents, the use of a fluorous phase, waste minimization, and highly selective reactions have been devised in many cases using nitro compounds Such recent progresses are described in this book General reviews for preparation of nitro compounds1 and for the reaction of nitro compounds2–5 are listed in the references REFERENCES... PREPARATION OF NITRO COMPOUNDS A number of nitro compounds used in natural product synthesis have been prepared by the nitration of alkyl halides Some recent examples are summarized in Table 2.4 β -Nitro carbonyl compounds are important for synthesis of natural products The reaction of alkyl vinyl ketones with sodium nitrite and acetic acid in THF gives the corresponding β -nitro carbonyl compounds in 42–82%.105 . THE NITRO GROUP IN ORGANIC SYNTHESIS The Nitro Group in Organic Synthesis. Noboru Ono Copyright © 2001 Wiley-VCH ISBNs: 0-471-31611-3 (Hardback); 0-471-22448-0 (Electronic) ORGANIC NITRO. more and more toward utilizing nitro compounds as reactive intermediates in organic synthesis. The activating effect of the nitro group is exploited in carrying out many organic reactions, and its. Displacement: The Influence of the Nitro Group by François Terrier Nitrocarbons by Arnold T. Nielsen THE NITRO GROUP IN ORGANIC SYNTHESIS Noboru Ono New York Chichester Weinheim Brisbane Singapore Toronto A