acidic and basic reagents

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Handbook of Reagents for Organic Synthesis Acidic and Basic Reagents Edited by Hans J. Reich The University of Wisconsin at Madison and James H. Rigby Wayne State University JOHN WILEY & SONS Chichester • New York • Weinheim • Brisbane • Toronto • Singapore

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Handbook of Reagents for Organic Synthesis

Acidic and Basic ReagentsEdited by

Hans J. ReichThe University of Wisconsin at Madison and

James H. RigbyWayne State University

JOHN WILEY & SONS Chichester New York Weinheim Brisbane Toronto Singapore

Copyright 1999

John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex P019 8SQ, England Telephone (+44) 1243 779777

Email (for orders and customer service enquiries): [email protected] Visit our Home Page on www.wileyeurope.com or www.wiley.com Reprinted February 2000, May 2001, November 2003, July 2005 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, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London WlT 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to [email protected], or faxed to (+44) 1243 770571. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on 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 should be sought.

Other Wiley Editorial Offices John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA Wiley-VCH Verlag GmbH, Boschstr. 12, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd, 33 Park Road, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809 John Wiley & Sons Canada Ltd, 22 Worcester Road, Etobicoke, Ontario, Canada M9W 1L1

British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 10: 0-471-97925-2 (H/B) ISBN 13: 978-0-471-97925-8 (H/B) Typeset by Thomson Press (India) Ltd., New Delhi. Printed and bound in Great Britain by Antony Rowe Ltd, Chippenham, Wiltshire. This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production.

Editorial BoardEditor-in-Chief Leo A. Paquette The Ohio State University, Columbus, OH, USAEditors Steven D. Burke University of Wisconsin at Madison, WI, USA Scott E. Denmark University of Illinois at Urbana-Champaign, IL, USA Dennis C. Liotta Emory University Atlanta, CA, USA Robert M. Coates University of Illinois at Urbana-Champaign, IL USA David J. Hart The Ohio State University Columbus, OH, USA Anthony J. Pearson Case Western Reserve University, Cleveland, OH, USA James H. Rigby Wayne State University Detroit, MI, USA Assistant Editors James P. Edwards Ligand Pharmaceuticals San Diego, CA, USA Mark Volmer Emory University Atlanta, GA, USA Rick L. Danheiser Massachusetts Institute of Technology, Cambridge, MA, USA Lanny S. Liebeskind Emory University Atlanta, GA, USA Hans J. Reich University of Wisconsin at Madison, WI, USA

William R. Roush University of Michigan MI, USA

International Advisory Board Leon A. Ghosez Universit Catholique de Louvain, Belgium Chun-Chen Liao National Tsing Hua University, Hsinchu, Taiwan Ryoji Noyori Nagoya University, Japan Pierre Potier CNRS, Gif-sur-Yvette France Hishashi Yamomoto Nagoya University, Japan Jean-Marie Lehn Universit Louis Pasteur Strasbourg, France Lewis N. Mander Australian National University, Canberra Australia Gerald Pattenden University of Nottingham UK W. Nico Speckamp Universiteit van Amsterdam The Netherlands Steven V. Ley University of Cambridge UK Giorgio Modena Universit di Padua Italy Edward Piers University of British Columbia, Vancouver Canada Ekkehard Winterfeldt Universitt Hannover Germany

Managing Editor Colin J. Drayton Woking, Surrey, UK

Preface

As stated in its Preface, the major motivation for our under taking publication of the Encyclopedia of Reagents for Organic Synthesis was "to incorporate into a single work a genuinely authoritative and systematic description of the utility of all reagents used in organic chemistry." By all accounts, this reference compendium has succeeded admir ably in attaining this objective. Experts from around the globe contributed many relevant facts that define the var ious uses characteristic of each reagent. The choice of a masthead format for providing relevant information about each entry, the highlighting of key transformations with illustrative equations, and the incorporation of detailed indexes serve in tandem to facilitate the retrieval of desired information. Notwithstanding these accomplishments, the editors have since recognized that the large size of this eight-volume work and its cost of purchase have often served to deter the placement of copies of the Encyclopedia in or near laboratories where the need for this type of insight is most critically needed. In an effort to meet this demand in a costeffective manner, the decision was made to cull from the major work that information having the highest probability for repeated consultation and to incorporate same into a set of handbooks. The latter would also be purchasable on a single unit basis. The ultimate result of these deliberations is the publica tion of the Handbook of Reagents for Organic Synthesis consisting of the following four volumes:

Reagents, Auxiliaries and Catalysts for C-C Bond Formation Edited by Robert M. Coates and Scott E. Denmark Oxidizing and Reducing Agents Edited by Steven D. Burke and Rick L. Danheiser Acidic and Basic Reagents Edited by Hans J. Reich and James H. Rigby Activating Agents and Protecting Groups Edited by Anthony J. Pearson and William R. Roush Each of the volumes contains a complete compilation of those entries from the original Encyclopedia that bear on the specific topic. Ample listings can be found to function ally related reagents contained in the original work. For the sake of current awareness, references to recent reviews and monographs have been included, as have relevant new pro cedures from Organic Syntheses. The end product of this effort by eight of the original editors of the Encyclopedia is an affordable, enlightening set of books that should find their way into the laboratories of all practicing synthetic chemists. Every attempt has been made to be of the broadest synthetic relevance and our expectation is that our colleagues will share this opinion. Leo A. Paquette Columbus, Ohio USA

Introduction

Recognizing the critical need for bringing a cost effective as well as handy reference work dealing with the most popular reagents in synthesis to the widest possible audi ence of practicing organic chemists, the editors of The Encyclopedia of Reagents for Organic Synthesis (EROS) have developed a list of the most important and useful reagents employed in contemporary organic synthesis. The result of this effort is a collection entitled "Handbook of Reagents for Organic Synthesis" that contains over 500 reagent entries from the original Encyclopedia that run the gamut of functions from oxidation and reduction to activation and protection. To assist the reader in quickly locating a reagent of interest, the "Handbook" has been divided into four volumes, each of which is devoted to a set of closely related reagents, these include: "Reagents, Auxiliaries and Catalysts for C-C Bond Forma tion"; "Oxidizing and Reducing Agents"; "Acidic and Basic Reagents"; Activating Agents and Protecting Groups". Compiled in the present volume, entitled "Acidic and Basic Reagents," is a group of articles on the most useful and important acidic and basic agents that were originally included in the very popular Encyclopedia of Reagents for Organic Synthesis. Each article contains all of the informa tion found in the original version as well as extensive list ings of functionally related reagents that are located in the full Encyclopedia. Following this Introduction are listings of Recent Review Articles and Monographs on subjects related in a general sense to the topic of acids and bases as well as relevant Organic Syntheses that deal with either the preparations or reactions of reagents featured in this volume. To make this work as up to date as possible, par ticular emphasis was placed on including references appear ing since the original publication date of EROS in 1995. It is hoped that by including these listings, the reader will be able to quickly access a broad range of information of interest that is beyond the scope of the reagent entries themselves.

Acids and bases are among the most fundamental and versatile reagents for effecting organic transformations, and in selecting candidate entries for inclusion in this par ticular collection, the editors adopted a fairly broad set of criteria for defining what exactly constitutes an acidic or basic reagent. Therefore, not only are the usual acids and bases such as hydrochloric acid, aluminum chloride, potas sium t-butoxide and so forth included, so are compounds that behave like acids or bases but that are normally clas sified in other ways. For instance, articles on ligands or complexing agents such as 18-crown-6, l,l'-bi-2,2'naphthol and triethylphosphite can also be found in this volume along with the more traditional Bronsted/Lewis acids and bases. Furthermore, in recognition of the growing importance of biocatalysts in the field of organic synthesis, articles on esterases and lipases are also included in this volume since, in the broadest sense, the net conversions effected by these enzymes can be viewed as being of an acidic or basic nature. In compiling the master list of reagents to be included in the "Handbook" the editors endeavored to consider not only species of the broadest current synthetic importance and accepted utility, but also reagents that may not yet be fully integrated into mainstream synthetic practice, but will certainly become so in the future. A good example of this is the entry on the very potent, but little used, phosphazene base P4-t-Bu, one of the so-called Schwesinger bases, which the editors believe will become, in the fullness of time, a more broadly used reagent. A number of reagents present in this four volume series were identified as exhi biting multiple applications that could have simultaneously placed them appropriately in several different volumes. To avoid unnecessary duplication, articles describing these types of reagents were assigned to a single volume and only cross references to these particular entries are included in the other relevant volumes. For example, the entry for ethylaluminum dichloride is found in the volume entitled "Activating Agents and Protecting Groups" with only a

xii

INTRODUCTION

"boiler plate" cross reference listing in this volume. Simi larly, hexamethyldisilazane can serve as a base in some instances, but it can also be employed to transfer Me3Si and, as such, will be found in the volume focusing on "Activating Agents and Protecting Gruops". The editors of The Encyclopedia of Reagents for Organic Synthesis hope that you find this compilation of the best

and most important acidic and basic reagents to be a valu able addition to your chemical library. Hans J. Reich The University of Wisconsin at Madison James H. Rigby Wayne State University

ContentsPreface Introduction Organic Synthesis Examples Recent Review Articles and Monographs Alumina Aluminum Chloride Aluminum Isopropoxide Antimony(V) Fluoride Barium Hydroxide Benzyltrimethylammonium Hydroxide (R)-l,l'-Bi-2,2'-naphthol (R)-1,l'-Bi-2,2'-naphthotitanium Dichloride (and Dibromide) (R) and (S)-2,2'-Bis(diphenylphosphino)-l,l'-binaphthyl Bis(tri-n-butyltin) Oxide Boron Tribromide Boron Trichloride Boron Trifluoride Etherate Bromodimethylborane Bromomagnesium Diisopropylamide Brucine n-Butyllithium s-Butyllithium t-Butyllithium n-Butyllithium-Potassium t-Butoxide Calcium Carbonate Calcium Hydride 10-Camphorsulfonic Acid Cerium (III) Chloride Cesium Carbonate Cesium Fluoride 2,4,6-Collidine Copper(I) Trifluoromethanesulfonate Copper(II) Trifluoromethanesulfonate 18-Crown-6 l,5-Diazabicyclo[4.3.0]non-5-ene 1,8-Diazabicyclo[5.4.0]undec-7-ene 2,6-Di-t-butylpyridine ix xi 1 6 9 12 16 19 24 27 29 35 38 42 44 47 50 59 61 63 66 74 81 86 88 89 91 94 97 99 104 105 116 118 123 125 131 Diethylaluminum Chloride Diisopropylethylamine Dimethylaluminum Chloride 4-Dimethylaminopyridine Esterases Ethylaluminum Dichloride Fluorosulfuric Acid-Antimony(V) Fluoride Formic Acid Hexamethyldisilazane Hexamethylphosphoric Triamide Hexamethylphosphorous Triamide Hydrazine Hydrobromic Acid Hydrochloric Acid Hydrogen Bromide Hydrogen Chloride Hydrogen Fluoride Hydrogen Iodide Imidazole Iron(III) Chloride Lipases Lithium Amide Lithium Bromide Lithium t-Butoxide Lithium Carbonate Lithium Chloride Lithium Diethylamide Lithium Diisopropylamide Lithium Hexamethyldisilazide Lithium Hydroxide Lithium Iodide Lithium N-Methylpiperazide Lithium Perchlorate Lithium Tetrafluoroborate Lithium 2,2,6,6-Tetramethylpiperidide 2,6-Lutidine Magnesium Bromide Magnesium Methoxide Mercury(II) Acetate Mercury(II) Chloride 132 134 137 140 143 146 151 155 158 160 166 169 173 178 183 185 187 190 194 195 199 204 207 208 209 210 211 213 221 224 227 228 229 231 232 235 237 239 240 246

viii

CONTENTS

Mercury(II) Trifluoroacetate Mesityllithium Methanesulfonic Acid Methylaluminum Bis(2,6-di-t-butyl-4-methylphenoxide) Methylaluminum Bis(2,6-di-t-butylphenoxide) Methylaluminum Dichloride Molecular Sieves Montmorillonite K10 Nitric Acid Phosphazene Base P4-t-Bu Phosphoric Acid Phosphorus(V) Oxide-Methanesulfonic Acid Polyphosphate Ester Polyphosphoric Acid Potassium Amide Potassium 3-Aminopropylamide Potassium t-Butoxide Potassium Carbonate Potassium Diisopropylamide Potassium Fluoride Potassium Hexamethyldisilazide Potassium Hydride Potassium Hydroxide Propionic Acid Pyridine Pyridinium p-Toluenesulfonate Pyrrolidine Quinine Quinoline Silver(I) Tetrafluoroborate Sodium Amide Sodium Carbonate Sodium Ethoxide Sodium Hexamethyldisilazide Sodium Hydride

248 251 252 254 257 258 259 262 266 270 272 273 277 279 285 288 290 296 298 300 303 307 310 313 314 318 319 322 324 327 329 333 334 338 340

Sodium Hydroxide Sodium Methylsulfinylmethylide ()-Sparteine Sulfur Dioxide Sulfuric Acid Sulfur Trioxide Tetra-n-butylammonium Fluoride Tetra-n-butylammonium Hydroxide Tetrafluoroboric Acid Tetrahydro-l-methyl-3,3-diphenyl-lH,3Hpyrrolo[1,2-c] [1,3,2]oxazaborole N,N,N',N'-Tetramethylethylenediamine 1,1,3.3-Tetramethylguanidine Tin(IV) Chloride Tin(II) Trifluoromethanesulfonate Titanium(IV) Chloride Titanium Tetraisopropoxide p-Toluenesulfonic Acid Tri-n-butyl(methoxy)stannane Tri-n-butyltin Trifluoromethanesulfonate Triethylamine Triethyl Phosphite Trifluoroacetic Acid Trifluoromethanesulfonic Acid Trimethyl Phosphite Trimethylsilyl Trifluoromethanesulfonate Triphenylarsine Triphenylcarbenium Tetrafluoroborate Zinc Bromide Zinc Chloride Zinc Iodide List of Contributors Reagent Formula Index Subject Index

343 344 350 352 357 360 364 367 368 372 376 380 383 389 392 398 402 405 409 410 415 419 421 425 427 431 434 437 440 448 451 459 463

List of ContributorsAhmed F. Abdel-Magid The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA Barium Hydroxide Lithium Hydroxide Potassium Hydroxide Lilly Research Laboratories, Indianapolis, IN, USA Hexamethyldisilazane Bio-Mga/Boehringer Ingelheim Research, Laval, Quebec, Canada Bromodimethylborane University of Connecticut, Storrs, CT, USA t-Butyllithium University of Amsterdam, The Netherlands Sulfur Trioxide University of Waterloo, Ontario, Canada Lithium Diisopropylamide University of Melbourne, Parkville, Victoria, Australia Titanium Tetraisopropoxide Eidgenossische Technische Hochschule, Zurich, Switzerland Mesityllithium

24 224 310

Benjamin A. Anderson

158

Paul C. Anderson

59

William F. Bailey

81

Bert H. Bakker

360

Wouter I. Iwema Bakker

213

Martin G. Banwell

398

Albert K. Beck

251

John L. Belletire

The University of Cincinnati, OH, USA Sodium Amide Georgia Institute of Technology, Atlanta, GA, USA 18-Crown-6 Eastern Illinois University, Charleston, IL, USA Magnesium Bromide The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA Benzyltrimethylammonium Hydroxide Tetra-n-butylammonium Hydroxide University of Oregon, Eugene, OR, USA Cesium Fluoride Tetrafluoroboric Acid University of North Carolina, Chapel Hill, NC, USA Hydrogen Bromide Hydrogen Chloride University of Wisconsin, Madison, WI, USA Sulfur Dioxide

329

Joachim Berkner

118

T. Howard Black

237

Mary Ellen Bos

27 367

Bruce P. Branchaud

99 368

Gary W. Breton

183 185

Steven D. Burke

352

452

LIST OF CONTRIBUTORS The University of Alabama, Tuscaloosa, AL, USA Magnesium Methoxide Potassium t-Butoxide Lithium t-Butoxide University of Waterloo, Ontario, Canada Lithium 2,2,6,6-Tetramethylpiperidide University of Amsterdam, The Netherlands Sulfur Trioxide Universit de Montreal, Quebec, Canada Lithium Bromide Lithium Iodide Lithium Perchlorate Indiana University, Bloomington, IN, USA Lithium Tetrafluoroborate North Carolina State University, Raleigh, NC, USA Lithium N-Methylpiperazide Emory University, Atlanta, GA, USA Boron Trifiuoride Etherate Eidgenssische Technische Hochschule, Zurich, Switzerland Mesityllithium Hoechst Celanese Corporation, Corpus Christi, TX, USA Hydrogen Fluoride University of Miami, Coral Gables, EL, USA Calcium Hydride Bowling Green State University, OH, USA Potassium Carbonate Sodium Hydroxide The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA Phosphorus(V) Oxide-Methanesulfonic Acid Polyphosphate Ester The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA Polyphosphoric Acid University of Wisconsin, Madison, WI, USA Hexamethylphosphoric Triamide Eli Lilly and Company, Lafayette, IN, USA Tri-n-butyltin Trifluoromethanesulfonate Scios Nova, Baltimore, MD, USA Formic Acid Propionic Acid Trifiuoroacetic Acid San Francisco State University, CA, USA Lithium Amide Scios Nova, Baltimore, MD, USA Bromomagnesium Diisopropylamide 239 290 208

Drury Caine

Mike Campbell

232

Hans Cerfontain

360

Andre B. Charette

207 227 229

Paul J. Coleman

231

Daniel L. Comins

228

Veronica Cornel

50

Robert Dahinden

251

Kenneth G. Davenport

187

Arnold Davis

89

Kurt D. Deshayes

296 343

Lisa A. Dixon

273 277

John H. Dodd

279

Robert R. Dykstra

160

Thomas M. Eckrich

409

Kirk F. Eidman

155 313 419

Ihsan Erden

204

Ronald H. Erickson

61

LIST OF CONTRIBUTORS Agnes Fabre The Ohio State University, Columbus, OH, USA Alumina Universit di Milano, Italy Esterases The Ohio State University, Columbus, OH, USA Alumina University of Oregon, Eugene, OR, USA Cesium Fluoride Tetrafluoroboric Acid Parke Davis Pharmaceutical Research Division, Ann Arbor, MI, USA Pyridinium p-Toluenesulfonate University of Guelph, Ontario, Canada Aluminum Chloride University of Miami, Coral Gables, FL, USA Calcium Hydride Potassium Hydride Sodium Hydride Emory University, Atlanta, GA, USA Pyrrolidine University of Waterloo, Ontario, Canada Lithium Hexamethyldisilazide Universit di Milano, Italy Esterases Bio-Mega/Boehringer Ingelheim Research, Laval, Quebec, Canada Bromodimethylborane Scios Nova, Baltimore, MD, USA p-Toluenesulfonic Acid Universitt Tbingen, Germany Trifluoromethanesulfonic Acid DuPont Merck, Wilmington, DE, USA Potassium Fluoride University of Iceland, Reykjavik, Iceland Lipases Hokkaido University, Sapporo, Japan Boron Tribromide University of Missouri-Columbia, MO, USA Sodium Methylsulfinylmethylide Giba-Geigy, Summit, NJ, USA Sodium Carbonate University of Chicago, IL, USA Hexamethylphosphorous Triamide Hydrogen Iodide

4539

Patrizia Ferraboschi

143

Alan S. Florjancic

9

Gregory K. Friestad

99 368

Adam A. Galan

318

Paul Galatsis

12

Robert E. Gawley

89 307 340

David Goldsmith

319

Matthew Gray

221

Paride Grisenti

143

Yvan Guindon

59

Gregory S. Hamilton

402

Michael Hanack

421

QiHan

300

Gudmundur G. Haraldsson

199

Shoji Hara

44

Michael Harmata

344

Roger Harrington

333

Ronald G. Harvey

166 190

454

LIST OF CONTRIBUTORS Bar-Ilan University, Ramat Gan, Israel 4-Dimethylaminopyridine University of Mnster, Germany ()-Sparteine Shanghai Institute of Organic Chemistry, Academia Sinica, China Triphenylarsine Nagoya University, Japan Aluminum Isopropoxide The Ohio State University, Columbus, OH, USA Alumina Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA Brucine Kent State University, OH, USA 2,6-Lutidine Eli Lilly and Company, Indianapolis, IN, USA Tin(II) Trifluoromethanesulfonate North Carolina State University, Raleigh, NC, USA Lithium N-Methylpiperazide Universit Bordeaux I, Talence, France Tri-n-butyl(methoxy)stannane University of California, Los Angeles, CA, USA Triphenylcarbenium Tetrafluoroborate Nagoya University, Japan (R)- and (S)-2,2'-Bis(diphenylphosphino)-l,l'-binaphthyl Nottingham University, UK Imidazole University of Leicester, UK Mercury(II) Acetate Mercury(II) Chloride Mercury(II) Trifluoroacetate St. Petersburg State University, Russia 2,6-Di-t-butylpyridine University of North Carolina, Chapel Hill, NC, USA Hydrogen Bromide Hydrogen Chloride Temple University, Philadelphia, PA, USA Sulfuric Acid Kent State University, OH, USA Copper(II) Trifluoromethanesulfonate The Ohio State University, Columbus, OH, USA Molecular Sieves 140

Alfred Hassner

Dieter Hoppe

350

Yao-Zeng Huang

431

Kazuaki Ishihara

16

Seiji Iwasa

9

Juan C. Jaen

63

Thomas E. Janini

235

Samantha Janisse

389

Sajan P. Joseph

228

Bernard Jousseaume

405

Michael E. Jung

434

Masato Kitamura

38

David W. Knight

194

Pavel Kocovsk

240 246 248

Rafael R. Kostikov

131

Paul J. Kropp

183 185

Grant R. Krow

357

Kenneth K. Laali

116

James C. Lanter

259

LIST OF CONTRIBUTORS Ellen M. Leahy Affymax Research Institute, Palo Alto, CA, USA 10-Camphorsulfonic Acid Quinine Brown University, Providence, RI, USA Nitric Acid Georgia Institute of Technology, Atlanta, GA, USA 18-Crown-6 Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA Tetra-n-butylammonium Fluoride Potassium Fluoride University of Southern California, Los Angeles, CA, USA Fluorosulfuric Acid-Antimony(V) Fluoride University of Southern California, Los Angeles, CA, USA Antimony(V) Fluoride Johannes Gutenberg University, Mainz, Germany Lithium Chloride Universidad Complutense de Madrid, Spain Methanesulfonic Acid Trifiuoromethanesulfonic Acid Nagoya University, Japan Methylaluminum Bis(2,6-di-t-butyl-4-methylphenoxide) Methylaluminum Bis(2,6-di-t-butylphenoxide) The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA 1,1,3,3-Tetramethylguanidine Merck Research Laboratories, Rahway, NJ, USA Tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pynolo[1,2-c] [1,3,2]oxazaborole University of Virginia, Charlottesville, VA, USA Zinc Bromide Zinc Chloride Zinc Iodide Ohio University, Athens, OH, USA Lithium Carbonate University of Kentucky, Lexington, KY, USA Phosphoric Acid Tokyo Institute of Technology, Japan (R)-1,1'-Bi-2,2'-naphthotitanium Dichloride (R)-1,1'-Bi-2,2'-naphthol R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA Hydrobromic Acid Hydrochloric Acid Hokkaido University, Sapporo, Japan Boron Trichloride

45591 322

Mark W. Ledeboer

266

Charles, L. Liotta

118

Hui-Yin Li

364 300

Xing-Ya Li

151

Xing-ya Li

19

Guido Lutterbach

210

Antonio Garcia Martinez

252 421

Keiji Maruoka

254 257

Cynthia A. Maryanoff

380

David J. Mathre

372

Glenn J. McGarvey

437 440 448

Mark C. McMills

209

Mark S. Meier

272

Koichi Mikami

35 29

John E. Mills

173 178

Norio Miyaura

47

456

LIST OF CONTRIBUTORS Tokyo Institute of Technology, Japan (R)-1,1'-Bi-2,2'-naphthol Nagoya University, Japan (R)- and (S)-2,2'-Bis(diphenylphosphino)-l,l'-binaphthyl University of Southern California, Los Angeles, CA, USA Antimony(V) Fluoride Fluorosulfuric Acid-Antimony(V) Fluoride Connecticut College, New London, CT, USA n-Butyllithium s-Butyllithium The Ohio State University, Columbus, OH, USA Cerium(III) Chloride Brown University, Providence, RI, USA Nitric Acid University of Bristol, UK Trimethylsilyl Trifluoromethanesulfonate Pfizer, Groton, CT, USA Triethyl Phosphite Trimethyl Phosphite University of Southern California, Los Angeles, CA, USA Antimony(V) Fluoride Fluorosulfuric Acid-Antimony(V) Fluoride The University of Cincinnati, OH, USA Sodium Amide The Ohio State University, Columbus, OH, USA Alumina Michigan State University, East Lansing, MI, USA Calcium Carbonate University of Oslo, Norway Titanium(IV) Chloride Abbott Laboratories, North Chicago, IL, USA Hydrazine Case Western Reserve University, Cleveland, OH, USA Copper(I) Trifluoromethanesulfonate Kent State University, OH, USA 2,6-Lutidine Gunma University, Kiryu, Japan Bis(tri-n-butyltin) Oxide Universit di Milano, Italy Esterases Air Products and Chemicals, Allentown, PA, USA 1,5-Diazabicyclo[4.3.0]non-5-ene l,8-Diazabicyclo[5.4.0]undec-7-ene 29

Yukihiro Motoyama

Ryoji Noyori

38

George A. Olah

19 151

Timo V. Ovaska

66 74

Leo A. Paquette

94

Kathlyn A. Parker

266

Gemma Perkins

427

Anthony D. Piscopio

415 425

G. K. Surya Prakash

19 151

R. Jeffery Rauh

329

Viresh H. Rawal

9

William Reusch

88

Frode Rise

392

Brian A. Roden

169

Robert G. Salomon

105

Paul Sampson

235

Hiroshi Sano

42

Enzo Santaniello

143

Ann C. Savoca

123 125

LIST OF CONTRIBUTORS Reinhard Schwesinger University of Freiburg in Breisgau, Germany Phosphazene Base P4-t-Bu Eidgenossische Technische Hochschule, Zurich, Switzerland Mesityllithium Reilly Industries, Indianapolis, IN, USA 2,4,6-Collidine Pyridine Quinoline Merck Research Laboratories, Rahway, NJ, USA Tetrahydro-1-methyl-3,3-diphenyl-1#,3#-pyrrolo[1,2-c] [1,3,2]oxazaborole Shanghai Institute of Organic Chemistry, Academia Sinica, China Triphenylarsine Procter & Gamble, Cincinnati, OH, USA Cesium Carbonate Brandeis University, Waltham, MA, USA Diethylaluminum Chloride Dimethylaluminum Chloride Ethylaluminum Dichloride Methylaluminum Dichloride University of Waterloo, Ontario, Canada Lithium 2,2,6,6-Tetramethylpiperidide Lithium Diethylamide Lithium Diisopropylamide Lithium Hexamethyldisilazide The R. W, Johnson Pharmaceutical Research Institute, Spring House, PA, USA Diisopropylethylamine Triethylamine Universitt Tbingen, Germany Trifluoromethanesulfonic Acid Hokkaido University, Sapporo, Japan Boron Tribromide University of Bristol, UK Trimethylsilyl Trifluoromethanesulfonate Bristol-Myers Squibb Co., Wallingford, CT, USA Potassium 3-Aminopropylamide Potassium Amide Potassium Diisopropylamide University of Waterloo, Ontario, Canada Lithium Diethylamide University of Oslo, Norway Titanium(IV) Chloride North Dakota State University, Fargo, ND, USA Tin(IV) Chloride

457270

Dieter Seebach

251

Angela R. Sherman

104 314 324

Ichiro Shinkai

372

Li-Lan Shi

431

Mark R. Sivik

97

Barry B. Snider

132 137 146 258

Victor Snieckus

232 211 213 221

Kirk L. Sorgi

134 410

Lakshminarayanapuram R. Subramanian Akira Suzuki

421

44

Joseph Sweeney

427

Katherine S. Takaki

288 285 298

Masao Tsukazaki

211

Kjell Undheim

392

David E. Volk

383

458

LIST OF CONTRIBUTORS The University of Sydney, NSW, Australia N,N,N',N'-Tetramethylethylenediamine University of Connecticut, Storrs, CT, USA t-Butyllithium University of Southern California, Los Angeles, CA, USA Antimony(V) Fluoride Fluorosulfuric Acid-Antimony(V) Fluoride Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT, USA Potassium Hexamethyldisilazide Sodium Hexamethyldisilazide Detroit Country Day School, Beverly Hills, MI, USA Sodium Ethoxide Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA Iron(III) Chloride Nycorned Innovation, Malmo, Sweden Silver(I) Tetrafluoroborate University of Waterloo, Ontario, Canada Lithium Diisopropylamide Ohio University, Athens, OH, USA Lithium Carbonate Emory University, Atlanta, GA, USA n-Butyllithium-Potassium t-Butoxide Nagoya University, Japan Methylaluminum Bis(2,6-di-t-butyl-4-methylphenoxide) Nagoya University, Japan Aluminum Isopropoxide Methylaluminum Bis(2,6-di-t-butylphenoxide) The Dow Chemical Company, Midland, MI, USA Montmorillonite K10 University of Miami, Coral Gables, FL, USA Potassium Hydride Shanghai Institute of Organic Chemistry, Academia Sinica, China Triphenylarsine 376

Simone C. Vonwiller

Nanette Wachter-Jurcsak

81

Qi Wang

19 151

Brett T. Watson

303 338

D. Todd Whitaker

334

Andrew D. White

195

Lars-G. Wistrand

327

Poh Lee Wong

213

Dennis Wright

209

Xiaoyang Xia

86

Hisashi Yamamoto

254

Hisashi Yamamoto

16 257

Mark W. Zettler

262

Xiaojie Zhang

307

Zhang-Lin Zhou

431

ORGANIC SYNTHESIS EXAMPLES

1

Organic Synthesis ExamplesMetalation"Erythro-Directed Reduction of a -Keto Amide: erythro-\(3-Hydroxy-2-methyl-3-phenylpropanoyl)piperidine," Fujita, M.; Hiyama, T. Org. Synth. 1990, 69, 44.Bu3SnCH2OCH2OCH3

"Asymmetric Synthesis of 4,4-Dialkylcyclohexenones from Chiral Bicyclic Lactams: (R)-4-Ethyl-4-allyl-2-cyclohexen-lone," Meyers, A. I.; Berney, D. Org. Synth. 1990, 69, 55.

"Ethyl 1-Naphthylacetate: Ester Homologation via Ynolate An ions," Reddy, R. E.; Kowalski, C. J. Org. Synth. 1992, 71, 146.

"9-Bromo-9-phyenylfluorene," Jamison, T. F.; Lubell, W. D.; Dener, J. M.; Krisch, M. J.; Rapoport, H. Org. Synth. 1992, 71, 220. "Intramolecular Oxidative Coupling of a Bisenolate: 4Methyltricyclo[2.2.2.03,5]octane-2,6-dione," Poupart, M.-A.; Lassalle, G.; Paquette, L. A. Org. Synth. 1990, 69, 173.

"Stereoselective Aldol Reaction of Doubly Deprotonated (R)(+)-2-hydroxy-l,2,2-triphenyl Ethyl Acetate (HYTRA): (R)-3hydroxy-4-methylpentanoic Acid," Braun, M.; Graf, S. Org. Synth. 1993, 72, 38. "2-Substituted Pyrroles from N-tert-Butoxycarbonyl-2bromopyrrole: N-tert-Butoxy-2-trimethylsilylpyrrole," Chen, W.; Stephenson, E. K.; Cava, M. P.; Jackson, Y. A. Org. Synth. 1991, 70, 151.

"Preparation and Use of (Methoxymethoxy) Methyl Lithium: l-(Hydroxymethyl)cycloheptanol," Johnson, C. R.; Medich, J. R.; Danheiser, R. L.; Romines, K. R.; Koyama, H.; Gee, S. K. Org. Synth. 1992, 71, 140.

"Synthesis of (S)-2-Methylproline: A General Method for the Preparation of -Branched Amino Acids," Beck, A. K.; Blank, S.; Job, K.; Seebach, D.; Sommerfeld, Th. Org. Synth. 1993, 72, 62.Avoid Skin Contact with All Reagents

2

ORGANIC SYNTHESIS EXAMPLES

"Bis(trifluoroethyl) (carboethoxymethyl)phosphenate," (Pa tois, C.; Savignac,P.;About-Jaudet, E.; Collignon, N. Org. Synth. 1995, 73, 152.

"7-Methoxyphthalide," Wang, X.; de Silva, S. O.; Reed, J. N.; Billadeau, R.; Griffen, E. J.; Chan, A.; Snieckus, V. Org. Synth. 1993, 72, 163.

"4-Ketoundecanoic Acid," Tschantz, M. A.; Burgess, L. E.; Meyers, A. I. Org. Synth. 1995, 73, 215.

"Synthesis of 7-Substituted Indolines via Directed Lithiation of 1 -(tert-Butoxycarbonyl)indoline: 7-Indoline Carboxaldehyde," Iwao, M.; Kuraishi, T. Org. Synth. 1995, 73, 85.

"Cyclopentanone Annulation via Cyclopropanone Derivatives. (3a,9b)-1,2,3a,4,5,9b-Hexahydro-9b-hydroxy-3a-methyl-3Hbenz[e]inden-3-one," Bradlee, M. J.; Helquist,P.Org. Synth. 1996, 74, 137.

"Regio- and Stereoselective Intramolecular Hydrosilation of -Hydroxy Enol Ethers: 2,3-syn-2-Methoxymethoxy-l,3nonanediol," Tamao, K.; Nakagawa, Y.; Ito, Y. Org. Synth. 1995, 73, 94.

"Detrifluoracetylative Diazo Group Transfer: (E)-l-Diazo-4phenyl-3-buten-2-one," Danheiser, R. L.; Miller, R. F.; Brisbois, R. G. Org. Synth. 1995, 73, 134.

"Regioselective Synthesis of 3-Substituted Indoles: 3Ethylindole," Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. Org. Synth. 1996, 74, 248.Lists of Abbreviations and Journal Codes on Endpapers

ORGANIC SYNTHESIS EXAMPLES

3

"Asymmetric Hydrogenation of 3-Oxo Carboxylates Using BINAP-Ruthenium Complexes: (R)-(-)-Methyl 3Hydroxybutyrate," Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R. Org. Synth. 1992, 71,1.

"(S)-(-)- and (R)-(+)-1,1'-Bi-2-Naphthol," Kazlauskas, R. J. Org. Synth. 1991, 70, 60.

"(3,3-Difluoroallyl)trimethylsilane," Gonzalez, J.; Foti, M. J.; Elsheimer, S. Org. Synth. 1993, 72, 225.

"Phenylthioacetylene," Magriotis, P. A.; Brown, J. T. Org. Synth. 1993, 72, 252.

"Stereoselective Alkene Synthesis via 1-chloro-l[(dimethyl)phenylsilyl] alkanes and -(dimethyl)phenylsilyl ketones: 6-methyl-6-dodecene," Barrett, A. G. M.; Flygare, J. A.; Hill, J. M.; Wallace, E. M. Org. Synth. 1995, 73, 50. "3-3-Dimethylpyrrole and 2,3,7,8,12,13,18-octaethylporphyrin," Sessler, J. L.; Mozaffari, A.; Johnson, M. R. Org. Synth. 1991, 70, 68.

"A Hydroxymethyl Anion Equivalent: Tributyl[(methoxymethoxy)methyl]stannane," Danheiser, R. L.; Romines, K. R.; Koyama, H.; Gee, S. K.; Johnson, C. R.; Medich, J. R. Org. Synth. 1992, 71, 133.

"An Improved Preparation of 3-Bromo-2-(H)-pyran-2-one. An Ambiphilic Diene for Diels-Alder Cycloadditions," Posner, G. H.; Afarinkia, K.; Dai, H. Org. Synth. 1995, 73, 231.

"Asymmetric Catalytic Glyoxalate-ene Reaction: Methyl (2R)2-Hydroxy-4-phenyl-4-pentenoate," Mikami, K.; Terada, M.; Narisawa, S.; Nakai, T. Org. Synth. 1992, 71, 14.Avoid Skin Contact with All Reagents

4

ORGANIC SYNTHESIS EXAMPLES

"1,3,5-Cyclooctatriene," Oda, M.; Kawase, T.; Kurata, H. Org. Synth. 1995, 73, 240.

"Phenyl Vinyl Sulfide," Reno, D. S.; Pariza, R. J. Org. Synth. 1996, 74, 124.

Acid Catalysts"3-Pyrroline," Meyers, A. I.; Warmus, J. S.; Dilley, G. J. Org. Synth. 1995, 73, 246. "(E)-1 -Benzyl-3-(1-iodoethylidene)piperidine: Nucleophilepromoted Alkyne-iminium Ion Cyclizations," Arnold, H.; Overman, L. E.; Sharp, M. J.; Witschel, M. C. Org. Synth. 1991, 70,111.

"Acetylenic Ethers from Alcohols and Their Reduction to Z- and E-enol Ethers: Preparation of 1-Menthoxy-l-butyne from Menthol and Converstion to (Z)- and (E )-1-Menthoxy-lbutene," Kann, N.; Bernardes, V.; Greene, A. E. Org. Synth. 1996, 74, 13.

"Tetrahydro-3-benzazepin-2-ones: Lead tetracetate oxidation of isoquinoline enamides," Lenz, G. R.; Lessor, R. A. Org. Synth. 1991, 70, 139.

"(R)-(+)-2-(Diphenylhydroxylmethyl)pyrrolidine," Nikolic, N. A.; Beak. P. Org. Synth. 1996, 74, 23. "Direct Degradation of the Biopolymer Poly[(R)-3hydroxybutyric acid] to (R)-3-hydroxybutanoic Acid and its Methyl Ester," Seebach, D.; Beck, A. K.; Breitschuh, R.; Job, K. Org. Synth. 1992, 71, 39.

"1,2,3-Triphenylcyclopropenium Bromide," Xu, R.; Breslow, R. Org. Synth. 1996, 74, 72.

"Preparation and Reactions of Alkenylchromium Reagents: 2-Hexyl-5-phenyl-l-penten-3-ol," Takai, K.; Sakogawa, K.; Kataoka, Y.; Oshima, K.; Utimoto, K. Org. Synth. 1993, 72, 180. "Diethyl (dichloromethyl)phosphonate. Preparation and use in the Synthesis of Alkynes: (4-Methoxyhenyl)ethyne," Marinetti, A.; Savignac, P. Org. Synth. 1996, 74, 108.

"Spiroannelation of Enol Silanes-2-oxo-5-methoxyspiro[5.4]decane," Lee, T. V.; Porter, J. R. Org. Synth. 1993, 72, 189.

Lists of Abbreviations and Journal Codes on Endpapers

ORGANIC SYNTHESIS EXAMPLES

5

Lewis Acids"Substitution Reactions of 2-Benzenesulfonyl Cyclic Ethers: Tetrahydro-2-(phenylethynyl)-2H-pyran," Brown, D. S.; Ley, S. V. Org. Synth. 1991, 70, 157.

"Nitroacetaldehyde Diethyl Acetal," Jger, V.; Poggendorf, P. Org. Synth. 1996, 74, 130.

Hydrolyses-Enzymatic"Lipase-Catalyzed Kinetic Resolution of Alcohols via Chloroacetate Esters: ()-(1R,2S)-trans-2-Phenylcyclohexanol and (+)(1S,2R)-trans-2-phenylcyclohexanol," Schwartz, A.; Madan, P.; Whitesell, J. K.; Lawrence, R. M. Org. Synth. 1990, 69, 1. "2-Methyl-l-3,-cyclopentanedione," Meister, P. G.; Sivik, M. R.; Paquette, L. A. Org. Synth. 1991, 70, 226.

"Asymmetric Catalytic Glyoxylate-ene-Reaction: Methyl (2R)-2-Hydroxy-4-phenyl-4-pentenoate," Mikami, K.; Terada, M.; Narisawa, S.; Nakai, T. Org. Synth. 1992, 71, 14.

"Enantioselective Saponification with Pig Liver Esterase (PLE): (lS,2S,3R)-3-Hydroxy-2-nitrocyclohexyl Acetate," Eberle, M.; Missbach, M.; Seebach, D. Org. Synth. 1990, 69, 19.

"Enantiomerically Pure Ethyl (R)- and (5')-2-Fluorohexanoate by Enzyme-Catalyzed Kinetic Resolution," Kalaritis, P.; Regenye, R. W. Org. Synth. 1990, 69, 10. "Ubiquinone-1," Naruta, Y.; Maruyama, K. Org. Synth. 1992, 71, 125.

"Enantioselective Hydrolysis of cis-3-5,-Diacetoxycyclopentene: (1R ,4S)-4-hydroxy-2-cyclopentenyl acetate," Deardorff, D. R.; Windham, C. Q.; Craney, C. L., Org. Synth. 1995, 73, 25. "(R)-(-)-2,2-Diphenylcyclopentanol," Denmark, S. E.; Marcin, L. R.; Schnute, M. E.; Thorarensen, A. Org. Synth. 1996, 74, 33.

Avoid Skin Contact with All Reagents

6

RECENT REVIEW ARTICLES AND MONOGRAPHS

Recent Review Articles and Monographs"Metalation and Electrophilic Substitution of Amine Deriva tives Adjacent to Nitrogen: -Metallo Amine Synthetic Equiva "Metalations by Organolithium Compounds," Mallan, J. M.; lents," Beak, P.; Zadjel, W. J.; Reitz, D. B. Chem. Rev. 1984, 84, Bebb, R. L. Chem. Rev. 1969, 69, 693. All. Preparative Polar Organometallic Chemistry, Brandsma, L.; "Generation and Reactions of sp2-Carbanionic Centers in the Verkruijsse, H. Springer-Verlag: Berlin, 1987. The Chemistry of Organolithium Compounds, Wakefield, B. Vicinity of Heterocyclic Nitrogen Atoms," Rewcastle, G.W.; KaJ.; Pergamon: Oxford, 1974. Organolithium Methods, Wakefield, tritzky, A.R. Adv. Heterocyclic Chem. 1993, 56, 155. "Lithioalkenes from Arylsulphonylhydrazones," Chamberlin, B. J. Academic: London, 1988. A. R.; Bloom, S. H. Org. React. 1990, 39,1. "Recent Applications "Selective Carbanion Chemistry and Anion-cation Interactions in Solution: A Survey," Seyden-Penne, J. New J. Chem. 1992, 16, of the Shapiro Reaction," Adlington, R. M.; Barrett, A. G. M. Acc. Chem. Res. 1983, 16, 55. 251. "Oxiranyl Anions and Aziridinyl Anions," Satoh, T. Chem. Rev. "Organometallics in Synthesis," Schlosser, M., Ed. Wiley: 1996, 96, 3303. Chichester, U.K., 1994. "Synthetic Uses of the 1,3-Dithiane Grouping from 1977"Lithium Chemistry: A Theoretical and Experimental 1988," Page, P. C. B.; van Niel, M. B.; Prodger, J. C. Tetrahedron Overview," Sapse, A.-M.; Schleyer, P. v. R. eds. NY, Wiley, 1995. 1989,45,7643. "Heteroatom-Faciliated Lithiations," Gschwend, H. W.; Ro "The Synthetic Utility of -Amino Alkoxides," Comins, D. L. driguez, H. R. Org. React. 1979, 26, 1. "Lateral Lithiation Re Synlett 1992, 615. actions Promoted by Heteroatomic Substituents," Clark, R.D.; Ja"Potassium Hydride in Organic Synthesis," Pinnick, H. W. Org. hangir, A. Org. React. 1995, 47, 1. Prep. Proc. Int. 1983, 75, 199. "Lewis Acid Complexation of Tertiary Amines and Related "Arene-catalysed Lithiation Reactions," Yus, M. Chem. Soc. Compounds: A Strategy for a Deprotonation and Stereocontrol," Rev. 1996, 25, 155. Kessar, S.V.; Singh, P. Chem. Rev. 1997, 97, 721. "Directed Lithiation of Aromatic Tertiary Amides: An Evolving Bases and Ligands Synthetic Methodology for Polysubstituted Aromatics," Beak, P.; Snieckus, V. Acc. Chem. Res. 1982, 15, 306. "Dipole- Stabilized "Hydroxide Ion Initiated Reactions Under Phase Transfer Catal ysis Conditions: Mechanism and Implications" Rabinovitz, M.; Carbanions: Novel and Useful Intermediates," Beak, P.; Reitz, Cohen, Y.; Halpern, M. Angew. Chem. Int. Ed. Engl. 1986, 25, D. B. Chem. Rev. 1978, 78, 275. "Aromatic Organolithium 960. Reagents Bearing Electrophilic Groups. Preparation by HalogenThe Chemistry of the Hydroxyl Group, Part 1; Fyfe, C. A. Wiley: Lithium Exchange," Parham, W. E.; Bradsher,C. K. Acc. Chem. New York, 1971. Res. 1982, 15, 300. "Superbases for Organic Synthesis" Schlosser, M. Pure Appl. "The Directed Ortho Metalation Reaction. Methodology, Ap Chem. 1988, 60, 1627. plications, Synthetic Links, and a Non-aromatic Ramification," "Specific Transition State Stabilization by Metal Ions in Re Snieckus, V. Pure Appl. Chem. 1990, 62, 2047. "Directed Or actions of Functionalized Crown Ethers," Cacciapaglia, R.; Mantho Metalation. Tertiary Amide and O-Carbamate Directors in dolini, L. Pure Appl. Chem. 1993, 65, 533. "Catalysis by Metal Synthetic Strategies for Polysubstituted Aromatics," Snieckus, V. Ions in Reactions of Crown Ether Substrates," Cacciapaglia, R.; Chem. Rev. 1990, 90, 879. Mandolini, L. Chem. Soc. Rev. 1993, 22, 221. "Synthesis and Reactions of Lithiated Monocyclic Azoles Con Hydrides of the Elements of the Main Groups, Wiberg, E.; Amtaining Two or More Heteroatoms. Part II: Oxazoles," Iddon, B. berger, E. Elsevier: New York, 1971. Heterocycles 1994 37, 1321. "Synthesis and Reactions of Lithi "Is N,N,N',N'-Tetramethylethylenediamine, Good Ligand for ated Monocyclic Azoles Containing Two or more Hetero-Atoms. Part III: Pyrazoles," Grimmett, M. R.; Iddon, B. Heterocycles, Lithium?" Collum, D. B. Acc. Chem. Res. 1992, 25, 448. "Regioselective Manipulation of Hydroxyl Groups via Organ1994, 37,2087. "Synthesis and Reactions of Lithiated Monocyclic otin Derivatives," David, S.; Hanessian, S. Tetrahedron 1985, 41, Azoles Containing 2 or more Hetero-Atoms. Part IV: Imidazoles," 643. Iddon, B.; Ngochindo, R. I. Heterocycles, 1994, 38, 2487. "Syn "Esterifications, Transesterifications, and Deesterifications Me thesis and Reactions of Lithiated Monocyclic Azoles Containing diated by Organotin Oxides, Hydroxides, and Alkoxides," MasTwo or More Hetero-atoms. Part V. Isothiazoles and Thiazoles," caretti, O.A.; Furlan, R.L.E. Aldrichimica Acta 1997, 30, 55. Iddon, B. Heterocycles 1995, 41, 533. "Metalation of Diazines," Turck, A.; Pl, N.; Quguiner, G. Heterocycles, 1994, 37, 2149. "4-Dialkylaminopyridines as Highly Active Acylation Cata "Synthesis and Reactions of Lithiated Monocyclic Azoles Con lysts," Hfie, G.; Steglich, W.; Vorbrggen, H. Angew. Chem. Int. taining Two or More Hetero-atoms. Part VI. Triazoles, Tetrazoles, Ed. Engl. 1978, 17,569. Oxadiazoles, and Thiadiazoles," Grimmett, M.R.; Iddon, B. Het"2,6-Di-tert-butylpyridine - An Unusual Base," Kanner, B. erocycles, 1995, 41, 1525. Heterocycles 1982, 18, 411.

Metalation

Lists of Abbreviations and Journal Codes on Endpapers

RECENT REVIEW ARTICLES AND MONOGRAPHS "Bicyclic Amidines as Reagents in Organic Synthesis," Oediger, H.; Mller, F.; Eiter, K. Synthesis 1972, 591. "The Baylis-Hillman Reaction: A Novel Carbon-Carbon Bond Forming Reaction," Basavaiah, D.; Rao, P.D.; Hyma, R.S. Tetra hedron 1996, 52,8001. Phase Transfer Catalysis Dehmlow, E. V. ed.; 2nd ed., Verlag Chemie: Deerfield Beach, FL, 1983. Salt Effects in Organic and Organometallic Chemistry Loupy, A.; Tchoubar, B.; VCH: Weinheim, 1992.

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Chiral Bases and Ligands"Enantioselective Synthesis with Lithium/()-Sparteine Carbanion Pairs," Hoppe, D.; Hense, T. Angew. Chem. Intl. Ed. Engl. 1997, 36, 2282. "Metallated 2-Alkenyl Carbamates: Chiral Homoenolate Reagents for Asymmetric Synthesis," Hoppe, D.; Kramer, T.; Schwark, J. -R.; Zschage, O. Pure Appl. Chem. 1990, 62, 1999. "Regioselective, Diastereoselective, and Enantioselective Lithiation-Substitution Sequences: Reaction Pathways and Syn thetic Applications," Beak, P.; Basu, A.; Gallagher, D.J.; Park, Y.S.; Thayumanavan, S. Acc. Chem. Res. 1996, 29, 552. "Some Stereochemical Aspects of Bisquinolizidine Alkaloids Sparteine Type," Boczo, W. Heterocycles 1992, 33, 1101. "Asymmetric Carbon-carbon Bond Formation Using Sulfoxide-stabilized Carbanions," Walker, A.J. Tetrahedron: Asymmetry 1992, 3, 961. "Asymmetric Synthesis Using Homochiral Lithium Amide Bases," Cox, P.J.; Simpkins, N.S. Tetrahedron: Asymm. 1991, 2, 1.

Protic Acid Catalysts"Polyphosphoric Acid as a Reagents in Organic Chemistry" Popp, F. D.; McEwen, W. E. Chem. Rev. 1958, 58, 321. Friedel-Crafts Alkylation Chemistry, Roberts, R. M.; Khalaf, A. A.; Markel Dekker: New York, 1984. Superacids, Olah, G. A.; Prakash, G. K. S.; Sommer, J.; Wiley, New York, 1985. "The Chemistry of Formic Acids and Its Simple Derivatives Gibson," H. W. Chem. Rev. 1969, 69, 673. "The Hydrogen Halides" Downs, A. J.; Adams, C. J. In Com prehensive Inorganic Chemistry; Bailar, J. C , Ed.; Pergamon: Ox ford, 1973; Vol. 2, p 1280. "The Combination of Hydrogen Fluoride with Organic Bases as Fluorination Agents," Yoneda, N. Tetrahedron 1991, 47, 5329. "Cleavage of Ethers," Bhatt, M. V.; Kulkarni, S. U. Synthesis, 1983, 249. Synthetic Reagents, Pizey, J. S. Ellis Horwood: Chichester, 1985; Vol. 6. "Trifluoromethanesulfonic Acid and Derivatives," Howells, R. D.; McCown, J. D. Chem. Rev. 1977, 77, 69. "Acid/Base-Induced Selectivity of Molecular Sieves in Cat alytic Conversion of Polar Molecules," Eder-Mirth, G.; Lercher, J. A. Recl. Trav. Chim. Pays-Bas 1996, 115, 157. "Enantioselective Protonation of Enolates and Enols," Fehr, C. Angew. Chem. Int. Ed. Engl. 1996, 35, 2566.

Boron Trifluoride and Its Derivatives Booth, H. S.; Martin, D. R.; Wiley: New York, 1949. "Reactions of Boron Trichloride with Organic Compounds" Gerrard, W.; Lappert, M. F. Chem. Rev. 1958, 58, 1081. Boron Fluoride and Its Compounds as Catalysts in Organic Chemistry Topchiev, A. V.; Zavgorodnii, S. V.; Paushkin, Ya. M.; Pergamon: New York, 1959. "Boron Halides" Greenwood, N. N.; Thomas, B. S. In Com prehensive Inorganic Chemistry; Trotman-Dickenson, A. F., Ed,; Pergamon: New York, 1973; Vol. 1, pp 956. "New Synthetic Applications of Dialkylboron Halide Reagents," Guindon, Y.; Anderson, P. C ; Yoakim, C.; Girard, Y.; Berthiaume, S.; Morton, H. E. Pure Appl. Chem. 1988, 60, 1705. "Lewis Acids and Selectivity in Organic Synthesis," Pons, J.M.; Santelli, M., CRC Press, 1995. "LiClO 4 in Ether-an Unusual Solvent," Waldmann, H. Angew. Chem. Int. Ed. Eng. 1991, 30, 1306. "Recent Developments in Preparative Sulfonation and Sulfa tion," Gilbert, E. E. Synthesis 1969, 3. "Novel Lewis Acid Catalysis in Organic Synthesis," Suzuki, K. Pure App. Chem. 1994, 66, 1557. "Iodotrimethylsilane-A Versatile Synthetic Reagent," Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225. "Trialkylsilyl Perfluoroalkanesulfonates: Highly Reactive Silylating Agents and Lewis Acids in Organic Synthesis," Emde, H.; Domsch, D.; Feger, H.; Frick, H.; Gtz, A.; Hergott, H. H.; Hofmann, K.; Kober, W.; Krgeloh, K.; Oesterle, T.; Steppan, W.; West, W.; Simchen, G. Synthesis 1982, 1. "Mechanisms of Epoxide Reactions," Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737. "Carbonyl Addition Reactions Promoted by Cerium Reagents," Imamoto, T. Pure & Appl. Chem. 1990, 62, 747. "Rare Earth Metal Trifluoromethanesulfonates as WaterTolerant Lewis Acid Catalysts in Organic Synthesis," Kobayashi, S. Synlett, 1994, 689. "Lewis-acid Catalysis of Carbon Carbon Bond Forming Reac tions in Water," Engberts, J.B.F.N.; Feringa, B.L.; Keller, E.; Otto, S. Rec. Trav. Chim. Pays-Bas 1996, 115, 457. "Lanthanides in Organic Synthesis," Kagan, H. B.; Namy, J. L. Tetrahedron 1986, 42, 6573. "Lanthanides in Organic Synthesis," Imamoto, T. Academic Press: London, 1994. "Application of Lanthanide Reagents in Organic Synthesis," Molander, G. A. Chem. Rev. 1992, 92, 29. "Organomercury Compounds in Organic Synthesis," Larock, R. C. Angew. Chem. Int. Ed. Engl. 1978, 17, 27. "Organomercurials in Organic Synthesis," Larock, R. C. Tetra hedron 1982, 38, 1713. "Organomercury Compounds in Organic Synthesis," Larock, R. C ; Springer: Berlin, 1985. "Solvomercuration/Demercuration Reactions in Organic Syn thesis," Larock, R. C ; Springer: Berlin, 1986.

Chiral Lewis Acids"Chiral Lewis Acids in Catalytic Asymmetric Reactions," Narasaka, K. Synthesis 1991, 1. "Synthesis and Applications of Binaphthylic C2-Symmetry Derivatives as Chiral Auxiliaries in Enantioselective Reactions"

Lewis AcidsLewis Acids and Selectivity in Organic Synthesis Pons, J.-M.; Santelli, M., Eds. CRC: Boca Raton, FL, 1995.

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RECENT REVIEW ARTICLES AND MONOGRAPHS

Rosini, C; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503. "Asymmetric Boron-Catalyzed Reactions" Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763. "Chiral Titanium Complexes for Enantioselective Addition of Nucleophiles to Carbonyl Groups," Duthaler, R.O.; Hafner, A. Chem. Rev. 1992, 92, 807. "Practical and Useful Methods for the Enantioselective Reduc tion of Unsymmetrical Ketones" Singh, V. K. Synthesis 1992, 605. "Asymmetric Syntheses with Chiral Oxazaborolidines" Wallbaum, S.; Martens, J. Tetrahedron: Asymmetry 1992, 3, 1475. "Oxazaborolidines and Dioxaborolidines in Enantioselective Catalysis," Lohray, B.B.; Bhushan, V. Angew. Chem. Int. Ed. Eng. 1992, 31, 729. "Catalytic Enantioselective C-C coupling - Allyl Transfer and Mukaiyama Aldol Reaction," Bach, T. Angew. Chem. I. E. Engl. 1994, 33, 417. "Chiral Lewis Acid Catalysts in Diels-Alder Cycloadditions: Mechanistic Aspects and Synthetic Applications of Recent Sys tems" Dias, L. C. J. Brazil Chem. Soc. 1997, 8, 289. "Enantioselective Synthesis with Optically Active Transitionmetal Catalysts," H. Brunner Synthesis 1988, 645. "Natural Products by Enantioselective Catalysis with Transition Metal Compounds," Brunner, H. Pure App. Chem. 1994, 66,2033. "Transition Metal or Lewis Acid-Catalyzed Asymmetric Re actions with Chiral Organosulfur Functionality," Hiroi, K. Rev. Heteroatom Chem. 1996, 14, 21. "Asymmetric Ene Reactions in Organic Synthesis" Mikami, K.; Shimizu, M. Chem. Rev. 1992, 92, 1021. "Asymmetric Catalysis for Carbonyl-Ene Reaction" Mikami, K.; Terada, M.; Narisawa, S.; Nakai, T. Synlett 1992, 255.

Solid Phase CatalystsMolecular Sieve Catalysts, Michiels, P.; De Herdt, O. C. E., Eds.; Pergamon: Oxford, 1987. An Introduction to Zeolite Molecular Sieves, Dyer, A. Wiley: New York, 1988. "Organic Reactions at Alumina Surfaces," Posner, G. H. Angew. Chem. Int. Ed. Engl. 1978, 17,487. "Organic Reactions on Alumina," Kabalka, G. W.; Pagni, R. M. Tetrahedron 1997, 53, 7999.

Biocatalytic Hydrolysis"Biocatalysis as a New Powerful Tool for the Synthesis of Enantiomerically Pure Chiral Building Blocks," Santaniello, E.; Ferraboschi, P. in Advances in Asymmetric Synthesis; Hassner, A., Ed., SAI: Greenwich, CT; Vol. 2; 1997. "Biocatalytic Deracemization Techniques. Dynamic Resolu tions and Stereoinversions," Stecher, H.; Faber, K. Synthesis 1997,1. "Enzymes in Organic Synthesis" Jones, J. B. Tetrahedron 1986, 42,3351. "General Aspects and Optimization of Enantioselective Bio catalysis in Organic Solvents: The Use of Lipases," Chen, C.-S.; Sih, C. J. Angew. Chem. Int. Ed. Engl. 1989, 28, 695. "Asymmetric Transformations Catalyzed by Enzymes in Or ganic Solvents," Klibanov, A. M. Acc. Chem. Res. 1990, 23, 114. "Pseudomonas fluorescens Lipase in Asymmetric Synthesis," Xie, Z.-F. Tetrahedron: Asymmetry 1991, 2, 733. "Esterolytic and Lipolytic Enzymes in Organic Synthesis," Boland, W.; Frl, C; Lorenz, M. Synthesis, 1991, 1049.

Lists of Abbreviations and Journal Codes on Endpapers

ALUMINA

9

AAlumina1[1344-28-1] Al 2 O 3 (MW 101.96) (a mildly acidic, basic, or neutral support for chromatographic separations; a reagent for catalyzing dehydration, elimination, ad dition, condensation, epoxide opening, oxidation, and reduction reactions) Alternate Name: -alumina. Physical Data: mp 2015 C; bp 2980 C; d 3.97 g c m - 3 . Solubility: slightly sol acid and alkaline solution. Form Supplied in: fine white powder, widely available in varying particle size (50-200 m; 70-290 mesh), in acidic (pH 4), basic (pH 10), and neutral (pH 7) forms. Drying: the activity of alumina has been classified by the Brockmann scale into five grades. The most active form, grade I, is obtained by heating alumina to 200 C while passing an inert gas through the system, or heating to ~400 C in an open vessel, followed by cooling in a dessicator. Addition of 3-4% (w/w) water and mixing for several hours converts grade I alumina to grade II. Other grades are similarly obtained (grade III, 5-7%; grade IV, 9-11%; grade V, 15-19% water). 2,3 Handling, Storage, and Precautions: inhalation of fine mesh alu mina can cause respiratory difficulties. Alumina is best handled under a fume hood and stored under dry, inert conditions.

tions, occur readily over alumina (eq 3). Stereoselective synthe ses of vinyl halides have been developed that take advantage of desilicohalogenation9 or deborohalogenation10 of vinylsilane or vinylboronic acid derived dihalides. Benzol[c]thiophene has been synthesized by dehydration of a sulfoxide precursor.11 The oxida tion of selenides to selenoxides and their elimination to alkenes can be accomplished in one step using basic alumina and t-Butyl Hydroperoxide in THF. 12

8

(1)

(2)

(3)

Alumina has been used for various dehydration reactions, including those leading to piperidines,13 pyrroles (eq 4) and pyrazoles,14 and other heterocycles.15 It is also an effective cat alyst for the selective protection of aldehydes in the presence of ketones. 16

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Introduction. Alumina is one of the most widely used packing materials for adsorption chromatography and is available in acidic, basic, and neutral forms. Use of the correct type is important to avoid unwanted reactions of the substrate being purified.1,3 Pos sessing both Lewis acidic and basic sites, alumina has been found to catalyze a wide range of reactions, generally under conditions that are milder and more selective than comparable homogeneous reactions. 1 Dehydration and Eliminations. One of the earliest uses of alumina as a catalyst was for the dehydration of alcohols. 4,5 These reactions generally require high temperature and yield primarily non-Saytzeff products. Complex terpenes have been dehydrated with Pyridine or Quinoline doped alumina (eq l). 6 b Numerous other groups can be eliminated in the presence of alumina, in cluding OR, OAc, O 3 SR, O2SR, and halides. 1,7 Some of these eliminations proceed under mild conditions,1 often during chro matographic purification (eq 2). 7d Sulfonates can be eliminated in the presence of acid and base sensitive groups, without skele tal rearrangements. However, a large excess of properly acti vated alumina is required, and poor stereo- and regiocontrol are observed.7e Dehydrohalogenations, particularly dehydrofluorina-

Addition and Condensation Reactions. Alumina promotes the addition of various heteroatom species, whether by electrophilic or nucleophilic processes. In contrast to the elimination reactions described earlier, alumina also promotes the intra molecular addition of OH and OR groups to isolated (eq 5) 6c and carbonyl-activated alkenes.17 It is also reported to catalyze the conjugate addition of other nucleophiles, such as amines. 18 In the presence of alumina, Iodine can be used to iodinate aromatics, hydroiodinate alkenes, and diiodinate alkynes (eq 6). 19 Hydrochlorinations and hydrobrominations of alkenes and alkynes give the Markovnikov products, with good stereoselectivity.20

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Avoid Skin Contact with All Reagents

10

ALUMINA

(6)

philes, such as alcohols, thiols, selenols, amines, carboxylic acids (eq 11),35 and peroxides.36 Use is made of this process in a route to (Z)-enamines (eq 12).37 Formation of C-C bonds by intramolec ular opening of epoxides has been reported (eq 13),38 as have alumina catalyzed epoxide formations23'39 and rearrangements.40

Aldol-type condensations between aldehydes and various ac tive methylene compounds,21 Michael reactions (eq 7),22 as well as Wittig-type reactions23 can be carried out on alumina under mild conditions, often without a solvent. An interesting nitroaldol reaction-cyclization sequence gives 2-isoxazoline 2-oxides with good diastereoselectivity (eq 8).24

(11) RX = MeO, 66%; PhS, 70%, PhSe, 95%; n-BuNH, 73%

(7) (12) (8)

trans:cis = 9:1

Orbital symmetry controlled reactions that have been promoted by alumina include the Diels-Alder,25 the ene,26 and the Carroll rearrangement.27 These reactions proceeded under milder condi tions and with greater stereoselectivity. In a spectacular exam ple, chromatographic purification promoted a diastereoselective intramolecular Diels-Alder that produced the verrucarol skeleton (eq 9).25b

(13)

(9)

Oxidations and Reductions. Posner has shown that Oppenauer oxidations, with Cl3CCHO or PhCHO as the hydrogen acceptors, are greatly accelerated in the presence of activated alumina.41 Secondary alcohols are oxidized selectively over pri mary alcohols (eq 14) and groups susceptible to other oxidants (sulfides, selenides, and alkenes) are unaffected. Even cyclobutanol, which is prone to fragmentation with one-electron oxidants, can be oxidized to cyclobutanone in 92% yield.(14)

Alkylation reactions that have been induced by alumina in clude per-C-methylation of phenol,28 intramolecular alkylation to yield a spiro-fused cyclopropane,29 and S-30 and O-alkylations (eq 10).31 The activation of Diazomethane by alumina has provided methods for the conversion of ketones to epoxides32 and for the selective monomethylation of dicarboxylic acids.33 Basic alumina has been used for the generation and trapping of dichlorocarbene.34

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The complementary reduction reaction (MeerweinPonndorf-Verley), using isopropanol as the hydride donor, is also facilitated by alumina and allows the selective reduction of aldehydes over ketones.42 Functional groups that survive these conditions include alkene, nitro, ester, amide, nitrile, primary and secondary iodides, and benzylic bromide. Air oxidation of a fluoren-9-ol to thefluoren-9-oneand thiols to disulfides are accelerated on the alumina surface.43 Alumina has also been used as a solid support for a variety of inorganic reagents,44 and for immobilizing chiral catalysts.45 Miscellaneous Reactions. Many rearrangements are cat alyzed by alumina.1 The Beckmann rearrangement46 of the Osulfonyloxime shown gives the expected amide with activated alumina, and the corresponding oxazoline with basic alumina (eq 15).46d Alumina has long been used for isomerization of ,-unsaturated ketones to the conjugated ketones.47 Isomerizations of alkynes to allenes,48 and allenes to conjugated dienoates49 have also been reported (eq 16).

Epoxides. Epoxides can be opened under mild, selective con ditions using alumina impregnated with a variety of nucleoLists of Abbreviations and Journal Codes on Endpapers

ALUMINA20. (15) 21. (16)

11

Kropp, P. J.; Daus, K. A.; Tubergen, M. W.; Kepler, K. D.; Wilson, V. P.; Craig, S. L.; Baillargeon, M. M.; Breton, G. W JACS 1993, 115, 3071, and references cited therein. Addition of HN3: Breton, G. W.; Daus, K. A.; Kropp, P. J. JOC 1992, 57, 6646. (a) Rosan, A.; Rosenblum, M. JOC 1975, 40, 3621. (b) Texier-Boullet, F.; Foucaud, A. TL 1982, 23, 4927. (c) Rosini, G.; Ballini, R.; Sorrenti, P. S 1983, 1014. (d) Varma, R. S.; Kabalka, G. W.; Evans, L. T.; Pagni, R. M. SC 1985, 15, 279. (e) Nesi, R.; Stefano, C ; Piero, S.-F. H 1985, 23, 1465. (f) Rosini, G.; Ballini, R.; Petrini, M.; Sorrenti, P. S 1985, 515. (g) Foucaud, A.; Bakouetila, M. S 1987, 854. (h) Moison, H.; TexierBoullet, F.; Foucaud, A. T 1987, 43, 537. (a) Rosini, G.; Marotta, E.; Ballini, R.; Petrini, M. S 1986, 237. (b) Ballini, R.; Petrini, M.; Marcantoni, E.; Rosini, G. S 1988, 231. Texier-Boullet, F.; Villemin, D.; Ricard, M.; Moison, H.; Foucaud, A. T 1985, 41, 1259. Isoxazoline: Rosini, G.; Galarini, R.; Marotta, E.; Righi, P. JOC 1990, 55, 781. Rosini, G.; Marotta, E.; Righi, E.; Seerden, J. P. JOC 1991, 56, 6258. (a) Parlar, H.; Baumann, R. AG(E) 1981, 20, 1014 (b) Koreeda, M.; Ricca, D. J.; Luengo, J. I. JOC 1988, 53, 5586. (a) Tietze, L. F.; Beifuss, U.; Ruther, M. JOC 1989, 54, 3120. (b) Tietze, L. F.; Beifuss, U. S 1988, 359. Pogrebnoi, S. I.; Kalyan, Y. B.; Krimer, M. Z.; Smit, W. A. TL 1987, 28, 4893. Cullinane, N. M.; Chard, S. J.; Dawkins, C. W. C. OSC 1963, 4, 520. Baird, R.; Winstein, S. JACS 1963, 85, 567. Villemin, D. CC 1985, 870. (a) Ogawa, H.; Chihara, T.; Teratani, S.; Taya, K. BCJ 1986, 59, 2481. (b) Cooke, P.; Magnus, P. CC 1976, 519. Hart, P. A.; Sandmann, R. A. TL 1969, 305. Ogawa, H.; Chihara, T.; Taya, K. JACS 1985, 107, 1365.

Alumina promotes the hydrolysis of acetates of primary alcohols,50 the deacylation of imides,51 the hydrolysis of sulfonylimines,52 and the decarbalkoxylation of -keto esters and carbamates.53 It can also be used for acylations and esterifications, with high selectivity for primary alcohols over secondary alcohols.54 Related Reagents. Molecular Sieves.1. Posner, G. H. AG(E) 1978, 77,487. 2. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals; Pergamon: New York, 1988; pp 20, 310. 3. (a) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel's Textbook of Practical Organic Chemistry; Longman-Wiley: New York, 1989; p 212. (b) FF 1967, 1, 19. 4. Knozinger, H. AG(E) 1968, 7, 791. 5. (a) Hershberg, E. B.; Ruhoff, J. R. OS 1937, 17, 25. (b) Newton, L. W.; Coburn, E. R. OSC 1955, 3, 312. (c) Sawyer, R. L.; Andrus, D. W. OSC 1955, 3, 276. 6. (a) von Rudloff, E. CJC 1961, 39, 1860. (b) Corey, E. J.; Hortmann, A. G. JACS 1965, 87, 5736. (c) Barrett, H. C ; Bchi, G. JACS 1967, 89, 5665. 7. (a) Kobayashi, S.; Shinya, M.; Taniguchi, H. TL 1971, 71. (b) Ishii, H.; Tozyo, X; Nakamura, M.; Funke, E. CPB 1972, 20, 203. (c) Gotthardt, H.; Hammond, G. S. CB 1974, 107, 3922. (d) Mayr, H.; Huisgen, R. AG(E) 1975, 14, 499. (e) Posner. G. H.; Gurria, G. M.; Babiak, K. A. JOC 1977, 42, 3173. (f) Vidal, J.; Huet, F. TL 1986, 27, 3733. 8. 9. 10. 11. 12. 13. 14. 15. (a) Strobach, D. R.; Boswell, G. A., Jr. JOC 1971, 36, 818. (b) Boswell, G. A., Jr. JOC 1966, 31, 991. (a) Miller, R. B.; McGarvey, G. JOC 1978, 43, 4424. (b) Miller, R. B.; McGarvey, G. SC 1977, 7, 475. Sponholtz, W. R., III; Pagni, R. M.; Kabalka, G. W.; Green, J. F.; Tan, L. C. JOC 1991, 56, 5700. Cava, M. P.; Pollack, N. M.; Mamer, O. A.; Mitchell, M. J. JOC 1971, 36, 3932. Labar, D.; Hevesi, L.; Dumont, W.; Krief, A. TL 1978, 1141. (a) Bourns, A. N.; Embleton, H. W.; Hansuld, M. K. OSC, 1963,4, 795. (b) Glacet, C ; Adrian, G. CR(C) 1969, 269, 1322. (a) Texier.-Boullet, F.; Klein, B.; Hamelin, J. S 1986, 409. (b) Tolstikov, G. A.; Galin, F. Z.; Makaev, F. Z. ZOR 1989, 25, 875. (a) LeBlanc, R. J.; Vaughan, K. CJC 1972, 50, 2544. (b) Higashino, T.; Suzuki, K.; Hayashi, E. CPB 1978, 26,3485. (c) Blade-Font, A. TL 1980, 21, 2443. (d) Hooper, D. L.; Manning, H. W.; LaFrance, R. J.; Vaughan, K. CJC 1986, 65, 250. (e) Hull, J. W., Jr.; Otterson, K.; Rhubright, D. JOC 1993, 58, 520.

22. 23. 24.

25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35.

Sarratosa, F. J. Chem. Educ. 1964, 41, 564. (a) Posner, G. H.; Rogers, D. Z. JACS 1977, 99, 8208. (b) Posner, G. H.; Rogers, D. Z. JACS 1977, 99, 8214. (c) Evans, D. A.; Golob, A. M.; Mandel, N. S.; Mandel, G. S. JACS 1978, 100, 8170. 36. Kropf, H.; Amirabadi, H. M.; Mosebach, M.; Torkler, A.; von Wallis, H. S 1983, 587. 37. 38. 39. Hudrlik, P. P.; Hudrlik, A. M.; Kulkarni, A. K. TL 1985, 26, 139. (a) Boeckman, R. K., Jr.; Bruza, K. J.; Heinrich, G. R. JACS 1978, 100, 7101. (b) Niwa, M.; Iguchi, M.; Yamamura, S. TL 1979, 4291. (a) Dhillon, R. S.; Chhabra, B. R.; Wadia, M. S.; Kalsi, P. S. TL 1974, 401. (b) Antonioletti, R.; D'Auria, M.; De Mico, A.; Piancatelli, G.; Scettri.A.T 1983,59, 1765. (a) Tsuboi, S.; Furutani, H.; Takeda, A. S 1987, 292. (b) Harigaya, Y.; Yotsumoto, K.; Takamatsu, S.; Yamaguchi, H.; Onda, M. CPB 1981, 29, 2557. (a) Posner, G. H.; Perfetti, R. B.; Runquist, A. W. TL 1976, 3499. (b) Posner, G. H.; Chapdelaine, M. J. S 1977, 555. (c) Posner, G. H.; Chapdelaine, M. J. TL 1977, 3227. Posner, G. H.; Runquist, A. W.; Chapdelaine, M. J. JOC 1977, 42, 1202. Also see: Suginome, H.; Kato, K. TL 1973, 4143. (a) Pan, H.-L.; Cole, C.-A.; Fletcher, T. L. S 1975, 716. (b) Liu, K.-T; Tong, Y.-C. S 1978, 669. Review: Laszlo, P. COS 1991, 7, 839. Recent examples: (a) Singh, S.; Dev, S. T 1993, 49,10959. (b) Lee, D. G.; Chen, T.; Wang, Z. JOC 1993, 58, 2918. (c) Morimoto, T.; Hirano, M.; Iwasaki, K.; Ishikawa, T. CL 1994, 53. (d) Santaniello, E.; Ponti, F.; Manzocchi, A. S 1978, 891. Soai, K.; Watanabe, M.; Yamamoto, A. JOC 1990, 55, 4832. (a) Craig, J. C ; Naik, A. R. JACS 1962, 84, 3410. (b) Gonzalez, A.; Galvez, C. S 1982, 946. (c) Luh, T.-Y; Chow, H.-F.; Leung, W. Y.; Tam, S. W.T1985, 41,519. (d) Nagano, H.; Masunaga, Y.; Matsuo, Y; Shiota, M. BCJ 1987, 60, 707. See also: (e) Mtayer, A.; Barbier, M. BSF 1972, 3625. Avoid Skin Contact with All Reagents

40.

41.

42. 43. 44.

16. Kamitori, Y.; Hojo, M.; Masuda, R.; Yoshida, T. TL 1985, 26, 4767. 17. McPhail, A. T.; Onan, K. D. TL 1973, 4641. 18. (a) Pelletier, S. W.; Venkov, A. P.; Finer-Moore, J.; Mody, N. V. TL 1980, 21, 809. (b) Pelletier, S. W.; Gebeyehu, G.; Mody, N. V. H 1982, 19,235. (c) Dzurilla, M.; Kutschy, P.; Kristian, P. S 1985, 933. 19. Pagni, R.; Kabalka, G. W.; Boothe, R.; Gaetano, K.; Stewart, L. J.; Conaway, R.; Dial, C ; Gray, D.; Larson, S.; Luidhardt, T. JOC 1988, 53, 4477.

45. 46.

1247.

ALUMINUM CHLORIDE(a) Marshall, J. A.; Roebke, H. JOC 1966, 31, 3109. (b) Hudlicky, T.; Srnak, T. TL 1981,22,3351. (c) Reetz, M. X; Wenderoth, B.; Urz, R. CB 1985, 118, 348. (d) Hatzigrigoriou, E.; Roux-Schmitt, M.-C.; Wartski, L. T 1988, 44, 4457. Also see: (e) Scettri, A.; Piancatelli, G.; D'Auria, M.; David, G. 7/1979, 35, 135. (a) Larock, R. C ; Chow, M.-S.; Smith, S. J. JOC 1986, 57, 2623. (b) Manning, D. T.; Coleman, H. A. J. JOC 1969, 34, 3248. Tsuboi, S.; Matsuda, T.; Mimura, S.; Takeda, A. OSC 1993, 8, 251. Johns, W. F.; Jerina, D. M. JOC 1963, 28, 2922. Boar, R. B.; McGhie, J. F.; Robinson, M.; Barton, D. H. R.; Horwell, D. C ; Stick, R. V. JCS(P1) 1975, 1237. Coutts, I. G. C ; Culbert, N. J.; Edward, M.; Hadfield, J. A.; Musto, D. R.; Pavlidis, V. H.; Richards, D. J. JCS(P1) 1985, 1829. (a) Greene, A. E.; Cruz, A.; Crabb, P. TL 1976, 2707. (b) van Leusen, A. M.; Strating, J. OSC 1988, 6, 981. (a) Posner, G. H.; Oda, M. TL 1981, 22, 5003. (b) Rana, S. S.; Barlow, J. J.; Matta, K. L. TL 1981, 22, 5007. (c) Posner, G. A.; Okada, S. S.; Babiak, K. A.; Miura, K.; Rose, R. K. S 1981, 789. (d) Nagasawa, K.; Yoshitake, S.; Amiya, T.; Ito, K. SC 1990, 20, 2033. (2)

48. 49. 50. 51. 52. 53. 54.

This is a result of the Lewis acidity of AlCl3 which complexes strongly with carbonyl groups.4 Adaptations of these basic reac tions have been reported.5 In chiral systems, inter- and intramolec ular acylations have been achieved without the loss of optical activity (eq 2).6

Friedel-Crafts chemistry at an asymmetric center generally pro ceeds with racemization, but the use of mesylates or chlorosulfonates as leaving groups has resulted in alkylations with excellent control of stereochemistry.7 The reactions proceed with inversion of configuration (eq 3). Cyclopropane derivatives have been used Viresh H. Rawal, Seiji Iwasa, as three-carbon units in acylation reactions (eq 4).8 In conjunc Alan S. Florjancic, & Agnes Fabre tion with triethylsilane, a net alkylation is possible under acylation The Ohio State University, Columbus, OH, USA conditions (eq 5).9 These conditions are compatible with halogen atoms present elsewhere in the molecule. Acylation reactions of phenolic compounds with heteroaromatic systems have also been accomplished (eq 6).10(3)

Aluminum Chloride1X = OSO2Me, OSO2Cl

[7446-70-0]

A1C13

(MW 133.34)(4)

(Lewis acid catalyst for Friedel-Crafts, Diels-Alder, [2 + 2] cycloadditions, ene reactions, rearrangements, and other reactions)

Physical Data: mp 190 C (193-194 C sealed tube); sublimes at (5) 180C; d2.44 g cm -3 . Solubility: sol many organic solvents, e.g. benzene, nitroben zene, carbon tetrachloride, chloroform, methylene chloride, nitromethane, and 1,2-dichloroethane; insol carbon disulfide. Form Supplied in: colorless solid when pure, typically a gray (6) or yellow-green solid; also available as a 1.0 M nitrobenzene solution. Handling, Storage, and Precautions: fumes in air with a strong odor of HC1. A1C13 reacts violently with H2O. All containers Treatment of aryl azides with AlCl3 has been reported to give should be kept tightly closed and protected from moisture.10 polycyclic aromatic compounds (eq 7),11 or aziridines when the Use in a fume hood. reactions are run in the presence of alkenes (eq 8).12 Friedel-Crafts Chemistry.1,2 A1C13 has traditionally been used in stoichiometric or catalytic3 amounts to mediate Friedel-Crafts alkylations and acylations of aromatic systems (eq 1).(7)

(1) n=l,2 Lists of Abbreviations and Journal Codes on Endpapers

(8)

ALUMINUM CHLORIDE

13(16)

The scope of Friedel-Crafts chemistry has been expanded be yond aromatic systems to nonaromatic systems, such as alkenes and alkynes and the mechanistic details have been investigated.13 The Friedel-Crafts alkylation14 and acylation15 of alkenes pro vide access to a variety of organic systems (eq 9). The acyla tion of alkynes provides access to cyclopentenone derivatives (eq 10).16 In addition, one can use this chemistry to access indenyl systems17 and vinyl chlorides.18 Allylic sulfones can undergo allylation chemistry (eq 11).19

Propargylic silanes undergo acylation to generate allenyl ketones (eq 17),25 while alkylsilanes afford cycloalkanones (eq 18).26

(17) (9)

(18) (10)

Several name reactions are promoted by AlCl3. For example, the Darzens-Nenitzescu reaction is simply the acylation of alkenes. The Ferrario reaction generates phenoxathiins from diphenyl ethers (eq 19).27 The rearrangement of acyloxy aromatic systems is known as the Fries rearrangement (eq 20).28 Aryl aldehydes are produced by the Gatterman aldehyde synthesis (eq 21).29 The initial step of the Haworth phenanthrene synthesis makes use of a Friedel-Crafts acylation.30 The acylation of phenolic compounds is called the Houben-Hoesch reaction (eq 22).31 The Leuckart amide synthesis generates aryl amides from isocyanates (eq 23).32

(11) (19)

The use of silyl derivatives in Friedel-Crafts chemistry has not only improved the regioselectivity but extended the scope of these reactions. Substitution at the ipso position occurs with aryl silanes (eq 12).20 The ability of silyl groups to stablize -carbenium ions (-effect) affords acylated products with complete control of regiochemistry (eq 13).21

(20)

(12)

(21)

(13)(22)

The use of silylacetylenes gives ynones (eq 14),22 cyclopen tenone derivatives (eq 15),23 and -amino acid derivatives (eq 16).24(23)

(14)

(15)

Amides can also be obtained by AlCl3 catalyzed ester amine exchange which proceeds primarily without racemization of chiral centers (eq 24).33 The reaction of phenols with -keto esters is known as the Pechmann condensation (eq 25).34 Aryl amines are used in the Riehm quinoline synthesis (eq 26).35 Aromatic sys tems may be coupled via the Scholl reaction (eq 27)36 and indoleAvoid Skin Contact with All Reagents

14

ALUMINUM CHLORIDE

derivatives are prepared in the Stolle synthesis (eq 28). 37 In the Zincke-Suhl reaction, phenols are converted to dienones (eq 29). 38(32) (24)

S:R = 82:18

AlCl 3 can also be used to catalyze [2 + 2] cycloaddition reac tions (eq 33) 43 and ene reactions (eq 34). 44

(25)

(33)

(26)

(34)

(27)

(28)

Rearrangements. A1C13 catalyzed rearrangement of hydro carbon derivatives to adamantanes has been well documented (eq 35). 45 Other rearrangements have been used in triquinane syn thesis (eq 36). 46

(35) (29)

Diels-Alder Reactions. There is some evidence that AlCl 3 catalysis of Diels-Alder reactions changes the transition state from a synchronous to an asynchronous one. 39 This also enhances asymmetric induction by increasing steric interactions at one end of the dieneophile. There are many examples of AlCl 3 promoted Diels-Alder reactions (eq 30). 40 Hetero-Diels-Alder reactions can be used to generate oxygen (eq 31) 41 and nitrogen (eq 32) 42 containing heterocycles.

(36)

Miscellaneous Reactions. A1C13 has been used to catalyze the addition of allylsilanes to aldehydes and acid chlorides (eq 37). 47 Cyclic ethers (pyrans and oxepins) have been prepared with hydroxyalkenes (eq 38). 48 The course of reactions between alde hydes and allylic Grignard reagents can be completely diverted to a-allylation by AlCl 3 (eq 39). 49 The normal course of the reaction gives -allylation products.

(37) (30)

(38)

(31) (39)

Lists of Abbreviations and Journal Codes on Endpapers

ALUMINUM CHLORIDE

15

AlCl3 can be used to remove t-butyl groups from aromatic rings (eq 40),50 thereby using this group as a protecting ele ment for a ring position. AlCl3 has also been used to remove p-nitrobenzyl (PNB) and benzhydryl protecting groups (eq 41).51 The combination of AlCl3 and Ethanethiol has formed the ba sis of a push-pull mechanism for the cleavage of many types of bonds including C-X,52 C-NO2,53 C=C,54 and C-O.55 Further more, AlCl3 has been used to catalyze chlorination of aromatic rings,56 open epoxides,57 and mediate addition of dichlorophosphoryl groups to alkanes.58

19. Trost, B. M.; Ghadiri, M. R. JACS 1984, 706, 7260. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. (a) Eaborn, C. JCS 1956, 4858. (b) Habich, D.; Effenberger, F. S 1979, 841. (a) Fleming, I.; Pearce, A. CC 1975, 633. (b) Fristad, W. E.; Dime, D. S.; Bailey, T. R.; Paquette, L. A. TL 1979, 1999. (a) Walton, D. R. M.; Waugh, F. JOM 1972, 37,45. (b) Newman, H. JOC 1973, 38, 2254. Karpf, M. TL 1982, 23, 4923. Casara, P.; Metcalf, B. W. TL 1978, 1581. Flood, T.; Peterson, P. E. JOC 1980, 45, 5006. Urabe, H.; Kuwajima, I. JOC 1984, 49, 1140. Ferrario, E. BSF 1911, 9, 536. (a) Blatt, A. H. OR 1942,1, 342. (b) Gammill, R. B. TL 1985, 26, 1385. Truce, W. E. OR 1957, 9, 37. Berliner, E. OR 1949, 5, 229. Spoerri, P. E.; Dubois, A. S. OR 1949, 5, 387. Effenberger, F.; Gleiter, R. CB 1964, 97, 472. Gless, R. D. SC 1986, 16, 633. Sethna, S.; Phadke, R. OR 1953, 7, 1.

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(41)

Related Reagents. Antimony(V) Fluoride; Ethylaluminum Dichloride; Hydrogen Fluoride; Iron(III) Chloride; Iron(III) Chloride-Alumina; Tin(IV) Chloride; Titanium(IV) Chloride; Zinc Chloride.

1.

(a) Thomas, C. A. Anhydrous Aluminum Chloride in Organic Chemistry; ACS Monograph Series; Reinholdt: New York, 1941. (b) Shine, H. J. Aromatic Rearrangements; Elsevier: Amsterdam, 1967. (c) FF 1967, 1, 24. (d) Olah, G. A. Friedel-Crafts Chemistry; Wiley: New York, 1973. (e) Roberts, R. M.; Khalaf, A. A. Friedel-Crafts Alkylation Chemistry; Marcel Dekker: New York, 1984. Gore, P. H. CR 1955, 55, 229. Pearson, D. E.; Buehler, C. A. S 1972, 533. (a) Tan, L. K.; Brownstein, S. JOC 1982, 47, 4737. (b) Tan, L. K.; Brownstein, S. JOC 1983, 48, 3389. Drago, R. S.; Getty, E. E. JACS 1988, 110, 3311. McClure, D. E.; Arison, B. H.; Jones, J. H.; Baldwin, J. J. JOC 1981, 46,2431. Piccolo, O.; Spreafico, F.; Visentin, G.; Valoti, E. JOC 1985, 50, 3945.

35. Elderfield, R. C ; McCarthy, J. R. JACS 1951, 73, 975. 36. Clowes, G. A. JCS(P1) 1968,2519. 37. Sumpter, W. C. CR 1944, 34, 393. 38. Newman, M. S.; Wood, L. L. JACS 1959, 81, 6450. 39. Tolbert, L. M.; Ali, M. B. JACS 1984, 106, 3806. 40. (a) Cohen, N.; Banner, B. L.; Eichel, W. F. SC 1978, 8,427. (b) Fringuelli, F.; Pizzo, F.; Taticchi, A.; Wenkert, E. SC 1979, 9, 391. (c) Ismail, Z. M.; Hoffmann, H. M. R. JOC 1981, 46, 3549. (d) Vidari, G.; Ferrino, S.; Grieco, P. A. JACS 1984, 106, 3539. (e) Angell, E. C ; Fringuelli, F.; Guo, M.; Minuti, L.; Taticchi, A.; Wenkert, E. JOC 1988, 53, 4325. 41. 42. 43. 44. Ismail, Z. M.; Hoffmann, H. M. R. AG(E) 1982, 21, 859. LeCoz, L.; Wartski, L.; Seyden-Penne, J.; Chardin, P.; Nierlich, M. TL 1989, 30, 2795. Jung, M. E.; Haleweg, K. M. TL 1981, 22, 2735. (a) Snider, B. B.; Rodini, D. J.; Conn, R. S. E.; Sealfon, S. JACS 1979, 101, 5283. (b) Mehta, G.; Reddy, A. V. TL 1979, 2625. (c) Snider, B. B. ACR 1980, 13, 426. (a) Bingham, R. C ; Schleyer, P. R. Top. Curr. Chem. 1971, 18, 1. (b) McKervey, M. A. CSR 1974, 3, 479. (c) McKervey, M. A. T 1980, 36,971. Kakiuchi, K.; Ue, M.; Tsukahara, H.; Shimizu, T.; Miyao, T.; Tobe, Y.; Odaira, Y.; Yasuda, M.; Shima, K. JACS 1989, 111, 3707. (a) Deleris, G.; Donogues, J.; Calas, R. TL 1976, 2449. (b) Pillot, J.-P.; Donogues, J.; Calas, R. TL 1976, 1871. Coppi, L.; Ricci, A.; Taddai, M. JOC 1988, 53,911. Yamamoto, Y.; Maruyama, K. JOC 1983, 48, 1564. Lewis, N.; Morgan, I. SC 1988, 18, 1783. Ohtani, M.; Watanabe, F.; Narisada, M. JOC 1984, 49, 5271.

2. 3. 4. 5. 6. 7. 8.

45.

46. 47. 48. 49. 50. 51.

Pinnick, H. W.; Brown, S. P.; McLean, E. A.; Zoller, L. W. JOC 1981, 46, 3758. 9. Jaxa-Chamiel, A.; Shah, V. P.; Kruse, L. I. JCS(P1) 1989, 1705. 10. (a) Pollak, A.; Stanovnik, B.; Tisler, M. JOC 1966, 31,4297. (b) Coates, W. J.; McKillop, A. JOC 1990, 55, 5418. 11. Takeuchi, H.; Maeda, M.; Mitani, M.; Koyama, K. CC 1985, 287. 12. Takeuchi, H.; Shiobara, Y.; Kawamoto, H.; Koyama, K. JCS(P1) 1990, 321. 13. 14. 15. (a) Puck, R.; Mayr, H.; Rubow, M.; Wilhelm, E. JACS 1986, 108, 7767. (b) Brownstein, S.; Morrison, A.; Tan, L. K. JOC 1985, 50, 2796. Mayr, H.; Striepe, W. JOC 1983, 48, 1159. (a) Ansell, M. F.; Ducker, J. W. JCS 1960, 5219. (b) Cantrell, T. S. JOC 1967,32,1669. (c)Groves, JK. CSR 1972, 1,73. (d)House,H. O.Modern Synthetic Reactions; Benjamin-Cummings: Menlo Park, CA, 1972; pp 786-816. (a) Martin, G. J.; Rabiller, C ; Mabon, G. TL 1970, 3131. (b) Rizzo, C. J.; Dunlap, N. A.; Smith, A. B. JOC 1987, 52, 5280. Maroni, R.; Melloni, G.; Modena, G. JCS(P1) 1974, 353. Maroni, R.; Melloni, G.; Modena, G. JCS(P1) 1973, 2491.

52. Node, M.; Kawabata, T.; Ohta, K.; Fujimoto, M.; Fujita, E.; Fuji, K. JOC 1984,49,3641. 53. Node, M.; Kawabata, T.; Ueda, M.; Fujimoto, M.; Fuji, K.; Fujita, E. TL 1982, 23,4047. 54. Fuji, K.; Kawabata, T.; Node, M.; Fujita, E. JOC 1984, 49, 3214. 55. Node, M.; Nishide, K.; Ochiai, M.; Fuji, K.; Fujita, E. JOC 1981, 46, 5163. 56. 57. 58. Watson, W.D. JOC 1985, 50, 2145. Eisch, J. J.; Liu, Z.-R.; Ma, X.; Zheng, G.-X. JOC 1992, 57, 5140. Olah, G. A.; Farooq, O.; Wang, Q.; Wu, A.-H. JOC 1990, 55, 1224. Paul Galatsis of Guelph, Ontario, Canada

16. 17. 18.

University

Avoid Skin Contact with All Reagents

16

ALUMINUM ISOPROPOXIDE

Aluminum Isopropoxide

1

propanol is distilled at reduced pressure and the residue is cooled and hydrolyzed with 6 N sulfuric acid to liberate crotyl alcohol from its aluminum derivative.

[555-31-7]

C 9 H 21 AlO 3

(MW 204.25)

(1)

(mild reagent for Meerwein-Ponndorf-Verley reduction;1 Oppenauer oxidation;13 hydrolysis of oximes;16 rearrangement of epox ides to allylic alcohols;17 regio- and chemoselective ring opening of epoxides;20 preparation of ethers21) Alternate Name: triisopropoxyaluminum. Physical Data: mp 138-142 C (99.99+%), 118C (98+%); bp 140.5 C;rf 1.035 g c m - 3 . Solubility: sol benzene; less sol alcohols. Form Supplied in: white solid (99.99+% or 98+% purity based on metals analysis). Preparative Methods: see example below. Handling, Storage, and Precautions: the dry solid is corrosive, moisture sensitive, flammable, and an irritant. Use in a fume hood.

The Meerwein-Ponndorf-Verley reduction of the ketone (3) involves formation of a cyclic coordination complex (4) which, by hydrogen transfer, affords the mixed alkoxide (5), hydrolyzed to the alcohol (6) (eq 2).4 Further reflection suggests that under forcing conditions it might be possible to effect repetition of the hydrogen transfer and produce the hydrocarbon (7). Trial indeed shows that reduction of diaryl ketones can be effected efficiently by heating with excess reagent at 250 C (eq 3).5

NMR Analysis of Aluminum Isopropoxide. Evidence from molecular weight determinations indicating that aluminum iso propoxide aged in benzene solution consists largely of the tetramer (1), whereas freshly distilled molten material is trimeric (2),2 is fully confirmed by NMR spectroscopy.3

(2)

(3)

Meerwein-Ponndorf-Verley Reduction. One use of the reagent is for the reduction of carbonyl compounds, particularly of unsaturated aldehydes and ketones, for the reagent attacks only carbonyl compounds. An example is the reduction of crotonaldehyde to crotyl alcohol (eq 1).1 A mixture of 27 g of cleaned Aluminum foil, 300 mL of isopropanol, and 0.5 g of Mercury(II) Chloride is heated to boiling, 2mL of carbon tetrachloride is added as catalyst, and heating is continued. The mixture turns gray, and vigorous evolution of hydrogen begins. Refluxing is continued until gas evolution has largely subsided (6-12 h). The solution, which is black from the presence of suspended solid, can be concentrated and the aluminum isopropoxide distilled in vacuum (colorless liquid) or used as such. Thus the undistilled solution prepared as described from 1.74 mol of aluminum and 500 mL of isopropanol is treated with 3 mol of crotonaldehyde and 1 L of isopropanol. On reflux at a bath temperature of 110 C, acetone slowly distills at 60-70C. After 8-9 h, when the distil late no longer gives a test for acetone, most of the remaining isoLists of Abbreviations and Journal Codes on Endpapers

A study6 of this reduction of mono- and bicyclic ketones shows that, contrary to commonly held views, the reduction proceeds at a relatively high rate. The reduction of cyclohexanone and of 2-methylcyclohexanone is immeasurably rapid. Even menthone is reduced almost completely in 2 h. The stereochemistry of the reduction of 3-isothujone (8) and of 3-thujone (11) has been ex amined (eqs 4 and 5). The ketone (8) produces a preponderance of the m-alcohol (9). The stereoselectivity is less pronounced in the case of 3-thujone (11), although again the cis-alcohol (12) predominates. The preponderance of the m-alcohols can be in creased by decreasing the concentration of ketone and alkoxide.(4)

(5)

ALUMINUM ISOPROPOXIDE

17

This reducing agent is the reagent of choice for reduction of enones of type (14) to the ,-unsaturated alcohols (15) (eq 6). Usual reducing agents favor 1,4-reduction to the saturated alcohol.7

(10)

Chiral acetals derived from ()-(2R,4R)-2,4-Pentanediol and ketone are reductively cleaved with high diastereoselectivity by a 1:2 mixture of diethylaluminum fluoride and pentafluorophenol.11 Furthermore, aluminum pentafluorophenoxide is a very powerful Lewis acid catalyst for the present reaction.12 The reductive cleav age in the presence of 5 mol % of Al(OC6F5)3 affords stereoselectively retentive reduced -alkoxy ketones. The reaction is an intramolecular Meerwein-Ponndorf-Verley reductive and The Meerwein-Ponndorf-Verley reduction of pyrimidin2(li/)-ones using Zirconium Tetraisopropoxide or aluminum iso- Oppenauer oxidative reaction on an acetal template (eq 11). propoxide leads to exclusive formation of the 3,4-dihydro isomer (eq 7).8 The former reducing agent is found to be more effective.(6)

(7)

(11)

Reductions with Chiral Aluminum Alkoxides. The re duction of cyclohexyl methyl ketone with catalytic amounts of aluminum alkoxide and excess chiral alcohol gives (S)-lcyclohexylethanol in 22% ee (eq 8).9

The direct formation of ,-alkoxy ketones is quite useful. Removal of the chiral auxiliary, followed by base-catalyzed elimination of the resulting -alkoxy ketone, easily gives an opti cally pure alcohol in good yield. Several examples of the reaction are summarized in Table 1.Table 1 Reductive Cleavages of Acetals Using Al(OC6F5)3 Catalyst

(8)

Isobomyloxyaluminum dichloride is a good reagent for reduc ing ketones to alcohols. The reduction is irreversible and subject to marked steric approach control (eq 9).10

R1 C5H11

R2 Me Me Me Me Et Me

Yield (%) 83 61 90 71 78 89

Ratio (S:R) 82:18 73:27 94:6 >99:1 92:8 95:5

(9)

i-Bu i-Pr

Ph Ph c-Hex

Diastereoselective Reductions of Chiral Acetals. Recently, it has been reported that Pentqfluorophenol is an effective accel erator for Meerwein-Ponndorf-Verley reduction.11 Reduction of 4-t-butylcyclohexanone with aluminum isopropoxide (3 equiv) in dichloromethane, for example, is very slow at 0 C (97% ee. In comparison, use of triethylamine in a solvent mixture of toluene and hexane leads to a 90:10 mixture of (Z)- and (E)-boron eno lates (4), which rearranges to generate the erythro product (5) as the major isomer in 65% yield and high enantiomeric excess (eq 6).10a,11

(8)

(9)

(6)

Aldol-like reactions between aldehydes and nitriles,16 alkylpyridines,17 2-methyloxazoles, 2-methylfhiazoles,18 glycolates, and thioglycolates19 are possible in the presence of boryl triflates and DIPEA. Methyl-O-allyl glycolate tin(II) (or boron) enolates, prepared easily using DIPEA as base, undergo Wittig rearrangement to afford -hydroxy esters with a high degree of diastereoselectivity (eq 10).20

(10)

Diisopropylethylamine also finds application in the prepa ration of titanium enolates from esters,21 aryl ketones,22 and oxazolidones.23 The stereoselective generation of silylketene acetals from alkyl esters and Triethylsilyl Perchlorate12 is quite effective using DI PEA as the base at 70 C in a 1:1 solvent mixture of CH2Cl2 and CCl4 (see 2,2,6,6-Tetramethylpiperidine). Phenols and enols can be O-methylated in moderate to good yields using Trimethylsilyldiazomethane with DIPEA in methanol-acetonitrile.13 Base-Promoted Alkylation. This sterically hindered amine is widely used in organic synthesis as a proton scavenger. Its lack of quatemization makes it an excellent choice of a base for use with very reactive alkylating agents.24 In the field of pro tecting group chemistry, DIPEA is a particularly useful base for protection of alcohols as substituted ethers.25 For example, the tertiary alcohol of mevalonic lactone can be protected as the pAvoid Skin Contact with All Reagents

136

DIISOPROPYLETHYLAMINE

methoxybenzyloxymethyl ether using an excess of DIPEA and 3 equiv of p-methoxybenzyl chloromethyl ether (eq 11).26

(15)

(11)

Addition of DIPEA to a mixture of phenylsulfenyl chloride and an unsaturated alcohol or carboxylic acid results in high yields of cyclic ethers or lactones, respectively.32 The presumed mechanism involves the intermediacy of an episulfonium ion (eq 16).

2,4-Disubstituted oxazolones are alkylated in high yields using alkyl halides with DIPEA as a base in DMF (eq 12).27 DIPEA can be used together with Triethyloxonium Tetrafluoroborate for the esterification of sterically hindered carboxylic acids.28

(16)

(12)

The alkylsulfination of diacetone-D-glucose with sulfinyl chlo rides and DIPEA in toluene at 78 C produces the (S)-sulfinates as the major products. Simply changing the base from DIPEA to pyridine and the solvent from toluene to THF results in a remark able stereochemical reversal, affording the (R)-sulfinates as the major products (eq 13).29

Eliminations. The eliminative deoxygenation of acetals into enol ethers is accomplished using Trimethylsilyl Trifluoromethanesulfonate and a slight excess of DIPEA (eq 17);33 similarly, treatment of 2-alkyloxazolidines with Chlorotrimethylsilane and DIPEA leads to N-(trimethylsilyloxyalkyl)enamines (eq 18).34 Thioacetals follow similar chemistry to furnish vinyl sulfides.35 Deoxygenation of sulfoxides with DIPEA and Iodotrimethylsil