Part B: Reactions and Synthesis

972 Pages·2001·33.37 MB·English

by  Francis A. Carey, Richard J. Sundberg (auth.)

Advanced Organic
•
Ch t
fY
FOURTH
effilS
EDITION
Part B: Reactions and Synthesis
Advanced Organic Chemistry
PART A: Structure and Mechanisms
PART B: Reactions and Synthesis
Advanced Organic
•
Ch t
emlS ry FOURTH
EDITION
Part B: Reactions and Synthesis
FRANCIS A. CAREY
and RICHARD J. SUNDBERG
University of Virginia
Charlottesville, Virginia
~Springer
Library of Congress Cataloging-in-Publication Data
Carey, Francis A., 1937-
Advanced organic chemistry/Francis A. Carey and Richard J. Sundberg.-4th ed.
p. em.
Includes bibliographical references and index.
Contents: pt. B. Reactions and synthesis
I. Sundberg, Richard J., 1938- II. Title.
QD251.2 .C36 2000
547-dc21
00-059652
Library of Congress Cataloging-in-Publication Data
Carey, Francis A., 1937-
Advanced organic chemistry/Francis A. Carey and Richard ). Sundberg.-4th ed.
p.cm.
Includes bibliographical references and index.
Contents: pt. B. Reactions and synthesis
I. Sundberg, Richard)., 1938-II. Title.
QD251.2 .C36 2000
547-dc21 00-059652
A C.I.P. record for this book is available from the Library of Congress
ISBN 978-3-662-38652-1 ISBN 978-3-662-39510-3 (eBook)
DOI 10.1007/978-3-662-39510-3
© 2001,1990,1984,1977 Springer Science+ Business Media New York
Originally published by Springer Science Business Media, Inc. in 2001
All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmit
ted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or
otherwise, without written permission from the Publisher. (Springer Science+Business Media,
LLC).
The front cover shows the key orbital interactions in the Diels-Alder reaction. The highest-occupied
molecular orbital (HOMO) of 1,3-butadiene and the lowest-unoccupied molecular orbital (LUMO)
of ethylene overlap in phase with one another allowing the reaction to occur in a single step.
10 9 8 7 6 5 4 3
springeronline.com
Preface to the Fourth Edition
Part B emphasizes the most important reactions used in organic synthesis. The material is
organized by reaction type. Chapters 1 and 2 discuss the alkylation, conjugate addition and
carbonyl addition/condensation reactions of enolates and other carbon nucleophiles.
Chapter 3 covers the use of nucleophilic substitution, both at saturated carbon and at
carbonyl groups, in functional group of interconversions. Chapter 4 discusses electrophilic
additions to alkenes and alkynes, including hydroboration. Chapter 5 discusses reduction
reactions, emphasizing alkene and carbonyl-group reductions. Concerted reactions,
especially Diels-Alder and other cycloadditions and sigmatropic rearrangements, are
considered in Chapter 6. Chapters 7, 8, and 9 cover organometallic reagents and
intermediates in synthesis. The main-group elements lithium and magnesium as well as
zinc are covered in Chapter 7. Chapter 8 deals with the transition metals, especially copper,
palladium, and nickel. Chapter 9 discusses synthetic reactions involving boranes, silanes,
and stannanes. Synthetic reactions which involve highly reactive intermediates-carboca
tions, carbenes, and radicals-are discussed in Chapter 10. Aromatic substitution by both
e1ectrophilic and nucleophilic reagents is the topic of Chapter 11. Chapter 12 discusses the
most important synthetic procedures for oxidizing organic compounds. In each of these
chapters, the most widely used reactions are illustrated by a number of specific examples
of typical procedures. Chapter 13 introduces the concept of synthetic planning, including
the use of protective groups and synthetic equivalents. Multistep syntheses are illustrated
with several syntheses of juvabione, longifolene, Prelog-Djerassi lactone, Taxol, and
epothilone. The chapter concludes with a discussion of solid-phase synthesis and its
application in the synthesis of polypeptides and oligonucleotides, as well as to combina
torial synthesis.
The control of reactivity to achieve specific syntheses is one of the overarching goals
of organic chemistry. In the decade since the publication of the third edition, major
advances have been made in the development of efficient new methods, particularly
catalytic processes, and in means for control of reaction stereochemistry. For example, the
scope and efficiency of palladium-catalyzed cross coupling have been greatly improved by
optimization of catalysts by ligand modification. Among the developments in stereocontrol
are catalysts for enantioselective reduction of ketones, improved methods for control of the
v
Vl stereoselectivity of Diels-Alder reactions, and improved catalysts for enantioselective
hydroxylation and epoxidation of alkenes.
PREFACE TO THE
This volume assumes a level of familiarity with structural and mechanistic concepts
FOURTH EDmON
comparable to that in the companion volume, Part A, Structure and Mechanisms. Together,
the two volumes are intended to provide the advanced undergraduate or beginning
graduate student in chemistry a sufficient foundation to comprehend and use the research
literature in organic chemistry.
Contents of Part B
Chapter 1. Alkylation of Nucleophilic Carbon Intermediates .......... .
1.1. Generation of Carbanions by Deprotonation .................... .
1.2. Regioselectivity and Stereoselectivity in Enolate Formation .......... . 5
1.3. Other Means of Generating Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.4. Alkylation of Enolates .................................. . 11
1.5. Generation and Alkylation of Dianions ....................... . 20
1.6. Medium Effects in the Alkylation of Enolates ................... . 20
1.7. Oxygen versus Carbon as the Site of Alkylation ................. . 23
1.8. Alkylation of Aldehydes, Esters, Amides, and Nitriles ............. . 28
1.9. The Nitrogen Analogs of Enols and Enolates-Enamines and Imine
Anions ............................................. . 31
1.10. Alkylation of Carbon Nucleophiles by Conjugate Addition .......... . 39
General References ................................... . 47
Problems 47
Chapter 2. Reaction of Carbon Nucleophiles with Carbonyl Groups . . . . . . 57
2.1. Aldol Addition and Condensation Reactions. . . . . . . . . . . . . . . . . . . . . 57
2.1.1. The General Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2.1.2. Mixed Aldol Condensations with Aromatic Aldehydes . . . . . . . . 60
2.1.3. Control of Regiochemistry and Stereochemistry of Mixed Aldol
Reactions of Aliphatic Aldehydes and Ketones . . . . . . . . . . . . . 62
2.1.4. Intramolecular Aldol Reactions and the Robinson Annulation . . . 89
2.2. Addition Reactions of !mines and Iminium Ions . . . . . . . . . . . . . . . . . . 96
2.2.1. The Mannich Reaction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
2.2.2. Amine-Catalyzed Condensation Reactions. . . . . . . . . . . . . . . . . 100
2.3. Acylation of Carbanions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Vll
viii 2.4. The Wittig and Related Reactions of Phosphorus-Stabilized Carbon
Nucleophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ill
CONTENTS OF PART B
2.5. Reactions of Carbonyl Compounds with oc-Trimethylsilylcarbanions. . . . . . 120
2.6. Sulfur Ylides and Related Nucleophiles . . . . . . . . . . . . . . . . . . . . . . . . 122
2.7. Nucleophilic Addition--Cyclization. . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
General References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Chapter 3. Functional Group Interconversion by Nucleophilic Substitution . . 141
3.1. Conversion of Alcohols to Alkylating Agents . . . . . . . . . . . . . . . . . . . . 141
3 .1.1. Sulfonate Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
3.1.2. Halides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
3.2. Introduction of Functional Groups by Nucleophilic Substitution at
Saturated Carbon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
3.2.1. General Solvent Effects ............................. . 147
3.2.2. Nitrites ........................................ . 150
3.2.3. Azides ........................................ . 150
3.2.4. Oxygen Nucleophiles .............................. . 152
3.2.5. Nitrogen Nucleophiles .............................. . 155
3.2.6. Sulfur Nucleophiles ............................... . 158
3.2.7. Phosphorus Nucleophiles ............................ . 158
3.2.8. Summary of Nucleophilic Substitution at Saturated Carbon ..... . 159
3.3. Nucleophilic Cleavage of Carbon-Oxygen Bonds in Ethers and Esters ... . 159
3.4. Interconversion of Carboxylic Acid Derivatives .................. . 164
3.4.1. Preparation of Reactive Reagents for Acylation ............. . 166
3.4.2. Preparation of Esters .......................... : .... . 172
3.4.3. Preparation of Amides. ............................. . 172
Problems 180
Chapter 4. Electrophilic Additions to Carbon-Carbon Multiple Bonds . . . . . 191
4.1. Addition of Hydrogen Halides.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
4.2. Hydration and Other Acid-Catalyzed Additions of Oxygen Nucleophiles . . 195
4.3. Oxymercuration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
4.4. Addition of Halogens to Alkenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
4.5. Electrophilic Sulfur and Selenium Reagents. . . . . . . . . . . . . . . . . . . . . . 209
4.6. Addition of Other Electrophilic Reagents . . . . . . . . . . . . . . . . . . . . . . . 216
4.7. Electrophilic Substitution Alpha to Carbonyl Groups. . . . . . . . . . . . . . . . 216
4.8. Additions to Allenes and Alkynes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
4.9. Addition at Double Bonds via Organoborane Intermediates . . . . . . . . . . . 226
4.9.1. Hydroboration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
4.9.2. Reactions of Organoboranes. . . . . . . . . . . . . . . . . . . . . . . . . . . 232
4.9.3. Enantioselective Hydroboration. . . . . . . . . . . . . . . . . . . . . . . . . 236
4.9.4. Hydroboration of Alkynes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
General References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240 IX
Problems .......................................... . 241
CONTENTS OF PART B
Chapter 5. Reduction of Carbonyl and Other Functional Groups ....... . 249
5.1. Addition of Hydrogen .................................. . 249
5. 1.1. Catalytic Hydrogenation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
5. 1.2. Other Hydrogen-Transfer Reagents .................... . 262
5.2. Group III Hydride-Donor Reagents .......................... . 262
5.2.1. Reduction of Carbonyl Compounds .................... . 262
5.2.2. Stereoselectivity of Hydride Reduction .................. . 273
5.2.3. Reduction of Other Functional Groups by Hydride Donors .... . 280
5.3. Group IV Hydride Donors ................................ . 286
5.4. Hydrogen-Atom Donors ................................. . 288
5.5. Dissolving-Metal Reductions .............................. . 290
5.5 .1. Addition of Hydrogen ............................. . 292
5.5.2. Reductive Removal of Functional Groups ................ . 296
5.5.3. Reductive Carbon-Carbon Bond Formation ............... . 299
5.6. Reductive Deoxygenation of Carbonyl Groups .................. . 307
5.7. Reductive Elimination and Fragmentation ..................... . 310
General References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Problems 316
Chapter 6. Cycloadditions, Unimolecular Rearrangements, and Thermal
Eliminations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
6.1. Cycloaddition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
6.1.1. The Diels-Alder Reaction: General Features . . . . . . . . . . . . . . . 332
6.1.2. The Diels-Alder Reaction: Dienophiles . . . . . . . . . . . . . . . . . . 339
6.1.3. The Diels-Alder Reaction: Dienes. . . . . . . . . . . . . . . . . . . . . . 345
6.1.4. Asymmetric Diels-Alder Reactions . . . . . . . . . . . . . . . . . . . . . 349
6.1.5. Intramolecular Diels-Alder Reactions. . . . . . . . . . . . . . . . . . . . 353
6.2. Dipolar Cycloaddition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
6.3. [2 + 2] Cycloadditions and Other Reactions Leading to Cyclobutanes . . . 367
6.4. Photochemical Cycloaddition Reactions. . . . . . . . . . . . . . . . . . . . . . . . 370
6.5. [3,3] Sigmatropic Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
6.5.1. Cope Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
6.5.2. Claisen Rearrangements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
6.6. [2,3] Sigmatropic Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . 394
6.7. Ene Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
6.8. Unimolecular Thermal Elimination Reactions. . . . . . . . . . . . . . . . . . . . 403
6.8.1. Cheletropic Elimination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
6.8.2. Decomposition of Cyclic Azo Compounds . . . . . . . . . . . . . . . . 405
6.8.3. fi Eliminations Involving Cyclic Transition States. . . . . . . . . . . . 408
General References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
Problems 414