Superbases for organic synthesis : guanidines, amidines and phosphazenes and related organocatalysts

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. 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.The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Ishikawa, Tsutomu.Superbases for organic synthesis : guanidines, amidines and phosphazenes and related organocatalysts / Tsutomu Ishikawa. p. cm. Includes bibliographical references and index. ISBN 978-0-470-51800-7 (cloth : alk. paper) 1. Amidines. 2. Guanidines. 3. Phosphazo compounds. 4. Organic bases. I. Title. Cover Page 1 Title: Superbases for Organic Synthesis: Guanidines, Amidines, Phosphazenes and Related Organocatalysts 3 ISBN 978-0470518007 4 Contents (with page links) 6 Preface 6 Acknowledgements 6 Contributors 6 1. General Aspects of Organosuperbases 6 2. Physico-Chemical Properties of Organosuperbases 6 3. Amidines in Organic Synthesis 6 4. Guanidines in Organic Synthesis 7 5. Phosphazene: Preparation, Reaction and Catalytic Role 8 6. Polymer-Supported Organosuperbases 8 7. Application of Organosuperbases to Total Synthesis 8 8. Related Organocatalysts (1): A Proton Sponge 9 9. Related Organocatalysts (2): Urea Derivatives 9 10. Amidines and Guanidines in Natural Products and Medicines 9 11. Perspectives 10 Index 10 Preface 11 Acknowledgements 13 Contributors 14 1 General Aspects of Organosuperbases 15 References 20 2 Physico-Chemical Properties of Organosuperbases 23 2.1 Introduction 23 2.2 Proton Sponges 24 2.3 Amidines 34 2.4 Guanidines 38 2.5 Phosphazenes 45 2.6 Guanidinophosphazenes 49 2.7 Other Phosphorus Containing Superbases: Verkade's Proazaphosphatranes 51 2.8 Theoretical Methods 55 2.9 Concluding Remarks 55 References 56 3 Amidines in Organic Synthesis 63 3.1 Introduction 63 3.2 Preparation of Amidines 66 3.3 Application of Amidines to Organic Synthesis 79 3.4 Amidinium Salts: Design and Synthesis 96 3.5 Concluding Remarks 100 References 100 4 Guanidines in Organic Synthesis 107 4.1 Introduction 107 4.2 Preparation of Chiral Guanidines 108 4.3 Guanidines as Synthetic Tools 113 4.4 Guanidinium Salt 139 4.5 Concluding Remarks 150 References 150 5 Phosphazene: Preparation, Reaction and Catalytic Role 159 5.1 Introduction 159 5.2 Deprotonative Transformations Using Stoichiometric Phosphazenes 164 5.3 Transformation Using Phosphazene Catalyst 178 5.4 Proazaphosphatrane Base (Verkade's Base) 190 5.5 Concluding Remarks 195 References 195 6 Polymer-Supported Organosuperbases 201 6.1 Introduction 201 6.2 Acylation Reactions 202 6.3 Alkylation Reactions 204 6.4 Heterocyclization 212 6.5 Miscellaneous 214 6.6 Concluding Remarks 219 References 219 7 Application of Organosuperbases to Total Synthesis 225 7.1 Introduction 225 7.2 Carbon–Carbon Bond Forming Reactions 225 7.3 Deprotection 239 7.4 Elimination 239 7.5 Ether Synthesis 244 7.6 Heteroatom Conjugate Addition 247 7.7 Isomerization 251 7.8 Concluding Remarks 261 References 261 8 Related Organocatalysts (1): A Proton Sponge 265 8.1 Introduction 265 8.2 Alkylation and Hetero Michael Reaction 266 8.3 Amide Formation 270 8.4 Carbon–Carbon Bond Forming Reaction 273 8.5 Palladium Catalysed Reaction 278 8.6 Concluding Remarks 282 References 282 9 Related Organocatalysts (2): Urea Derivatives 287 9.1 Introduction 287 9.2 Bisphenol as an Organoacid Catalyst 288 9.3 Urea and Thiourea as Achiral Catalysts 291 9.4 Urea and Thiourea as Chiral Catalysts 296 9.5 Concluding Remarks 305 References 306 10 Amidines and Guanidines in Natural Products and Medicines 309 10.1 Introduction 309 10.2 Natural Amidine Derivatives 309 10.3 Natural Guanidine Derivatives 313 10.4 Medicinal Amidine and Guanidine Derivatives 317 References 322 11 Perspectives 329 References 333 Index (with page links) 335 A 335 B 336 C 336 D 336 E 337 F 337 G 337 H 338 I 338 J 338 L 338 M 338 N 338 O 338 P 339 Q 339 R 339 S 339 T 340 U 340 V 340 W,Y,Z 340

Guanidines, amidines and phosphazenes have been attracting attention in organic synthesis due to their potential functionality resulting from their extremely strong basicity. They are also promising catalysts because of their potential for easy molecular modification, possible recyclability, and reduced or zero toxicity. Importantly, these molecules can be derived as natural products – valuable as scientists move towards “sustainable chemistry”, where reagents and catalysts are derived from biomaterial sources.

Superbases for Organic Synthesis is an essential guide to these important molecules for preparative organic synthesis. Topics covered include the following aspects:

• an introduction to organosuperbases

• physicochemical properties of organic superbases

• amidines and guanidines in organic synthesis

• phosphazene: preparation, reaction and catalytic role

• polymer-supported organosuperbases

• application of organosuperbases to total synthesis

• related organocatalysts: proton sponges and urea derivatives

• amidines and guanidines in natural products and medicines

Superbases for Organic Synthesis is a comprehensive, authoritative and up-to-date guide to these important reagents for organic chemists, drug discovery researchers and those interested in the chemistry of natural products.

Guanidines, amidines and phosphazenes have been attracting attention in organic synthesis due to their potential functionality resulting from their extremely strong basicity. They are also promising catalysts because of their potential for easy molecular modification, possible recyclability, and reduced or zero toxicity. Importantly, these molecules can be derived as natural products – valuable as scientists move towards "sustainable chemistry", where reagents and catalysts are derived from biomaterial sources.

Superbases for Organic Synthesis is an essential guide to these important molecules for preparative organic synthesis. Topics covered include the following aspects:

• an introduction to organosuperbases
• physicochemical properties of organic superbases
• amidines and guanidines in organic synthesis
• phosphazene: preparation, reaction and catalytic role
• polymer-supported organosuperbases
• application of organosuperbases to total synthesis
• related organocatalysts: proton sponges and urea derivatives
• amidines and guanidines in natural products and medicines

Superbases for Organic Synthesis is a comprehensive, authoritative and up-to-date guide to these important reagents for organic chemists, drug discovery researchers and those interested in the chemistry of natural products.

Guanidines, amidines and phosphazenes have been attracting attention in organic synthesis due to their potential functionality resulting from their extremely strong basicity. They are also promising catalysts because of their potential for easy molecular modification, possible recyclability, and reduced or zero toxicity. Importantly, these molecules can be derived as natural products – valuable as scientists move towards "sustainable chemistry", where reagents and catalysts are derived from biomaterial sources. Superbases for Organic Synthesis is an essential guide to these important molecules for preparative organic synthesis. Topics covered include the following aspects: an introduction to organosuperbases physicochemical properties of organic superbases amidines and guanidines in organic synthesis phosphazene: preparation, reaction and catalytic role polymer-supported organosuperbases application of organosuperbases to total synthesis related organocatalysts: proton sponges and urea derivatives amidines and guanidines in natural products and medicines Superbases for Organic Synthesis is a comprehensive, authoritative and up-to-date guide to these important reagents for organic chemists, drug discovery researchers and those interested in the chemistry of natural products. * First book dealing with the synthesis and chemistry of the superbases guanidines, amidines and phosphazenes ; widely-used tools in preparative organic chemistry * Hot topic area because of superbase's chemical properties, potential as catalysts, and derivation from sustainable biomaterial sources * Essential guide which includes details of physical properties, biological roles, synthetic applications, appearance and synthesis as natural products, and use in medicinal chemistry * "Guanidines in Organic Synthesis" was one of the top 5 most downloaded papers of 2006 in the leading organic chemistry journal Synthesis - Ishikawa is the author of that review, and develops the subject area further in this book" This work deals with the synthesis and chemistry of the superbases guanidines, amidines and phosphazenes. The book also includes details of physical properties, biological roles, synthetic applications, appearance and synthesis as natural products, and use in medicinal chemistry