Organic Reactions, Volume 114 E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Serie: Organic Reactions
• Sprache: Englisch

Veröffentlichungsjahr: 2024

Beschreibung

A carefully curated review of the scientific literature, Volume 114 of Organic Reactions presents critical discussions of widely used organic reactions or particular steps of a reaction. The material is treated from a preparative viewpoint, with emphasis on limitations, interfering influences, effects of structure and the selection of experimental techniques. The work includes tables that contain all possible examples of the reaction under consideration. Detailed procedures illustrate the significant modifications of each method. Launched in 1942, the Organic Reactions series today is a leading secondary- and tertiary-level source for organic chemists across the world.

Leseprobe

TABLE OF CONTENTS

COVER

TABLE OF CONTENTS

TITLE PAGE

COPYRIGHT

INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942

INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008

PREFACE TO VOLUME 114

CHAPTER 1: THE CLOKE–WILSON REARRANGEMENT

ACKNOWLEDGMENTS

INTRODUCTION

MECHANISM AND STEREOCHEMISTRY

SCOPE AND LIMITATIONS

APPLICATIONS TO SYNTHESIS

COMPARISON WITH OTHER METHODS

EXPERIMENTAL CONDITIONS

EXPERIMENTAL PROCEDURES

TABULAR SURVEY

REFERENCES

CHAPTER 2: THE KINUGASA REACTION

ACKNOWLEDGMENTS

INTRODUCTION

MECHANISM

STEREOCHEMISTRY AND CONSTITUTIONAL ISOMERISM

SCOPE AND LIMITATIONS

APPLICATIONS TO SYNTHESIS

COMPARISON WITH OTHER METHODS

EXPERIMENTAL CONDITIONS

EXPERIMENTAL PROCEDURES

TABULAR SURVEY

REFERENCES

CHAPTER 3: ENANTIOSELECTIVE PICTET–SPENGLER REACTIONS

ACKNOWLEDGMENTS

INTRODUCTION

MECHANISM AND STEREOCHEMISTRY

SCOPE AND LIMITATIONS

APPLICATIONS TO SYNTHESIS

COMPARISON WITH OTHER METHODS

EXPERIMENTAL CONDITIONS

EXPERIMENTAL PROCEDURES

TABULAR SURVEY

REFERENCES

SUPPLEMENTAL REFERENCES

CUMULATIVE CHAPTER TITLES BY VOLUME

AUTHOR INDEX, VOLUMES 1‐114

CHAPTER AND TOPIC INDEX, VOLUMES 1‐114

END USER LICENSE AGREEMENT

List of Illustrations

Chapter 1

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Figure 1 Modulating the reactivity of cyclopropanes.

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Chapter 2

Figure 1 Methods of β‐lactam ring construction.

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Figure 2 Stereochemical pathway of the first and the second step of the Kinu...

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Figure 3 Structures of ligands L11‐L16.

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Figure 4 Non‐racemic five‐membered cyclic nitrones 12 and 14–16, as well as ...

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Figure 5 Cyclic, five‐membered nitrones and terminal alkynes derived from su...

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Figure 6 Chiral ligands used in enantioselective Kinugasa reactions.

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Figure 7 Representative monocyclic β‐lactam antibiotics.

Figure 8 Thienamycin (54), the first member of the carbapenem family.

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Figure 9 Ezetimibe (59), a cholesterol absorption inhibitor.

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Figure 10 Chiral imines derived from α‐oxyaldehydes, α...

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Figure 11 Chiral bidentate ligands used in enantioselective Gilman–Speeter r...

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Figure 12 Chiral, dimeric rhodium(II) complexes used in intramolecular C–H i...

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Chapter 3

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Guide

COVER

TABLE OF CONTENTS

SERIES PAGE

TITLE PAGE

COPYRIGHT

INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942

INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008

PREFACE TO VOLUME 114

BEGIN READING

CUMULATIVE CHAPTER TITLES BY VOLUME

AUTHOR INDEX, VOLUMES 1‐114

CHAPTER AND TOPIC INDEX, VOLUMES 1‐114

END USER LICENSE AGREEMENT

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FORMER MEMBERS OF THE BOARD OF EDITORS AND DIRECTORS

JEFFREY AUBÉ

MARISA C. KOZLOWSKI

JOHN E. BALDWIN

STEVEN V. LEY

DALE L. BOGER

JAMES A. MARSHALL

JIN K. CHA

MICHAEL J. MARTINELLI

ANDRÉ B. CHARETTE

STUART W. MCCOMBIE

ENGELBERT CIGANEK

SCOTT J. MILLER

DENNIS CURRAN

JOHN MONTGOMERY

SAMUEL DANISHEFSKY

LARRY E. OVERMAN

HUW M. L. DAVIES

ALBERT PADWA

SCOTT E. DENMARK

T. V. RAJANBABU

VICTOR FARINA

JAMES H. RIGBY

PAUL FELDMAN

WILLIAM R. ROUSH

JOHN FRIED

TOMISLAV ROVIS

JACQUELYN GERVAY‐HAGUE

SCOTT D. RYCHNOVSKY

STEPHEN HANESSIAN

MARTIN SEMMELHACK

LOUIS HEGEDUS

CHARLES SIH

PAUL J. HERGENROTHER

AMOS B. SMITH, III

DONNA M. HURYN

BARRY M. TROST

JEFFREY S. JOHNSON

PETER WIPF

LAURA KIESSLING

FORMER MEMBERS OF THE BOARD NOW DECEASED

ROGER

ADAMS

HERBERT

O.

HOUSE

HOMER

ADKINS

JOHN

R.

JOHNSON

WERNER

E.

BACHMANN

ROBERT

M.

JOYCE

PETER

BEAK

ROBERT

C.

KELLY

ROBERT

BITTMAN

ANDREW

S.

KENDE

A. H.

BLATT

WILLY

LEIMGRUBER

VIRGIL

BOEKELHEIDE

FRANK

C.

MC

GREW

GEORGE

A.

BOSWELL

, 

JR

.

BLAINE

C.

MC

KUSICK

THEODORE

L.

CAIRNS

JERROLD

MEINWALD

ARTHUR

C.

COPE

CARL

NIEMANN

DONALD

J.

CRAM

LEO

A.

PAQUETTE

DAVID

Y.

CURTIN

GARY

H.

POSNER

WILLIAM

G.

DAUBEN

HANS

J.

REICH

LOUIS

F.

FIESER

HAROLD

R.

SNYDER

HEINZ

W.

GSCHWEND

MILÁN

USKOKOVIC

RICHARD

F.

HECK

BORIS

WEINSTEIN

RALPH

F.

HIRSCHMANN

JAMES

D.

WHITE

Organic Reactions

VOLUME 114

EDITORIAL BOARD

P. ANDREWEVANS, Editor‐in‐Chief

STEVEN M. WEINREB, Executive Editor

EDITORIAL BOARD

P.

ANDREW

EVANS

,

Editor‐in‐Chief

STEVEN

M.

WEINREB

,

Executive Editor

DAVID

B.

BERKOWITZ

BO

QU

PAUL

R.

BLAKEMORE

KEVIN

H.

SHAUGHNESSY

REBECCA

L.

GRANGE

STEVEN

D.

TOWNSEND

DENNIS

G.

HALL

BEN

W. H.

TURNBULL

JEFFREY

B.

JOHNSON

CHRISTOPHER

D.

VANDERWAL

JEFFREY

N.

JOHNSTON

MARY

P.

WATSON

JOSHUA

G.

PIERCE

BARRY B. SNIDER, Secretary

JEFFERY B. PRESS, Treasurer

DANIELLESOENEN, Editorial Coordinator

DENALINDSAY, Secretary and Processing Editor

LANDY K. BLASDEL, Processing Editor

TINAGRANT, Processing Editor

ENGELBERTCIGANEK, Editorial Advisor

ASSOCIATE EDITORS

LUISA CARRILLO

EFRAÍM REYES

MAREK CHMIELEWSKI

DANIEL SEIDEL

BARTŁOMIEJ FURMAN

SEBASTIAN STECKO

RAFEŁ KUTASZEWICZ

ARTUR ULIKOWSKI

RUBÉN MANZANO

URUE URIA

MICHAŁ MICHALAK

JOSE L. VICARIO

LIHER PRIETO

KAROL WOŁOSEWICZ

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Library of Congress Cataloging‐in‐Publication Data:

ISBN: 978‐1‐394‐19499‐5

INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942

In the course of nearly every program of research in organic chemistry, the investigator finds it necessary to use several of the better‐known synthetic reactions. To discover the optimum conditions for the application of even the most familiar one to a compound not previously subjected to the reaction often requires an extensive search of the literature; even then a series of experiments may be necessary. When the results of the investigation are published, the synthesis, which may have required months of work, is usually described without comment. The background of knowledge and experience gained in the literature search and experimentation is thus lost to those who subsequently have occasion to apply the general method. The student of preparative organic chemistry faces similar difficulties. The textbooks and laboratory manuals furnish numerous examples of the application of various syntheses, but only rarely do they convey an accurate conception of the scope and usefulness of the processes.

For many years American organic chemists have discussed these problems. The plan of compiling critical discussions of the more important reactions thus was evolved. The volumes of Organic Reactions are collections of chapters each devoted to a single reaction, or a definite phase of a reaction, of wide applicability. The authors have had experience with the processes surveyed. The subjects are presented from the preparative viewpoint, and particular attention is given to limitations, interfering influences, effects of structure, and the selection of experimental techniques. Each chapter includes several detailed procedures illustrating the significant modifications of the method. Most of these procedures have been found satisfactory by the author or one of the editors, but unlike those in Organic Syntheses, they have not been subjected to careful testing in two or more laboratories. Each chapter contains tables that include all the examples of the reaction under consideration that the author has been able to find. It is inevitable, however, that in the search of the literature some examples will be missed, especially when the reaction is used as one step in an extended synthesis. Nevertheless, the investigator will be able to use the tables and their accompanying bibliographies in place of most or all of the literature search so often required. Because of the systematic arrangement of the material in the chapters and the entries in the tables, users of the books will be able to find information desired by reference to the table of contents of the appropriate chapter. In the interest of economy, the entries in the indices have been kept to a minimum, and, in particular, the compounds listed in the tables are not repeated in the indices.

The success of this publication, which will appear periodically, depends upon the cooperation of organic chemists and their willingness to devote time and effort to the preparation of the chapters. They have manifested their interest already by the almost unanimous acceptance of invitations to contribute to the work. The editors will welcome their continued interest and their suggestions for improvements in Organic Reactions.

INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008

In the intervening years since “The Chief” wrote this introduction to the second of his publishing creations, much in the world of chemistry has changed. In particular, the last decade has witnessed a revolution in the generation, dissemination, and availability of the chemical literature with the advent of electronic publication and abstracting services. Although the exponential growth in the chemical literature was one of the motivations for the creation of Organic Reactions, Adams could never have anticipated the impact of electronic access to the literature. Yet, as often happens with visionary advances, the value of this critical resource is now even greater than at its inception.

From 1942 to the 1980's the challenge that Organic Reactions successfully addressed was the difficulty in compiling an authoritative summary of a preparatively useful organic reaction from the primary literature. Practitioners interested in executing such a reaction (or simply learning about the features, advantages, and limitations of this process) would have a valuable resource to guide their experimentation. As abstracting services, in particular Chemical Abstracts and later Beilstein, entered the electronic age, the challenge for the practitioner was no longer to locate all of the literature on the subject. However, Organic Reactions chapters are much more than a surfeit of primary references; they constitute a distillation of this avalanche of information into the knowledge needed to correctly implement a reaction. It is in this capacity, namely to provide focused, scholarly, and comprehensive overviews of a given transformation, that Organic Reactions takes on even greater significance for the practice of chemical experimentation in the 21st century.

Adams' description of the content of the intended chapters is still remarkably relevant today. The development of new chemical reactions over the past decades has greatly accelerated and has embraced more sophisticated reagents derived from elements representing all reaches of the Periodic Table. Accordingly, the successful implementation of these transformations requires more stringent adherence to important experimental details and conditions. The suitability of a given reaction for an unknown application is best judged from the informed vantage point provided by precedent and guidelines offered by a knowledgeable author.

As Adams clearly understood, the ultimate success of the enterprise depends on the willingness of organic chemists to devote their time and efforts to the preparation of chapters. The fact that, at the dawn of the 21st century, the series continues to thrive is fitting testimony to those chemists whose contributions serve as the foundation of this edifice. Chemists who are considering the preparation of a manuscript for submission to Organic Reactions are urged to contact the Editor‐in‐Chief.

PREFACE TO VOLUME 114

The precision of naming takes away from the uniqueness of seeing.

Pierre Bonnard, Painter

An eponym honors and acknowledges a significant accomplishment by naming it after a person, object, or location. Today, we use eponyms for all manner of things and even to navigate – specific landmarks make something instantly recognizable and thus simplify directions (e.g., the Eiffel Tower, the Taj Mahal, Summer Palace, London Bridge, etc). Every aspect of modern life is now replete with examples, including science, medicine, technology, politics, literature, etc. The eponym is particularly important as a shorthand in many aspects of science, albeit there is often a primary and secondary hierarchy to enable scientists to precisely identify the relevant research more efficiently. Indeed, eponyms have become a so‐called second language and are often a major component of the jargon that is so pervasive in many scientific fields. In organic chemistry, the naming of organic reactions has become a central theme that can be traced back to the nineteenth century, although the assignment of names can be controversial because, unlike the science it represents, it is based on many factors and is often subjective because the name(s) can reflect a different stage in a reaction's development! For instance, the first name reaction is the 1870 Lieben Haloform Reaction, although it was first reported by Georges‐Simon Serullas in 1822. Nevertheless, the name reaction is now a central part of the language of organic chemistry in which the reaction type is sometimes added to further identify the process (e.g., Cope Rearrangement, Friedel‐Crafts Acylation, Stille Cross‐Coupling, etc.). In some cases, multiple names are used because of concurrent contributions (e.g., Buchwald‐Hartwig Amination) or to recognize further developments of a specific process (e.g., Horner‐Wadsworth‐Emmons Wittig Olefination). The name reaction thus describes a kind of prototypical process in the context of the changes in bonding; however, the specific context is dramatically different and, as such, aligns with Bonnard's vision that the precision of naming is not a substitute for the uniqueness of seeing. Although the name can provide instant recognition, some of the more obscure processes are not as easily identified. Furthermore, the names can often be misleading and thereby lead to the amplification of a misconception about the origin of a process. Despite the pros and cons of name reactions, they have become a critical aspect of the language of organic chemistry and represent the essence of Organic Reactions, a preeminent reference work for the synthetic organic chemistry community that curates all the examples of a particular reaction to illustrate the breadth of the process. This volume contains three chapters on name reactions: the Cloke–Wilson Rearrangement, the Kinugasa reaction, and the Pictet–Spengler reaction.

The first chapter by Efraím Reyes, Liher Prieto, Rubén Manzano, Luisa Carrillo, Uxue Uria, and Jose L. Vicario provides a detailed account of the Cloke–Wilson Rearrangement, which is the heteroatom equivalent of the vinylcyclopropane‐cyclopentene rearrangement to afford heterocycles. The reaction is named after the seminal reports by Cloke and Wilson in 1929 and 1947, respectively. The former reported the rearrangement of the imine of cyclopropyl phenyl ketone at 200 °C to afford 2‐phenylpyrroline, whereas the latter described the preparation of 2,3‐dihydrofuran through the thermal rearrangement of cyclopropanecarboxaldehyde at 375–500 °C. These examples illustrate that the rearrangement of cyclopropanes requires high temperatures despite their inherent ring and torsional strain, which has prompted the examination of the factors that permit milder reaction conditions. To this end, the addition of substituents that either increase ring strain or the polarity of the C‐C bond (e.g., donor‐acceptor cyclopropanes) has been examined. Alternatively, activating the cyclopropane with various reagents and catalysts has further broadened the scope to permit the rearrangement to proceed under milder conditions.

The Mechanism and Stereochemistry section outlines thermal and photochemical rearrangements that proceed through either a concerted or a biradical process depending on the cyclopropane structure, making this aspect challenging to control. For instance, adding donor and acceptor substituents lowers the barrier for the rearrangements, which are stereoselective rather than stereospecific, because of the biradical character of the reactive intermediate. The photochemical reactions proceed at room temperature and have been theoretically corroborated to involve biradical intermediates. This section also describes a series of Lewis acid‐ or Brønsted acid‐catalyzed reactions that proceed in a stepwise manner through zwitterionic intermediates. Notably, the formation of an achiral intermediate enables a chiral Brønsted acid catalyst to facilitate the only enantioselective variant of this process. The Lewis base mediated reactions utilizing a stoichiometric promoter or catalyst have also been explored to facilitate stereospecific rearrangements. The Scope and Limitations section describes using the Cloke–Wilson Rearrangement to prepare dihydrofurans, dihydropyrroles, dihydrothiophenes, and dihydroisoxazole‐2‐oxides. The first two sections are further subdivided into the type of carbonyl functionality employed (e.g., aldehydes, ketones, carboxylates, carboxamides, etc.), including variations in substitution on these substrates. The section is completed with the sulfa‐ and nitro‐variants of the Cloke–Wilson rearrangement, which are rare and thus may well provide future opportunities for reaction development.

The Applications to Synthesis section provides excellent examples that showcase the various adaptations of the rearrangement in the total synthesis of natural products to prepare an array of oxygen and nitrogen heterocycles. The Comparison with Other Methods section delineates several alternative approaches to unsaturated five‐membered heterocycles, including dihydrofurans, pyrrolines, and dihydrothiophenes. There is also an extensive discussion of cycloadditions and sequential processes that afford similar heterocycles. The Tabular Survey is primarily organized in terms of the heterocyclic product formed and then by the nature of the starting cyclopropane substrate. Overall, this is an excellent chapter on an important reaction that will be invaluable to anyone interested in this transformation.

The second chapter by Marek Chmielewski, Rafał Kutaszewicz, Artur Ulikowski, Michał Michalak, Karol Wołosewicz, Sebastian Stecko, and Bartłomiej Furman provides a detailed account of the historical development of the Kinugasa reaction, which is the union of copper acetylides with nitrones to afford β‐lactams. Kinugasa and Hashimoto described the first example of this process in 1972 using copper phenyl acetylide and several diaryl nitrones to afford cis‐disubstituted β‐lactams. Even though the reaction affords the appropriate stereochemistry for preparing a wide range of clinically important antibiotics, has excellent atom‐economy, and employs stable starting materials, the reaction lay dormant for nearly three decades! Although copper acetylides were widely utilized in Sonogashira and Glaser couplings that were prevalent at the same time, they were ignored as coupling partners for nitrones in 1,3‐dipolar cycloadditions. The renaissance of this transformation has been ascribed to the independent development of the copper‐catalyzed Huigsen cycloaddition (CuAAC) by Meldal and Sharpless. Notably, the Sonogashira reaction is the subject of an upcoming chapter in Organic Reactions.

The Mechanism and Stereochemistry section outlines several possible mechanistic pathways that involve a 1,3‐dipolar cycloaddition followed by a rearrangement. Although theoretical and experimental studies support a ketene‐based pathway, two mechanistic variants for this process are presented. A third mechanistic possibility is also outlined, which involves an initial [3+2] cycloaddition (to form an isoxazoline), followed by a [3+2] cycloreversion and a Staudinger‐type [2+2] cycloaddition, albeit this model does not explain the stereochemical outcome. The section on stereochemistry and constitutional isomerism delineates the origin of stereocontrol and the influence of substituents, including their effect on enantioselectivity. The section is further subdivided into the impact of a stereocenter in either the alkyne or nitrone fragments, including the influence of stereochemistry in both components in the context of matched and mismatched combinations. The section is completed with a discussion of several enantioselective variants that deliver both cis‐ and trans‐cycloadducts. A very attractive aspect of this chapter is that the authors have meticulously delineated the origin of stereocontrol in every aspect of this process, which will be invaluable to the reader. The Scope and Limitations section is subdivided by the type of nitrone, namely diaryl nitrones (achiral‐ and chiral‐based substituents), other acyclic variants, and five‐ and six‐membered cyclic nitrones. The section on five‐membered derivatives is further split into achiral and chiral nitrones reacting with achiral and chiral alkynes, which provides a guide to the stereochemical possibilities. This chapter section also extensively discusses enantioselective and intermolecular Kinugasa reactions.

The section on Applications to Synthesis provides examples of using the methodology to prepare some important natural products and pharmaceutically relevant targets. The Comparison with Other Methods section describes the most widely used alternative methods for assembling β‐lactams, including cycloaddition, cyclization, carbenoid insertion, and ring expansion reactions. The Tabular Survey mirrors the Scope and Limitations section in that the primary rubric is based on the type of nitrone employed, followed by the corresponding alkyne, which makes analyzing the tables effortless for the reader. Overall, this is a very important chapter that I believe will be of significant interest to heterocyclic and medicinal chemists.

The third chapter by Daniel Seidel outlines the development of the enantioselective Pictet–Spengler reaction, which involves the condensation of a ketone or aldehyde with an amine that is tethered to an aryl group to promote intramolecular addition to the iminium ion with concomitant rearomatization. Hence, the reaction is often envisioned as an intramolecular variant of the Mannich and Friedel‐Crafts reactions that represents an important method for preparing a variety of alkaloids. The first Pictet–Spengler reaction was reported in 1911 by Amé Pictet and Theodor Spengler and involved the acid‐promoted condensation of β‐phenylethylamine and dimethoxymethane to form tetrahydroisoquinoline. This process is also feasible with electron‐rich heteroaromatic derivatives, such as indoles and pyrroles, which proceed under milder reaction conditions. An early example of the heteroaromatic variant involved the condensation of tryptamine and paraldehyde to afford 1‐methyltryptoline. More recently, the enzyme‐catalyzed variant that proceeds under relatively mild reaction conditions has been reported, which extends the scope of this venerable process.

The Mechanism and Stereochemistry section delineates two convergent pathways: a 6‐endo‐trig ring‐closure followed by elimination or an alternative 5‐endo‐trig with a 1,2‐alkyl shift. Although theoretical studies support the former process, recent work provides insight into factors that can switch the process to favor the latter pathway. The section is then split by Lewis Acid promoters based on BINOL and pseudoephedrine, in addition to a section on Brønsted acid variants. The latter section includes Brønsted acid catalysts derived from chiral ureas that have been successfully implemented in this process. It also describes the enantioselective acyl‐Pictet Spengler reaction, which involves the intermediacy of an N‐acyliminium ion using chiral ureas and chiral phosphoric acid as organocatalysts. A model for asymmetric induction accompanies each method to guide the reader and thus provide insight into developing new variants. The Scope and Limitations section is organized in the context of stoichiometric Lewis acid‐promoted reactions followed by catalytic methods. Notably, the latter section is more extensive and further subdivided by the substrate and the type of catalyst (vide supra). For instance, the section is split into the asymmetric reactions of tryptamines, β‐phenethylamines and related reactions with the various organocatalysts, including dual catalysis. The chapter also has a section on catalytic cascade reactions that feature an enantioselective Pictet–Spengler reaction.

The Applications to Synthesis section illustrates the breadth of this process in complex alkaloid synthesis to provide the reader with an appreciation of the synthetic utility of this transformation. The Comparison with Other Methods section describes the related enantioselective methods, which involve the asymmetric reduction and addition to cyclic imines, in which the latter are either preformed or generated in situ through oxidation. The Tabular Survey parallels the Scope and Limitations section in the context of substrates to facilitate identifying a specific process of interest. This chapter gives the reader an excellent perspective on the development of enantioselective variants of this venerable reaction.

I want to take this opportunity to thank Dr. Joseph S. Ward for the creation of the new Organic Reactions website (https://www.organicreactions.org) and Dr. Michael J. Evans for transferring and maintaining the content. We hope the new site will make it easier to find content and provide a better interface with the Organic Reactions readership. I also want to acknowledge Dr. Angie R. Angeles for her continued outreach efforts to promote Organic Reactions, including the new website. Her efforts have improved our visibility with younger members of the community who may not be acquainted with this venerable publication. I am sure Roger Adams would approve of the recent changes and be proud that after 80+ years, the publication he initiated is still an essential resource for practicing synthetic organic chemists in academia and industry.

I would be remiss if I did not acknowledge the entire Organic Reactions Editorial Board for their collective efforts in steering this volume through the various stages of the editorial process. I thank Christopher D. Vanderwal (Chapter 1), Jeffrey B. Johnson (Chapter 2), and Paul R. Blakemore (Chapter 3), who served as the Responsible Editors to marshal the chapters through the various phases of development. I am also deeply indebted to Dr. Danielle Soenen for her continued and heroic efforts as the Editorial Coordinator; her knowledge of Organic Reactions is critical to maintaining consistency in the series. Dr. Dena Lindsay (Secretary to the Editorial Board) is thanked for coordinating the contributions of the authors, editors, and publishers. In addition, the Organic Reactions enterprise could not maintain the quality of production without the efforts of Dr. Steven M. Weinreb (Executive Editor), Dr. Engelbert Ciganek (Editorial Advisor), Dr. Landy Blasdel (Processing Editor), and Dr. Tina Grant (Processing Editor). I would also like to acknowledge Dr. Barry B. Snider (Secretary) for keeping everyone on task and Dr. Jeffery Press (Treasurer) for ensuring we remain fiscally solvent!

I am also indebted to past and present members of the Board of Editors and Board of Directors for ensuring the enduring quality of Organic Reactions. The distinctive format of the chapters, in conjunction with the curated tables of examples, makes this series of reviews both unique and exceptionally valuable to the practicing synthetic organic chemist.

P. Andrew Evans

Kingston

Ontario, Canada

CHAPTER 1THE CLOKE–WILSON REARRANGEMENT

EFRAÍM REYES, LIHER PRIETO, RUBÉN MANZANO, LUISA CARRILLO, UXUE URIA AND JOSE L. VICARIO

Department of Organic and Inorganic Chemistry, Faculty of Science and Technology, University of the Basque Country, UPV/EHU, E‐48080, Bilbao, Spain

Edited by CHRIS VANDERWAL

CONTENTS

ACKNOWLEDGMENTS

INTRODUCTION

MECHANISM AND STEREOCHEMISTRY

Thermal and Photochemical Cloke–Wilson Rearrangements: Concerted or Biradical Processes

Lewis or Brønsted Acid Promoted Cloke–Wilson Rearrangement: Stepwise Processes

Lewis Base Promoted Cloke–Wilson Rearrangement: Stepwise Processes

SCOPE AND LIMITATIONS

The Cloke–Wilson Rearrangement for the Synthesis of Dihydrofurans

Rearrangement of Cyclopropanecarbaldehydes

Rearrangement of Cyclopropyl Ketones

Acylcyclopropane Substrates

1,1‐Diacylcyclopropane Substrates

1‐Alkoxycarbonyl‐, 1‐Amidocarbonyl‐, 1‐Sulfonyl‐ and 1‐Cyanocyclopropyl Ketone Substrates

Rearrangement of Cyclopropanecarboxylates

Cyclopropane‐1,1‐dicarboxylate Substrates

Rearrangement of Cyclopropanecarboxamides

The Aza‐Cloke–Wilson Rearrangement for the Synthesis of Dihydropyrroles

Rearrangement of Cyclopropyl Aldimines

Rearrangement of Cyclopropyl Ketimines

Rearrangement of Cyclopropanecarboxamides and Related Compounds

Rearrangement of Cyclopropyl Azoles

The Sulfa‐Cloke–Wilson Rearrangement for the Synthesis of Dihydrothiophenes

The Nitro‐Cloke–Wilson Rearrangement for the Synthesis of Dihydroisoxazole‐2‐oxides

APPLICATIONS TO SYNTHESIS

(+)‐Norrisolide

Cuspidan B

(+)‐Dodecan‐4‐olide

(+)‐Dihydropyrenolide D

Berkelic Acid Core

Formal Synthesis of (±)‐Aspidospermine

Formal Synthesis of (±)‐Mesembrine

(±)‐Dehydrotubifoline

COMPARISON WITH OTHER METHODS

EXPERIMENTAL CONDITIONS

Thermal Cloke–Wilson Rearrangement

Lewis Acid or Brønsted Acid Catalyzed/Promoted Cloke–Wilson Rearrangement

Lewis Base Catalyzed/Promoted Cloke–Wilson Rearrangement

Cloke–Wilson Rearrangement under Organometallic Activation

EXPERIMENTAL PROCEDURES

3‐(

trans

‐4‐Acetyl‐2‐phenyl‐2,3‐dihydrofuran‐3‐yl)‐6‐methyl‐4

H

‐chromen‐4‐one [Cloke–Wilson Rearrangement of a 1,1‐Diacylcyclopropane under Thermal Conditions].

1‐(2‐Methyl‐5‐ethenyl‐4,5‐dihydrofuran‐3‐yl)ethan‐1‐one [Ni(0)‐Catalyzed Cloke–Wilson Rearrangement of a 1,1‐Diacyl‐2‐vinylcyclopropane]

(2,5‐Diphenyl‐4,5‐dihydrofuran‐3‐yl)(phenyl)methanone [DABCO‐Catalyzed Cloke–Wilson Rearrangement of a 1,1‐Diacylcyclopropane]

2‐Phenyl‐3,5,6,7‐tetrahydrobenzofuran‐4(2

H

)‐one [

p‐

TsOH‐Catalyzed Cloke–Wilson Rearrangement of a 1,1‐Diacylcyclopropane]

Benzyl (

S

)‐5‐(4‐methoxyphenyl)‐2‐methyl‐4,5‐dihydrofuran‐3‐carboxylate [Chiral‐Acid‐Catalyzed Enantioselective Cloke–Wilson Rearrangement of a 1‐Alkoxycarbonylcyclopropyl Ketone]

Methyl 5‐[(

tert

‐butyldiphenylsilyl)methyl]‐2‐methoxy‐4,5‐dihydrofuran‐3‐carboxylate [TiCl

4

‐Promoted Cloke–Wilson Rearrangement of a Cyclopropane‐1,1‐dicarboxylate]

(5

S

)‐5‐Phenyldihydrofuran‐2(3

H

)‐one [LiCl/Me

3

N⋅HCl‐Promoted Cloke–Wilson Rearrangement of a Cyclopropane Hemimalonate]

Benzyl Benzyl[(6

S

,8a

R

)‐octahydroindolizin‐6‐yl]carbamate [NH

4

Cl‐Promoted Aza‐Cloke–Wilson Rearrangement of a Cyclopropyl Ketimine]

1,2,5‐Triphenyl‐4,5‐dihydro‐1

H

‐pyrrole‐3‐carbonitrile [Aza‐Cloke–Wilson Rearrangement of a Cyclopropyl Ketimine under Thermal Conditions]

Methyl 1‐Benzyl‐2,5‐diphenyl‐4,5‐dihydro‐1

H

‐pyrrole‐3‐carboxylate [Ni(ClO

4

)

2

⋅6H

2

O‐Promoted Aza‐Cloke–Wilson Rearrangement of a Cyclopropyl Ketimine]

TABULAR SURVEY

Chart 1. Ligands and Catalysts Used in the Tables

Table 1. Cloke‐Wilson Rearrangement for the Synthesis of Dihydrofurans

Table 1A. Cloke‐Wilson Rearrangement of Cyclopropanecarbaldehydes

Table 1B. Cloke‐Wilson Rearrangement of Cyclopropyl Ketones

Table 1C. Cloke‐Wilson Rearrangement of Cyclopropanecarboxylates

Table 1D. Cloke‐Wilson Rearrangement of Cyclopropanecarboxamides

Table 2. Aza‐Cloke‐Wilson Rearrangement for the Synthesis of Dihydropyrroles

Table 2A. Aza‐Cloke‐Wilson Rearrangement of Cyclopropyl Aldimines

Table 2B. Aza‐Cloke‐Wilson Rearrangement of Cyclopropyl Ketimines

Table 2C. Aza‐Cloke‐Wilson Rearrangement of Cyclopropanecarboxamides and Related Compounds

Table 2D. Aza‐Cloke‐Wilson Rearrangement of Cyclopropyl Azoles

Table 3. Sulfa‐Cloke‐Wilson Rearrangement for the Synthesis of Dihydrothiophenes

Table 4. Nitro‐Cloke‐Wilson Rearrangement for the Synthesis of Dihydroisoxazole-2-oxides

REFERENCES

ACKNOWLEDGMENTS

The authors thank the Spanish MCIU (FEDER‐PID2020‐118422‐GB‐I00) and the Basque Regional Government (IT908‐16 and postdoctoral contract to R. M.) for financial support.

INTRODUCTION

Cyclopropanes that are directly substituted with carbonyl, thiocarbonyl, or imino groups undergo Cloke–Wilson rearrangement under diverse reaction conditions to provide dihydrofurans, dihydrothiophenes, or dihydropyrroles, respectively (Scheme 1). This reaction can also be regarded as the heteroatom equivalent of the vinylcyclopropane rearrangement1,2 that relies on the release of ring strain to facilitate ring opening, which ultimately leads to the formation of significantly less‐strained five‐membered heterocyclic compounds.

Scheme 1

The reaction is named after the authors who published the first two seminal reports: in 1929, Cloke reported the formation of 2‐phenylpyrroline (2) by heating cyclopropyl phenyl ketimine (1) at 195–200 °C (Scheme 2);3 some years later, the thermal rearrangement of cyclopropanecarbaldehyde (3) to 2,3‐dihydrofuran (4) was described by Wilson (Scheme 3).4

Scheme 2

Scheme 3

Despite their inherent high ring and torsional strain, cyclopropanes are kinetically rather inert, as seen by the harsh reaction conditions that are required to facilitate the rearrangement. Consequently, most studies of this reaction have focused upon identifying milder reaction conditions. One approach has been to incorporate additional substituents into the cyclopropane scaffold that could facilitate the rearrangement process, either by increasing the ring strain (e.g., using alkylidenecyclopropanes as substrates)5–9 or by increasing the polarity of the C–C bond undergoing cleavage during the rearrangement process (Fig. 1). One of the best examples of this strategy involves using cyclopropanes with an electron‐withdrawing and an electron‐donating substituent at vicinal positions, which results in donor‐acceptor cyclopropanes.10 The second approach involves the use of external reagents able to activate the cyclopropane and thereby facilitate the rearrangement process. This concept has led to the identification of suitable catalysts or promoters for this reaction, which are, in the broadest sense, either Brønsted acids, Lewis acids, Lewis bases, or organometallic complexes. All these advances have contributed to broadening the scope of this transformation and to demonstrating its potential applicability as a general tool for the synthesis of densely functionalized dihydrofurans, dihydrothiophenes, dihydropyrroles, and related scaffolds.

Figure 1 Modulating the reactivity of cyclopropanes.

This chapter covers the entire range of reaction manifolds for the Cloke–Wilson rearrangement that have been developed since the first examples of the reaction were reported. Heteroatom variants such as the analogous aza‐ and sulfa‐Cloke–Wilson rearrangement are also included. Although a range of reviews have been published in related areas, no review has focused completely on the Cloke–Wilson reaction and all of its variants. Several general reviews have been published covering the chemistry of cyclopropanes11–17 and their use in synthesis.18–22 In addition, the reactivity of electrophilic23 or nucleophilic24 cyclopropanes has also been highlighted and the particular behavior of donor‐acceptor cyclopropanes has received special attention in recent years.25–37 More focused reviews of the chemistry of acyl‐substituted cyclopropanes or the corresponding imines have also been published,38,39 and the most relevant advances regarding the reactivity of vinylcyclopropanes40–42 and the vinylcyclopropane rearrangement2 have also been reviewed.

MECHANISM AND STEREOCHEMISTRY

The mechanism of the Cloke–Wilson rearrangement varies depending on the reaction conditions employed for the activation of the starting material. Nevertheless, the number of detailed studies directed towards the elucidation of the mechanism of this reaction is very limited and are focused on explaining the outcome of the reaction, based on the particular structure of the starting cyclopropane substrate and the influence of the substitution pattern, rather than the elucidation of the mechanistic pathway for the reaction.

Thermal and Photochemical Cloke–Wilson Rearrangements: Concerted or Biradical Processes

For reactions occurring under thermal activation, a concerted mechanism is typically proposed. The C–C bond cleavage of the cyclopropane ring‐opening event is proposed to take place simultaneously with formation of the C–O bond, wherein one of the carbonyl electron lone‐pairs is involved, leading to the final five‐membered heterocyclic product (Scheme 4). The overall process is thermodynamically favored due to the release of ring strain from the conversion of the starting three‐membered carbocycle to the five‐membered heterocyclic adduct.

Scheme 4

The high kinetic stability of simple unsubstituted cyclopropyl ketones and imines generally requires harsh reaction conditions for the rearrangement, such as those employed initially by Cloke and Wilson in their seminal studies (Schemes 2 and 3). A critical development in this process stemmed from recognizing that placing an electron‐donating substituent R2 vicinal to the electron‐withdrawing acyl substituent on the cyclopropane creates a push‐pull effect, which leads to increased polarization of the C–C bond that undergoes ring cleavage, thus facilitating the rearrangement process.

The key role played by the electron‐donating substituent in accelerating the Cloke–Wilson rearrangement has been studied by computational methods.43,44 These studies indicate a clear trend, in which increasing the electron‐donating nature of the R2 group and the electron‐withdrawing nature of the acyl group leads to a kinetically more‐favored process. Incorporating additional donor or acceptor substituents further lowers the calculated activation energies for the rearrangement process.44 This study also points towards the fact that simple phenyl or methyl substituents provide enough electron donation for a reaction to be feasible under relatively mild reaction conditions.

Calculations also reveal similar activation energies for the reaction with either the cis‐ or trans‐substituted donor‐acceptor cyclopropanes. Despite these computational studies, there is no definitive experimental evidence demonstrating that chiral information is transferred from the starting material to the final product under thermal conditions. However, the employment of an enantioenriched cyclopropane substrate has been used in many cases to confirm or disprove whether a particular Cloke–Wilson rearrangement has proceeded through a concerted reaction pathway.

Other studies have proposed that the transition‐state structures have biradical character in the concerted rearrangement process, which parallels the mechanism considered for the related vinylcyclopropane–cyclopentene rearrangement.2,45,46 In particular, the rearrangement of a variety of diastereomerically pure, racemic polysubstituted cyclopropyl methyl ketones 5