Organic Reactions, Volume 112, Parts A and B E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Serie: Organic Reactions
- Sprache: Englisch
A carefully curated review of the scientific literature, Volume 112 of Organic Reactions commemorates the 50th anniversary of the Ugi reaction. It explores the practical and theoretical aspects of one of the most widely used reactions in organic chemistry, focusing on the main Ugi reaction as well as on its many variants. This volume is published in two parts, A and B. Launched in 1942, the Organic Reactions series today is a leading secondary- and tertiary-level source for organic chemists across the world.
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Seitenzahl: 396
Veröffentlichungsjahr: 2023
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Table of Contents
COVER
Title Page
COPYRIGHT
INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942
INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008
PREFACE TO VOLUME 112
ROBERT CHARLES KELLY NOVEMBER 28, 1939 – MAY 22, 2022
Volume 112a
CHAPTER 1: A HALF‐CENTURY OF THE UGI REACTION: CLASSIC VARIANT
INTRODUCTION
MECHANISM AND STEREOCHEMISTRY
SCOPE AND LIMITATIONS
APPLICATIONS TO SYNTHESIS
COMPARISON WITH OTHER METHODS
EXPERIMENTAL CONDITIONS
EXPERIMENTAL PROCEDURES
TABULAR SURVEY
REFERENCES
Volume 112b
CHAPTER 2: A HALF‐CENTURY OF THE UGI REACTION: MODIFIED VARIANTS
INTRODUCTION
MECHANISM AND STEREOCHEMISTY
SCOPE AND LIMITATIONS
APPLICATIONS TO SYNTHESIS
COMPARISON WITH OTHER METHODS
EXPERIMENTAL CONDITIONS
EXPERIMENTAL PROCEDURES
TABULAR SURVEY
REFERENCES
CUMULATIVE CHAPTER TITLES BY VOLUME
AUTHOR INDEX, VOLUMES 1–112
CHAPTER AND TOPIC INDEX, VOLUMES 1–112
END USER LICENSE AGREEMENT
List of Illustrations
Chapter 1
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11
Scheme 12
Scheme 13
Scheme 14
Scheme 15
Scheme 16
Scheme 17
Scheme 18
Scheme 19
Scheme 20
Scheme 21
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Scheme 50
Scheme 51
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Scheme 53
Scheme 54
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Scheme 56
Scheme 57
Scheme 58
Scheme 59
Scheme 60
Scheme 61
Scheme 62
Scheme 63
Scheme 64
Scheme 65
Chapter 2
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11
Scheme 12
Scheme 13
Scheme 14
Scheme 15
Scheme 16
Scheme 17
Scheme 18
Scheme 19
Scheme 20
Scheme 21
Scheme 22
Scheme 23
Scheme 24
Scheme 25
Scheme 26
Scheme 27
Scheme 28
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Scheme 32
Scheme 33
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Scheme 48
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Scheme 50
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Scheme 54
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Scheme 65
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Scheme 106
Scheme 107
Scheme 108
Scheme 109
Scheme 110
Scheme 111
Scheme 112
Scheme 113
Scheme 114
Guide
Cover
Table of Contents
Series Page
Title Page
Title Page
Copyright
INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942
INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008
PREFACE TO VOLUME 112
ROBERT CHARLES KELLY NOVEMBER 28, 1939 – MAY 22, 2022
Begin Reading
AUTHOR INDEX, VOLUMES 1–112
CHAPTER AND TOPIC INDEX, VOLUMES 1–112
WILEY END USER LICENSE AGREEMENT
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FORMER MEMBERS OF THE BOARD OF EDITORS AND DIRECTORS
JOHN
E.
BALDWIN
MARISA
C.
KOZLOWSKI
DALE
L.
BOGER
STEVEN
V.
LEY
JIN
K.
CHA
JAMES
A.
MARSHALL
ANDRÉ
B.
CHARETTE
MICHAEL
J.
MARTINELLI
ENGELBERT
CIGANEK
STUART
W.
MCCOMBIE
DENNIS
CURRAN
SCOTT
J.
MILLER
SAMUEL
DANISHEFSKY
JOHN
MONTGOMERY
HUW
M. L.
DAVIES
LARRY
E.
OVERMAN
SCOTT
E.
DENMARK
ALBERT
PADWA
VICTOR
FARINA
T. V.
RAJANBABU
PAUL
FELDMAN
JAMES
H.
RIGBY
JOHN
FRIED
WILLIAM
R.
ROUSH
JACQUELYN
GERVAY
‐
HAGUE
TOMISLAV
ROVIS
STEPHEN
HANESSIAN
SCOTT
D.
RYCHNOVSKY
LOUIS
HEGEDUS
MARTIN
SEMMELHACK
PAUL
J.
HERGENROTHER
CHARLES
SIH
DONNA
M.
HURYN
AMOS
B.
SMITH
, III
JEFFREY
S.
JOHNSON
BARRY
M.
TROST
LAURA
KIESSLING
PETER
WIPF
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 112a
EDITORIAL BOARD
P. ANDREWEVANS, Editor‐in‐Chief
STEVEN M. WEINREB, Executive Editor
JEFFREY
AUBÉ
JOSHUA
G.
PIERCE
DAVID
B.
BERKOWITZ
BO
QU
PAUL
R.
BLAKEMORE
JENNIFER
M.
SCHOMAKER
REBECCA
L.
GRANGE
KEVIN
H.
SHAUGHNESSY
DENNIS
G.
HALL
STEVEN
D.
TOWNSEND
JEFFREY
B.
JOHNSON
CHRISTOPHER
D.
VANDERWAL
JEFFREY
N.
JOHNSTON
MARY
P.
WATSON
STEFAN
LUTZ
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
ULI KAZMAIER
ANGELIKA ULLRICH
Organic Reactions
VOLUME 112b
EDITORIAL BOARD
P. ANDREWEVANS, Editor‐in‐Chief
STEVEN M. WEINREB, Executive Editor
JEFFREY
AUBÉ
JOSHUA
G.
PIERCE
DAVID
B.
BERKOWITZ
BO
QU
PAUL
R.
BLAKEMORE
JENNIFER
M.
SCHOMAKER
REBECCA
L.
GRANGE
KEVIN
H.
SHAUGHNESSY
DENNIS
G.
HALL
STEVEN
D.
TOWNSEND
JEFFREY
B.
JOHNSON
CHRISTOPHER
D.
VANDERWAL
JEFFREY
N.
JOHNSTON
MARY
P.
WATSON
STEFAN
LUTZ
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
ULI KAZMAIER
ANGELIKA ULLRICH
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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 112
Looking for a Needle in a Haystack
Washington Irving, 1808
The preparation and identification of functional molecules with specific properties is a challenging and time‐consuming process that is analogous to “finding a needle in a haystack,” the modern version of Sir Thomas More's 1532 idiom looking for “a needle in a meadow.” Interestingly, the idiom's origin can be traced to Arab and Chinese proverbs that date back over 2000 years in the latter case. The modern version is from 1808 in Part 20 of Salmagundi by Washington Irving and others and can be used to describe many aspects of scientific discovery, which is often an arduous and frustrating process. Consequently, developing methods that circumvent the challenges associated with conventional discovery methods aligns with science fiction author Keith DeCandido's notion of “just bring a magnet” to find the needle! For example, drug discovery inspired the development of high‐throughput screening techniques that enable the simultaneous analysis of thousands of compounds to identify those with the right properties for lead development. In this context, the specific biological target behaves as the “magnet” to identify the so‐called “needle.” Although the requirement of analyzing many compounds may be counterintuitive, automation eliminates the mundane task of removing one straw at a time. Combinatorial synthesis is another excellent example of generating thousands of compounds to ensure the “haystack” contains the “needle” to permit detailed structure‐activity relationship studies for lead optimization.
The Organic Reactions series is distinct in that it curates all the information on a specific transformation and thus provides a unique way of “finding a needle in a haystack.” When founding Organic Reactions eighty years ago, Roger Adams recognized that much of the relevant information and know‐how was often available; however, identifying and translating this uniformly across the chemical research landscape was quite challenging. Moreover, he appreciated that consistently organizing the data in a single venue had significant merit well before the advent of computers and the associated search engines. To this end, the authors generally tabulate all the known examples of a transformation to permit the interrogation of a proposed process, thereby allowing one to determine its feasibility on a specific substrate. Despite all the progress in chemical informatics, Organic Reactions still represents a unique resource that provides the proverbial “magnet” to “find the needle” and can thereby mitigate hours of arduous investigation. The chapters also delineate the mechanistic and experimental nuances that are equally important to the practicing synthetic organic chemist, which permits the development of adaptations to expand the scope and define the limitations of the process. The two chapters in this volume by Angelika Ullrich and Uli Kazmaier delineate half a century of the Ugi and related reactions, which provide the community with an outstanding resource on this important multicomponent reaction and its associated variations.
The first chapter describes the classic four‐component Ugi reaction, which combines a carboxylic acid, a carbonyl compound, an amine, and an isocyanide to prepare α‐amino acids and peptides. The introduction provides an overview of the kinetic and thermodynamic features of three types of multicomponent reactions and their relevance to reactions that employ isocyanates. For instance, Passerini and coworkers described the first three‐component process that combines an isocyanate with a carboxylic acid and a carbonyl compound to afford α‐acyloxycarboxamides in the 1920s. An initial impediment to the broad adoption of the Passerini reaction was the limited availability of isocyanates, which Ugi resolved in 1958 by using a formamide dehydration reaction that ultimately led to the Ugi adaptation of including an amine as the fourth component.
The Mechanism and Stereochemistry section outlines the currently accepted mechanism that Ugi originally postulated in 1967, which is supported by kinetic data and calculations. The section also defines stereoselective Ugi reactions, which are rare since the reaction tends to afford mixtures of stereoisomers. Fortunately, this seeming drawback can in fact be an asset in drug discovery where both diastereoisomers may be of interest. Nevertheless, the chapter nicely documents the key to achieving good stereocontrol, which tends to rely on amines with cleavable chiral groups analogous to a classic chiral auxiliary.
The Scope and Limitations section is organized by the substrate (e.g., isocyanide, carbonyl compounds and preformed imines, carboxylic acids, and amines), which acts as an intuitive guide for selecting reaction conditions. For example, the type of isocyanide is subdivided into cleavable and convertible isocyanides, where the amide is not the desired product. The carbonyl component includes formaldehyde, aldehydes, and ketones, traversing the entire functionalization array from methylene to quaternary centers. The section on aldehydes with α‐leaving groups permits access to β‐functionalized α‐amino acid derivatives. The carboxylic acid component is remarkably versatile, in that aryl, alkyl, and α,β‐unsaturated acids can be employed. Finally, the process is optimal with primary amines, including ammonia, cleavable amines, unsaturated amines, hydrazines, and hydroxylamines. Notably, secondary amines do not undergo the acyl shift and are covered in the accompanying chapter on the modified Ugi reaction.
The Applications to Synthesis section describes selected applications for preparing drugs and drug‐like molecules, including several natural products. The Comparison with Other Methods section compares the Ugi and Passerini reactions and briefly surveys the standard methods for preparing peptides and forming peptide bonds. The enormous Tabular Survey incorporates reactions reported through the end of 2012, covering the first fifty years of the Ugi reaction. The tables are arranged by isocyanide in order of increasing carbon count, followed by the carboxylic acid, carbonyl component, and amine, to permit the quick identification of the optimal combination for preparing a particular intermediate. This is an excellent chapter on an important transformation relevant to synthetic, medicinal, and bioorganic chemistry.
The second chapter on the modified Ugi reaction focuses on half a century of modifications that employ alternative reaction conditions and components, multifunctional substrates, and reactions that deploy more or less than four components. The key mechanistic and stereochemical aspects mirror the classic variant described in the preceding chapter.
