Organic Reactions, Volume 113 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 113 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.
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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 113
CHAPTER 1: TRANSITION‐METAL‐CATALYZED ALKYL–ALKYL CROSS‐COUPLING REACTIONS
INTRODUCTION
MECHANISM AND STEREOCHEMISTRY
SCOPE AND LIMITATIONS
APPLICATIONS TO SYNTHESIS
COMPARISON WITH OTHER METHODS
EXPERIMENTAL CONDITIONS
EXPERIMENTAL PROCEDURES
TABULAR SURVEY
REFERENCES
SUPPLEMENTAL REFERENCES
CHAPTER 2: HYDROZIRCONATION OF ALKYNES
ACKNOWLEDGEMENTS
INTRODUCTION
MECHANISM
STEREOCHEMISTRY
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 1–113
CHAPTER AND TOPIC INDEX, VOLUMES 1–113
END USER LICENSE AGREEMENT
List of Illustrations
Chapter 1
Scheme 1
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Chapter 2
Scheme 1
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Scheme 9
Figure 1 Possible insertion pathways of a terminal alkyne into the zirconium...
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Scheme 17
Scheme 18
Figure 2 MicroED solid-state structure of Cp
2
Zr(H)Cl dimer with bridging hyd...
Figure 3 X‐ray crystal structure of the borane complex of Cp
2
Zr(H)Cl with br...
Figure 4 X‐ray crystal structure of the cationic complex [Cp
2
Zr(Cl)OEt
2
]
+
...
Figure 5 Side view of the X‐ray crystal structure of Cp*
2
ZrH
2
.
Scheme 19
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Scheme 27
Figure 6 Additional examples for bridge‐stabilized 1,1‐bimetallic and agosti...
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Guide
COVER PAGE
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 113
BEGIN READING
AUTHOR INDEX, VOLUMES 1–113
CHAPTER AND TOPIC INDEX, VOLUMES 1–113
WILEY END USER LICENSE AGREEMENT
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FORMER MEMBERS OF THE BOARD OF EDITORS AND DIRECTORS
JEFFREY
AUBÉ
LAURA
KIESSLING
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
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
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 113
EDITORIAL BOARD
P. ANDREWEVANS, Editor‐in‐Chief
STEVEN M. WEINREB, Executive Editor
DAVID
B.
BERKOWITZ
JOSHUA
G.
PIERCE
PAUL
R.
BLAKEMORE
BO
QU
REBECCA
L.
GRANGE
KEVIN
H.
SHAUGHNESSY
DENNIS
G.
HALL
STEVEN
D.
TOWNSEND
JEFFREY
B.
JOHNSON
CHRISTOPHER
D.
VANDERWAL
JEFFREY
N.
JOHNSTON
MARY
P.
WATSON
JOHN
MONTGOMERY
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
DESIRAE L. CROCKER
COURTNEY V. HAMMILL
TAKANORI IWASAKI
NOBUAKI KAMBE
JOHN A. MILLIGAN
PETER WIPF
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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 113
They say opposites attract, but like meets like, too.
Ruth Downie, 2015
A Year of Ravens
The construction of functional molecules in a predictable manner is predicated on the ability to design and implement a specific synthetic strategy. Consequently, translating a retrosynthetic analysis into practice requires the identification of successful tactics and thus constitutes the most time‐consuming and tedious aspect of such an endeavor. One of the overarching strengths of the Organic Reactions series is the collation of reaction conditions in curated tables that enable the reader to a priori select the appropriate tactics to expedite the implementation of a proposed synthetic sequence. The two chapters in this particular volume focus on transition‐metal‐catalyzed alkyl‐alkyl cross‐coupling reactions that form challenging carbon‐carbon bonds and on the hydrozirconation of alkynes to generate reactive carbon nucleophiles for electrophilic functionalization and cross‐coupling reactions. Hence, the two chapters provide important reactions that align with the notion that “opposites attract, but like meets like, too” since they both feature cross‐ and homo‐coupling reactions. In contrast to conventional cross‐coupling reactions that primarily proceed through a heterolytic‐type process, homolytic processes now permit both cross‐ and homo‐coupling reactions. Although the homolytic pathway has often been derided because of the challenges associated with controlling chemo‐, regio‐, and stereoselectivity, the ability to promote selective cross‐coupling reactions through radical intermediates has significantly broadened the scope of these types of transformations.
The first chapter by Takanori Iwasaki and Nobuaki Kambe provides a definitive treatise on transition‐metal‐catalyzed alkyl‐alkyl cross‐coupling reactions, the development of which has proven particularly challenging. The coupling of unsaturated partners (i.e., forming bonds between sp and sp2 components) has been extensively studied and was the subject of the 2010 Nobel Prize in Chemistry. Ironically, the reactions between sp3‐hybridized carbon atoms predate the former and can be traced to the seminal studies of Kharash in the 1940s. Independent studies by several groups in the 1970s illuminated the problems associated with controlling efficiency and selectivity in alkyl‐alkyl coupling, stemming from undesirable side reactions. Hence, progress was limited until the 1990s when alkyl halides were identified as promising coupling partners, thereby inspiring the remarkable progress in the 2000s that led to the development of a series of important reactions, including enantioselective variants.
The Mechanism and Stereochemistry section defines the two catalytic cycles that have been used to rationalize these reactions. For instance, Type A proceeds by a more conventional process, triggered by oxidative addition with the alkyl halide, which is supported by the isolation of the oxidative addition adduct and kinetic studies. In contrast, Type B is initiated by a transmetallation or complexation of the organometallic reagent, which differs significantly based on the metal complex and the type of ligand. For example, the Kumada–Tamao–Corriu cross‐coupling reaction catalyzed by nickel or palladium utilizes 1,3‐butadiene as a ligand that dimerizes to form a high‐oxidation state bis‐π‐allyl metal complex that reacts directly with the Grignard reagent. This section also addresses the stereochemical aspects of the reaction in the context of the electrophile (alkyl halide or pseudohalide) and nucleophile (organometallic reagent). In the former case, the process can be either stereospecific or stereoselective, which is relevant to developing the enantioselective variations. The catalyst impacts the stereochemical outcome for the alkyl electrophiles, which is ascribed to the switch from a heterolytic to a homolytic pathway (vide supra). Hence, tailoring the metal complex has far‐reaching implications that expand the scope and permit the construction of challenging carbon‐carbon bonds in a predictable manner. In contrast, the stereochemistry of the alkylmetal reagents is rarely examined because of problems with their stereochemical lability, albeit a few seminal studies are described to provide insight into the current challenges. The section on the relative reactivity of various electrophiles and nucleophiles offers further insight into designing optimal combinations for a specific coupling reaction.
The Scope and Limitations section commences with a chart summarizing the current scope and limitations for the metal catalysts and coupling partners to define the remaining knowledge gaps in this area. This section is organized by the type of metal catalyst (e.g., Cu, Ni, Pd, Ag, Fe, and Co), which is important given the differences in the reaction mechanisms. The sections are further subdivided into the kind of organometallic reagent (Mg, Li, Mn, Zn, Sm, and B), the degree of alkyl substitution and the nature of the leaving group, e.g., the copper‐catalyzed cross‐coupling of primary alkyl halides and pseudohalides with an array of alkyl Grignard reagents (primary, secondary, and tertiary). The nickel and palladium sections also include the merits of different ligands (e.g., phosphine, nitrogen‐based, N‐heterocyclic carbene, and π‐carbon ligands) that have been employed. The section on asymmetric variants of the alkyl‐alkyl cross‐coupling reaction is important and timely because it clearly illustrates that this process is very much in its infancy and has immense synthetic possibilities. Notably, the enantioconvergent reactions generally require a nickel complex with chiral diamine and triamine ligands to access the requisite alkyl radical intermediate for the enantioconvergent process (e.g., Suzuki‐Miyaura, Negishi, and Kumada‐Tamao‐Corriu cross‐coupling reactions).
The Applications to Synthesis section highlights several adaptations of the reaction in natural‐product synthesis that involve forming racemic and achiral carbon‐carbon bonds. The Comparison with Other Methods section critically assesses homocoupling reactions of alkyl halides and alkylmetal reagents, including reductive cross‐electrophile coupling, cross‐coupling of alkyl transition‐metal reagents, and cross‐coupling reactions with unsaturated partners followed by reduction. The Tabular Survey is organized by the type of substitution of the electrophile and alkylmetal reagent (e.g., primary alkyl halides with primary alkylmetals) and then further subdivided by the kind of organometallic reagent (e.g., Mg, Zn, B, etc.), to permit the identification of a specific reaction combination of interest. This outstanding chapter on an important class of cross‐coupling reactions complements the extensive studies with unsaturated variants. Hence, the chapter should interest anyone wishing to develop new variants or employ this type of transformation in target‐directed synthesis.
The second chapter by John A. Milligan, Courtney V. Hammill, Desirae L. Crocker, and Peter Wipf describes the hydrozirconation of alkynes, which has been the subject of intensive investigation. Although hydrometallation can be accomplished with early‐ and late‐transition metals, the former permits the stoichiometric conversion of unactivated alkenes and alkynes into various organic compounds by functionalizing the isolable σ‐bonded organometallic intermediate. The chapter primarily focuses on the synthetic utility of zirconocene hydrochloride (Cp2Zr(H)Cl, Schwartz Reagent), which can be accessed directly or prepared in situ from either zirconocene dichloride or dihydride. The reagent was first prepared and utilized for hydrozirconation alkenes and alkynes in the late 1960s and early 1970s by Wailes and coworkers. This chapter delineates the evolution of the hydrozirconation reaction with this reagent and the reactions of the zirconium‐carbon σ‐bond with a range of electrophiles, which has proven to be a versatile and general methodology.
The Mechanism and Stereochemistry section outlines the challenges with the hydrozirconation of alkenes and alkynes, which are formally equilibrium processes initiated by forming a transient π‐complex en route to the thermodynamically more favorable σ‐complex. Hydrozirconation is analogous to hydroboration since it proceeds through a four‐centered, concerted asynchronous transition state. Although zirconocene hydrochloride is commonly employed, these species can also be accessed from β‐hydride elimination, albeit the mechanistic details of this process have not been reported. This section highlights the limitations of the current theoretical studies that focus entirely on ethylene and acetylene, which suggest the chlorine and hydrogen ligands are at opposing ends during the addition and that the hydrozirconation process is fully reversible at room temperature. The authors outline important stereochemical aspects through key experimental observations and the impact of solvent on kinetic and thermodynamic control. In addition, the implication of steric and electronic factors in both the reagent and the substrate on regio‐ and stereoselectivity provides the reader with a comprehensive summary of the factors that control reactivity and selectivity in this process.
The Scope and Limitations section begins with an overview of the functional‐group tolerance of the hydrozirconation reaction, which is highly selective for alkynes in the presence of an array of reactive functionalities. Chemoselectivity is further addressed with bimetallic zirconocenes that permit the selective functionalization of the zirconium‐carbon bond. The alkenyl zirconocene intermediate is versatile as exemplified by its ability to undergo protonation, deuteration, halogenation, oxidation, and hydrogenation reactions, including insertion reactions with carbon monoxide and isonitriles. Notably, the alkenylzirconocene intermediates undergo homocoupling in the presence of either copper(II) halides or oxovanadium reagents to afford 1,4‐butadienes (vide supra). Alternatively, simple halide displacement reactions afford organophosphorus, organosulfur, and organoselenium compounds, as well as amines and enamines. The copper‐catalyzed displacement of O‐benzoylhydroxylamine with an alkenylzirconocene is particularly pertinent since it provides an attractive method for the regio‐ and stereodefined construction of acyclic enamines. Furthermore, the ability to transmetallate zirconium with several main‐group elements and transition metals (e.g., Al, B, Cu, Ni, Pd, etc.) followed by the stereospecific alkylation with various carbon electrophiles highlights the synthetic utility of this transformation for the stereoselective construction of cyclic and acyclic olefins. The authors also discuss cationic zirconocenes that promote additions to aldehydes and the ring opening of epoxides facilitated by the enhanced Lewis acidity of the alkenylzirconocene intermediate. This section is completed with miscellaneous reactions, limitations, and side reactions to provide the reader with further insight into the remaining challenges associated with these transformations.
The Applications to Synthesis section delineates several examples of preparing complex natural products, illustrating the versatility of the process for the total synthesis of important bioactive agents. The Comparison with Other Methods section primarily focuses on hydroboration, hydrostannylation, and other hydrometallations of alkynes but it also covers haloalkene insertion reactions to afford the regioisomeric 1,1‐alkenylzirconocene intermediate. The Tabular Survey follows the same organization as Scope and Limitations, wherein the specific type of functionalization is listed separately to permit the reader to identify the appropriate reaction of interest. This is an outstanding chapter on an important transformation that will be a valuable and practical resource to the synthetic community, particularly given that zirconocene hydrochloride is commercially available.
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 many stages of the editorial process. I want to thank Dr. John Montgomery, Dr. Kevin H. Shaughnessy (Chapter 1), and Dr. Steven M. Weinreb (Chapter 2) 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 publisher. 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 unique 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 1TRANSITION‐METAL‐CATALYZED ALKYL–ALKYL CROSS‐COUPLING REACTIONS
TAKANORI IWASAKI
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8656, Japan
NOBUAKI KAMBE
Research Center for Environmental Preservation, Osaka University, 2‐4 Yamadaoka, Suita, Osaka 565‐0871, Japan
Edited by JOHN MONTGOMERY AND KEVIN SHAUGHNESSY
CONTENTS
INTRODUCTION
MECHANISM AND STEREOCHEMISTRY
General Catalytic Cycles
Catalytic Cycles Triggered by Oxidative Addition (Type A)
Catalytic Cycles Triggered by Transmetalation or Complexation (Type B)
Stereochemistry of Alkyl Electrophiles
Stereochemistry of Alkylmetal Reagents
Relative Reactivity of Alkyl Halides and Other Electrophiles
Relative Reactivity of Alkylmetal Reagents
SCOPE AND LIMITATIONS
Copper‐Catalyzed Cross‐Coupling
Grignard Reagents
Other Nucleophiles
Nickel‐Catalyzed Cross‐Coupling
Phosphine Ligand Systems
Nitrogen‐Based Ligand Systems
π‐Carbon Ligand Systems
Palladium‐Catalyzed Cross‐Coupling
Phosphine Ligand Systems
N
‐Heterocyclic Carbene Systems
π‐Carbon Ligand Systems
Silver‐Catalyzed Cross‐Coupling
Iron‐Catalyzed Cross‐Coupling
Cobalt‐Catalyzed Cross‐Coupling
Asymmetric Reactions
Asymmetric Suzuki–Miyaura Coupling
Asymmetric Negishi Coupling
Asymmetric Kumada–Tamao–Corriu Coupling
APPLICATIONS TO SYNTHESIS
Synthesis of Bioactive Compounds
Synthesis of Fatty Acids
COMPARISON WITH OTHER METHODS
Homo‐Coupling Reactions
Homo‐Coupling of Alkyl Halides
Homo‐Coupling of Alkylmetal Reagents
Reductive Cross‐Electrophile Coupling
Cross‐Coupling Using Alkyl Transition‐Metal Reagents
Alkylation of Alkylcuprates
Alkylation of Nickelalactones
Construction of Saturated Carbon Skeletons by Reduction
EXPERIMENTAL Conditions
General Conditions
Metal Catalysts
Additives
Organometallic Reagents
EXPERIMENTAL PROCEDURES
3‐(Pent‐4‐enyl)non‐8‐enylbenzene [Cu‐Catalyzed Kumada–Tamao–Corriu Cross‐Coupling of a Secondary Alkyl Iodide].
(
S
)‐1‐Bromo‐4‐[(2‐cyclohexylpropoxy)methyl]benzene [Cu‐Catalyzed Stereospecific Kumada–Tamao–Corriu Cross‐Coupling between Secondary Alkyls].
1‐Bromo‐4‐hexylbenzene [Ni‐Catalyzed Kumada–Tamao–Corriu Coupling].
(
E
)‐Octadec‐9‐enoic Acid [Ni‐Catalyzed Iterative Coupling of a Bromo Carboxylic Acid by in Situ Protection].
Ethyl Pentadec‐10‐ynoate [Pd‐Catalyzed Suzuki–Miyaura Cross‐Coupling Reaction].
8‐(1,3‐Dioxolan‐2‐yl)‐2,2‐dimethyloctanenitrile [Pd‐Catalyzed Negishi Cross‐Coupling Reaction].
2,2‐Dimethyl‐1‐phenyldecane [Ag‐Catalyzed Kumada–Tamao–Corriu Cross‐Coupling Reaction].
1‐
tert
‐Butoxycarbonyl‐4‐(3,3‐dimethylbutyl)piperidine [Co‐Catalyzed Kumada–Tamao–Corriu Cross‐Coupling Reaction].
5‐Cyclohexyl‐4‐methyl‐
N,N
‐diphenylpentanamide [Ni‐Catalyzed Asymmetric Suzuki–Miyaura Cross‐Coupling].
(
S
)‐1‐(Benzyloxy)‐3‐(1‐cyclopentylpropyl)benzene [Ni‐Catalyzed Asymmetric Negishi Cross‐Coupling Reaction].
TABULAR SURVEY
Chart 1. Nitrogen-Based Ligands Used in Tables
Chart 2. N-Heterocyclic Carbene Ligands Used in Tables
Chart 3. Phosphine-Based Ligands Used in Tables
Chart 4. Other Ligands and Ligand Precursors Used in Tables
Chart 5. Catalysts and Catalyst Precursors Used in Tables
Table 1. Coupling Reactions between Primary Alkyl Halides and Primary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
C. Alkylborane Reagents
D. Alkyl Derivatives of Other Metals
Table 2. Coupling Reactions between Primary Alkyl Halides and Secondary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
D. Alkyl Derivatives of Other Metals
Table 3. Coupling Reactions between Primary Alkyl Halides and Tertiary Alkylmetals
A. Alkyl Grignard Reagents
D. Alkyl Derivatives of Other Metals
Table 4. Coupling Reactions between Secondary Alkyl Halides and Primary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
C. Alkylborane Reagents
D. Alkyl Derivatives of Other Metals
Table 5. Coupling Reactions between Secondary Alkyl Halides and Secondary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
C. Alkylborane Reagents
D. Alkyl Derivatives of Other Metals
Table 6. Coupling Reactions between Secondary Alkyl Halides and Tertiary Alkylmetals
A. Alkyl Grignard Reagents
Table 7. Coupling Reactions between Tertiary Alkyl Halides and Primary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
D. Alkyl Derivatives of Other Metals
Table 8. Coupling Reactions between Tertiary Alkyl Halides and Secondary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
Table 9. Coupling Reactions between Tertiary Alkyl Halides and Tertiary Alkylmetals
A. Alkyl Grignard Reagents
B. Alkylzinc Reagents
REFERENCES
SUPPLEMENTAL REFERENCES
INTRODUCTION
Transition‐metal‐catalyzed cross‐coupling reactions are fundamentally important and particularly useful transformations for organic synthesis. Indeed, they are now widely employed in constructing carbon frameworks in an array of organic compounds. The simplest variant for cross‐coupling is the reaction between organohalides and organometallic reagents, which results in two different carbon centers being connected by a single bond (Scheme 1). The significance of this transformation in the chemical, material, and biological sciences, as well as industrial chemistry has prompted the development of various adaptations, which resulted in the Nobel Prize in Chemistry in 2010 for “palladium‐catalyzed cross‐coupling in organic synthesis”.
Scheme 1
Cross‐coupling of unsaturated carbon moieties (i.e., forming bonds at sp‐ and sp2‐hybridized carbon centers) has been the subject of extensive study since the early 1970s and has been applied to the synthesis of organic molecules that contain conjugated π‐electron systems. Cross‐coupling reactions between sp3‐hybridized carbon moieties have a long history, dating back to the 1940s1 and the pioneering studies of the early 1970s;2–4 however, limited attention has been paid to alkyl–alkyl cross‐coupling reactions until recently, which is due, in part, to the difficulties associated with undesirable side‐reactions that result in low selectivity and efficiency. Nevertheless, in the late 1990s, alkyl halides were recognized as promising coupling partners in cross‐coupling reactions,5 which led to remarkable progress in the 2000s in this undeveloped field. Various practical methods for alkyl–alkyl cross‐coupling, including asymmetric versions, have now been established by using combinations of suitable ligands and transition‐metal catalysts. These reactions promise to provide not only straightforward and powerful tools for constructing carbon chains in organic synthesis but also novel methods for creating asymmetric carbon centers.
This chapter describes transition‐metal‐catalyzed cross‐coupling reactions between sp3‐carbons, specifically the reactions of alkyl halides or pseudohalides with alkylmetal reagents. With regard to the scope of the halides that can be used in these reactions: except for a few cases, coupling reactions of allylic (pseudo)halides are not covered here because they are reactive toward nucleophiles and can undergo nucleophilic substitution in the absence of a catalyst; their chemistry with transition metals is discussed in published chapters dealing with allylic substitutions via allylmetal intermediates.6–8 Coupling reactions using allylic and benzylic organometallic reagents are included here, but the alkylations of metal enolates and related stabilized carbanions are excluded. The Scope and Limitations section is divided into subsections according to transition‐metal catalysts followed by reagents or ligand systems. Independent subsections are allocated to reagents, reactivities, and asymmetric cross‐coupling reactions.
Some excellent reviews are available on coupling reactions employing alkyl halides9–14 or alkylmetal reagents15 and both,14,16–21 including asymmetric variants.22–26
MECHANISM AND STEREOCHEMISTRY
General Catalytic Cycles
Catalytic pathways of cross‐coupling reactions can be classified into two types, as shown in Scheme 2. In Type A, a low‐valent metal species (TM) first reacts with an organo (pseudo)halide (R1–X) and then reacts further with an organometallic compound (R2–M), giving rise to the coupled product (R1–R2). This is a common pathway for the cross‐coupling of aryl and vinyl halides, as well as for alkyl halides, and has stimulated numerous synthetic applications using palladium and nickel catalysts. In the Type B pathway, the metal catalyst reacts with these two reagents in the reverse order, i.e., first with an organometallic compound and then with an alkyl halide. Copper‐catalyzed cross‐coupling is a typical example of this type of mechanism. Reactions of alkyl halides using various transition metals such as rhodium, cobalt, iron, vanadium, as well as nickel and palladium often proceed via this pathway. In both pathways, the formation of a carbon–carbon bond proceeds via reductive elimination of a diorganometal intermediate (TMR1R2 or TMR1R2X), although a one‐step mechanism without the formation of a TMR1R2 (TMR1R2X) intermediate cannot be ruled out. The mechanistic details and active catalytic species vary according to the catalytic system. Single‐electron‐transfer (SET) processes appear to be involved in some cases, especially in the Type B pathway.
Scheme 2
Transition metals with low oxidation states undergo oxidative addition to organic halides. This process generally proceeds via the conventional concerted mechanism with the contribution of π‐bond orbitals when aryl or vinyl halides are employed. In the case of alkyl halides, this concerted mechanism is less favorable, and SN2 or SET mechanisms are frequently operative. Strongly electron‐donating ligands such as trialkylphosphines and N‐heterocyclic carbenes (NHCs) are commonly employed as ligands. Chelating amine and π‐carbon ligands are also an attractive choice for alkyl–alkyl cross‐coupling.
Catalytic Cycles Triggered by Oxidative Addition (Type A)
The palladium‐catalyzed Suzuki–Miyaura coupling of alkyl halides using bulky trialkylphosphines proceeds via the Type A pathway, which is triggered by the oxidative addition of Pd(0) into the alkyl halides and thus involves successive steps of oxidative addition, transmetalation, and reductive elimination (Scheme 3
