Organic Reactions, Volume 89

By Wiley

The latest volume in this series for organic chemists in industry presents critical discussions of widely used organic reactions or particular phases 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.

• Language: English
• Publisher: Wiley
• Release date: Feb 8, 2016
• ISBN: 9781119266525

Book preview

Table of Contents

Cover

Title Page

Copyright

Introduction to the Series Roger Adams, 1942

Introduction to the Series Scott E. Denmark, 2008

Preface to Volume 89

Chapter 1: Olefin Ring-Closing Metathesis

Introduction

Mechanism

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 1-89

Chapter and Topic Index, Volumes 1-89

End User License Agreement

List of Illustrations

Chapter 1: Olefin Ring-Closing Metathesis

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

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Scheme 15

Scheme 16

Scheme 17

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Scheme 19

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Schemes 22

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Scheme 30

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Scheme 32

Schemes 33

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Schemes 43

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Schemes 49

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Schemes 180

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Schemes 188

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Schemes 192

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Schemes 197

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Schemes 199

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Schemes 201

Scheme 202

Schemes 203

Scheme 204

List of Tables

Chapter 1: Olefin Ring-Closing Metathesis

Table A Reviews of Applications of the Ring-Closing Metathesis Reaction

Chart 1 Catalysts Used in Tables

Chart 2 Ligands Used in Tables

Table 1 Synthesis of Carbocycles

Table 2A Synthesis of Cyclic Amines

Table 2B Synthesis of Cyclic Ethers

Table 2C Synthesis of Phosphorus-Containing Heterocycles

Table 2D Synthesis of Phosphorus-Containing Heterocycles

Table 2E Synthesis of Sulfur-Containing Heterocycles

Table 2F Synthesis of Sulfonamide-Containing Heterocycles

Table 2G Synthesis of Boron-Containing Derivatives

Table 2H Synthesis of Unsaturated Lactams

Table 2I Synthesis of Cyclic Peptides

Table 2j Synthesis of Unsaturated Lactones

Table 2K Synthesis of other Heterocycles Containing Multiple Heteroatoms

Table 3 Synthesis of Supramolecular Compounds

Table 4 Tandem Methathesis Reactions

ADVISORY BOARD

John E. Baldwin

Peter Beak

Dale L. Boger

George A. Boswell, Jr.

André B. Charette

Engelbert Ciganek

Dennis Curran

Samuel Danishefsky

Huw M. L. Davies

John Fried

Jacquelyn Gervay-Hague

Heinz W. Gschwend

Stephen Hanessian

Richard F. Heck

Louis Hegedus

Robert C. Kelly

Andrew S. Kende

Laura Kiessling

Steven V. Ley

James A. Marshall

Michael J. Martinelli

Stuart W. McCombie

Jerrold Meinwald

Scott J. Miller

Larry E. Overman

Leo A. Paquette

Gary H. Posner

T. V. RajanBabu

Hans J. Reich

James H. Rigby

William R. Roush

Scott D. Rychnovsky

Martin Semmelhack

Charles Sih

Amos B. Smith, III

Barry M. Trost

Milán Uskokovic

James D. White

Peter Wipf

FORMER MEMBERS OF THE BOARD NOW DECEASED

Roger Adams

Homer Adkins

Werner E. Bachmann

A. H. Blatt

Robert Bittman

Virgil Boekelheide

Theodore L. Cairns

Arthur C. Cope

Donald J. Cram

David Y. Curtin

William G. Dauben

Louis F. Fieser

Ralph F. Hirshmann

Herbert O. House

John R. Johnson

Robert M. Joyce

Willy Leimgruber

Frank C. McGrew

Blaine C. McKusick

Carl Niemann

Harold R. Snyder

Boris Weinstein

Organic Reactions

Volume 89

Editorial Board

Scott E. Denmark, Editor-in-Chief

Jeffrey Aubé

Jin K. Cha

André Charette

Vittorio Farina

Paul L. Feldman

Dennis G. Hall

Paul J. Hergenrother

Jeffrey S. Johnson

Marisa C. Kozlowski

Gary A. Molander

John Montgomery

Steven M. Weinreb

Robert M. Coates, Secretary University of Illinois at Urbana-Champaign, Urbana, Illinois

Jeffery B. Press, Secretary Press Consulting Partners, Brewster, New York

Linda S. Press, Editorial Coordinator

Dena Lindsay, Editorial Assistant

Associate Editor

Larry Yet

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Library of Congress Catalog Card Number: 42-20265

ISBN: 978-1-119-21121-1

Introduction to the Series 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 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 89

The Prefaces to Volumes 76, 80, and 84 highlighted the enormous impact of transition metal catalysis in synthetic organic chemistry. Three of the last 14 Nobel Prizes in Chemistry have been awarded for the discovery and development of transition metal catalyzed reactions that fundamentally changed the practice of organic synthesis (2001: reduction/oxidation (Knowles, Noyori and Sharpless); 2005: olefin metathesis (Chauvin, Grubbs, Schrock); 2010: cross coupling (Heck, Negishi, Suzuki)). Of the 17 chapters published in the Organic Reactions series since the diamond anniversary Volume 75 (2011), 12 have involved transition metal catalyzed transformations! The impact of catalysis using transition metal complexes and reagents on the practice of synthetic organic chemistry cannot be overstated and continues to grow exponentially. In fact, the research in this field is so intense that the resulting literature quickly becomes too massive to compile in the comprehensive fashion characteristic of Organic Reactions.

Of the three major topics celebrated by Chemistry Nobel Prizes, reduction/oxidation as well as cross-coupling are well-represented in the volumes of Organic Reactions. However, not surprisingly given the vast literature in the field, no chapter on any aspect of olefin metathesis has appeared. In fact, such a chapter had been commissioned more than a decade ago when it was still conceivable to cover one of the more important versions of olefin metathesis in organic synthesis, namely ring-closing metathesis (RCM). However, that chapter languished as the author changed locations and the literature ballooned. Much to my amazement, shortly after beginning my tenure as Editor in Chief, that author expressed renewed interest in completing the chapter and true to his word, Volume 89 comprises the results of those heroic efforts.

Dr. Larry Yet has composed the most definitive review of the family of olefin ring-closing metathesis reactions ever to appear in the! literature. Despite the appearance of literally dozens of journal reviews, book chapters, and encyclopedia entries, this contribution stands out for its comprehensive coverage of ring-closing metathesis reactions that create carbocycles, heterocycles, macrocycles, supramolecular assemblies, and polypeptides. In view of the enormous number of synthesis endeavors that construct natural products and therapeutic agents, Dr. Yet has provided an extensive overview of how RCM has revolutionized the ability to disconnect target molecules in fundamentally different ways. Some of the most recent advances in ring-closing metathesis such as enantioselective processes using chiral catalysts, solid phase transformations, and tandem metathesis reactions are covered as well. True to the spirit of Organic Reactions chapters, Dr. Yet has provided critical guidance for the selection of an appropriate catalyst for a given class of substrate and important insights in the role of olefin substitution for the most successful pairwise combination of addends.

Compiling the comprehensive Tabular Survey represented a monumental undertaking for a single author. Although the Tables cover the literature up to 2010, Dr. Yet has provided Supplemental References at the end of the chapter, organized by Table, that bringe the literature coverage through 2013.

Volume 89 represents the tenth single chapter volume to be produced in our 74-year history. Such single-chapter volumes represent definitive treatises on extremely important chemical transformations. The organic chemistry community owes an enormous debt of gratitude to the authors of such chapters for the generous contribution of their time, effort, and insights on reactions that we clearly value. Moreover, this volume also represents the largest single chapter every produced in the Organic Reactions series and we are very grateful to Anita Lekhwani and her colleagues at Wiley for their assistance in accommodating this massive work in a single bound volume.

It is appropriate here to acknowledge the expert assistance of the entire editorial board, in particular André Charette who shepherded this massive chapter to completion. The contributions of the author, editors, and the publisher were expertly coordinated by the board secretary, Robert M. Coates. In addition, the Organic Reactions enterprise could not maintain the quality of production without the dedicated efforts of its editorial staff, Dr. Linda S. Press, Dr. Danielle Soenen, and Ms. Dena Lindsey. Insofar as the essence of Organic Reactions chapters resides in the massive tables of examples, the author's and editorial coordinators' painstaking efforts are highly prized.

Scott E. Denmark

Urbana, Illinois

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Richard F. Heck

August 15, 1931–October 10, 2015

Richard F. Heck, a giant in the field of organic chemistry, died on October 9, 2015. Beginning in the late 1950's, Heck envisioned that as the art of organic synthesis grew there would be a need for catalytic, organometallic-mediated bond-forming reactions that were tolerant of a wide range of functional groups. Research investigations led him to the Pd(0)/Pd(II) cycle of oxidative addition and reductive elimination, by which carbon-X bonds are catalytically converted to carbon-carbon and carbon-heteroatom bonds. His investigations laid the groundwork for all catalytic, organometallic, bond-forming processes that are used currently in modern organic synthesis.

The epic importance of catalytic palladium-mediated, carbon-carbon bond formation only slowly became apparent to the organic synthesis community. When his Organic Reactions chapter appeared in 1982, coverage of all the literature required only 45 pages (including tables!). By 2002, applications of his chemistry in synthesis had grown to the extent that the Organic Reactions chapter published that year, limited to the subset of intramolecular Heck Reactions, covered 377 pages. Moreover, the original 45 page chapter, despite its size, it is the most highly cited chapter in the Organic Reactions series with over 1500 citations!

Professor Heck received number of awards for his seminal contributions to chemistry, most notably sharing the Chemistry Nobel Prize in 2010. Among his many professional activities, he served as a member of the Editorial Board of Organic Reactions, Inc. from 1973–1985.

On a personal note, Dick Heck had already been publishing on palladium-catalyzed carbon-carbon bond formation for ten years, at the time that I joined the chemistry faculty of the University of Delaware in 1982. It was apparent that the intramolecular Heck reaction could be a powerful transformation. I sketched out some possible applications to Dick and offered to help his students, but he was not interested. He preferred to continue exploring new reactivity, initiating both Suzuki coupling and the Sonogashira reaction. Although he was the first to fully characterize a π-allylmetal complex and to elucidate the mechanism of cobalt-catalyzed alkene hydroformylation, he most enjoyed discussing the addition of formate to the palladium-catalyzed carbonylation reaction, leading to the formation of aldehydes. Even in retirement, Dick was eager to keep up with the literature, so I would send a selection of the most interesting articles every few months. He found the Catellani protocol particularly intriguing. He had thought that the carbon-palladium bond would be far too labile to allow such cascade transformations.

Dick is remembered for the key role he played as a pioneer in applying transition metal catalysis to the synthesis of complex organic molecules, both in academics and in industry. Before Grubbs, Schrock, Buchwald or Hartwig–indeed, before Stille, Suzuki, Negishi, Tsuji, Trost or Sonogashira–there was Heck pointing the way. From the late 1950's on, his contributions provided the creative spark that ignited this essential subdiscipline of synthetic methodology. In the words of Professor E. J. Corey: Of all the individuals who have contributed to the spectacular progress in palladium catalyzed synthesis, there is no one whose work is as seminal or significant than that of Richard F. Heck.

Douglass F. Taber, University of Delaware

November 10, 2015

Chapter 1

Olefin Ring-Closing Metathesis

Larry Yet

Department of Chemistry, University of South Alabama, Mobile, Alabama 36688-0002

Contents

Introduction

Mechanism

Scope and Limitations

Catalyst Selection

Effects of Olefin Substitution

Synthesis of Carbocycles

Synthesis of Heterocycles

Synthesis of Nitrogen-Containing Heterocycles

Synthesis of Oxygen-Containing Heterocycles

Synthesis of Phosphorus-Containing Heterocycles

Synthesis of Silicon-Containing Heterocycles

Synthesis of Sulfur-Containing Heterocycles

Synthesis of Boron-Containing Heterocycles

Synthesis of Unsaturated Lactams

Synthesis of Unsaturated Lactones

Synthesis of Macrocycles

Synthesis of Cyclic Amino Acids and Peptidomimetics

Synthesis of Supramolecular Compounds

Enantioselective Synthesis with Chiral Catalysts

Tandem Metathesis Reactions

Solid-Phase Synthesis of Cyclic Alkenes

Ring-Closing Metathesis Reactions under Microwave Irradiation

Applications to Synthesis

Comparison with Other Methods

Experimental Conditions

General Reaction Conditions

Special Reaction and Purification Conditions

Experimental Procedures

3-Cyclopentene-1,1-dicarboxylic Acid Diethyl Ester [Ring-Closing Metathesis of Diethyl Diallylmalonate and Various Methods for Removal of Ruthenium Byproducts].⁵⁰⁰

[Removal of Ruthenium Byproducts with Tris(hydroxymethyl)phosphine].⁴⁹⁹

[Removal of Ruthenium Byproducts with Silica Gel/Activated Carbon].⁵⁰²

4,4-Dicarboethoxy-1,2-dimethylcyclopentene [Ring-Closing Metathesis of a Sterically Hindered Diene Ester].⁵¹, ⁶⁸

(1S,2S,3S)-4-Cyclohexen-1,2,3-triol [Ring-Closing Metathesis of a Diene Triol].⁵⁰⁸

(R)-2-Isopropenyl-3-methyl-5,6-dihydro-2H-pyran [Asymmetric Ring-Closing Metathesis of an Achiral Diene with a Chiral Molybdenum Catalyst].³¹⁹

1-Tosyl-2,3-dihydro-1H-pyrrole [Ring-Closing Metathesis of a Dienesulfonamide].¹²⁵

1,1-Dioxo-2,3,6,7-tetrahydro-1H-[1,2]thiazepine-7-carboxylic Acid Isopropyl Ester [Ring-Closing Metathesis of a Diene Sulfonamide with a Polymer-Bound Ruthenium Catalyst].⁵⁰⁹

tert-Butyl (S)-1-[(S)-5-Oxo-2,5-dihydrofuran-2-yl]-2-phenylethylcarbamate [Ring-Closing Metathesis in the Presence of a Lewis Acid to Form a γ-Lactone].²²¹

tert-Butyl (3S,6S,E)-3-(Methoxycarbonyl)-5,12-dioxo-1-oxa-4-azacyclododec-8-ene-6-carbamate [Ring-Closing Metathesis of a Dipeptide Analog].²⁶³

2-(3-Butenyl)-4-methyl-2,5-dihydrofuran [Ring-Opening Metathesis/Ring-Closing Metathesis Sequence in the Presence of Ethylene].⁵¹⁰

1-Isopropyl-2-pyrrolidinone [Tandem Metathesis/Hydrogenation Sequence of an N-Allyl α,β-Unsaturated Amide].⁵¹¹

Tabular Survey

Chart 1 Catalysts Used in Tables

Chart 2 Ligands Used in Tables

Table 1 Synthesis of Carbocycles

Table 2A Synthesis of Cyclic Amines

Table 2B Synthesis of Cyclic Ethers

Table 2C Synthesis of Phosphorus-Containing Heterocycles

Table 2D Synthesis of Phosphorus-Containing Heterocycles

Table 2E Synthesis of Sulfur-Containing Heterocycles

Table 2F Synthesis of Sulfonamide-Containing Heterocycles

Table 2G Synthesis of Boron-Containing Derivatives

Table 2H Synthesis of Unsaturated Lactams

Table 2I Synthesis of Cyclic Peptides

Table 2J Synthesis of Unsaturated Lactones

Table 2K Synthesis of other Heterocycles Containing Multiple Heteroatoms

Table 3 Synthesis of Supramolecular Compounds

Table 4 Tandem Methathesis Reactions

References

Introduction

Olefin metathesis was defined for the first time by Calderon in 1967 as a catalytically induced reaction wherein olefins undergo bond reorganization resulting in a redistribution of alkylidene moieties.¹, ² The first observation of the metathesis of propene at high temperature was reported in 1931; the first catalyzed metathesis reactions were discovered in the 1950's when industrial chemists at Du Pont, Standard Oil, and Phillips Petroleum reported that propene led to ethylene and 2-butenes when it was heated with molybdenum on alumina.³, ⁴ The first polymerization of norbornene by the WCl6/Et2AlCl system was independently reported in 1960 by Eleuterio⁴ and by Truett.⁵

The number of applications of olefin metathesis in organic synthesis has increased exponentially in the last two decades. Many reviews and monographs have documented the significant advances in this field.⁶–²⁵ Olefin metathesis, a process in which alkylidene groups are exchanged by the scission of carbon–carbon double bonds of alkenes, can be organized into four main categories: (1) cross-metathesis (CM),²⁶ in which two different alkenes undergo an intermolecular reaction to form new olefinic products; (2) ring-opening metathesis polymerization (ROMP), which involves the ring-opening of strained olefins to afford polymeric olefin compounds; (3) ring-opening metathesis (ROM), which also involves ring-opening of strained olefins in the presence of an alkene to generate a diene product; and (4) ring-closing metathesis (RCM), a procedure in which a diene undergoes cyclization to afford cyclic alkenes (Scheme 1). Many examples of each of the four types of olefin metathesis reactions are reported, and each occupies a prominent and useful place in organic synthesis. This chapter focuses on the olefin ring-closing metathesis reaction.

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Scheme 1

Olefin ring-closing metathesis (RCM) was first applied in organic synthesis in 1980, but the catalysts employed at that time were undefined and poorly characterized.²⁷, ²⁸ These early catalysts showed high activity but poor compatibility with polar functional groups, making them unattractive for the synthesis of complex molecules. Ruthenium catalysts that could polymerize functionalized monomers via metathesis were discovered in the late 1980's, although these catalysts were still undefined.²⁹, ³⁰

The discovery of well-defined metal alkylidene complexes with excellent functional-group tolerance, such as Schrock's molybdenum complex 1³¹ and Grubbs's ruthenium complexes 2 and 3,³², ³³ allowed applications of RCM in organic synthesis to increase at a rapid pace. The reaction can now be carried out under mild conditions with alkene precursors containing many common functional groups. Moreover, it has achieved strategy-level status in the total syntheses of many natural products and therapeutic agents that bear alkenes, and alkene synthons. This chapter will focus on developments in ring-closing metathesis reactions up to 2010.

Mechanism

The original mechanism, proposed in 1971 by Yves Chauvin, for the ring-closing metathesis reaction of dienes with ruthenium and molybdenum complexes is now generally accepted.³⁴ Chauvin convincingly demonstrated that metal-catalyzed olefin metathesis is the result of a non-pair-wise exchange of alkylidene fragments. The process consists of a sequence of formal [2+2] cycloadditions/cycloreversions involving alkenes, metal carbenes, and metallacyclobutane intermediates. Thus, diene 4 first reacts with the active metal carbene species [M]=CH2 to generate metallacyclobutane 6 via a [2+2] cycloaddition process, which leads to the formation of alkylidene 7 (Scheme 2). Alkylidene 7 then undergoes a further [2+2] cycloaddition to generate metallacyclobutane 8, which upon cycloreversion affords cyclic alkene 5 and regenerates the metal carbene.

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Scheme 2

In principle, each of the individual steps in the catalytic cycle is reversible, and an equilibrium mixture of olefins can be obtained. The forward reaction can be entropically driven because RCM transforms one substrate molecule into two products, where a volatile alkene (often ethene or propene) is removed as it is formed. The reaction can be driven by carrying it out at a high reaction temperature and/or by bubbling an inert gas through the reaction mixture to assist removal of the volatile alkene byproduct. The reverse reaction is also slowed if the product has a more highly substituted double bond than the substrate, because most metathesis catalysts are sterically sensitive. The use of high dilution conditions favors ring-closing metathesis of a diene substrate over competing polymerization via acyclic diene metathesis (ADMET).

Mechanistic studies employing ³¹P NMR magnetization transfer experiments and other ¹H NMR and UV–vis spectroscopic techniques suggest that the overall catalytic cycle for ruthenium complexes proceeds according to the mechanism outlined in Scheme 3.³⁵–³⁷ The first step, catalyst initiation, involves dissociation of one PCy3 ligand to afford the highly reactive 14-electron monophosphine intermediate 9. The reaction of intermediate 9 with an olefinic substrate generates the metal monophosphine/olefin complex 10 in the second step. Finally, coupling of the olefin and alkylidene ligands within the coordination sphere of the ruthenium metal produces metallacyclobutane intermediate 11. Metallacyclobutane 11 can break down productively to form a new olefin and a new metal alkylidene product or unproductively to regenerate the starting materials.

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Scheme 3

The overall catalytic activity of the ruthenium complex as outlined in Scheme 3 is dictated by the relative rates of three processes: (1) phosphine dissociation (initiation, k1), (2) phosphine recoordination (k–1), and (3) olefin binding