Cover Page

Advisory Board

John E. Baldwin

Peter Beak

Dale L. Boger

André B. Charette

Engelbert Ciganek

Dennis Curran

Samuel Danishefsky

Huw M. L. Davies

John Fried

Jacquelyn Gervay-Hague

Heinz W. Gschwend

Stephen Hanessian

Louis Hegedus

Paul J. Hergenrother

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

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

George A. Boswell, Jr.

Theodore L. Cairns

Arthur C. Cope

Donald J. Cram

David Y. Curtin

William G. Dauben

Richard F. Heck

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

Mil'an Uskokovic

Boris Weinstein

Organic Reactions

Volume 93

Editorial Board

Scott E. Denmark, Editor-in-Chief

Jeffrey Aubé

David B. Berkowitz

David B. Berkowitz

Carl Busacca

Jin K. Cha

P. Andrew Evans

Paul L. Feldman

Dennis G. Hall

Donna M. Huryn

Marisa C. Kozlowski

Gary A. Molander

John Montgomery

Albert Padwa

Tomislav Rovis

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

Danielle Soenen, Editorial Coordinator

Landy K. Blasdel, Editorial Assistant

Dena Lindsay, Editorial Assistant

Linda S. Press, Editorial Consultant

Engelbert Ciganek, Editorial Advisor


Associate Editors

Alan R. Burns

Hon Wai Lam

Iain D. Roy

Iain D. Roy



Wiley Logo

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 93

Boron has all the best tunes

A. J. Downs in

“Chemistry of Aluminum, Gallium, Indium and Thallium”

It is ironic that a book dedicated to the chemistry of the heavier elements in Group 13 would bemoan the dominance of the lightest, boron. The reality is, however, that for applications in synthetic chemistry, boron is unparalleled in its versatility to facilitate the formation of new carbon-carbon and carbon-heteroatom bonds in myriad structural settings with extraordinary generality and selectivity.

Undoubtedly, the ease with which boron engages in so many diverse chemical transformations can be ascribed to its unique ability to exist in both tricoordinate and tetracoordinate constitutions and to interconvert between them with relative ease. As a consequence, boron can function as a Lewis acidic species (6 electron, neutral) and a Lewis basic species (8 electron, anionic), which enables both electrophilic and nucleophilic character to be expressed. No other element has such chemical virtuosity and the manifestations of its unique behavior continue to be developed. As a testimony to the remarkable and enduring impact of organoboron chemistry, it is worth noting that the 1979 Nobel Prize in Chemistry was shared by Herbert C. Brown and Georg Wittig “for their development of the use of boron- and phosphorus-containing compounds, respectively, into important reagents in organic synthesis.” Thirty-eight years later, there has been no surcease in advances.

One of the most frequently employed classes of organoboron compounds are boronic acids and their esters. In the past 30 years, boronic acids have emerged as one of the most capable placeholders for entry into dozens of catalytic cycles involving transition-metal catalysts. In this capacity, boron easily exchanges with various transition metals to deliver all manner of organic building blocks into constructive, bond forming cycles. Perhaps the most famous is the transmetalation to palladium in the Suzuki-Miyaura cross-coupling reaction (also recognized with a shared Nobel Prize in 2010).

In a landmark report in 1997, Tamio Hayashi and coworkers described another facile transmetalation of boronic acids to rhodium complexes to enable the conjugate addition of organic moieties to α,β-unsaturated carbonyl compounds. For decades, this powerful transformation, namely, 1,4-addition had been the purview of organocopper chemistry, but the difficulty in developing enantioselective variants hindered widespread application. With the discovery that readily available and shelf-stable boronic acids could serve as precursors, the development of enantioselective additions using chirally modified rhodium catalysts was very soon introduced. Twenty years later, this reaction has achieved strategy level status, thanks to the efforts of many laboratories world-wide.

One of those laboratories is directed by Professor Hon Wai Lam (Nottingham, UK) who together with coworkers and coauthors Alan R. Burns and Iain D. Roy have taken on the enormous task of compiling the first, comprehensive disquisition on the entire scope and application of this tremendously powerful reaction. Professor Lam and his coauthors have constructed an outstanding chapter that encompasses the full range of the electron-deficient alkenes that successfully engage in the process, including the breadth of substitution patterns most commonly employed in the additions. Moreover they have thoroughly evaluated the various families of chiral ligands that are effective in promoting high enantioselectivities, including novel classes of phosphorus, sulfur, olefinic, and hybrid ligands. Not surprisingly, given the power of this transformation, applications in the synthesis of natural products abound, and the authors have selected illustrative examples to highlight the utility of the reaction. In one of the most comprehensive treatments, the authors have detailed the use of other classes of organometallic reagents that are susceptible to catalysis by rhodium as well as other transition-metal catalyzed additions of organoboron reagents. Together with ten detailed experimental procedures, this chapter constitutes a dream field guide for the user to identify the best method applicable to solve their particular challenge.

The Tabular Survey comprises 25 tables organized by both substrate structure and organoboron reagent with such a fine granularity as to facilitate with ease the identification of product types sought by those interested in using these methods.

Volume 93 represents the fourteenth single chapter volume to be produced in our 76-year history (seventh in the past fourteen volumes!). 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.

It is appropriate here to acknowledge the expert assistance of the entire editorial board, in particular Tomislav Rovis and Gary Molander who shepherded this 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. Danielle Soenen, Dr. Linda S. Press, Dr. Dena Lindsey, and Dr. Landy Blasdel. Insofar as the essence of Organic Reactions chapters resides in the massive tables of examples, the authors' and editorial coordinators' painstaking efforts are highly prized.

Scott E. Denmark
Urbana, Illinois