Organic Reactions, I by Barbara Duke

FORMER MEMBERS OF THE BOARD OF EDITORS AND DIRECTORS

JEFFREY AUBÉ LAURA KIESSLING
JOHN E. BALDWIN MARISA C. KOZLOWSKI
PETER BEAK STEVEN V. LEY
DALE L. BOGER JAMES A. MARSHALL
JIN K. CHA MICHAEL J. MARTINELLI
ANDRÉ B. CHARETTE STUART W. MCCOMBIE
ENGELBERT CIGANEK SCOTT J. MILLER
DENNIS CURRAN JOHN MONTGOMERY
SAMUEL DANISHEFSKY LARRY E. OVERMAN
HUW M. L. DAVIES 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
JEFFREY S. JOHNSON BARRY M. TROST
ROBERT C. KELLY 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
ROBERT BITTMAN ANDREW S. KENDE
A. H. BLATT WILLY LEIMGRUBER
VIRGIL BOEKELHEIDE FRANK C. MC GREW
GEORGE A. BOSWELLJR. 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 105

EDITORIAL BOARD

P. ANDREW EVANS, Editor‐in‐Chief

STEVEN M. WEINREB, Executive Editor

DAVID B. BERKOWITZ JEFFREY N. JOHNSTON
PAUL R. BLAKEMORE ALBERT PADWA
SCOTT E. DENMARK JENNIFER M. SCHOMAKER
REBECCA L. GRANGE KEVIN H. SHAUGHNESSY
DENNIS G. HALL CHRISTOPHER D. VANDERWAL
DONNA M. HURYN MARY P. WATSON
JEFFREY B. JOHNSON

BARRY B. SNIDER, Secretary

JEFFERY B. PRESS, Treasurer

DANIELLE SOENEN, Editorial Coordinator

DENA LINDSAY, Secretary and Processing Editor

LANDY K. BLASDEL, Processing Editor

DEBRA DOLLIVER, Processing Editor

ENGELBERT CIGANEK, Editorial Advisor

ASSOCIATE EDITORS

VARINDER K. AGGARWAL
KUMAR D. ASHTEKAR
BABAK BORHAN
ENGELBERT CIGANEK
BEATRICE S. L. COLLINS
ANA B. CUENCA
ELENA FERNÁNDEZ
ARVIND JAGANATHAN
DONALD S. MATTESON
DANIEL C. WHITEHEAD

 

 

 

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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 105

Janus: The Roman god with two faces that look to the future and to the past–the god of beginnings, gates, transitions, time, duality, doorways, passages, frames, and endings.

Source: Wikipedia

The ability to look to the past and the future represents the very essence of an Organic Reactions chapter. For instance, a chapter exhaustively documents the past efforts within a specific reaction manifold, while also identifying critical knowledge gaps that present the reader with potential future research endeavors. The Roman god Janus is generally depicted as having the two identical faces in a back‐to‐back orientation, albeit in the original depiction, the faces were different (with and without a beard). Notably, the ability to discriminate between two similar faces is omnipresent in stereoselective organic synthesis, as exemplified by the ability to promote si over re face selectivity in the addition of a nucleophile to a carbonyl group in the presence of a chiral catalyst. There are many other examples of this general principle, each having its challenges defined within a specific mechanistic construct. The following triumvirate of chapters focuses on reactions that share this important ability: to differentiate similar groups, faces, and termini in molecules resulting in highly chemo‐, regio‐ and stereoselective processes. Although the reactions in each chapter are mechanistically orthogonal, they each embody and illustrate the so‐called Janus effect. For instance, the first chapter outlines the enantioselective halofunctionalization of olefins, which differentiates the two olefin faces. The second chapter details the diboration of unsaturated compounds to afford unsymmetrical geminal and vicinal diboranes. The final chapter on the Matteson reaction details the stereoselective rearrangement of tetracoordinate boronate anions.

The first chapter by Kumar D. Ashtekar, Arvind Jaganathan, Babak Borhan, and Daniel C. Whitehead provides an outstanding account of the enantioselective halofunctionalization of alkenes. The seminal work on this transformation can be traced back to Bartlett and Tarbell in the mid‐1930s and the mechanistic interpretation of the anti‐stereoselectivity to Kimball shortly thereafter. Surprisingly, the area remained relatively dormant for approximately forty years until a series of reports on stereoselective intramolecular halocyclizations, specifically iodocyclizations. Nevertheless, the challenging issue of controlling facial selectivity was primarily ignored until Ishihara's landmark work, which demonstrated that the BINOL‐derived phosphorimidate promotes a stereoselective iodo‐polyene cyclization, albeit using a stoichiometric amount of the reagent. This chapter catalogs the development of this process from a mechanistic nuance into a powerful synthetic tool to facilitate the enantioselective halofunctionalization of alkenes. The Mechanism and Stereochemistry section highlights the need to avoid molecular halogens, which are too reactive to serve as viable halenium ion sources because they promote a competing and inherently nonselective background reaction. Hence, a series of less reactive halogenating agents are used along with different catalytic activation methods, namely, Brønsted acid catalysis, Lewis acid catalysis, Lewis base catalysis, and phase‐transfer catalysis. The Scope and Limitations component is organized by the halogen (Cl, Br, and I), with various nucleophiles (carboxylic acids, alcohols, amines, carbamates, thioimidates, halogens, water, and carbon nucleophiles) in the context of inter‐ and intramolecular additions with substituted alkenes. Notably, there is also a section on the desymmetrization and kinetic resolution reactions of alkenes that may be of interest to the reader. The Applications to Synthesis illustrate applications to the synthesis of several important natural products, and the Comparison with Other Methods section provides a direct comparison with the less well‐developed sulfeno‐ and selenofunctionalizations of alkenes. The organization of the Tabular Survey mirrors the Scope and Limitations, thereby making it easy for the reader to traverse between the two and identify a specific transformation. Overall, this is an outstanding chapter on a particularly important and useful process that will be a valuable resource to the synthetic community.

The second chapter by Ana B. Cuenca and Elena Fernández provides an excellent account of the diboration of unsaturated compounds, which is a particularly useful process for constructing geminal and vicinal diboranes, including unsaturated vicinal diboranes. The first direct addition of diboron compounds to unsaturated substrates, described by H. I. Schlesinger in 1954, resulted from the uncatalyzed addition of diboron tetrachloride to ethylene. Although there were follow‐up studies, the instability of the tetra(halo)diboron reagents limited their practical value for general applications. Nevertheless, in a groundbreaking paper in 1993, Akira Suzuki reported the first syn‐selective transition‐metal‐catalyzed diboration of alkynes with a tetraalkoxydiboron reagent, which prompted an explosion of interest in the development of this process. This chapter captures the historical development and important advances with various π‐components and describes the breadth of the recent developments in this active field of research. For instance, the Mechanism and Stereochemistry section delineates both uncatalyzed and transition‐metal‐ and Lewis‐base catalyzed processes. It also nicely outlines the origin of syn‐ and anti‐addition in the context of regio‐, chemo‐, and stereoselective additions, including enantioselective reactions. The Scope and Limitations component is subdivided into geminal and vicinal diboration where the latter is organized by the type of π‐component: alkenes, alkynes, allenes, arynes, dienes, α,β‐unsaturated carbonyls compounds, including a section on aldehydes, ketones, thiocarbonyls, and imines. The Applications to Synthesis provides several examples of the synthesis of natural products and pharmaceutically relevant agents, and the Comparison with Other Methods section provides a comprehensive assessment of other methods commonly deployed to construct these structural motifs. The Tabular Survey incorporates reactions reported up to April 2020. The tables follow the organization of the Scope and Limitations (i.e., geminal and vicinal diboration), where the latter is further subdivided into the type of π‐component framework (alkene, alkyne, allene, etc.) and kind of substitution (internal, terminal) to facilitate the identification of a specific reaction combination. Overall, this is a significant and timely chapter on an important transformation that continues to attract attention.

The third chapter by Donald S. Matteson, Beatrice S. L. Collins, Varinder K. Aggarwal, and Engelbert Ciganek chronicles the Matteson Reaction, which is the nucleophilic displacement of a suitable leaving group from the α‐carbon of an alkylboronic ester via a tetracoordinate boronate anion. The reaction was discovered serendipitously and became more broadly useful when it was demonstrated that the addition of (dichloromethyl)lithium to boronic esters results in an efficient 1,2‐metallate transposition to (α‐chloroalkyl)boronic esters. The chapter delineates the evolution of this reaction into one that provides the ability to generate multiple stereogenic centers with exquisite control, allowing construction of an array of challenging synthetic targets. The Mechanism and Stereochemistry section of this chapter outlines the basis for the spontaneous rearrangement of tetracoordinate boronate anions derived from boronic esters that contain an adjacent leaving group. This section outlines the two main methods that have been employed to generate enantiomerically‐enriched species, namely, a chiral boronate or a chiral carbanion. It also details the impact of matched and mismatched scenarios, the role of Lewis acids, the origin of epimerization and a discussion of other nucleophiles. The Scope and Limitations is also sub‐divided into sections on chiral auxiliary and chiral carbanion approaches, providing the opportunity to compare and contrast the merits of these approaches. Notably, the former component discusses methods for preparing (α‐haloalkyl)boronic esters, different homologation modes, and some limitations. This section is further subdivided into the types of nucleophiles that have been successfully employed (carbon, nitrogen, oxygen, etc.), including some unpublished work from the Matteson laboratory. The chiral carbanion section delineates the work with chiral (α‐chloroalkyl)lithium reagents and chiral α‐lithioalkyl carbamates and esters, which includes a discussion of their limitations. There is also a section on potential new applications and extensions, which may be appealing to some readers. The Applications to Synthesis component is a real tour de force, with examples of natural products and pharmaceuticals that range from insect pheromones to a FLAP enzyme inhibitor. A particular highlight is the ability to asymmetrically C1‐deuterate prochiral glycerol to prepare a chiral variant by adding a deuterium atom. The Comparison with Other Methods section provides an exhaustive account of the preparation methods of substrates and similar products. The Tabular Survey parallels the Scope and Limitations in the context of auxiliary and chiral carbanions, with the former divided into the number of leaving groups and the type of nucleophile. Overall, this chapter provides the reader with a critical overview of this transformation's evolution and recent developments to provide a unique treatise on an important named reaction.

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 editorial process's various stages. I would like to thank Scott E. Denmark (Chapter 1) and Dennis G. Hall (Chapter 2), who were the Responsible Editors for the first two chapters. I was responsible for marshaling Chapter 3 through the later phases of development after Jeffrey S. Johnson's early involvement. I am also deeply indebted to Dr. Danielle Soenen for her 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 authors', editors', and publishers' contributions. In addition, the Organic Reactions enterprise could not maintain the quality of production without the efforts of Dr. Steven Weinreb (Executive Editor), Dr. Engelbert Ciganek (Editorial Advisor), Dr. Landy Blasdel (Processing Editor), and Dr. Debra Dolliver (Processing Editor). I would also like to acknowledge Dr. Barry R. Snider (Secretary) for keeping everyone on task and Dr. Jeffery Press (Treasurer) for making sure that we are 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 collated tables of examples, make this series of reviews both unique and exceptionally valuable to the practicing synthetic organic chemist.

P. Andrew Evans

Kingston

Ontario, Canada

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Heinz W. Gschwend

April 12, 1936 – June 16, 2019

Heinz Gschwend was a superb synthetic chemist and an extraordinary drug hunter by applying rationale, skills and experience paired with instinct and pragmatism. Despite his capabilities, he remained humble, used an inclusive style as leader, and was a great coach and mentor to many who were lucky to cross his path.

He was born in the Bernese Oberland, Switzerland, in the town of Brienz. He valued and bonded to this spectacular part of the Swiss Alps his whole life and kept connections with family and friends throughout his life. Heinz studied chemistry at the Federal Institute of Technology in Zürich (ETH) and joined the group of Albert Eschenmoser for his PhD thesis, for which ETH awarded him the coveted Silver Medal for excellence. During this time and the following postdoctoral stay at Harvard University in the group of R. B. Woodward, he instrumentally contributed to the total synthesis of vitamin B12, by many considered to be the Mount Everest of total synthesis at that time.

He remained on the East Coast of the United States together with his wife Katharina Gschwend‐Steen and joined Ciba Pharmaceutical in Summit NJ, in 1967, where he refined his medicinal chemistry and drug discovery skills, taking positions with increasing amount of responsibilities, finally heading drug discovery at the site. It was during this time that Heinz could realize the dream of every medicinal chemist to be instrumentally involved in the discovery of novel drug molecules that will become successful therapeutics. These efforts resulted in the marketed drugs Benazepril, an ACE‐inhibitor to lower blood pressure, and Letrozole, an aromatase inhibitor to treat hormone‐responsive breast cancer.

In 1989, he moved to Basel, Switzerland, to head the Central Research Laboratories and take responsibility for the two subsidiaries in Takarazuka, Japan, and Macclesfield, UK. These institutes ran traditionally a highly diverse research portfolio, including polymer chemistry, agrochemicals, dyes, drug discovery, synthetic methodologies and material science. Heinz was tasked to reorganize this fragmented portfolio. With his leadership, the focus was reoriented to three major topics with pharmaceutical applications in mind: material sciences, carbohydrates and nucleic acids. The way he approached this difficult task was unique during these times: rather than relying on external consultants or his own opinion, he chose an inclusive approach and encouraged scientists internally to provide input and proposals, which formed the basis for the new scientific focus. The antisense oligonucleotide projects, in collaboration with ISIS Pharmaceuticals (now Ionis) and internal biology, resulted in the identification of novel chemical matter that is still used now and reflects a benchmark in the field of modified oligonucleotides.

Heinz moved back to the US and joined Arris Pharmaceuticals, an emerging Bay Area biotech company to take on multiple senior roles, including the role as Executive Vice President of Research and Preclinical Development. In 1998, he became an independent consultant and besides advising many biotech companies with his synthetic and drug discovery experience, he supported multiple Venture firms with his knowledge.

While Heinz was highly successful in drug discovery, he never lost his passion for synthetic chemistry. Over decades, he built and assembled a collection of useful and important reactions. Whenever synthetic problems were up for discussion, he would often remember the specifics for a key transformation and be able to pull it out from his formidable stack of index cards. He was the senior author of the very important Organic Reactions chapter on Heteroatom‐Facilitated Lithiations (Gschwend, H, W.; Rodriguez, H. R. Org. React. 1979, 24, 1). With close to a thousand citations, it is one of the most cited chapters in this series. This eventually led to his appointment to the Editorial Board of Organic Reactions from 1982 to 1989, a role he took very seriously and was greatly proud of. He also served as Chairman of the Gordon Research Conference on Heterocyclic Chemistry in 1988. Heinz was a humble giant in the world of chemistry.

In retirement, Heinz enjoyed the simple pleasures of tending to his fruit trees, chopping wood, playing tennis, hiking along the Sonoma Coast and enjoying the local wineries. He was a devoted father, grandfather and attentive family man. Musical aptitude was apparent for many generations in Heinz's family and he expertly played classical pieces on the piano right up to the time of his passing.

Heinz passed away on June 16, 2019 with his wife, Cynthia, at his side. He is survived by his brother Martin Gschwend, Switzerland, his wife, Cynthia Healy of Santa Rosa, California, sons Dominik of Rockledge, Florida, Daniel of Windham, New Hampshire, Gregory of New York, N.Y., Connery of Georgetown, Washington D.C. and three grandchildren, Kyle, Kaelin and Andrew.

Heinz Moser

Novartis

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Hans J. Reich

May 6, 1943 – May 1, 2020

Hans J. Reich was born in Danzig, Germany, and emigrated to Canada in 1950. After earning a B.Sc. at the University of Alberta in 1964, he entered graduate school at UCLA. He received a Ph.D. with D. J. Cram in 1968. Reich met his future wife, Ieva, while they were both graduate students at UCLA. Reich spent two years doing postdoctoral work supported by a Canadian National Research Council Postdoctoral Fellowship, the first at Cal Tech with J. D. Roberts, and the second at Harvard with R. B. Woodward. In 1970, Reich joined the faculty at the University of Wisconsin at Madison. He was promoted to Associate Professor in 1976 and to full Professor in 1979. From 1975 to 1979 he held a Sloan Fellowship. Professor Reich has held visiting Professorships at the University of Marburg in Germany, the Louis Pasteur University in Strasbourg, France, and the University of Alicante, Spain.

In the Chemistry Department, Reich was Chair of the Organic Division from 1991 to 1999 and Associate Chair of the Department from 1999 to 2005. His contributions to the Department and the UW‐Madison campus more broadly were recognized by the Helfaer Professorship in Chemistry, the Professor James W. Taylor Excellence in Teaching Award (1994) and the University of Wisconsin Mid‐Career Award (1995).

Reich's scholarly achievements were recognized by the Arfvedson‐Schlenck Prize (Lithium Award) sponsored by the German Chemical Society (2007) and the James Flack Norris Award in Physical Organic Chemistry sponsored by the American Chemical Society (2012).

In his 43 years as a faculty member Reich served as research supervisor for 39 Ph.D. students, 18 M.S. students and 59 undergraduate researchers. He published more than 150 papers in refereed journals, 9 review articles and a computer program. His most cited paper, on the selenoxide elimination, received over 900 citations up to the time of his death.

During his time at Wisconsin Reich taught a number of courses, both at the undergraduate level, where he initiated and regularly taught Chemistry 547, Advanced Organic Chemistry, and at the graduate level, where he taught Chemistry 605, Structure Determination Using Spectroscopic Methods (mainly NMR) annually from 1981 until after his retirement. This course was legendary among many generations of Wisconsin graduate students. Reich reached over 1000 chemists through an ACS continuing education short course, Frontiers of Organic Chemistry, from 1982 to 2007.

His research program was supported continuously by the National Science Foundation from 1972 to 2010, and sporadically by the National Institutes of Health (National Institute for Arthritis, Digestive Diseases and Kidneys, National Institute for Environmental Health Sciences), by grants from private funds and industrial sources. The program explored the synthetic and mechanistic aspects of organoselenium, organosilicon, and organolithium compounds. His efforts included smaller forays into organotellurium, organotin, organoantimony, organosulfur and organoiodine compounds.

Reich's work in organoselenium chemistry was aimed at developing methods for performing previously difficult or impossible chemical transformations of organic molecules using the special properties of this element. One of the methods developed (the selenoxide elimination to form α,β‐unsaturated carbonyl compounds and other alkenes) has become a standard procedure adopted by chemists throughout the world; this chemistry is covered in many undergraduate textbooks. His work with selenium compounds also contributed to understanding the chemical aspects of the role this essential trace element plays in metabolism.

Work in the synthetic area was always supported and enhanced by clarifiying mechanistic studies, especially when an unexpected chemical event jeopardized the synthetic utility of the reactions being developed. When he became seriously interested in organolithium chemistry in the mid 1980's his work took a decidedly stronger mechanistic organometallic turn. This experimentation, which made heavy use of NMR spectroscopic investigations, contributed substantially to our understanding of the chemical behavior of these widely used, highly reactive and structurally complicated reagents. He firmly established the presence of multiple aggregation states and identified changes in structure and reactivity that occurred under different conditions. His students developed a Rapid‐Inject NMR apparatus capable of operation down to –140 °C, and the group used this device to perform the first accurate measurements of the reactivity of specific oligomers, such as the dimer and tetramer of n‐butyllithium, the monomer, dimer and tetramer of several enolates, and of oligomers of aryllithium reagents.

Reich had an extraordinary commitment to the assembly of data that would be broadly useful to organic chemists, and to making this information available to other scholars and students. The Division of Organic Chemistry of the American Chemical Society recently launched an Organic Chemistry Data website (https://organicchemistrydata.org/) that is largely based on resources that Reich developed over many years. He also served for many years on the Board of Editors for Organic Reactions.

Reich had an unusual and appealing personality. He was deeply insightful, and he was direct in his communications. As one colleague observed, he could explain to you why your favorite hypothesis could not possibly be correct in a way that did not leave you feeling bad. For this reason, he was widely sought among colleagues and students for advice and guidance. Hans Reich is deeply missed by his wife, fellow chemist Dr. Ieva Reich, his former students, his colleagues at UW‐Madison and by friends and fellow scholars around the world.

Samuel H. Gellman,

University of Wisconsin–Madison