Organic Reactions

By Wiley

The 96th 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: Aug 14, 2018
• ISBN: 9781119456858

Book preview

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 96

Through many faces We have returned to the source Everything was Hydrogen But the Earth has bound it. Now, it is being freed. It invites us to move machines, Arms and legs a billion times, Letting us explore Comets, moons and planets.

Mario Markus, Chemical Poems One On Each Element Dos Madres Press: Loveland; 2013, p 7.

Hydrogen was the first element formed after the Big Bang and is the most comment element in the Universe. It was discovered in 1766 by Henry Cavendish who took great pleasure in demonstrating its ability to combine in dramatic fashion with air (oxygen was not yet discovered) producing water. The formation of water as the product of that reaction gave name to the element from the Greek hydro (water) and genēs (maker). This universally popular demonstration also proved that water was not an element as it clearly arose from more fundamental components.

Despite its abundance, very little free hydrogen exists in the Earth's atmosphere (0.00055%), but thanks to the ubiquitous presence of water on Earth, it represents 10.82% by mass of the oceans! Moreover, thanks to the evolution of photosynthesis, all of the biomass on the Earth contains carbon‐hydrogen bonds created from carbon dioxide and water.

The addition of molecular hydrogen to organic compounds has a long and storied history bracketed by two landmark Nobel Prizes in Chemistry. The first to Paul Sabatier for his method of hydrogenating organic compounds in the presence of finely disintegrated metals and the second to William S. Knowles and Ryoji Noyori for their work on chirally catalyzed hydrogenation reactions. The two chapters in this volume have the introduction of hydrogen to unsaturated compounds in common; but only partly.

The first chapter, authored by Lei Shi and Yong‐Gui Zhou, represents a significant advance in the introduction of hydrogen to unsaturated groups, in this case the enantioselective reduction of heteroaromatic compounds. The pervasive occurrence of saturated heterocycles in bioactive compounds demands a general and selective procedure to access these privileged building blocks. Saturation of readily available heteroaromatic precursors represents one of the most atom‐economical and widely applicable approaches. However, this process has been difficult to accomplish compared to the saturation of carbocyclic aromatic compounds for several reasons. First, six‐membered heterocyclic compounds enjoy a high level of aromatic stabilization thus requiring forcing conditions and reduction of five‐membered ring heterocycles leads to catalyst poisoning by binding of the heteroatoms to the metals. In recent years, the introduction of new metal complexes along with other types of catalysis has to a large extent solved this problem.

Professor Zhou is a world leader in the development of new ligands and metal complexes designed to effect the enantioselective reduction of both classes of heteroaromatic compounds. In this comprehensive account, the authors detail the latest advances in the use of iridium, rhodium and ruthenium catalysts (often activated by iodine) to effect the enantioselective reduction of pyridines, quinolines, isoquinolines, quinoxalines, indoles and pyrroles. Many examples of highly selective reductions are described with high catalyst turnover and excellent chemical yields. Although the atom economy of catalytic hydrogenation is hard to surpass, some of these reductions require high pressures (700 psi) to effect reduction. Alternative methods have been developed in recent years that combine hydride donors inspired by NADH (Hantzsch ester) together with chiral phosphoric acids as the proton sources. High selectivities have been achieved for certain classes of substrates. At the end of each section, the authors have provided recommendations for the best combination of catalyst and conditions for each substrate class.

The second chapter represents a reaction that also adds hydrogen to an unsaturated linkage, but not at both ends. In this case, the second addend is an acyl group representing the formal addition of an aldehyde across a double bond known as hydroacylation. Hydroacylation bears a close resemblance to hydroformylation, one of the largest transition‐metal‐catalyzed reactions performed on an industrial scale. For applications in organic synthesis, hydroacylation can be conducted both intra‐ and intermolecularly and additions to alkenes, alkynes and carbonyl compounds have been developed. Much of the pioneering work in recent years on the development of enantioselective variants of this process has been carried out in the laboratories of Professor Vy M. Dong at the University of California‐Irvine. We are tremendously grateful that Prof. Dong together with coauthors Kevin G. M. Kou and Diane M. Le have agreed to compose the definitive chapter on this highly versatile transformation. These experts have produced an outstanding treatise that covers the entire scope of substrate type and preferred catalysts/ligand combinations to effect the most efficient and selective process. The challenges associated with hydroacylation include the propensity toward decarbonylation of the critical acylmetal intermediate, resulting in simple reduction of the formyl precursor. However, new strategies have been introduced in recent years to ameliorate this problem, particularly for intermolecular reactions. The authors have provided a highly practical user's guide to enable the practitioner to select the catalyst and conditions that are most likely to lead to success. Fascinating new variants that allow the use of formates and formamides in hydroacylation for the construction of esters and lactams are also included. Of particular note are the high enantioselectivities now achievable for the construction of cyclic ketones and lactones.

It is appropriate here to acknowledge the expert assistance of the entire editorial board, in particular Gary A. Molander (Chapter 1) and Paul Feldman (Chapter 2) who shepherded this volume to completion. The contributions of the authors, editors, and publisher were expertly coordinated by the board secretary, Dena Lindsay. 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. Landy Blasdel and Dr. Robert Coates. 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

Andrew S. Kende: (1932 – 2018)

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Andrew S. (Andy) Kende was born in Budapest, Hungary in 1932. With World War II impending, his family immigrated to the United States in 1939 settling in the Bronx where he received his earliest schooling. The family relocated to the suburb of Evanston, IL where Andy was educated through high school. A portent of things to come, he later described being fascinated with chemistry at six years old: It's always seemed to me an interesting way to structure information, he said. Things relate in a sensible way.

At an early age, Andy exemplified the excellence he would later encourage in his students. He was the winner of the National Westinghouse Science Talent Search at age 15 where he bested a future National Academy member and former President of the American Chemical Society Ronald Breslow, who as fate would have it, would later become Andy's graduate school lab mate at Harvard. At 16, he enrolled at the University of Chicago. After earning a 2‐year A.B. degree, Andy moved to Florida State University for his B.S. in chemistry. He received his Ph.D. degree in Organic Chemistry in 1957 at Harvard working with the Nobel Laureate Professor Robert B. Woodward. His doctoral work elucidated new pathways for the reactions of aliphatic diazo compounds with ketenes and led to the first spectroscopic characterization of pure cyclopropanone. With the assistance of an NRC‐American Cancer Society Postdoctoral Fellowship (1956–57), Andy moved from Harvard to the UK's University of Glasgow to work with another Nobel Laureate, Sir Derek H. R. Barton, where he demonstrated the structure of the major photoisomerization product of dehydroergosteryl acetate.

Andy joined Lederle Laboratories in 1957–58 where his excursion into natural products chemistry continued as part of the team that synthesized the antibiotic tetracycline. In 1968 he accepted an appointment as Professor of Chemistry at the University of Rochester. His research program there focused on three principal themes: early work in organic photochemistry, pericyclic reactions, and total synthesis.

Andy joined the editorial board of Organic Reactions in 1970 while William Dauben was Editor‐in‐Chief. During his twelve‐year term on the editorial board, Organic Reactions published ten volumes. Because of Andy's avid interest in the Organic Reactions organization, he was elected to the Board of Directors in 1980. He assumed the role of Editor‐in‐Chief in 1984 and held that position for five years before handing the mantle to Leo Paquette. Andy remained on the Board of Directors until his resignation in 2013. During his four decades with Organic Reactions, Andy was responsible for the appointment of an additional Editorial Board secretary. This position was required as Organic Reactions grew from publishing roughly a single volume annually to its current multiple volumes a year.

Andy was also a member of the Editorial Board and Editor of Volume 64 of Organic Syntheses. He subsequently joined the Board of Directors and served as President of Organic Syntheses, Inc. from 2002–2012. In this latter role, he oversaw the beginning of Organic Syntheses transition from a purely print format to the current electronic and print publications.

Because of Andy's well‐known fondness for good food and wine, combined with his involvement in both the Organic Reactions and Organic Syntheses organizations, there was a good‐spirited competition of the organizations' dinners held at each annual or bi‐annual meeting to determine which dinner was best. Andy, of course, was the sole judge.

Andy held many honors. He was an associate editor of the ACS Journal of Organic Chemistry for 12 years. He was a member of the Editorial Advisory Boards of Chemical Reviews and Synthetic Communications. Andy held a Guggenheim Fellowship and presented invited lectures, including several Gordon Conference lectures, NSF Workshops in Natural Products Chemistry, and the International Symposium on Anthracycline Chemistry, as well as plenary lectures at the Royal Society of Chemistry, the International Conference on Heterocyclic Chemistry, and the Medicinal Chemistry Symposium. He was awarded a Japan Society for Promotion of Science Fellowship and also received an ACS Cope Senior Scholar Award. Several of Andy's compounds were patented and he was chosen 'inventor of the year' by the Rochester Patent Law Association in 1979.

After his retirement from teaching 1998, he continued productive research until 2002, when Andy and his wife, Fran, moved to Scottdale, AZ. During the next 16 years, Andy and Fran continued to indulge their passion for travel and good food. Andy was a lifelong lover of good food of all types (particularly meat and potatoes but famously not fish), prepared and served well. As in everything he did, he brooked no incompetence in either area.

Andy demanded excellence from all of those around him; students, staff, and faculty. His vision, imagination, and vast knowledge of organic chemistry were a valuable resource and set a standard which I tried to emulate. His selfless and energetic service to the field of organic chemistry was exemplary. Andy enjoyed teaching and was a demanding instructor, but his real thrill was in mentoring and training his graduate students. He mentored over 50 postdocs and 50 graduate students during his career. At Rochester, Andy had the reputation for demanding scientific excellence and would not settle for less than the pursuit of science at the highest level. The lessons they learned from him – about chemistry, about working hard and achieving excellence – have remained with them over the years.

Yuh‐geng Tsay, an early Ph.D. student, remembers that whenever Andy returned from a business trip, he would stop by the lab first to see how everyone was doing. This type of work ethic has inspired us not only to work hard, but to have a sense of urgency in everything you do. His teaching style empowered us to solve any technical challenge and to be independent problem solvers.

Lanny Liebeskind, a Ph.D. student in the mid ‘70’s, remembers walking into Andy's lab for the first time as a new graduate student. I remember asking Andy when I should start my research. His succinct answer, in effect, was ‘Now!’ says Liebeskind, the vice provost for strategic research initiatives and Samuel Dobbs Professor of Chemistry at Emory University. I got the message loud and clear. It was a bit like being dropped into a professional sports team where the coach is constantly challenging you to push yourself beyond the comfort level. In doing so, you grew in ways as a scholar and person that you never would have on your own. Tsay had a similar experience. When I toured Professor Kende's labs, I noticed there was a memo from him posted in each cubicle of his graduate students and postdocs. Two key phrases stood out that got my attention. ‘When you are here, you should roll up your sleeves and work. If you cannot manage at least two experiments at the same time, you don’t belong in this group.'

In 1980 while Chair, Andy Kende recruited me to Rochester to join him and Dick Schlessinger as part of a group doing complex molecule synthesis. I will always be grateful to him for this opportunity that has done so much for my career and me personally.

Andy and Fran were also justifiably immensely proud of their son, Mark, who has gone on to considerable distinction in academia as a constitutional law scholar holding the James Madison Chair in Constitutional Law at the Drake