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.

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 21^st 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 21^st 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.

The wings of transformation are born of patience and struggle.

Janet S. Dickens

The ability to control chemical reactivity and selectivity represents the very essence of modern synthetic organic chemistry, albeit these goals often pose complex challenges for chemists engaged in discovering new chemical reactions. For instance, highly reactive reagents often demonstrate low selectivity, limit substrate scope, and lead to competing side reactions. Consequently, many reactive intermediates are best generated from less reactive precursors under mild and often catalytic conditions to mitigate some of these detrimental issues. The ability to “mask” and “trigger” chemical reactivity provides a measurable strategic advantage that often underpins the evolution of a basic synthetic method into a sophisticated and practical process with fewer limitations. Hence, the challenges encountered in developing such a transformation are indeed “born of patience and struggle,” which may disguise the extensive experimentation required to enable the “metamorphosis” of a simple hypothesis into a robust chemical transformation.

The Organic Reactions series provides an enduring narrative that showcases the so‐called “life‐cycle” of these developments, which can be ascribed to the unique blueprint provided by Roger Adams at the outset of this venerable series in 1942. As part of this vision, the chapters are written by recognized experts in the field in a consistent and unified format to disseminate critical features of the transformation that enables the practicing synthetic organic chemist to gain the in‐depth understanding and insight necessary to utilize the reaction successfully. For example, the chapters dissect crucial elements of a process within the context of the reaction mechanism and stereochemistry, scope and limitations, applications to synthesis, a comparison with other methods, and critical experimental details and procedures. For this reason, Organic Reactions chapters provide unparalleled insights into the various underpinnings of an important chemical reaction that would be challenging to assimilate, even with modern computerized search engines.

This single‐chapter volume by Frank S. Guziec, Jr. and Lynn James Guziec provides a comprehensive treatise on extrusion reactions, which involve the loss of a small, stable inorganic molecule, such as carbon dioxide and nitrogen, or an atom, such as sulfur, from an organic precursor. Hence, the chapter deals with the notion of “unmasking” chemical reactivity to access arenes, dihydroarenes, heteroarenes, dienes, and polyenes and other challenging targets. The chapter provides an update on the extrusion of carbon dioxide and nitrogen in retro‐Diels‐Alder reactions (Volumes 52 and 53); however, the related Ramberg‐Bäcklund reaction with the extrusion of sulfur dioxide (Volumes 25 and 62) and the Eschenmoser‐type ring‐contraction‐extrusion reaction are not included. The introduction briefly defines extrusion and cheletropic processes, which are formally a type of pericyclic reaction that proceeds via a cyclic transition state with reorganization of σ‐ and π‐bonds. The mechanistic aspects of these reactions remain relatively poorly understood, and most of our insight is gleaned by inference rather than actual mechanistic studies. For instance, the stereochemical outcome of thermal and photochemical extrusion of sulfur dioxide from 3‐sulfolenes provides complementary stereochemistry that is ascribed to the difference in the mechanism. The thermal extrusion is a disrotatory process according to the Woodward‐Hoffmann rules, whereas the corresponding photochemical process involves a conrotatory mechanism from an excited state intermediate. The mechanistic aspects of the extrusion of other groups, namely, sulfur monoxide, carbon monoxide, and molecular nitrogen illustrate the challenges in delineating a unified approach, given the subtle differences in each extrusion process. The section also describes how structural features in a series of bicyclic ketones provide insight for the observed extrusion rates, using kinetic studies and calculations.

The Scope and Limitations section is organized by the product (e.g., arenes, dihydroarenes, heterocycles, dienes, and polyenes) and then further subdivided by the type of extrusion (e.g., carbon monoxide, carbon dioxide, sulfur, sulfur dioxide, sulfur monoxide, selenium and tellurium, oxygen, and nitrogen), including reductive extrusion reactions. Notably, the extrusion process is subdivided by the nature of the dienophile often involved in the extrusion process, namely, benzynes, alkynes, alkenes, etc. A particular highlight is the extrusion of carbon monoxide from cyclopentadienone–polyacetylene adducts, which represents a powerful method for the iterative preparation of dendrimeric structures to form higher‐generation dendrimers. Additional sections focus on tandem extrusion reactions and include a section on ‘click’ reactions of triazines and tetrazines that showcase both creative and useful applications of this chemistry. The chapter also contains several sections on comparative studies, which, in conjunction with the Tabular Survey, provide the reader with the additional insight needed to select the appropriate precursor for the desired extrusion reaction.

The Applications to Synthesis section describes the use of the methodology to prepare arenes, heterocycles, dienes, and polyenes that have been subsequently employed to synthesize alkaloids and pheromones. There is also an extensive section on “click and release” reactions, which have been used in the development of prodrugs in medicinal chemistry. The Comparison with Other Methods section outlines a few related strategies for the de novo synthesis of arenes and 1,3‐dienes to provide the reader with a broader perspective on how the extrusion reactions compare with existing methods. The Tabular Survey incorporates reactions reported through early 2021. The organization mirrors the Scope and Limitations in that the reactions are organized by the product in the context of the type of extrusion process, which permits the identification of the optimal extrusion process for accessing a particular target. Overall, this is an excellent chapter on a venerable and important transformation relevant to modern synthetic, medicinal, and bioorganic chemistry.

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' stages. I want to thank Dr. Stuart McCombie and Dr. Jin K. Cha, who served as Responsible Editors to marshal the chapter through the various phases of development. I am also deeply indebted to Dr. Danielle Soenen for her continued and heroic efforts as the Editorial Coordinator; her knowledge of Organic Reactions is critical to maintaining consistency in the series. Dr. Dena Lindsay (Secretary to the Editorial Board) is thanked for coordinating the authors', editors', and publishers' contributions. In addition, the Organic Reactions enterprise could not maintain the quality of production without the efforts of Dr. Steven M. Weinreb (Executive Editor), Dr. Engelbert Ciganek (Editorial Advisor), Dr. Landy Blasdel (Processing Editor), and Dr. Tina Grant (Processing Editor). I would also like to acknowledge Dr. Barry B. Snider (Secretary) for keeping everyone on task and Dr. Jeffery Press (Treasurer) for his fiscal diligence.

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 specific format of the chapters, in conjunction with the collated tables of examples, makes this series of reviews both unique and exceptionally valuable to the practicing synthetic organic chemist.

P. Andrew Evans

Kingston

Ontario, Canada