ADVISORY BOARD

FORMER MEMBERS OF THE BOARDNOW DECEASED

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.

Your fair discourse hath been as sugar,

Making the hard way sweet and delectable.

William Shakespeare

Richard II, act 2, sc. 3, l. 6‐7

Cycloadditions can hardly be described as sweet and delectable; however, the impact of these transformations often circumvents protracted and time‐consuming alternatives for the de novo construction of carbocycles and heterocycles. The following single‐volume chapter by Arnaud Martel, Robert Dhal, Catherine Gaulon, Mathieu Yves Laurent, and Gilles Dujardin describes the inverse‐electron‐demand oxa‐Diels–Alder (IODA) reactions of α,β‐unsaturated carbonyl compounds with electron‐rich dienophiles to prepare 3,4‐dihydro‐2H‐pyrans. The history of dihydropyrans can be traced back to the late 1800s when Perkin first described their preparation through a simple dehydration reaction; however, their importance may be more significantly connected to the pioneering work of Emil Fischer, who first generated glycals (dihydropyrans derived from sugars) in 1913. It is therefore with some irony that the very same dihydropyrans would later feature so prominently in the synthesis of complex sugars, and that their construction can be achieved by a simple adaptation of the conventional Diels‐Alder reaction. Indeed, the importance of the classical Diels‐Alder process was elegantly delineated by Corey in 2002.

“If one chemical reaction had to be selected from those in the repertoire of synthetic organic chemists as the most useful and powerful construction, it was clear by 1970 that the Diels‐Alder reaction would be the logical choice. Its application not only leads to a strong increase in molecular complexity (molecular size, topology, stereochemistry, functionality and appendages), but also can result in structures that lend themselves to additional amplification of complexity by the use of other powerful synthetic reactions.”

E. J. Corey (Angew. Chem. Int. Ed. 2002, 41, 1650).

The inverse‐electron‐demand oxa‐Diels–Alder (IODA) reaction represents an important variant of the classical Diels‐Alder process, which, as noted, provides a very powerful approach to generating molecular complexity. Nevertheless, the critical developments in the IODA reaction followed from the foundation established by the more venerable counterpart, and arguably with the relevance of dihydropyrans already well established. As with the development of many reactions, the preliminary discovery provided dogma that delayed the full exploitation of this conceptionally useful process. For instance, the first example of the IODA reaction by Sherlin in 1938 involved the dimerization of acrolein, which was closely followed by the dimerization of methyl vinyl ketone by Alder in 1941. Although the crossed variant was initially restricted to highly electron‐rich dienophiles, as exemplified by the thermal reactions of enamines and enol ethers, the intermolecular IODA process has now been extended to a variety of alkenes using a wide range of activated oxadienes that contain an array of substituents on the 4π component. This chapter provides an historical perspective of the development of IODA reactions and delineates the various advances that pertain to asymmetric variants, particularly the advent of catalytic methods. Notably, the chapter outlines the scope and limitations, which identify knowledge gaps and provide the reader with a perspective of the critical contributions and their impact, while also highlighting the current limitations and how these are manifested in target‐directed synthesis. Furthermore, in the Comparison with Other Methods section, the authors list representative alternative approaches that provide this important motif. The Tabular Survey is organized by the function of the oxadiene that undergoes the IODA, which makes identification of the optimal reaction and the associated conditions relatively easy for the reader to identify.

I would like to take this opportunity to acknowledge Scott E. Denmark's tenure as Editor‐in‐Chief and President of Organic Reactions, Inc. Remarkably, he oversaw the completion of 30 volumes that boast 69 chapters including nearly 20,000 pages encompassing an array of modern synthetic reactions. His intrepid leadership and pursuit of excellence has elevated the Organic Reactions brand into one of the leading reference texts in the chemical literature. Volume 100 was a landmark publication, featuring a who's who list of authors using a truncated format. While OR will continue to provide the most definitive reviews of specific reactions, the format has been changed and in the future the tables and references will no longer be comprehensive, but rather will list what the author believes are the most relevant examples to assist the reader in their reaction selection. Additionally, we are now publishing Organic Reactions volumes quarterly, so please add this to your calendar to make sure you can obtain the latest installment of this venerable series.

Finally, I would be remiss if I did not acknowledge the entire Organic Reactions Editorial Board for their collective efforts in steering this chapter through the various stages of the editorial process. I would like to particularly thank Steven Weinreb, who served as the Responsible Editor and worked tirelessly with the authors to ensure the completion of this chapter. I am also deeply indebted to Dr. Danielle Soenen for her continuous efforts as the Editorial Coordinator; her knowledge of Organic Reactions is a critical component to maintaining consistency in the series. Dr. Dena Lindsay (Secretary to the Editorial Board) is thanked for coordinating the contributions of the authors, editors and publisher. In addition, the Organic Reactions enterprise could not maintain the quality of production without the efforts of Steven Weinreb (Executive Editor), Dr. Linda S. Press (Editorial Consultant), Dr. Engelbert Ciganek (Editorial Advisor), Dr. Landy Blasdel (Processing Editor) and Dr. Debra Dolliver (Processing Editor). I would also like to acknowledge Dr. Jeffery Press (Secretary‐Treasurer) for his constant effort to keep everyone on task and his attention to making sure that we are fiscally solvent!

In summary, I am indebted to all the people that work so hard to maintain the 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 useful to the practicing synthetic organic chemist.