PREFACE TO VOLUME 114

The precision of naming takes away from the uniqueness of seeing.

Pierre Bonnard, Painter

An eponym honors and acknowledges a significant accomplishment by naming it after a person, object, or location. Today, we use eponyms for all manner of things and even to navigate - specific landmarks make something instantly recognizable and thus simplify directions (e.g., the Eiffel Tower, the Taj Mahal, Summer Palace, London Bridge, etc). Every aspect of modern life is now replete with examples, including science, medicine, technology, politics, literature, etc. The eponym is particularly important as a shorthand in many aspects of science, albeit there is often a primary and secondary hierarchy to enable scientists to precisely identify the relevant research more efficiently. Indeed, eponyms have become a so-called second language and are often a major component of the jargon that is so pervasive in many scientific fields. In organic chemistry, the naming of organic reactions has become a central theme that can be traced back to the nineteenth century, although the assignment of names can be controversial because, unlike the science it represents, it is based on many factors and is often subjective because the name(s) can reflect a different stage in a reaction's development! For instance, the first name reaction is the 1870 Lieben Haloform Reaction, although it was first reported by Georges-Simon Serullas in 1822. Nevertheless, the name reaction is now a central part of the language of organic chemistry in which the reaction type is sometimes added to further identify the process (e.g., Cope Rearrangement, Friedel-Crafts Acylation, Stille Cross-Coupling, etc.). In some cases, multiple names are used because of concurrent contributions (e.g., Buchwald-Hartwig Amination) or to recognize further developments of a specific process (e.g., Horner-Wadsworth-Emmons Wittig Olefination). The name reaction thus describes a kind of prototypical process in the context of the changes in bonding; however, the specific context is dramatically different and, as such, aligns with Bonnard's vision that the precision of naming is not a substitute for the uniqueness of seeing. Although the name can provide instant recognition, some of the more obscure processes are not as easily identified. Furthermore, the names can often be misleading and thereby lead to the amplification of a misconception about the origin of a process. Despite the pros and cons of name reactions, they have become a critical aspect of the language of organic chemistry and represent the essence of Organic Reactions, a preeminent reference work for the synthetic organic chemistry community that curates all the examples of a particular reaction to illustrate the breadth of the process. This volume contains three chapters on name reactions: the Cloke-Wilson Rearrangement, the Kinugasa reaction, and the Pictet-Spengler reaction.

The first chapter by Efraím Reyes, Liher Prieto, Rubén Manzano, Luisa Carrillo, Uxue Uria, and Jose L. Vicario provides a detailed account of the Cloke-Wilson Rearrangement, which is the heteroatom equivalent of the vinylcyclopropane-cyclopentene rearrangement to afford heterocycles. The reaction is named after the seminal reports by Cloke and Wilson in 1929 and 1947, respectively. The former reported the rearrangement of the imine of cyclopropyl phenyl ketone at 200 °C to afford 2-phenylpyrroline, whereas the latter described the preparation of 2,3-dihydrofuran through the thermal rearrangement of cyclopropanecarboxaldehyde at 375-500 °C. These examples illustrate that the rearrangement of cyclopropanes requires high temperatures despite their inherent ring and torsional strain, which has prompted the examination of the factors that permit milder reaction conditions. To this end, the addition of substituents that either increase ring strain or the polarity of the C-C bond (e.g., donor-acceptor cyclopropanes) has been examined. Alternatively, activating the cyclopropane with various reagents and catalysts has further broadened the scope to permit the rearrangement to proceed under milder conditions.

The Mechanism and Stereochemistry section outlines thermal and photochemical rearrangements that proceed through either a concerted or a biradical process depending on the cyclopropane structure, making this aspect challenging to control. For instance, adding donor and acceptor substituents lowers the barrier for the rearrangements, which are stereoselective rather than stereospecific, because of the biradical character of the reactive intermediate. The photochemical reactions proceed at room temperature and have been theoretically corroborated to involve biradical intermediates. This section also describes a series of Lewis acid- or Brønsted acid-catalyzed reactions that proceed in a stepwise manner through zwitterionic intermediates. Notably, the formation of an achiral intermediate enables a chiral Brønsted acid catalyst to facilitate the only enantioselective variant of this process. The Lewis base mediated reactions utilizing a stoichiometric promoter or catalyst have also been explored to facilitate stereospecific rearrangements. The Scope and Limitations section describes using the Cloke-Wilson Rearrangement to prepare dihydrofurans, dihydropyrroles, dihydrothiophenes, and dihydroisoxazole-2-oxides. The first two sections are further subdivided into the type of carbonyl functionality employed (e.g., aldehydes, ketones, carboxylates, carboxamides, etc.), including variations in substitution on these substrates. The section is completed with the sulfa- and nitro-variants of the Cloke-Wilson rearrangement, which are rare and thus may well provide future opportunities for reaction development.

The Applications to Synthesis section provides excellent examples that showcase the various adaptations of the rearrangement in the total synthesis of natural products to prepare an array of oxygen and nitrogen heterocycles. The Comparison with Other Methods section delineates several alternative approaches to unsaturated five-membered heterocycles, including dihydrofurans, pyrrolines, and dihydrothiophenes. There is also an extensive discussion of cycloadditions and sequential processes that afford similar heterocycles. The Tabular Survey is primarily organized in terms of the heterocyclic product formed and then by the nature of the starting cyclopropane substrate. Overall, this is an excellent chapter on an important reaction that will be invaluable to anyone interested in this transformation.

The second chapter by Marek Chmielewski, Rafal Kutaszewicz, Artur Ulikowski, Michal Michalak, Karol Wolosewicz, Sebastian Stecko, and Bartlomiej Furman provides a detailed account of the historical development of the Kinugasa reaction, which is the union of copper acetylides with nitrones to afford ß-lactams. Kinugasa and Hashimoto described the first example of this process in 1972 using copper phenyl acetylide and several diaryl nitrones to afford cis-disubstituted ß-lactams. Even though the reaction affords the appropriate stereochemistry for preparing a wide range of clinically important antibiotics, has excellent atom-economy, and employs stable starting materials, the reaction lay dormant for nearly three decades! Although copper acetylides were widely utilized in Sonogashira and Glaser couplings that were prevalent at the same time, they were ignored as coupling partners for nitrones in 1,3-dipolar cycloadditions. The renaissance of this transformation has been ascribed to the independent development of the copper-catalyzed Huigsen cycloaddition (CuAAC) by Meldal and Sharpless. Notably, the Sonogashira reaction is the subject of an upcoming chapter in Organic Reactions.

The Mechanism and Stereochemistry section outlines several possible mechanistic pathways that involve a 1,3-dipolar cycloaddition followed by a rearrangement. Although theoretical and experimental studies support a ketene-based pathway, two mechanistic variants for this process are presented. A third mechanistic possibility is also outlined, which involves an initial [3+2] cycloaddition (to form an isoxazoline), followed by a [3+2] cycloreversion and a Staudinger-type [2+2] cycloaddition, albeit this model does not explain the stereochemical outcome. The section on stereochemistry and constitutional isomerism delineates the origin of stereocontrol and the influence of substituents, including their effect on enantioselectivity. The section is further subdivided into the impact of a stereocenter in either the alkyne or nitrone fragments, including the influence of stereochemistry in both components in the context of matched and mismatched combinations. The section is completed with a discussion of several enantioselective variants that deliver both cis- and trans-cycloadducts. A very attractive aspect of this chapter is that the authors have meticulously delineated the origin of stereocontrol in every aspect of this process, which will be invaluable to the reader. The Scope and Limitations section is subdivided by the type of nitrone, namely diaryl nitrones (achiral- and chiral-based substituents), other acyclic variants, and five- and six-membered cyclic nitrones. The section on five-membered derivatives is further split into achiral and chiral nitrones reacting with achiral and chiral alkynes, which provides a guide to the...