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 p-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 p-component: alkenes, alkynes, allenes, arynes, dienes, a,ß-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 p-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 a-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 (a-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 (a-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 (a-chloroalkyl)lithium reagents and chiral a-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...