Organocatalysis Eric

T he field of asymmetric catalysis is dedicated to the development of efficient catalytic methods for the construction of chiral molecules and has been dominated by the use of organometallics and enzymes for most of its history. However, in the past decade, the concept of organocatalysis has emerged as a discrete strategy for addressing modern day challenges in chemistry. It has become widely appreciated that small molecule organic catalysts can hold a wide range of practical advantages relative to macromolecular or precious metal catalysts, including air and water stability, low cost, availability from renewable resources, and relative nontoxicity. With the dramatic recent expansion of research efforts in organocatalysis throughout the world, synthetically useful transformations based on new reactivity concepts have been identified, often with no counterpart in the more established catalysis regimens. To that end, this PNAS Special Feature on organocatalysis offers a sampling of the current state of the field and how some of the most significant challenges are being addressed by its leading researchers. To make the different catalysis concepts readily apparent, the papers in this issue are organized based on modes of catalytic reactivity. In many cases, these generic modes of reactivity are executed by very different types of catalyst scaffolds. For example, the first pair of manuscripts highlights desymmetrization reactions catalyzed by Lewis base organocatalysts with either a tetrazole-bearing peptide or primary amine scaffold (1, 2). The next subset of manuscripts represents the alternative case, in which relatively similar types of aminocatalysts provide paths to a diverse array of catalytic platforms for the α-, β-, and γfunctionalization of carbonyl compounds (3–6). This section highlights examples from the fields of iminium, enamine, dienamine, and singly occupied molecular orbital (SOMO) catalysis, in which mechanistic insight, reaction partner scope, or product accessibility has been expanded in significant ways. The next classification of articles is somewhat broader and includes those modes of activation that are catalyzed by nonamine-centered Lewis bases (7–10). Although there are fewer established modes of generic activation that fall into this category, the potential for reaction discovery in this arena is evident from the highlighted examples, which represent quite disparate modes of activation arising from phosphorus, chalcogen, and N-heterocyclic carbene catalysts. Finally, several papers highlight the development of transformations through the combined action of multiple activation modes. This is illustrated in the final grouping of articles on noncovalent interactions (11, 12). Either through combination with established covalent-based modes of activation or in concert with other noncovalent approaches, these manuscripts make it evident that anion-binding and hydrogenbonding catalysis represent rich areas for the development of reactivity concepts.