Asymmetric Catalysis by Chiral Hydrogen‐Bond Donors

Abstract Hydrogen bonding is responsible for the structure of much of the world around us. The unusual and complex properties of bulk water, the ability of proteins to fold into stable three‐dimensional structures, the fidelity of DNA base pairing, and the binding of ligands to receptors are among the manifestations of this ubiquitous noncovalent interaction. In addition to its primacy as a structural determinant, hydrogen bonding plays a crucial functional role in catalysis. Hydrogen bonding to an electrophile serves to decrease the electron density of this species, activating it toward nucleophilic attack. This principle is employed frequently by Nature's catalysts, enzymes, for the acceleration of a wide range of chemical processes. Recently, organic chemists have begun to appreciate the tremendous potential offered by hydrogen bonding as a mechanism for electrophile activation in small‐molecule, synthetic catalyst systems. In particular, chiral hydrogen‐bond donors have emerged as a broadly applicable class of catalysts for enantioselective synthesis. This review documents these advances, emphasizing the structural and mechanistic features that contribute to high enantioselectivity in hydrogen‐bond‐mediated catalytic processes.