Catalytic Deracemization of Benzylic Stereocenters

Benzylic stereocenters are ubiquitous privileged motifs in pharmaceuticals, natural products, and bioactive molecules, with their absolute configuration directly governing the biological performance of parent compounds. Catalytic deracemization, which enables quantitative conversion of racemates to a single target enantiomer with a 100% theoretical yield, represents an atom-economical and indispensable complement to de novo asymmetric synthesis for accessing enantioenriched compounds bearing benzylic stereocenters. This review systematically summarizes state-of-the-art advances in the catalytic deracemization of benzylic sp3 stereocenters, classifying all established methodologies into two categories by catalyst-substrate interaction mode: the covalent/coordination-bonding mode, which relies on covalent/coordination bonds with polar functional groups as core "chemical handles", and the non-covalent interaction mode, which leverages non-covalent interactions including hydrogen bonding and electrostatic effects. For each category, we detail reaction design, catalytic system features, substrate scope, and underlying mechanisms, organized by substrate "chemical handle" types. Future efforts should be directed toward developing novel binding modes to break "chemical handle" constraints, enabling late-stage deracemization of complex molecules, integrating emerging technologies, and establishing mechanism-guided rational catalyst design.