Mechanism-Inspired Chiral Binuclear Cu Catalysis for Click Chemistry: Highly Efficient Kinetic Resolution to α-Quaternary Amino Acid Derivatives

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a cornerstone reaction in modern chemistry. Although binuclear catalytic mechanisms have been widely proposed and certain binuclear complexes exhibit good activity, asymmetric CuAAC still relies on the in situ assembly of copper salts with chiral ligands. Herein, guided by the postulated reaction mechanism, we employ a preassembled chiral binuclear copper catalyst with a well-defined chiral pocket to achieve efficient kinetic resolution of alkyne-functionalized azlactones with azides. This catalyst contains two copper(I) ions within a single chiral ligand framework, providing a rigid planar scaffold, stable coordination geometry, and a semicircular chiral cavity. Both triazole products and recovered azlactones are obtained in high enantiopurity and can be rapidly converted into chiral α-quaternary amino acid derivatives. This study establishes chiral binuclear copper complexes as an effective platform for enantioselective CuAAC.