Protease-Catalyzed Aldol Condensation To Access Axially and Centrally Chiral Biaryls

Abstract Asymmetric synthesis of axially chiral biaryls with multiple stereogenic elements remains challenging. Herein, we report an enzymatic asymmetric aldol condensation via desymmetrization that constructs carbon-centered stereocenters and biaryl axes simultaneously. This biocatalytic strategy affords a range of atropisomers with high diastereo- and enantioselectivities (up to >99:1 er and >19:1 dr). The protocol operates at high substrate loadings under mild conditions and tolerates a range of substrates, giving products containing both axial and central chirality.