Enantioselective Synthesis of Axially Chiral Tetraphenylethenes via NHC-Catalyzed Desymmetrization and Following Kinetic Resolution.

Abstract

Herein, we report an efficient method for the enantioselective construction of axially chiral tetraphenylethylene (TPE) via N-heterocyclic carbene (NHC)-catalyzed desymmetrization of prochiral isophthalaldehyde-derived TPEs. Both aliphatic alcohols and phenols were well-tolerated, affording the atropisomeric TPEs in good yields and enantioselectivities. Mechanistic investigations reveal that desymmetrization is a key contributor to enantioselective control, and the following kinetic resolution further enhances the enantioselectivity. Gram-scale synthesis and late-stage functionalization of pharmaceuticals further validated the practicality and potential of this method.