Nickel(II)/BINOL-catalyzed enantioselective C–H activation via desymmetrization and kinetic resolution

Abstract

Abstract The field of nickel catalysis has witnessed remarkable growth in recent years. However, the use of nickel catalysts in enantioselective C–H activation remains a daunting challenge because of their variable oxidation states, intricate coordination chemistry, and unpredictable reactivity patterns. Herein, we report an enantioselective C–H activation reaction catalyzed by commercially available and air-stable nickel(II) catalyst. Readily available and simple (S)-BINOL is used as a chiral ligand. This operationally simple protocol enables the synthesis of planar chiral metallocenes in high yields with excellent enantioselectivity through desymmetrization and kinetic resolution. Air-stable planar chiral nickelacycle intermediates are first synthesized via enantioselective C–H nickelation and shown to be possible intermediates of the reaction. Deuterium-labeling studies, alongside the characterization and transformation of chiral nickel(II) species, suggest that C–H cleavage is the enantio-determining step. Moreover, the large-scale synthesis and diverse synthetic transformations underscore the practicality of this protocol.