Cooperative Copper/Lipase Catalysis for the Chemoenzymatic Dynamic Kinetic Resolution (DKR) of Bis(hetero)arenols

Chemoenzymatic dynamic kinetic resolution (DKR), which combines a metal racemization catalyst with an enzyme, has been demonstrated as an elegant solution to deliver centrally and axially chiral products from their racemates. Bis-(hetero)-arenols have found wide applications as chiral organocatalysts, phosphine-containing ligands, and photoelectric materials. However, the current chemoenzymatic DKR strategy has not yet been applied to bis-(hetero)-arenols due to their more stable axial chirality and higher redox potential under oxidative conditions. Herein, we developed an efficient DKR method to access chiral bis-(hetero)-arenols from racemic derivatives under cooperative copper and enzyme catalysis. The utilization of copper catalysis successfully realized the racemization of bis-(hetero)-arenols under aerobic conditions, which was also compatible with enzyme catalysis, endowing the chemoenzymatic DKR with high efficiency and selectivity. In this way, not only a benzofuran moiety but also a benzothiophene or carbazole unit could be tolerated in the axial scaffold to deliver optically active products with high enantioselectivity. The methylene-locked axially chiral skeletons display potentially superior circularly polarized luminescence (CPL) as small organic optoelectronic molecules. Mechanistic investigations suggest that chirality inversion in bis-(hetero)-arenols proceeds via reversible single-electron oxidation, with the intermediacy of <i>O</i>-radical species to significantly decrease the energy barrier for axial rotation.