Atroposelective Synthesis of Styrenes by Alcohol-Dehydrogenase-Catalyzed Dynamic Kinetic Resolution

Atropisomeric styrenes, the alkenyl analogues of biaryls, have attracted considerable interest as chiral ligands and organocatalysts. Herein, an atroposelective dynamic kinetic resolution was reported using alcohol dehydrogenase from Ralstonia sp. as the catalyst. Employing a structure-guided protein engineering approach, we successfully enhanced the enzymatic reactivity, enabling the highly stereoselective synthesis of axially chiral styrenes in both R and S configurations (yields up to 99% and ee up to 98%). Notably, we discovered that the stereoinversion observed in Y150A and Y150I variants originated from a reconfigured proton relay network, where the substrate’s phenolic hydroxyl group directly interacted with the H147 residue. This catalytic strategy provides a valuable addition to the enzymatic toolbox, facilitating the stereocontrolled synthesis of challenging atropisomeric scaffolds.