Continuous-flow chemoenzymatic conversion of racemic alcohols to enantiopure alcohols and amines

The conversion of racemic alcohols to enantiopure alcohols and amines is of significant importance yet presents considerable challenges. Herein, we achieved this goal by developing continuous-flow chemoenzymatic systems. In chemical module, a ruthenium (II)-N-heterocyclic carbene (Ru-NHC) catalyst immobilized on dendritic organosilica nanoparticle (DON) was prepared, which exhibited high activity and selectivity in the dehydrogenative oxidation of racemic alcohols to ketones. In enzymatic module, a ketoreductase and an amine dehydrogenase were individually co-immobilized with a cofactor-regenerating enzyme (glucose dehydrogenase) on DON for the enantioselective conversion of ketones to chiral alcohols and amines, respectively. The integration of the two modules in continuous-flow systems enabled the efficient chemoenzymatic deracemization and asymmetric amination of racemic alcohols (9 examples) with the maximum space-time yields of 6.8 and 5.8 g L-1 h-1, respectively, underscoring the practical utility of the continuous-flow chemoenzymatic systems.