Efficient chemoenzymatic cascade reaction for one-pot enantioselective synthesis of chiral indole derivatives in water

Abstract

One-pot chemoenzymatic cascade process integrating the merits of biocatalysis and chemical catalysis has become a promising method for the efficient synthesis of complex chiral compounds. Herein, we designed a chemoenzymatic one-pot cascade system in water, involving UiO-67 catalyzed Michael addition and ketoreductases catalyzed CO asymmetric reduction with stereocomplementary selectivity. After studying experimental conditions systematically, a series of chiral indole derivatives with complementary (R)- or (S)-configurations were successfully synthesized with high yields (up to 92 %) and excellent stereoselectivity (up to 99 % ee). The strategy is environmentally friendly, mild and highly stereoselective, demonstrating the significant potential of one-pot chemoenzymatic cascade reaction in green synthetic chemistry and sustainable development.