Combining the Nonnatural Activity of Lipase and Electrocatalysis in One Pot: Sustainable and Regioselective Synthesis of C-3 Alkylated Oxindoles

Abstract

In this study, we report an environment-friendly protocol by integrating the nonnatural catalytic activity of lipase with electrocatalysis for synthesizing C-3 alkylated oxindoles, which are part of many natural and pharmaceuticals products. Gratifyingly, Candida antarctica lipase B (CALB) is found to be highly active and regioselective for catalyzing the nonnatural C-3 alkylation reaction at indole when combined with an electrochemical C-2 oxidation process in the same vessels. Further, the generality and feasibility of the developed protocol are shown by employing several functional groups on the indole moiety and obtaining the desired products in moderate to good yield. Besides, the control experiments are set up along with the molecular docking studies to substantiate the role of the active site of Candida antarctica lipase B (CALB) in carrying out the regioselective C-3 alkylation reaction. In addition, control experiments and cyclic voltammetry are performed to get insight into the electrochemical C-2 oxidation process and as a result, a plausible mechanism for the integrated process is presented.