Electricity-driven sustainable synthesis of 2-aminobenzonitriles through C–C bond cleavage of isatins: post-functionalization via one-pot integration with enzyme catalysis

Abstract

Herein, we report an electricity-mediated sustainable synthesis of 2-aminobenzonitriles, which serve as essential building blocks for numerous pharmaceuticals, by using isatins and hydroxylamine as starting materials. Furthermore, electricity served as an efficient and environmentally friendly mediator, promoting the C–C cleavage of isatin derivatives to afford the desired products in good to excellent yields. The scope and practicality of the method were validated through the screening of isatins bearing different substituents. Moreover, this electrochemical protocol was successfully integrated with an α-amylase-catalyzed aza-Michael addition in a one-pot system, providing pharmaceutically relevant β-aminocarbonyl compounds via C–N bond formation. Additionally, mechanistic insights obtained from control experiments and cyclic voltammetry studies suggest that 2-(2-aminophenyl)-2-oxoacetate serves as a key intermediate during the electrochemical step.