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 have been validated through a 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 the formation of 2-(2-aminophenyl)-2-oxoacetate serves as a key intermediate during the electrochemical step.