Electrochemical [3 + 2] cycloaddition of anilines and enamine ketones: construction of 3-benzoylindole derivatives

Abstract

This article describes an eco-friendly and atom-economical electrochemical protocol for the intermolecular [3 + 2] cycloaddition to synthesize 3-benzoylindole derivatives in synthetically viable yields. The oxidative cycloaddition proceeds under transition-metal-free and strong-oxidant-free conditions, generating H₂ and (Me)₂NH as the byproducts, thereby aligning with green chemistry principles. Furthermore, the methodology exhibits exceptional synthetic versatility through successful late-stage diversification and compatibility with structurally diverse substrates. Preliminary cytotoxic evaluation via CCK-8 assays against two human carcinoma cell lines revealed potent bioactivity profiles, establishing a foundation for systematic exploration of indole-based pharmacophores. This protocol offers a sustainable alternative to conventional synthetic strategies while expanding the functionalization landscape of heteroaromatic systems.