Electrochemical Oxidation-Induced Difunctionalization of the Sulindac Alkene Moiety with Diselenides.

The structural modification of drug molecules is a fundamental approach to optimizing lead compounds designed to achieve concurrent improvements in efficacy, pharmacokinetics, and safety. Herein, we disclose an efficient and eco-benign electrochemical oxidative protocol for regioselective and chemoselective difunctionalization of the sulindac alkene scaffold under transition-metal-free, exogenous oxidant-free, and base-free conditions. This methodology delivers diverse sulindac derivatives in moderate to excellent yields (up to 92%) with a broad functional group tolerance. Mechanistic studies reveal a radical-radical cross-coupling process, offering a novel strategy for alkene difunctionalization.