Catalytic Electrophilic C–H Sulfenylation of Indoles with Disulfides under Ball Milling

Abstract

Inspired by mechanic force induced S–S bridge activation in a protein context, we have developed the first mechanochemical electrophilic C–H sulfenylation of indoles in combination with iodine catalysis. Differing from previous relevant methods that typically necessitate either intrinsically reactive sulfur sources or external forceful conditions but at the expense of atom economy and environmental benignity, our strategy disclosed herein capitalizes on readily available disulfides as sulfenylation reagents promoted by ball milling, thereby rendering rapid synthesis of indolyl sulfides with broad structural diversity under aerobic oxidation and solvent-minimum and metal-free conditions. Moreover, mechanistic studies reveal that the solid and liquid grinding auxiliaries synergistically facilitate this process.