Accelerated Thioarylation of Arenes Using Lewis Acid and Lewis Base Dual Catalysis

Biaryl sulfides are valuable motifs in pharmaceuticals and functional materials and thus require efficient synthetic methods that operate rapidly and under mild conditions. We recently reported a method for the synthesis of biaryl sulfides via the reaction of arenes with iron(III)-activated saccharin-based thioaryl reagents. However, this approach proved to be less effective for electron-deficient thioaryl groups, which required prolonged reaction times and more forcing conditions. Here, we present an improved procedure featuring a dual catalytic system in which diphenyl selenide acts as a Lewis base cocatalyst to accelerate iron-catalyzed thioarylation at room temperature. This modification significantly enhances the reactivity of electron-deficient saccharin-based reagents, broadening the substrate scope and enabling late-stage functionalization of complex molecules such as natural products and pharmaceuticals. The synthetic utility of this dual catalytic thioarylation reaction is demonstrated with a concise synthesis of the HIV-1 reverse transcriptase inhibitor L-737,126 and late-stage functionalization of the painkiller naproxen.