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.
Okunade et al. (Mon,) studied this question.