Difunctionalization of unsaturated hydrocarbons via EDA complexes to access pentafluorosulfanyl thioethers

Recently, the pentafluorosulfanyl (SF5) group has attracted considerable interest from medicinal chemists owing to its capacity to significantly enhance the pharmaceutical properties of small-molecule drug candidates. However, a general method for three-component pentafluorosulfanylation of electron-deficient alkenes remains elusive. Herein, we present an electron donor-acceptor (EDA) complex photoactivation strategy for the thiopentafluorosulfanylation of unsaturated hydrocarbons, including electron-deficient alkenes, alkynes, 1,6-enynes, and even acetylene gas. The utility of this approach is demonstrated through the synthesis of a diverse array of pentafluorosulfanyl thioethers and the late-stage functionalization of complex molecules, including pharmaceuticals, natural products, and amino acid derivatives. This work establishes a framework for designing atom-economical difunctionalization reactions that employ green LEDs under mild conditions. Moreover, mechanistic studies support an EDA complex-mediated pathway and identify ArSCl as a key intermediate formed upon generation of the thiyl radical. The pentafluorosulfanyl group is prized in medicinal chemistry for improving physicochemical properties of small molecules, yet its general incorporation into electron-deficient alkenes remains challenging. Here, the authors report EDA photoactivation enabling thiopentafluorosulfanylation of unsaturated hydrocarbons to access diverse thioethers.