Single-Electron-Transfer-Generated Aryl Sulfonyl Ammonium Salt: Metal-Free Photoredox-Catalyzed Modular Construction of Sulfonamides

Sulfonamides are prominently featured in organic synthesis and medicinal chemistry. Yet, a general synthetic platform for the modular construction of aryl sulfonamides remains elusive. Herein, a metal-free photoredox-catalyzed three-component construction of aryl sulfonamides via an aryl sulfonyl ammonium salt intermediate, which was generated in situ via a SET event, has been established. A variety of structurally diverse primary, secondary, and tertiary aryl sulfonamides were synthesized rapidly from abundant amines or sodium azide under mild conditions. Notably, the primary aliphatic amine, which remains challenging in the Cu-catalyzed protocols, worked well in this approach. Moreover, aryl sulfonyl fluoride can be accessed smoothly as well, using potassium hydrogen fluoride as the nucleophile. The potential utility of this conversion is demonstrated in the facile construction of three bioactive drug compounds. Preliminary mechanistic studies have revealed that the aryl sulfonyl radical and aryl sulfonyl ammonium salt are the key intermediates in this mechanistically innovative methodology.