Metal-Free Electrochemical Synthesis of Sulfonamides Directly from (Hetero)arenes, SO2 , and Amines

Abstract

Sulfonamides are among the most important chemical motifs in pharmaceuticals and agrochemicals. However, there is no methodology to directly introduce the sulfonamide group to a non-prefunctionalized aromatic compound. Herein, we present the first dehydrogenative electrochemical sulfonamide synthesis protocol by exploiting the inherent reactivity of (hetero)arenes in a highly convergent reaction with SO₂ and amines via amidosulfinate intermediate. The amidosulfinate serves a dual role as reactant and supporting electrolyte. Direct anodic oxidation of the aromatic compound triggers the reaction, followed by nucleophilic attack of the amidosulfinate. Boron-doped diamond (BDD) electrodes and a HFIP-MeCN solvent mixture enable selective formation of the sulfonamides. In total, 36 examples are demonstrated with yields up to 85 %.

Keywords: electrochemistry; green chemistry; oxidation; radical reactions; sulfonamides.