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 %.

Multicomponent reactions and photo/electrochemistry join forces: atom economy meets energy efficiency

“…The same group implemented the reported procedure for the synthesis of sulfonamides. 311 Following the general mechanism explained above, electron-rich (hetero)arenes, SO 2 , and amines can be incorporated in the final product in a onestep synthetic procedure. The scale-up of the reaction delineated was also successfully accomplished, employing a simple H-type glass cell divided by a glass frit.…”

Advances in photochemical and electrochemical incorporation of sulfur dioxide for the synthesis of value-added compounds

“…The SO 2 concentration can be easily determined by iodometry 52 and the handling proved to be simple and safe. 44,53,54 For instance, such stock solutions have been used in MeCN, DMSO or DMF in studies on cathodic SO 2 reduction studies or the synthesis of sulfones from alkyl halides. [55][56][57][58][59][60] laboratory.…”

“…Finally, a second anodic oxidation step accomplishes the desired product. 53,54 Just recently, the first electrochemical synthesis of sulfamides mediated by catalytic amounts of iodide 44 was reported (Scheme 2) with yields up to 93% (9). Sulfamides are an Liao and coworkers reported the electrochemical cyclization reaction from N-aryl cyanamides with terminal alkene to Nsulfonylimines (Scheme 3, A) via trifluoromethylation and SO 2 insertion by using Langlois' reagent (CF 3 SO 2 Na) as CF 3 and SO 2 source.…”

Recent Advances in the Electrochemical Synthesis of Organosulfur Compounds

“…Very recently, a novel protocol for the electrochemical dehydrogenative sulfonamide synthesis from electron‐rich aromatic compounds, amines and SO 2 was reported by Waldvogel and co‐workers [47] . In this case, an in situ formed amidosulfinate intermediate served the dual role of nucleophile and supporting electrolyte.…”