Ruthenium Catalyzed Mechanochemical Transformation of Sulfonamide Group to Fluoro, Trifluoromethyl, and Trifluoromethoxy Functionalities

Abstract A convenient route for the mechanochemical synthesis of fluorinated aromatic compounds, that is, fluoro, trifluoromethyl, and trifluoromethoxy arenes, has been developed via pyrylium tetrafluoroborate (Pyry‐BF 4 )‐mediated desulfonamidative cross‐coupling of primary sulfonamides under the synergy of a piezoelectric material BaTiO 3 , and Ru‐catalysis. This is the first‐ever report on the selective transformation of sulfonamide (SO 2 NH 2 ) functionality to CF 3 /OCF 3 /F group in a single step under mechanochemical ball‐milling conditions. Considering the importance of primary sulfonamides as the valuable pharmacophores, the present desulfonamidative cross‐coupling approach could have potential to get synthetic utility in pharmaceutical industries for the late‐stage functionalization of sulfonamide drugs and related active pharmaceutical ingredients (APIs).