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

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-BF4)-mediated desulfonamidative cross-coupling of primary sulfonamides under the synergy of a piezoelectric material BaTiO3, and Ru-catalysis. This is the first-ever report on the selective transformation of sulfonamide (SO2NH2) functionality to CF3/OCF3/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).