Sulfur-assisted ring contraction of polyfluoroalkylthiopyran derivatives as a route to functionalized fluorine-containing thiophenes

•2-Chloro-2-(trifluoromethyl)-3,6-dihydro-2H-thiopyran reacts with bromine giving two diastereomeric dibromo derivatives.•The addition of bromine to 6-(polyfluoroalkyl)-2H-thiopyran occures as regioselective trans-process at C3C4 double bonds.•Dibromides react with sodium acetate in acetic acid giving high yields of 2-(acetoxymethyl)-5-(polyfluoroalkyl)thiophenes.•A plausible pathway of the formation of thiophenes from dibromides includes the participation of thiiranium intermediates.•A simple and convenient procedure for the preparation of 2-(hydroxymethyl)-5-(polyfluoroalkyl)thiophenes was elaborated.

A synthetic route to functionalized α-(polyfluoroalkyl)thiophenes based on the reactions of ring contraction of polyfluoroalkyl substituted thiopyran derivatives has been explored. Potent 6-membered precursors for the preparation of thiophenes were obtained by the addition of bromine to the double bonds of 2-chloro-2-(trifluoromethyl)-3,6-dihydro-2H-tetrahydrothiopyran and 6-(polyfluoroalkyl)-2H-thiopyrans. The reactions of the resulted 4,5-dibromo-2-chloro-2-(trifluoromethyl)tetrahydrothiopyrans and trans-3,4-dibromo-6-(polyfluoroalkyl)-3,4-dihydro-2H-thiopyrans with sodium acetate in acetic acid produced 2-(acetoxymethyl)-5-(polyfluoroalkyl)thiophenes. Base-catalyzed methanolysis of the acetoxymethyl derivatives allowed preparing the corresponding 2-(hydroxymethyl)-5-(polyfluoroalkyl)thiophenes. The mechanism, which includes formation and nucleophilic cleavage of thiiranium cations, has been suggested for the transformation of dibromothiopyran derivatives to substituted thiophenes.

Graphical abstract4,5-Dibromo-2-chloro-2-(trifluoromethyl)tetrahydrothiopyran and 3,4-dibromo-6-(polyfluoroalkyl)-3,4-dihydro-2H-thiopyrans were prepared by the addition of bromine to 2-chloro-2-(trifluoromethyl)-3,6-dihydro-2H-thiopyran and to 6-(polyfluoroalkyl)-2H-thiopyrans, respectively. Basing on the reaction of dibromides with sodium acetate in acetic acid, convenient procedures for the preparation of 2-(acetoxymethyl)- and 2-(hydroxymethyl)-5-(polyfluoroalkyl)thiophenes were developed.Figure optionsDownload full-size imageDownload as PowerPoint slide