Trifluoromethylthiolation of Arenes Using Lewis Acid and Lewis Base Dual Catalysis.

Abstract

Incorporation of the highly lipophilic trifluoromethanesulfenyl group into bioactive molecules facilitates transport through lipid membranes, and thus, CF3S-containing compounds are important for drug discovery. Although reagents and procedures have been reported for arene trifluoromethylthiolation, methods are still required that are applicable to a diverse substrate scope and can be performed under mild conditions. Here, we describe a rapid and efficient approach for the trifluoromethylthiolation of arenes by catalytic activation of N-trifluoromethylthiosaccharin using a combination of iron(III) chloride and diphenyl selenide. This dual catalytic process allowed regioselective functionalization of a wide range of arenes and N-heterocycles under mild conditions and was used for the trifluoromethylthiolation of bioactive compounds such as tyrosine and estradiol.