Trifluoromethylthiolation of Arenes Using Lewis Acid and Lewis Base Dual Catalysis
Lachlan J. N. Waddell, Claire Wilson, Andrew Sutherland
Abstract
High Resolution Image Download MS PowerPoint Slide Incorporation of the highly lipophilic trifluoromethanesulfenyl group into bioactive molecules facilitates transport through lipid membranes, and thus, CF 3 S-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.