Photoinduced regioselective trifluoroalkylation of ketene dithioacetals with CF3SO2Na

Abstract

Fluoroorganic chemistry continues to be a fascinating tool for various areas including pharmaceuticals, agrochemicals, and materials. The incorporation of trifluoromethyl functional groups can yield remarkable changes in the chemical stability, metabolic stability and liposolubility of functional molecules. The development of efficient methods to synthesize trifluoromethyl compounds is of significant importance, and radical trifluoromethylation of alkenes is a highly attractive strategy for synthesizing trifluoromethylated compounds. In this study, regioselective hydrotrifluoromethylation of ketene dithioacetals with CF₃SO₂Na was achieved via a visible-light-promoted radical-polar process under mild and operationally simple conditions, using an inexpensive organic photocatalyst. The protocol features a low-cost catalyst, good functional group tolerance, a relatively broad substrate scope, and good to excellent yields. Gram-scale preparation and synthetic applications demonstrate opportunities to rapidly construct complex molecules. Mechanistic studies indicated that the transformation involves a regioselective radical addition/radical-polar crossover process.