Mild trifluoromethylsulfinylation of alcohols and amines <i>via N</i> -hydroxyphthalimide- <i>O</i> -trifluoromethanesulfinate

Direct and efficient trifluoromethylsulfinylation of alcohols and amines is highly desirable in the drug design field. Herein, we report a simple trifluoromethylsulfinylation of alcohols and amines at room temperature under remarkably mild conditions, enabled by a powerful <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate. This protocol was conducted under activator and additive-free conditions, and is effective for the direct transfer of the CF₃S(O) group to a series of alkyl alcohols, alkyl amines and aromatic amines with good to excellent yields and superb functional group tolerance, as well as facile extension to late-stage trifluoromethylsulfinylation of complex biologically active alcohols and amines. Preliminary mechanistic experiments suggest that the direct nucleophilic attack of the highly active <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate is the key factor for the success of the electrophilic trifluoromethylsulfinylation of alcohols and amines in the absence of any activators or additives.