Abstract A mild trifluoromethylation reaction of N, N-disubstituted hydroxylamines that is tolerant towards a variety of functional groups, including nitriles, alcohols, ketones, esters, amides, imides, and nitrogen heterocycles, is reported. The key feature of this reaction is the activation of the CF 3 reagent with either trimethylsilyl triflate or LiClO 4 and partial or full deprotonation of the substrate with tetramethylguanidine or lithium diisopropylamide. ...