Chemoselective N- and O-Difluoromethylation of 2-Pyridones, Isoquinolinones, and Quinolinones with TMSCF2Br

An operationally simple protocol for direct N- and O-difluoromethylation of 2-pyridones, quinolinones, and isoquinolinones using commercially available TMSCF₂Br is disclosed. The chemoselectivity is modulated by simple variations in temperature, solvent, and strength of the base. Diverse, synthetically relevant functional groups are tolerated, including functional groups that have reported reactivity with TMSCF₂Br. Gram-scale reactions to prepare both N- and O-difluoromethyl compounds are included.