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.

Automated summary

A straightforward protocol for direct difluoromethylation of specific organic compounds is presented, showing tolerance towards various functional groups. The selectivity of the reaction can be modulated by simple variations in reaction conditions. Gram-scale reactions for preparing difluoromethyl compounds are demonstrated.