Chlorodifluoromethyl aryl ketones and sulfones as difluorocarbene reagents: The substituent effect

Recent synthetic methods towards the –OCHF2 moiety

“…The formation of the active carbene is based on the F2ClC-SO2Ph bond breaking, which is much slower than the breaking of the CF2Cl-CO bond in 2- [18] confirming thus the better results of sulfones and giving precisions on the influence of the substituents on the efficiency of this transformation. Indeed, electron-withdrawing substituted sulfones, and especially chlorodifluoromethyl p-chlorophenyl sulfone and chlorodifluoromethyl p-nitrophenyl sulfone, appeared to be the best difluorocarbene sources.…”

Late-stage difluoromethylation: concepts, developments and perspective

“…165 As an extension of their work, Hu and co-workers published an additional report in 2011 on the effect of aromatic ring substituents on the reactivity of these difluorocarbene reagents (Scheme 40C). 166 Substituent effects were more pronounced for the sulfone-based reagents. Extensive screening revealed that p-chlorophenyl chlorodifluoromethyl sulfone and p-nitrophenyl chlorodifluoromethyl sulfone were the most efficient for transferring difluorocarbene to phenols.…”

Recent Advances in the Synthetic Application of Difluorocarbene

“…21 Further investigations into the influence of the substituents on the phenyl group of the sulfone reagent showed that an electron-donating group reduces the yield significantly, while an electron-withdrawing group increases the yield (Scheme 3). 30 Scheme 2 Difluoromethylation of phenols with chlorodifluoromethyl phenyl sulfone 21…”