Difluoroacetic Acid as a New Reagent for Direct C–H Difluoromethylation of Heteroaromatic Compounds – Scope, Limitations and Perspectives

John Nielsen shows the use of difluoroacetic acid in the C–H difluoromethylation of heteroaromatic compounds.

For a long time, the introduction of the difluoromethyl moiety in drug candidates was hampered by the limited number of synthetic methods. Early methods consisted of converting aldehyde groups into difluoromethyl groups. Unfortunately, very toxic, corrosive, volatile or explosive reagents had to be used for these transformations. Difluoroacetic acid is an inexpensive and off-the-shelf reagent. Professor John Nielsen and his group from the University of Copenhagen (Denmark) have successfully performed the late-stage C–H mono- and bis-difluoromethylation of several pharmaceutically interesting heteroaromatic scaffolds using this reagent.


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