Solid-State Radical C-H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials

The application of piezoelectricity for the generation of trifluoromethyl (CF3) radicals is reported together with the development of a method for the mechanochemical C-H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C-H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.