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

177 Citations2020
Yadong Pang, Joo Won Lee, Koji Kubota

The first application of piezoelectricity for the generation of trifluoromethyl (CF3) radicals is reported together with the development of a method for the mechanochemical C-H trifLUorometrichylation of aromatic compounds, which represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.

Abstract

<jats:title>Abstract</jats:title><jats:p>The application of piezoelectricity for the generation of trifluoromethyl (CF<jats:sub>3</jats:sub>) 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.</jats:p>