Regioselective Direct C–H Trifluoromethylation of Pyridine

Abstract

A highly efficient and regioselective direct C-H trifluoromethylation of pyridine based on an <i>N</i>-methylpyridine quaternary ammonium activation strategy has been developed. A variety of trifluoromethylpyridines can be obtained in good yield and excellent regioselectivity by treating the pyridinium iodide salts with trifluoroacetic acid in the presence of silver carbonate in <i>N,N</i>-dimethylformamide. The protocol features good functional group compatibility, easily available starting materials, and operational simplicity. Controlled experiments showed that the reaction may involve a nucleophilic trifluoromethylation mechanism.