Benzylic C(sp3)-H Perfluoroalkylation of Six-Membered Heteroaromatic Compounds

Successful benzylic C(sp(3))-H trifluoromethylation, pentafluoroethylation, and heptafluoropropylation of six-membered heteroaromatic compounds were achieved as the first examples of a practical benzylic C(sp(3))-H perfluoroalkylation. In these reactions, BF2CnF2n+1 (n= 1-3) functioned as both a Lewis acid to activate the benzylic position and a CnF2n+1 (n= 1-3) source. The perfluoroalkylation proceeded at both terminal and internal positions of the alkyl chains. Perfluoroalkylated products were obtained in moderate to excellent yields, even on gram scale, and in a sequential procedure without isolation of the intermediates. By using this method, trifluoromethylation of a bioactive compound, as well as introduction of a CF3 group into a bioactive molecular skeleton, proceeded regioselectively.