4-Position-Selective C-H Perfluoroalkylation and Perfluoroarylation of Six-Membered Heteroaromatic Compounds
Masahiro Nagase1, Yoichiro Kuninobu1,2, Motomu Kanai1,2
1Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
The first 4-position-selective C-H perfluoroalkylation and perfluoroarylation of six-membered heteroaromatic compounds were achieved using nucleophilic perfluoroalkylation and perfluoroarylation reagents. The regioselectivity was controlled by electrophilically activating the heteroaromatic rings, while sterically hindering the 2-position, with a sterically bulky borane Lewis acid. The reaction proceeded in good yield, even in gram scale, and by a sequential reaction without isolating the intermediates. This reaction could be applied to late-stage trifluoromethylation of a bioactive compound.
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