title: Benzylic C(sp(3) )H Perfluoroalkylation of Six-Membered Heteroaromatic Compounds.
abstract: 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, BF2 Cn F2n+1 (n=1-3) functioned as both a Lewis acid to activate the benzylic position and a Cn F2n+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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan). kuninobu@mol.f.u-tokyo.ac.jp.|ERATO (Japan) Science and Technology Agency (JST), Kanai Life Science Catalysis Project, Tokyo 113-0033 (Japan). kuninobu@mol.f.u-tokyo.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kuninobu
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagase
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan). kanai@mol.f.u-tokyo.ac.jp.|ERATO (Japan) Science and Technology Agency (JST), Kanai Life Science Catalysis Project, Tokyo 113-0033 (Japan). kanai@mol.f.u-tokyo.ac.jp.
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
mesh_terms: D000478:Alkylation; D001593:Benzyl Compounds / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D001593:Benzyl Compounds; D006571:Heterocyclic Compounds; D006845:Hydrocarbons, Fluorinated
keywords: Lewis acids; arenes; boranes; fluorine; heterocycles