Copper-Catalyzed Late-Stage Benzylic C(sp3)-H Trifluoromethylation

Direct trifluoromethylation of C(sp(3))-H bonds, especially in late stages, remains a formidable challenge. Herein, we describe the copper-catalyzed benzylic C(sp(3))-H trifluoromethylation. With Cu(I) or Cu(II) as the catalyst, (bpy) Zn(CF3)(2) (bpy = 2,2'-bipyridine) as the CF3 source, and NFSI (or Selectfluor) as the oxidant, site-selective benzylic C(sp(3))-H trifluoromethylation is successfully implemented in high efficiency under mild conditions. The protocol not only exhibits broad substrate scope and wide functional-group compatibility but also allows efficient late-stage C(sp(3))-H trifluoromethylation of natural products or drug derivatives.