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

Summary Direct trifluoromethylation of C(sp3)–H bonds, especially in late stages, remains a formidable challenge. Herein, we describe the copper-catalyzed benzylic C(sp3)–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(sp3)–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(sp3)–H trifluoromethylation of natural products or drug derivatives.