Trifluoroethylation and Pentafluoropropylation of C(sp3)-H Bonds.

Abstract

Polyfluorinated substituents often enhance effectiveness, improve the stability within metabolic processes, and boost the lipophilicity of biologically active compounds. However, methods for their introduction into aliphatic carbon chains remain very limited. A potentially general route to integrate the fluorinated scaffolds into organic molecules involves insertion of fluorine-containing carbenes into C(sp3)-H bonds. The electron-withdrawing characteristics of perfluoroalkyl groups enhances the reactivity of these carbenes which should enable the functionalization of unactivated C(sp3)-H bonds. Curiously, it appears that use of perfluoroalkyl-containing carbenes in alkane C-H functionalization is exceedingly rare. This concept describes photolysis, enzymatic catalysis, and transition metal catalysis as three primary approaches to C(sp3)-H functionalization by trifluoromethylcarbene and its homologues.