Selective Quadruple C(sp3)-F Functionalization of Polyfluoroalkyl Ketones

The significance of organofluorine compounds has inspired the establishment of numerous methods for the functionalization of rather inert C-F bonds. Despite advances achieved in the manipulation of C(sp2)-F bonds by employing transition-metal catalysts, such as Pd, Rh, Cu, Ni, Ru, and Ir, strategies that address the paucity of effective pathways for selective activation of multiple C(sp3)-F bonds remained challenging. In this context, we present an unprecedented coupling-aromatization-cyclization reaction of polyfluorinated ketones with diverse N- and S-nucleophiles that forms regiodefined perfluoroalkylated naphtho[1,2-b]furan/benzofuran derivatives by harnessing Co-promoted distinctive quadruple C(sp3)-F bonds cleavage relay. This chemistry involving controlled and successive selective defluorination at heteronuclear centers would greatly contribute to the preparation of drug-like heterocycles as well as the late-stage elaboration of biorelevant compounds. Controlled experiments and DFT theoretical studies revealed that the combination of cheap cobalt salt with Cs2CO3 enable expeditious C-F functionalization. [Display omitted] •First example of consecutive selective quadruple C(sp3)-F functionalization•Selectively and controllably partial defluorination at heteronuclear sites•Conversion to value-added chemicals by using polyfluorocarbons and nucleophiles•DFT calculations were performed to support mechanistic proposal Chemistry; Organic Chemistry; Organic Chemistry Methods