Regioselective Difluoroalkylation of 2‐Pyridones with Fluoroalkyl Bromides Enabled by a Nickel(II) Catalyst

Regioselective C-H difluoroalkylation of diverse 2-pyridones with ethyl bromodifluoroacetates and bromodifluoroacetamides is accomplished by using a (dppf)NiCl₂ catalyst under mild conditions. This efficient protocol could deliver a variety of C-3 difluoroalkylated pyridones with the tolerance of a range of highly susceptible functionalities, such as -Cl, -Br, -I, -COMe, -CN, -NMe₂ and -NO₂, including heteroarenes like pyridinyl, furanyl, thiophenyl and carbazolyl moieties. A preliminary mechanistic study suggests the radical pathway for the reaction involving fluoroalkyl radical intermediate.