Insertion of Difluorocarbene into Nickel Complexes to Access Chloro(Bromo, iodo)Difluoromethylarenes

The fluorinated functional groups represent privileged and irreplaceable motifs in pharmaceuticals and agrochemicals. However, certain fluorinated group-containing compounds, including trifluoromethyl group have recently been classified as per- and polyfluoroalkyl substances (PFAS) due to their high stability, environmental mobility and toxicity. Fortunately, halodifluoromethyl groups (-CF₂X, X = Cl, Br, I) can be degraded into nonpersistent compounds and serve as the halogen bond donors, which are distinctive among fluorinated substituents. Despite the importance of these groups, a general method for the installment of halodifluoromethyl groups into aromatics remains underexplored. Here we report a facile and efficient synthesis of chloro(bromo, iodo)difluoromethylarenes through nickel-mediated halodifluoromethylation of (hetero)aryl chlorides(bromides) with TMSCF₂Cl or TMSCF₂Br. The distinct reaction mechanism involves the insertion of difluorocarbene into the in situ generated aryl nickel(II) halide complex (Ar-Ni(II)-X), followed by oxidant-induced reductive elimination from the resulting aryldifluoromethyl nickel(II) intermediate (ArCF₂-Ni(II)-X).