Nickel-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane

The nickel-catalyzed cross-coupling difluoromethylation of the Grignard reagents with difluoroiodomethane is shown to provide the corresponding aromatic difluoromethyl products in excellent to moderate yields. The difluoromethylation proceeds smoothly within 1 h at room temperature with 1.5 equiv of the Grignard reagents in the presence of Ni(cod) 2 /TMEDA (2.5–0.5 mol %). Mechanistic studies clarify that the oxidative addition of the Ni(0) catalyst to difluoroiodomethane provides the TMEDA–Ni(II)(CF 2 H)I complex. This intermediate is transformed to TMEDA–Ni(II)(CF 2 H)Ph via transmetalation with PhMgBr. The reductive elimination takes place to give the aromatic cross-coupling difluoromethylation product along with regeneration of the TMEDA–Ni(0) catalyst. Electron paramagnetic resonance (EPR) and radical clock analyses of the nickel-catalyzed reaction provide no EPR active Ni(I) and Ni(III) species at around g = 2 and only a trace amount of the cyclization product.