Title: Nickel-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane
Abstract: 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)(CF2H)I complex. This intermediate is transformed to TMEDA–Ni(II)(CF2H)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.
Publication Year: 2018
Publication Date: 2018-08-21
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 37
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