Precatalyst Effects on Pd-Catalyzed Cross-Coupling Difluoromethylation of Aryl Boronic Acids

The Pd-catalyzed difluoromethylation of aryl boronic acids with difluoroiodomethane is shown to provide the difluoromethyl compounds in high to moderate yields by Pd­(PPh₃)₂/DPEphos catalyst in H₂O/toluene. Mechanistic studies show that the oxidative addition by Pd­(PPh₃)₄ rather than Pd₂(dba)₃ precatalyst to difluoroiodomethane provides a square-planar trans-(PPh₃)₂Pd­(II)­(CF₂H)I complex defined by X-ray crystallographic analysis. The trans-(PPh₃)₂Pd­(CF₂H)I complex is transformed to cis-(PPh₃)₂Pd­(CF₂H)­Ph detected by low temperature NMR analysis, via transmetalation with phenylboronic acids. The reductive elimination occurs via ligand exchange to DPEphosPd­(CF₂H)­Ph to give Ph–CF₂H (t_1/2 = 144.7 min at 20 °C) with formation of the Pd(0)­(PPh₃)₂/DPEphos catalyst.