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 (t1/2 = 144.7 min at 20 °C) with formation of the Pd(0)­(PPh3)2/DPEphos catalyst.