Selective enhancement effects of silver salts on the transition metal-catalyzed synthesis of gem-difluorinated heterocyclics using 2,2-difluorohomopropargyl amides

The addition of silver salts had an effect on the catalyst activity in the Pd(0)-catalyzed cyclization-coupling tandem reaction, as well as in the Rh(I)-catalyzed Pauson–Khand reaction. The cationic palladium complex generated from Pd(PPh3)4 (2.5 mol%) with AgSbF6 (1.5 equiv.) activates the triple bond of 2,2-difluoropropargylic amides to give the 4,5-disubstituted 3,3-difluoro-γ-lactams, through a sequential 5-endo-dig cyclization and cross-coupling reaction. The γ-lactam was transformed into ring-opened monofluorovinylic compounds after silica-gel chromatography. Pauson–Khand reaction of fluorinated 1,7-enyne amides using catalytic amounts of [Rh(COD)2]2 (5 mol%) and AgOTf (20 mol%) gave the corresponding gem-difluorinated bicyclic lactam.

Graphical abstractThe cationic palladium complex generated from Pd(PPh3)4 (2.5 mol%) with AgSbF6 (1.5 equiv.) activates the triple bond of 2,2-difluoropropargylic amides to give the 4,5-disubstituted 3,3-difluoro-γ-lactams, through a sequential 5-endo-dig cyclization and cross-coupling reaction. Figure optionsDownload full-size imageDownload as PowerPoint slide