Direct Functionalizations of Carbon-Hydrogen Bonds Catalyzed by Palladium/Bidentate Nitrogen-based Ligand Complexes

Previously, we accidentally found bidentate nitrogen-based ligands, in particular, 1,10-phenanthroline well work in palladium-catalyzed direct C-H bond arylation reaction of 5-membered heteroarenes. With this finding, we then explored catalytic utilities of the palladium/bidentate nitrogen-based ligand systems. Firstly, we extensively examined the utility for the direct C-H bond arylation of heteroarenes, and revealed that the catalytic system showed high activity for the reaction. A wide variety of C-H bonds on heteroarenes were arylated with the catalytic system. Importantly, the arylation at C4-position of azoles proceeded with high efficiency without any additives except base. A variety of multi-functionalized azole syntheses were also investigated, and we achieved a synthetic method of three different aryl groups introduced azoles from unfunctionalized azoles via simple sequential arylation reactions with a sole catalytic system. We also investigated the utilities of this catalytic system to oxidative coupling of terminal alkynes and azoles to result in good efficiency. One of the important features of this catalytic system is non-use of a phosphine ligand. With this feature, we achieved direct C-H bond arylation of thiocarbonylated compounds, that was hardly achieved because of the direct reaction of thiocarbonyl groups and phosphine ligands to result in loss of catalytic activity. To gain the insight of the reaction mechanism of this reaction with thiocarbonylated compounds, several control experiments were carried out.