N -Heterocyclic Carbene–Palladium Complex IPent An -PdCl ₂ -Im: Highly Efficient for Buchwald–Hartwig Amination of Heteroaryl Chlorides with Heteroaryl Amines

A new bulky N -heterocyclic carbene–palladium complex, IPent An -PdCl 2 -Im, was synthesized and characterized and exhibited excellent catalytic activity in the amination of various heteroaryl chlorides with heteroaryl amines at low catalyst loading. It was successfully utilized for the high-yield synthesis of different commercial pharmaceuticals, drug intermediates, and candidate drugs. The DFT calculations suggest that the auxiliary ligand N -methylimidazole significantly influences catalytic activity by enhancing the stability of [Pd(0)-(NHC)] species, slowing the formation rate of palladium black, and extending the catalyst’s lifetime. In addition, N -methylimidazole can also make the [Pd(0)-(NHC)] species more electron-donating, facilitating the oxidative addition step in the catalytic cycle.