A Bulky and Electron-Rich N‑Heterocyclic Carbene–Palladium Complex (SIPr)^Ph₂Pd(cin)Cl: Highly Efficient and Versatile for the Buchwald–Hartwig Amination of (Hetero)aryl Chlorides with (Hetero)aryl Amines at Room Temperature

A bulky and electron-rich N-heterocyclic carbene–palladium complex (SIPr)^Ph₂Pd­(cin)Cl was synthesized and characterized. It was found to be highly efficient and versatile for the coupling of different (hetero)­aryl chlorides with various (hetero)­aryl amines at room temperature, especially for the challenging amination of five- or six-membered ring heteroaryl chlorides with five- or six-membered ring heteroaryl amines. It was also successfully applied with high yields to the synthesis of various commercial pharmaceuticals and candidate drugs or compounds with potential pharmacological activities. All of these demonstrate its excellent catalytic efficacy in Buchwald–Hartwig amination and broad application prospects in relevant pharmaceutical preparations. DFT calculations suggest that the steric-induced electronic interaction makes the ligand more electron-donating, and the steric effect effectively regulates the rotation of the iPr-Ph-iPr group in the catalyzed system due to the introduction of the diphenyl skeleton. Considering the electronic effect and the steric effect together, the oxidative addition activation barriers of the (SIPr)^Ph₂ and (SIPr) ligands are close to each other. Reductive elimination is the rate-determining step of the (SIPr)^Ph₂Pd­(cin)­Cl-catalyzed system in the catalytic cycle, and the appropriate steric hindrance of the (SIPr)^Ph₂ ligand greatly reduces the energy barrier of this step. The perfect combination of the electron-donating and steric hindrance abilities of the ligand significantly improves the catalytic activity.