Well-defined, air- and moisture-stable palladium–imidazo[1,5-a]pyridin-3-ylidene complexes: a versatile catalyst platform for cross-coupling reactions by L-shaped NHC ligands

Abstract

We describe the development of [(NHC)Pd(cinnamyl)Cl] complexes of ImPy (ImPy = imidazo[1,5-a]pyridin-3-ylidene) as a versatile class of precatalysts for cross-coupling reactions. These precatalysts feature fast activation to monoligated Pd(0) with 1 : 1 Pd to ligand ratio in a rigid imidazo[1,5-a]pyridin-3-ylidene template. Steric matching of the C5-substituent and N2-wingtip in the catalytic pocket of the catalyst framework led to the discovery of ImPyMesDipp as a highly reactive imidazo[1,5-a]pyridin-3-ylidene ligand for Pd-catalyzed cross-coupling of nitroarenes by challenging C–NO₂ activation. Kinetic studies demonstrate fast activation and high reactivity of this class of well-defined ImPy–Pd catalysts. Structural studies provide full characteristics of this new class of imidazo[1,5-a]pyridin-3-ylidene ligands. Computational studies establish electronic properties of sterically-restricted imidazo[1,5-a]pyridin-3-ylidene ligands. Finally, a scalable synthesis of C5-substituted imidazo[1,5-a]pyridin-3-ylidene ligands through Ni-catalyzed Kumada cross-coupling is disclosed. The method obviates chromatographic purification at any of the steps, resulting in a facile and modular access to ImPy ligands. We anticipate that well-defined [Pd–ImPy] complexes will find broad utility in organic synthesis and catalysis for activation of unreactive bonds.