Copper supported on acid-modified manganese oxide octahedral molecular sieves (Cu/H-OMS-2) was prepared and found to be a versatile catalyst for the oxidative synthesis of 3-aroylimidazopyridines with a broad substrate scope. Cu/H-OMS-2 that was characterized by BET, XRD, XPS, FTIR, TEM, SEM, H₂-TPR and O₂-TPD techniques could also be used to synthesize 3-aroylimidazopyrimidines and applied in one-pot, three-component reactions of ketones, aldehydes and 2-aminopyridines. The catalytic system employs low loading Cu as the catalytic metal and support H-OMS-2 as the electron-transfer mediator (ETM) to sequentially lower the redox energy barrier, which generates a low-energy pathway and enables the reaction to proceed in a biomimetic way. Moreover, Cu/H-OMS-2 could be reutilized 4 times with a slight decrease in the catalytic activity.