Cu-catalyzed Direct C-H Amination Of Quinoline N-oxides

In this thesis, the construction of C-N bond to synthesize a series of2-aminoquinoline N-oxides based on Cu-catalyzed C-H activation was studied. The main results obtained were as follows:2-Aminoquinolines exist widely in pharmaceuticals and biological activity antagonists. Their high incidence of pharmacological activity has stimulated many research efforts to prepare such a core. There are some disadvantages with procedures reported in literatures, such as requirement of the expensive starting materials (2-cholorquinoline,2-mercaptoquinoline), harsh reaction conditions and low efficiency. Therefore, development of a simple, highly efficient and atomic economic method to synthesize2-aminoquinolines is a big challenge.Hence, we have developed an extremely simple and highly efficient protocol to synthesize a series of2-aminoquinoline N-oxides (Scheme1). Directly C-H/N-H dehydrogenative coupling reaction of heterocyclic N-oxides with secondary aliphatic amines could proceed smoothly in the presence of CuI (10mol%) as a catalyst, air as oxidant, toluene as solvent, giving a series of bioactive2-aminoheterocyclic N-oxide derivatives in up to96%yields. This method features a simple system, high efficiency, atomic economy, environmental friendliness, low reaction temperature and under ligand, additives, base and external oxidant free conditions. Air as oxidant is green and environmental friendly. Based on the results obtained, literature reported and density functional theory (DFT) calculation, a plausible pathway was proposed as shown in Scheme2.