Studies On Copper-Catalyzed Coupling Reactions Of Oxime Acetates

As one of important classess of nitrogen-containing compounds, oximes and their derivatives play important roles on synthetic amine, drug intermediates and other active biological compounds. At the same time oximes have very wide range of uses in the protection and deprotection of aldehydes and ketones, Beckmann rearrangement, and aldoxime dehydration to synthesize nitriles. Recently with the establishment of theoretical exploration and new catalytic system of transition metal catalyzed reactions, considerable progress has been made on transition metal catalyzed oximes and derivatives amination reactions, cyclization reactions and coupling reactions to build new C-C and C-N bonds. Learning the progresses of these reactions, combined with our development of reductive acylation of ketoximes with NaHSO3to synthesis enamide, the thesis highlighted our new method of copper-catalyzed coupling of oxime acetates with aldehydes for synthesis of pyridines.Pyridines have a wide range of applications in many natural products, medicinal compounds and functional materials molecular. Although many synthetic methods of pyridines have been developed, to seek a new way with strong tolerance of functional groups, the raw material easily obtained to synthesis pyridine is still one of the synthetic directions chemists are trying to explore. After we discuss the progress of CuI-catalyzed the N-O cleavage of oximes to form enamides under the acylation of Ac2O, combined with the theoretical studies of the reactions of transition metal catalyzed oxime compounds, we designed to the new coupling reactions of copper-catalyzed oxime acetate and aldehyde followed by couping and cyclization of previous product and another molecule oxime to prepare tri-substituted pyridine compounds. Fortunately, we achieved the above objectives with experiments, and synthesized of a series of pyridine compounds with aromatic ring oxime acetates and various aldehydes in the presence of copper bromide.Our developed new method, is more suitable to cyclic keoxime acetates. And aromatic aldehydes containing different substituent groups (including fluoro, nitro, etc.) can be smoothly passed through the approach to give the corresponding pyridine compounds. For in depth study of the mechanism of this reaction, we experimented the coupling reactions of two different molecules oxime acetates and aldehydes, and then this coupling ring closure reaction mechanism had been speculated combined with the results of the analysis and relatedreportes in the literature. In summary, our reported method, copper-catalyzed coupling reactions of oxime acetates and aldehyde to synthesize pyridine compounds, not only reduces the economic cost, operating easier with good functional group tolerance, but also uses environmental friendliness copper salt catalyst, in line with the current development of green chemistry prospects.