Investigation On Copper-catalyzed Synthetic Transformations Of Oxime Acetates Into Nitrogen-containing Heterocyclic Compounds

Ketoxime acetate derivatives are very valuable compounds, which have been widely applied as versatile building blocks in organic synthesis. Especially, it provided convenient methods to a broad range of N-containing heteropolycycles by transition metal catalysis. And the ketoxime acetates were prepared from corresponding ketone, hydroxylamine hydrochloride and anhydride under mild conditions. In the past few decades, advancements in intramolecular Heck cyclization of oxime esters has been made to afford functionalized pyrrole derivatives. With the continuous development of the transition metal-catalyzed(ruthenium, rhodium, and palladium) synthetic organic chemistry, the copper-catalyzed transformation of oxime esters has triggered widespread interest. In practice, copper-catalyzed coupling of ketoxime acetate derivatives have emerged as a promising approaches to the synthesis of aza- heterocycles in synthetic organic chemistry. This thesis starts from the cleavage of N–O and construction of C–N bonds introduced copper-catalyzed cyclization of oxime esters for the synthesis of valuable nitrogen heterocyclic compounds.We have developed a Cu-catalyzed three component cascade reaction for the synthesis of polysubstituted pyridines from ketoxime acetates, aldehydes, and activated methylene compounds under mild conditions. In this procedure, the N–O bond reductive cleavage directly leads to the generation or regeneration of the active metal catalyst. Moreover, this transformation successfully extends its application to construct bipyridine and nicotinamide derivatives and attractive structures containing L(-)-carvone and β- ionone natural scaffolds. Notably, bipyridine compounds have been widely used as fundamental part of ligands in organic synthesis.Then, we have developed a copper-catalyzed cascade condensation for divergent syntheses of functionalized isoquinolines and indolo[1,2-a]quinazolines from 2-haloketoxime acetates. Compared with the traditional method s, this protocol provides a powerful method for the synthesis of indolo[1,2-a]quinazolines through direct conversion of unactivated indole. Moreover, this method features operational simplicity, no need for additional ligands, and excel ent functional group tolerance, which makes it have potential synthetic applications.