Reparation Of Fused Nitrogen Heterocycles Via Metal-Catalyzed Cyclization Actions

Heterocyclic compounds are worth our attention for many reasons; chief among them are their biological activities, and many drugs are heterocycles. Therefore, organic chemists have been making extensive efforts to produce these heterocyclic compounds by developing new and efficient synthetic transformations. Among a variety of new synthetic transformations, metal-catalyzed reactions are some of the most attractive methodologies for synthesizing heterocyclic compounds, since a metal catalyzed reaction can directly construct complicated molecules from readily accessible starting materials under mild conditions.This thesis addresses the use of three new methods involving metal catalyzed cyclization for the synthesis of fused nitrogen heterocycles.Part one describes cobalt-catalyzed oxidative [3+2] cycloaddition cascades. Heterocyclic N-ylide was prepared from tertiary amine by a cobalt-catalyzed oxidation. By virtue of this intermediate, a regioselective synthesis of various dihydropyrrolo[2,1-a]isoquinolines was obtained via a [3+2] cycloaddition cascade of dihydroisoquinoline esters with nitroolefins. N-Sulfuryl Aldimines could undergo the cascade cycloaddition reaction under standard conditions. Compared to the nitro group (-NO2), the Ts (4-Me-PhSO2-) group was a poor leaving groups for this reaction. As a result, the isolated cycloaddition products were present in the form of hexahydroimidazo[2,1-a]isoquinolines. A multi-component reaction for the synthesis of5,6-dihydroimidazo[2,1-a]isoquinolines were also realized under almost the same conditions. This method is particularly suitable for the synthesis of tricyclic nitrogen heterocycles due to its simple manipulation, wide scope of the reaction substrates and excellent regioselectivity. Preliminary investigations on mechanism indicate that a single electron transfer process may be involved in the presence of cobalt catalyst.Part two presents a cerium(Ⅲ)-catalyzed [3+2] cascade cyclization. A general and practical route to the synthesis of mutisubstituted pyrrolo[1,2-a]quinolines has been devoloped from2-alkylazaarenes and nitroolefins using cerium chloride as a catalyst. This protocol featured ready availability of the starting materials, the operational simplicity and high regioselectivity to access multifunctionalized pyrrolo[1,2-a]quinolines with the formation of multiple C-C and C-N bonds in one-pot. In addition, various substitution patterns and functional group were found to be compatible under the optimized conditions, which was lacking in existing procedure. The intermediate Michael adduct was isolated and gave the final product in high yield in the presence of cerium chloride. Presumably, this process involves Michael addition followed by subsequent cyclization, thereby leading to the final product.Part three describes a single-step elaboration of pyrazolo[1,5-a]quinoline structure using a conceptually distinct copper-promoted oxidative coupling approach. Various of polysubstituted pyrazolo[1,5-a]quinoline derivatives were synthesis from2-alkylazaarenes and nitriles involving a oxidative C-C/N-N bond-formation cascade. The reaction allows the facile generation of diversity in the construction of pyrazolo[1,5-a]quinolines, which are important privileged structures.