Metal-free Synthesis Of (Fused) Five-membered Nitrogen-containing Heterocycles Via Tandem Reaction

The synthesis of relevant organic compounds is a main topic in academic and industrial chemistry. Besides selectivity, the main goals are efficiency, compatibility with the environment, preservation of our resources, and reduction in production costs. An attractive way to address these criteria is the development of cascade (domino) processes. In contrast with the traditional stepwise synthesis, the cascade reactions allow the synthesis of complex molecules from simple starting materials with multiple bonds formed.Although a great number of metal-based catalysts have been successfully employed in organic synthesis, metal-catalyzed protocols usually have several inherent limitations, including moisture sensitivity, costly metal catalysts and environmental toxicity. Meanwhile, pharmaceutical guideline has dramatically lowered the limits of trace metal impurities in pharmaceuticals. Therefore, there is still a need to develop metal-free method in organic synthesis, which is very significant in view of environmental and economical considerations.This paper mainly discussed the following contents:In Chapter1, the definition and advantage of tandem reaction were given. The progress of indole skeleton synthesis via tandem reaction was mainly reviewed.In Chapter2,9H-pyrido[2,3-b]indole derivatives were achieved by a tandem reaction from chalcone and2-(2-aminophenyl)acetonitrile. It was proposed that a key intermediate-2-amino-indole was formed in situ, followed by Michael addition with chalcone, condensation with carbonyl group, dehydration and aromatization.In Chapter3,I2-TBHP was used as metal-free catalyst for the synthesis of imidazo[1,2-a]pyridine from aminopyridines and nitroolefins. The reaction probably processed sequentially Michael addition and oxidative coupling.In Chapter4, symmetrical9,9’-bis(1H-indol-3-yl)-fluorene and9,9’-bis(1H-indol-3-yl)-4,5-diazafluorene were synthesized in the presence of methane sulfonic acid. These products with big aromatic conjugate system were obtained from indole,9-Fluorenone or4,5-Diazafluoren-9-one via a tandem double Friedel-Crafts alkylation.All products were structurally characterized by1H NMR,13C NMR and MS spectra. Key product was also determined by CCDC x-ray analysis.