Studies On The Diversity Oriented Synthesis Via The Cascade Reactions Based On Electron Deficient Enamines

As a rapid and efficient synthetic method, cascade reaction has become one of the main tools of current organic synthesis. This dissertation mainly reports the cascade reaction-based diversity oriented synthesis of small molecuse such as aromatics, nitrogen heterocyclic and other nitrogen containing compounds. The content consists of two main sections: the multicomponent reactions based on the secondary amine-catalyzed multicomponent reactions via electron deficient enamine intermediates and the enaminone participated cascade reactions.In the first section, we firstly investigated the synthesis of 6-unsubstituted3,4-dihydropyrimidinones and thiones via the three-component reactions of propiolates, aldehydes, thiourea/urea. In the presence of a secondary amine, the propiolates were activated by forming enamino esters intermediates which initiated a series of subsequent transformations with catalysis of an acid to producte a number of unprecendented 6-unsubstituted 3,4-dihydropyrimidinones and thiones conveniently.Based on the analogous catalytic strategy, we then managed to realize the three-component reactions of propiolates, α,β-unsaturated aldehydes and amines to selectively synthesize 1,4- and 1,2-dihydropyridines via the catalytic system of secondary amine/acid. Generally, when conventional primary amines were used as substrates, 1,4-dihydropyridines were provided. On the other hand, when2-aminopyridine used as the amine component, the reaction model was changed to selectively yield 1,2-dihydropyridines owing to the strong electron withdrawing effect of the pyridine ring to the amino group.Subsequently, on the basis of the above results, we studied and established the diastereoselective three-component cascade reactions for the synthesis of tetrahydropyridine fused bicyclic compounds. The synthesis employed propiolates,α,β-unsaturated aldehydes, o-aminophenols or linear amino alcoholsas starting materials and successfully synthesized tetrahydropyridine fused oxazoles or oxazines with the catalysis of secondary amine/acid. This synthetic protocol was highly diastereoselective since all products provided by the reactions possess trans relative configuration on C2 and C4 sites of tetrahydropyridine ring.In the the research of the second main section, we firstly developed the the synthesis of 1,3,5-triacylbenzenes by the cyclotrimerization of enaminones. In lacticacid/water system, a series of 1,3,5-triacylbenzenes were smoothly synthesized using enamiones. In addition, 1,3,5-benzenetricarboxylates could also be accessed by using propiolates via the activation of secondary amine through similar reaction. Finally, we established the synthetic method for α-ketoamides via the cleavage of enaminone C=C double bond via oxidative copper catalysis. This method exhibited broad application scope by tolerating the synthesis of both N,N-disubstituted and N-mono substituted α-ketoamides.