Studies On Transition-Metal Catalyzed Tandem Cyclization Reaction For The Synthesis Of Heterocyclic Compounds

Heterocycles are ubiquitous in natural products, pharmaceuticals, organic materials, and numerous functional molecules. As a consequence, developing new simple and efficient syntheses of heterocycles has always been a thread in the synthetic community. Tandem reactions, which can utilize few steps to obtain more complex chemical structure, has played an important role in asymmetric synthesis and the synthesis of heterocyclic compounds. With the skillfully design of catalyst and substrate, tandem reactions will become more and more important synthetic method. In this paper, we are interested in the transition metal-catalyzed tandem cyclization reaction and its application in organic synthesis, which including three chapters:In Chapter I, we have given a brief summary on the recent studies about the application and synthetic method of1,2,3,4-tetrahydroquinoline compounds. With the method of condensation of aniline and two molecules of aldehyde, we developed an iron(â…¢) chloride-mediated domino Mannich and intramolecular Friedel-Crafts alkylation followed by intermolecular Friedel-Crafts alkylation reactions of aliphatic aldehydes with aromatic amines, efficient synthesis of polysubstituted1,2,3,4-tetrahydroquinoline derivatives.In Chapter II, we have introduced the theoretical background of gold, platinum activated alkynyl and summarized the recent research on gold, platinum-catalyzed epoxy alkyne compound cyclization reaction and cyclization, migration reaction involving heteroatom. Firstly, we designed a platinum-catalyzed reaction of an epoxy alkynyl allyl ether to a spirobenzo[h]chromanone. Three rings with a spirocarbon can be efficiently formed in one reaction. Secondly, the reaction conditions were optimized, and the scope of this reaction was investigated. Thirdly, we have also discussed the electronic effect of substituents on the aromatic ring and proposed a reasonable reaction mechanism. The reaction proceeds through several challenging steps including epoxy alkyne cyclization,[1,2]-alkyl migration, allyl shift, aromatic cyclization in a cascade manner.In Chapter III, firstly, we summarized recent researches on gold-catalyzed cyclization of alkynylaziridine and gold-catalyzed hydroamination of aminoallene. Then, we designed a gold-catalyzed rearrangement reaction of alkynylaziridine indoles for the synthesis of spiro-tetrahydro-p-carbolines. Thirdly, the reaction conditions were optimized, and the scope of this reaction was investigated. Finally, we have also separated the intermediate compound and proposed a reasonable reaction mechanism. This reaction involves an intramolecular Friedelâ–¡Crafts type addition reaction of alkynylaziridine indole and a hydroamination reaction of aminoallene intermediate.