Study On Synthesis Of Pyrrolidinyl-dispirooxindole And Pyran Fused Pyrazole Derivatives Via Asymmetric Organocatalysis

Asymmetric organocatalysis has distinctive advantages in the construction of sophisticated compounds with multi-chiral centers.In this paper,the asymmetric organocatalytic synthesis of 3,3’-pyrrolidinyl-dispirooxindole compounds and pyran fused pyrazole derivatives has been researched.This paper is divided into three parts:In the first chapter,this chapter introduces the research progress of asymmetric organocatalytic construction of indole spirocycle skeleton compounds.Compounds containing indole spirocycle skeleton are widely found in natural products and medicated molecules,and their synthesis methods have been paid much more attention.Asymmetric organocatalysis,as one of the three asymmetric synthesis strategies paralleled with asymmetric metal catalysis and enzyme catalysis,has developed rapidly in the past two decades.The advantages of organocatalysis including: low toxicity of catalyst,simple operation,mild reaction conditions and environmental friendliness.In particular.The development of novel asymmetric organocatalytic reactions has become one of the most effective strategies for the synthesis of complex indole spirocycle compounds containing multiple chiral senters.In the second chapter,the asymmetric synthesis of 3,3’-pyrrolidinyldispirooxindole derivatives has become one of the hot spots in orgaic synthesis.This kind of compounds own good biological activity and racemate and diastereoselective synthesis have been achieved,but there are few reports on enantioselective synthesis.We have developed an asymmetric [3+2] cascade cyclization reaction catalyzed by quinine-derived squaramide catalyst,and successfully synthesized 3,3’-pyrrolidinyldispirooxindole compounds with four contiguous stereogenic centers and two of which are contiguous chiral stereocenters with satisfying results.As an electrophilic substrate,the designed benzylidene oxindoles compounds do not need to be pre-activated by electron-deficient groups and can be well adapted to the reaction system.The reaction has a good range of substrate application with high yields.The application potentiality of this reaction was further proved by the gram-scale amplification experiment.In the third chapter,pyran fused pyrazole derivatives widely exist in natural products and have been developed for the study of medicated molecules.We developed a strategy using organo-bifunctional catalysts to realize the asymmetric cascade cyclization of pyrazolone and conjugated alkyne ketones.In this reaction,a series of pyran fused pyrazole with chiral centers were synthesized.