Copper-Catalyzed Asymmetric Michael/Cyclization Tandem Reaction To Construct Spirooxindole Compounds In Aqueous Media

Spirooxindole skeletons widely exist in many natural products and bioactive compounds.In drug research,they have shown great medicinal potential.Therefore,more and more organic chemists and pharmaceutical chemists are committed to the study of spirooxindole compounds.The rapid development of asymmetric organic catalysis technology provides more possibilities for the construction of spirooxindole compounds.In the field of organic synthesis,Michael addition reaction is one of the most important strategies for constructing C-C bonds.In particular,Michael addition initiated tandem reactions have significant advantages in the efficient synthesis of cyclic compounds with complex multi-cyclic structures,so it is one of the excellent synthesis strategies for constructing spirooxindole skeletons.Water as the solvent has many advantages,such as safety,green,and ease of operation and so on.This has attracted the attention of many organic chemists,threrefore,plenty of aqueous organic reactions have been developed,and aqueous asymmetric reactions have also been developed in time.This work introduced the method to construct the chiral spirooxindole compounds by Michael/cyclization tandem reaction in aqueous media.This paper is mainly divided into three chapters:In chapter 1,the review of the synthesis methods of spirooxindole compounds and the research progress in aqueous asymmetric catalysis were introduced.Firstly,the structural characteristics and medicinal value of spirooxindole compounds were introduced,and then the synthesis methods of spirooxindole compounds were summarized,including achiral synthesis and chiral synthesis induced by different types of chiral catalysts.Secondly,the recent asymmetric reactions in aqueous media were introduced,including recent asymmetric Michael addition reactions and other types of asymmetric reactions in aqueous media.In chapter 2,the research on the topic of copper-catalyzed asymmetric Michael/cyclization tandem reaction to construct spirooxindole compounds in aqueous media was carried out.It was mainly described in terms of the proposal and design of the subject,the specific optimization of reaction conditions,the research on the substrate scope,the gram scale experiment,the determination of absolute configuration and the research on the reaction mechanism.In chapter 3,the names of commonly used experimental instruments and reagents were summarized,the general synthesis steps of reaction substrates were described,and various characterization data of the products were listed.In summary,this paper developed an asymmetric Michael/cyclization tandem reaction between isatin derived β,γ-unsaturated α-ketoesters and 4-hydroxycoumarins catalyzed by the copper in aqueous media.This is a new method for constructing spirooxindole skeletons containing an all-carbon quaternary chiral center.