Study On Synthesis Of Pyrrolidinyl-Spirooxindole And Bispiro-Pyrazolone Compounds Via Asymmetric Organocatalysis

Bifunctional orgnocatalysis has unique advantages in the construction of compounds with multi-chiral centers,quaternary carbon centers and spiro ring skeletons.In this thesis,the related studies on the asymmetric synthesis of pyrrolidinylspirooxindole and bispiro-pyrazolone derivatives via bifunctional organocatalysis are conducted,including the following four parts:Chapter 1: First,this chapter introduces the birth and rise of organocatalysis,and then summarizes several fundamental organocatalytic modes,and finally focuses on the introduction of bifunctional organocatalysts and bifunctional organocatalytic modes.Chapter 2: The asymmetric construction of pyrrolidinyl-spirooxindole compounds has attracted the interest of synthetic chemists because of these compounds are widely existed in natural products and drug molecules.The beginning of this chapter introduces the research progress of the synthesis of spiro[indoline-3,3'-pyrrolidine] compounds and the latest research progress of o-hydroxybenzaldehyde methylenediamine ylide.On this basis,a variety of spiro[indoline-3,3'-pyrrolidine]s with quaternary and continuous chiral centers are synthesized in good yields with excellent stereoselectivities through an asymmetric,intermolecular and formal [3+2] cyclization reaction catalyzed by a bifunctional organocatalyst.It is worth noting that the hydroxyl and trifluoromethyl groups on the substrates play an important role in the reaction.Chapter 3: Spiro-pyrazolone compounds have been proved to have a wide range of biological activities and medicinal value in the continuous exploration of organic chemists and pharmaceutical chemists,and most of the previous work reported by synthetic chemists was the synthesis of spiro-pyrazolone compounds with only one spiro atom.The beginning of this chapter introduces the reactions involving oxindole ketoesters and vinylogy-pyrazolone.On this basis,we have developed an efficient approach for synthesis of a variety of bispiro-pyrazolone compounds with two chiral spiro atoms by using oxindole ketoesters and vinylogy-pyrazolone via bifunctional thiourea catalyst.Chapter 4: In summary,efficient and asymmetric synthesis of pyrrolidinylspirooxindole compounds and bispiro-pyrazolone compounds via bifunctional organocatalysis under mild conditions.The thesis enriches the synthetic methods of chiral spiro compounds,and demonstrates the advantages of bifunctional organocatalysis in asymmetric tandem cyclization.Finally,the effect of the auxiliary group on the substrate or the catalyst,the relationship between the catalyst structure and the catalytic effect,and the role conversion of the substrate and the catalyst are proposed.