【作者】 李宁；

【导师】 汪志勇；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2023， 硕士

【摘要】 螺氧化吲哚骨架广泛存在于许多天然产物和生物活性化合物中,在药物研究中,它们显示出巨大的药用潜力。因此,越来越多的有机化学家和药物化学家致力于螺氧化吲哚化合物的研究中。不对称有机催化技术的飞速发展为螺氧化吲哚化合物的构建提供了更多的可能性。在有机合成领域中,Michael反应是构建C-C键至关重要的策略之一,尤其是Michael加成引发的串联反应在高效合成具有复杂多元环结构的环状化合物时具有明显的优势,是构建螺氧化吲哚骨架的优良策略之一。随着水作为溶剂安全、绿色、易于操作等优点被有机化学家注意到,越来越多的水相有机反应被开发了出来,水相不对称反应也应运而生。本论文介绍的工作就是在水相中发展的Michael/环化串联反应构建手性螺氧化吲哚化合物。本论文主要分三个章节进行介绍:第一章综述了螺氧化吲哚化合物的合成方法以及水相不对称催化研究进展。首先介绍了螺氧化吲哚化合物的结构特点以及药用价值,然后总结了螺氧化吲哚化合物的合成方法,包括非手性合成和不同类型手性催化剂诱导下的手性合成。其次对水相不对称反应进行了介绍,并简述了在水介质中的不对称Michael反应以及其他类型的不对称反应。第二章开展了铜催化不对称水相Michael/环化串联反应构建螺氧化吲哚化合物课题的研究,主要按照课题的提出与设计、反应条件的具体优化过程、反应底物范围的研究、克规模实验、绝对构型的确定和反应机理的研究等方面展开叙述。第三章总结了常用的实验仪器名称、实验试剂名称,描述了反应底物的一般合成步骤并列举了产物的各种表征数据。综上所述,本论文发展了在水介质中铜催化的靛红衍生的β,γ-不饱和α-酮酯和4-羟基香豆素之间的不对称Michael/环化串联反应。这是一种构建含手性季碳中心的螺氧化吲哚骨架的新方法。更多还原

【Abstract】 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.更多还原