内半缩醛在有机催化不对称反应中的应用
发布时间：2018-08-13 13:34
【摘要】：有机催化的不对称合成从2000开始引起了世界各地的科学家们广泛的关注,并收获了丰硕的科研成果。从新型催化剂的研发,复杂反应机理的探索和证明,到新奇路线的巧妙设计和多手性中心骨架的构建以及最后的工业化运用,使得有机催化在不对称领域占有了重要的位置。因此,发展新的适用于有机催化的底物并得到一些特定的骨架具有重要的意义。本论文主要围绕一个全新的有机催化底物—内半缩醛,展开-系列的研究。氢化香豆素骨架广泛的存在于活性天然产物中,由廉价易得的香豆素出发,不对称修饰氢化香豆素骨架具有重要意义。论文的第一部分提出了一个全新的“开-关”策略。首先,还原氢化香豆素中的内酯为内半缩醛完成“开”的步骤,再以手性仲胺为催化剂,催化内半缩醛和缺电子的烯烃发生不对称的Michael反应,最后氧化内半缩醛为内酯完成“关”的步骤。该反应具有产率高和立体选择性好(大部分ee＞99%),容易操作,环境友好等优点。最终的产物可以通过一系列的衍生获得了多种不同骨架的具有光学活性的化合物。值得注意的是,这是首次把内半缩醛运用在有机催化的不对称合成中,为未来该领域的研究开辟了一条新的道路。螺环氧化吲哚骨架由于其优秀的生理学和药学活性一直以来都是不对称合成中的热点。尤其是螺环为全手性中心的六元碳环化合物的合成备受化学家们的关注。论文的第二部分报道了一个使用不对称[2+2+2]串联策略,通过有机/有机双催化体系构建六元碳环化合物。该产物包括六个连续的手性中心,而且其中一个手性中心为季碳,同时还包含螺环氧化吲哚骨架部分。于此同时,该反应是继内半缩醛运用在有机催化的不对称合成中的又一个新的拓展。
[Abstract]:The asymmetric synthesis of organic catalysis has attracted the attention of scientists all over the world since 2000, and has yielded fruitful results. From the research and development of new catalyst, the exploration and proof of complex reaction mechanism, the ingenious design of novel route, the construction of multi-chiral center skeleton and the final industrial application, organic catalysis occupies an important position in the field of asymmetry. Therefore, it is of great significance to develop new substrates suitable for organic catalysis and obtain some specific skeletons. This paper focuses on a new organic catalytic substrate-internal semi-acetal, starting-series of research. Hydrocoumarin skeleton widely exists in active natural products. It is of great significance to modify the hydrocoumarin skeleton asymmetrically from the cheap and easily available coumarin skeleton. In the first part of this paper, a new strategy of "on-off" is put forward. First, the lactone in the hydrogenated coumarin was used as the inner hemiacetal to complete the "opening" step, and then the asymmetric Michael reaction between the inner hemiacetal and the electron-deficient olefins was catalyzed with chiral secondary amine as the catalyst. The final oxidation of the inner half acetal for lactone to complete the "pass" step. This reaction has the advantages of high yield, good stereoselectivity (most ee > 99%), easy operation and environmental friendliness. The final product can be derived by a series of derivatives to obtain a variety of different skeletons with optical active compounds. It is worth noting that this is the first time that inner hemiacetal has been used in organic catalyzed asymmetric synthesis, which opens a new way for future research in this field. The spirocyclic indole skeleton has been a hot spot in asymmetric synthesis due to its excellent physiological and pharmaceutical activity. In particular, the synthesis of hexagonal carbon compounds with snail ring as a full chiral center has attracted much attention of chemists. In the second part of this paper, an asymmetric [222] tandem strategy is used to construct hexagonal carbocyclic compounds by organic / organic double catalysis system. The product consists of six consecutive chiral centers, one of which is quaternary carbon, and also contains the spirocyclic indole skeleton. At the same time, the reaction is a new extension of the application of inner hemiacetal in organic catalyzed asymmetric synthesis.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O621.251
本文编号：2181149
[Abstract]:The asymmetric synthesis of organic catalysis has attracted the attention of scientists all over the world since 2000, and has yielded fruitful results. From the research and development of new catalyst, the exploration and proof of complex reaction mechanism, the ingenious design of novel route, the construction of multi-chiral center skeleton and the final industrial application, organic catalysis occupies an important position in the field of asymmetry. Therefore, it is of great significance to develop new substrates suitable for organic catalysis and obtain some specific skeletons. This paper focuses on a new organic catalytic substrate-internal semi-acetal, starting-series of research. Hydrocoumarin skeleton widely exists in active natural products. It is of great significance to modify the hydrocoumarin skeleton asymmetrically from the cheap and easily available coumarin skeleton. In the first part of this paper, a new strategy of "on-off" is put forward. First, the lactone in the hydrogenated coumarin was used as the inner hemiacetal to complete the "opening" step, and then the asymmetric Michael reaction between the inner hemiacetal and the electron-deficient olefins was catalyzed with chiral secondary amine as the catalyst. The final oxidation of the inner half acetal for lactone to complete the "pass" step. This reaction has the advantages of high yield, good stereoselectivity (most ee > 99%), easy operation and environmental friendliness. The final product can be derived by a series of derivatives to obtain a variety of different skeletons with optical active compounds. It is worth noting that this is the first time that inner hemiacetal has been used in organic catalyzed asymmetric synthesis, which opens a new way for future research in this field. The spirocyclic indole skeleton has been a hot spot in asymmetric synthesis due to its excellent physiological and pharmaceutical activity. In particular, the synthesis of hexagonal carbon compounds with snail ring as a full chiral center has attracted much attention of chemists. In the second part of this paper, an asymmetric [222] tandem strategy is used to construct hexagonal carbocyclic compounds by organic / organic double catalysis system. The product consists of six consecutive chiral centers, one of which is quaternary carbon, and also contains the spirocyclic indole skeleton. At the same time, the reaction is a new extension of the application of inner hemiacetal in organic catalyzed asymmetric synthesis.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O621.251
【相似文献】
相关硕士学位论文 前2条
1 李志龙;内半缩醛在有机催化不对称反应中的应用[D];西南交通大学;2016年
2 曾静;光学活性丁内半缩醛的合成及在天然生物碱合成中的应用[D];厦门大学;2007年
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