轴手性双咔啉氮氧化物催化的不对称硅氢化反应研究

发布时间：2019-07-09 07:39

【摘要】：手性胺是手性碳与氮原子相连的一类非常有意义的化合物。它们是很多化合物的中间体,在医药、农药、食品等领域有着广泛的应用。因此,用不对称合成法直接制备这类手性化合物十分重要。本文对手性胺的不对称合成作了初步的探讨,内容主要分为两章。第一章是概括近年来亚胺不对称还原的研究进展,主要是布朗斯特酸和路易斯碱两类有机小分子催化剂催化的(酮)亚胺还原的研究概况。第二章是在课题组前人工作的基础上,继续探究轴手性双咔啉氮氧化物对酮亚胺的不对称还原活性。我们首先在C-3,C-3′位以酰胺的形式结合不同的手性氨基酸甲酯,发现除脯氨酸甲酯取代基酰胺外,其它酰胺均具有两套~1H和~(13)C核磁谱数据,这似乎是混合物谱图。但是通过进一步分析,证明其为单一的手性酰胺。在考察其对酮亚胺的催化效果后,发现脯氨酸甲酯取代基酰胺有67%ee。在此基础上,将酰胺的氮进一步氧化生成轴手性双咔啉N,N′-双氧型催化剂,并考察了其在酮亚胺的不对称催化还原反应中的对映选择性。实验结果表明:该反应能够在温和条件(0℃)下于16-24 h内顺利完成,并有可观的产率(90%)。当底物具有供电子基时,反应的对映选择性普遍较好(70%ee)。其中C-3和C-3′位具有苯丙氨酸甲酯取代基的双咔啉N,N′-双氧化物具有最佳的对映选择性(80%)。综上所述,本研究设计合成了结构新颖、性能良好的轴手性双咔啉类催化剂。不仅筛选出了最优催化剂和催化条件,还对底物进行了扩展,在此基础上对反应机理进行了初步探讨和研究,这为催化剂的后续开发和应用提供了理论和实验基础。
文内图片：

图片说明：典型手性胺药物
[Abstract]:Chiral amines are a kind of very meaningful compounds which are linked by chiral carbon to nitrogen atoms. They are intermediates of many compounds, and have wide application in the fields of medicine, pesticide, food and the like. Therefore, it is important to prepare such chiral compounds directly by asymmetric synthesis. In this paper, the asymmetric synthesis of the chiral amine in this paper is mainly discussed, and the content is mainly divided into two chapters. The first chapter is an overview of the research on the asymmetric reduction of the imines in recent years, mainly the research on the reduction of the (ketone) imine catalyzed by the two kinds of organic small molecular catalysts of the Bronsted acid and the Lewis base. The second chapter, on the basis of the previous work of the research group, continues to explore the asymmetric reduction activity of the chiral dicyandiamide on the ketoimine. We first combined different chiral amino acid methyl esters in the form of C-3 and C-3, and found that the other alicyclic amines have two sets of ~ 1H and ~ (13) C nuclear magnetic spectrum data, which appears to be the spectrogram of the mixture. But by further analysis it is shown that it is a single chiral polar amine. After examining its catalytic effect on the ketoimine, it was found that the methyl ester of the proline methyl ester was 67% ee. On the basis of this, the N, N-, N-, and N-type catalysts for the further oxidation of the amine with nitrogen were carried out, and their enantioselectivity in the asymmetric catalytic reduction of the ketoimine was investigated. The experimental results show that the reaction can be successfully completed in the range of 16-24 h under mild conditions (0.degree. C.) and has a considerable yield (90%). When the substrate has an electron donor, the enantioselectivity of the reaction is generally good (70% ee). In which the C-3 and the C-3 have the optimum enantioselectivity (80%) of the dicyandiamide N, N--dioxides with the phenylalanine methyl ester substituent. To sum up, the present study has been designed and synthesized a new-structure, well-behaved, chiral, double-polar-type catalyst. Not only the optimal catalyst and the catalytic conditions are selected, but also the substrate is expanded, and the mechanism of the reaction is discussed and studied, which provides a theoretical and experimental basis for the subsequent development and application of the catalyst.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251

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