芳基烯基酮的高效催化Nazarov反应：茚满酮类化合物的合成

发布时间：2018-07-03 13:01

本文选题：Nazarov反应 + 芳基烯基酮　；参考：《西南大学》2017年硕士论文

【摘要】：茚满酮类化合物的核心结构为芳基并五元环结构,因其存在于大量天然产物和一些药物分子当中,该类结构的合成近年来受到广泛的关注。合成茚满酮类化合物方法有很多,其结构中的五元环往往是合成重点,而Nazarov反应是一类非常重要的构建五元环的方法。该方法利用二烯酮结构化合物通过Lewis酸或Bronst酸作用发生分子内4π电环化过程,顺旋关环得到环戊烯酮结构。在I.N.Nazarov首次报道了这个反应后,该反应被广泛的用于构建五元环状化合物并取得了很大进展,期间发展了较多类型的反应底物以及催化剂。Trauner小组在2003年首次报道了该反应的不对称催化,使传统的Nazarov反应的研究更加多元化。但将芳基烯基酮作为二烯酮类似物做Nazarov反应的研究目前发展较少且反应催化结构相对单一,反应底物活性较高。本文针对文献中存在的问题进行了深入研究,将文献中芳基烯基酮的1,3-二羰基结构替换为甲基,在低活性反应物条件下对催化剂进行了三方面工作的研究。1、混合路易斯酸本文设计催化剂时受到了Pd催化工作的启发,拟设计一种具有双活化模式的催化体系,在经过筛选后发现铁盐和硼酸的组合能够有效的提高反应效率,并且经过一系列的实验研究发现用3,5-二三氟甲基苯硼酸与Fe(OTf)3的比例为1:2时反应效率最高。在该条件下进行了底物扩展,发现该条件下低活性的芳基烯基酮特别是含有吸电子取代基的芳基烯基酮均能很好的发生Nazarov反应,得到了大于80%的产率和较好的非对映选择性。并利用该催化模式成功的合成了天然产物片段。通过对反应产物的结构鉴定发现该条件下的反应产物为热力学稳定产物,随后对该反应的机理进行了探究,在实验基础上推测出可能的反应机理。2、不对称研究的尝试在上述氯化亚铁离子交换法催化芳基烯基酮的Nazarov反应取得一定成果后,本文拟利用手性Salan配体代替联吡啶配体,初步尝试该反应的不对称研究工作。但在配体合成过程中我们发现传统的配体合成路线较为复杂,因此我们尝试对传统的配体合成路线进行改进,最终优化了Salen配体的合成路线,并利用该合成路线制得了一系列的Salen配体。最后用这些配体对芳基烯基酮的Nazarov反应进行了不对称的尝试。
[Abstract]:The core structure of ninemanone compounds is aryl pentacrone structure. Because of its existence in a large number of natural products and some drug molecules, the synthesis of this kind of structure has received extensive attention in recent years. There are many methods for synthesizing ninemanone compounds, and the five-member ring in its structure is often the focus of synthesis, while Nazarov reaction is a very important method to construct five-member ring. In this method, the structure of cyclopentenone was obtained by the intramolecular electrocyclization of 4 蟺 by the interaction of Lewis acid or Bronst acid. After I.N. Nazarov first reported the reaction, the reaction was widely used to construct a five-member ring compound and a lot of progress was made. More types of substrates and catalyst. Trauner group first reported the asymmetric catalysis of the reaction in 2003, which made the traditional Nazarov reaction more diversified. However, the research on the Nazarov reaction of arylenyl ketone as a dienone analogue is less developed, the catalytic structure of the reaction is relatively single, and the substrate activity is relatively high. In this paper, the existing problems in the literature have been studied in depth, and the structure of aryl alkenyl ketones has been replaced by methyl group, and the structure of 1'3 'dicarbonyl group has been replaced by methyl group. The catalyst was studied in three aspects under the condition of low activity reactants. 1. The mixed Lewis acid catalyst was inspired by PD catalytic work, and a catalytic system with double activation mode was designed. After screening, it was found that the combination of iron salt and boric acid could effectively improve the reaction efficiency, and through a series of experimental studies, it was found that the reaction efficiency was the highest when the ratio of 3o 5- difluoromethylphenyl boric acid to Fe (OTF) 3 was 1:2. It was found that the low activity aryl alkenyl ketones, especially the aryl alkenyl ketones containing electron absorbent substituents, could react well with Nazarov reaction under this condition, and the yield was more than 80% and the enantioselectivity was better than 80%. The natural product fragments were successfully synthesized by this catalytic model. It was found that the reaction product under this condition was thermodynamically stable, and the mechanism of the reaction was studied. On the basis of experiments, the possible mechanism of reaction. 2. An asymmetric study attempt was made. After the above results were achieved in the Nazarov reaction of aryl alkenyl ketones catalyzed by the iron-exchange method mentioned above, the chiral Salan ligand was proposed to replace the bipyridine ligand, and the chiral Salan ligand was used to replace the bipyridine ligand. A preliminary attempt was made to study the asymmetry of the reaction. However, in the process of ligand synthesis, we found that the traditional ligand synthesis route is more complex, so we try to improve the traditional ligand synthesis route, and finally optimize the Salen ligand synthesis route. A series of Salen ligands were prepared by this synthetic route. Finally, these ligands were used to asymmetric Nazarov reaction of aryl alkenyl ketones.
【学位授予单位】：西南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O625.42

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