铱催化C-H键直接芳基化反应研究

发布时间：2018-02-28 12:04

  本文关键词： 铱 sp~3C-H键 芳基化 肟醚 二芳基高碘化物 sp~2C-H键 含氮杂环 烯烃　出处：《扬州大学》2016年硕士论文　论文类型：学位论文

【摘要】：研究生期间我的研究内容主要分为以下三个部分：].铱催化sp3C-H键直接芳基化反应的研究过渡金属催化活化碳氢键的方法已经成为有机合成中不可或缺的一部分,近年来该领域已受到化学界的高度关注。脂肪族的碳氢键广泛存在于有机分子中,如何高效和高选择性的实现其官能团化,构建新的碳碳键和碳杂原子键,至今仍然是一个巨大的挑战。在过渡金属催化下,可以实现直接碳氢键的芳基化,这相对于传统的有机合成方法有着巨大的优势,能够克服传统方法中需要多步才能实现的反应。β芳基化的酮肟是可以转换为许多天然产物和药物分子的重要结构单元,我们利用三价铱金属配合物作为催化剂,芳基高碘化物作为芳基源,首次成功通过sp3 C-H键活化实现了在肟醚β位引入芳基的反应。该方法具有原子经济、较好的反应底物兼容性和较高的区域选择性等特点。最后通过密度泛函理论(DFT)计算,从理论的角度解释了反应的形成过程。2.铱催化含氮杂环化合物直接芳基化反应研究杂环化合物包括吡啶,吡嗪,喹啉,吡唑,异恶唑等是许多药物以及生物活性分子中常见的结构,我们设想一种可靠的杂环化合物直接芳基化方法将会意义重大。我们通过不断的探索和反应条件的优化,寻找出最佳的反应条件。利用[IrCp*Cl2]2作为催化剂,AgNTf2作为添加剂,PivOH,4A MS和溶剂环己烷,二芳基高碘化物作为芳基源,在1000C条件下成功实现了杂环化合物的芳基化。在该反应体系下,得到的是单一的单取代芳基化产物,并且通过GC-MS没有观测到二取代的副产物。该转化不仅能够兼容六元杂环,五元杂环也可以得到较高产率的芳基化产物。该转化对于修饰药物以及生物活性分子具有很好的实.用价值和应用前景。3.芳基以及烯基化合物邻位C-H键直接芳基化研究尽管sp2 C-H键的直接芳基化反应已经被深入的研究,包括使用Pd,Ni,Cu,Ru,Rh等过渡金属,但是Ir(Ⅲ)催化芳香化合物的直接芳基化反应仍然很少。我们利用半三明治结构的三价铱配合物作为催化剂,成功实现了芳基化合物的sp2C-H键的芳基化,该反应体系具有非常高的官能团兼容性。包括吡啶类化合物,酰胺类化合物以及肟醚类化合物都能很好的得到芳基化的目标产物。同时,烯基类化合物在酰胺,肟醚以及羧酸的导向基团存在下能够顺利的实现C-H键的芳基化。值得注意的是,这些偶联反应发生完全得到的是Z式。这种立体选择性是非常有价值的,因为它具有潜在的合成应用。
[Abstract]:As a graduate student, my research is mainly divided into the following three parts:] .Iridium catalyzed direct arylation of sp3C-H bond; transition metal catalytic activation of hydrocarbon bonds has become an indispensable part of organic synthesis. In recent years, this field has attracted great attention in chemistry. Aliphatic carbon-hydrogen bonds are widely found in organic molecules. How to efficiently and selectively realize their functionalization and construct new carbon-carbon bonds and carbon hetero-atomic bonds. It is still a huge challenge. Arylation of direct hydrocarbon bonds can be achieved under the catalysis of transition metals, which has great advantages over traditional organic synthesis methods. The ketone oxime of 尾 arylation is an important structural unit that can be converted into many natural products and drug molecules. We use the metal complexes of iridium trivalent as the catalyst. Aryl polyiodides as aryl sources were successfully activated by sp3 C-H bond for the first time to realize the introduction of aryl groups to the 尾 site of oxime ether. Better substrate compatibility and higher regioselectivity. Finally, the density functional theory (DFT) is used to calculate, The formation process of the reaction was explained theoretically. 2. Direct arylation of heterocyclic compounds containing nitrogen catalyzed by iridium; heterocyclic compounds including pyridine, pyrazine, quinoline, pyrazole, pyrazole, pyrazine, pyrazine, pyrazine, pyrazine, pyrazine. Isoxazole and so on are common structures in many drugs and bioactive molecules, so it would be important to imagine a reliable method of direct arylation of heterocyclic compounds. Using [IrCp*Cl2] 2 as catalyst and solvent cyclohexane as additive, the arylation of heterocyclic compounds was successfully realized at 1000C by using [IrCp*Cl2] 2 as catalyst and solvent cyclohexane and diaryl polyiodide as aryl source. A single monosubstituted arylation product was obtained, and no disubstituted by-products were observed by GC-MS. High yield arylation products can also be obtained from quaternary heterocyclic compounds. The conversion has a good effect on modifying drugs and bioactive molecules. The value and application prospect. 3. Aryl group and direct aryl group of O-C-H bond of alkenyl compounds. Although the direct arylation of sp2 C-H bonds has been studied in depth, The direct arylation of aromatic compounds catalyzed by Ir- (鈪，

本文编号：1547226