基于钯催化双齿导向的碳氧芳基化反应的研究

发布时间：2018-06-12 08:07

本文选题：钯催化 + 碳氢活化　；参考：《南京理工大学》2016年硕士论文

【摘要】：碳氢键(C-H)是构成有机化合物的最基本化学键之一,碳氢键的活化反应是近年来有机合成领域的一大热点,吸引着越来越广泛的化学工作者的关注。过渡金属催化的碳氢键活化反应由于其具有良好的原子经济性、环境友好,符合现代绿色化学发展趋势而受到人们的广泛关注。近十年来,利用分子内导向策略选择性活化特定碳氢键成为研究者们的兴趣所在。因此,本论文研究了基于高效双齿导向的碳氢芳基化反应体系,成功合成了一系列芳基化产物,主要内容如下：1.基于8-氨基喹啉导向Pd催化的烯烃C-H芳基化反应的研究碳碳双键是有机合成中的常用分子砌块,且多具有生物活性。相比较于反式烯烃领域经取代的巨大成功而言,相对不稳定的顺式烯烃则研究甚少。过渡金属钯(Pd)催化C-H芳基化反应的研究是碳氢活化领域研究最早,且最为成熟的反应类型。本课题探究了以Pd催化,8-氨基喹啉导向,芳基碘试剂为偶联剂,选择性地活化烯烃上C-H键,实现丙烯酰胺类底物上的顺式芳基化反应的方法。该方法能够以高产率和优异的选择性合成一系列顺式肉桂酸类衍生物。通过实验对比发现,氧化剂过硫酸氢钾复合盐(oxone)的加入对反应选择性的提高有巨大的作用。因此,该氧化剂的加入有效抑制了Heck反应历程,即抑制反式产物的产生,进而有效提高了反应的顺反选择性。2.基于2-毗啶酰胺导向Pd催化的氨基酸C-H芳基化反应的初步研究氨基酸分子,作为蛋白质和肽链的次级结构,同样也可以作为手性分子骨架、手性配体及手性催化剂等,在有机合成和生物分子领域具有重要的应用价值。然而,天然基因编码的氨基酸分子的数量有限,造成其在食品、医药、材料等多方面的应用受到极大的限制。因此,开发出能够对氨基酸进行修饰的方法学研究成为亟待解决的问题。本课题致力于Pd催化,2-吡啶酰胺导向,芳基碘试剂为偶联剂,氨基酸D-α-苯基甘氨酸底物上碳氢芳基化反应的研究,实现底物侧链苯基上C(sp2)-H芳基化,成功合成含天然手性中心的氨基酸小分子,达到对天然氨基酸侧链修饰的目的。
[Abstract]:C-H) is one of the most basic chemical bonds of organic compounds. The activation of hydrocarbon bonds is a hot spot in the field of organic synthesis in recent years, attracting more and more attention of chemists. Transition metal-catalyzed carbon-hydrogen bond activation has attracted wide attention due to its good atomic economy, environmental friendliness and modern green chemistry. In the last decade, selective activation of specific hydrocarbon bonds using intramolecular orientation strategies has been of interest to researchers. Therefore, a series of arylation products were successfully synthesized based on the highly efficient bidentate oriented arylation reaction system. The main contents are as follows: 1: 1. Studies on C-H arylation of olefin catalyzed by 8-aminoquinoline-directed PD; carbon-carbon double bonds are commonly used molecular blocks in organic synthesis and have many biological activities. Relative instability of cis-olefins is less studied than the great success of substitution in the field of trans olefin. The study of C-H arylation catalyzed by transition metal palladium (PD) is the earliest and most mature reaction type in the field of hydrocarbon activation. In this paper, the method of selective activation of C-H bond on olefin with PD catalyzed 8-aminoquinoline orientation and aryl iodine reagent as coupling agent has been studied to realize cis arylation on acrylamide substrates. This method can synthesize a series of cis cinnamic acid derivatives with high yield and excellent selectivity. It was found that the addition of oxidant potassium persulfate (KH _ 2SO _ 4) had a great effect on the selectivity of the reaction. Therefore, the addition of the oxidant effectively inhibited the Heck reaction process, that is, the production of trans-products was inhibited, and the cis-trans-selectivity of the reaction was improved effectively. A preliminary study on the arylation of Amino acids C-H catalyzed by 2-pyridamide-directed PD; Amino acid molecules, as the secondary structures of protein and peptide chains, can also be used as chiral molecular skeletons, chiral ligands and chiral catalysts, etc. It has important application value in the field of organic synthesis and biomolecules. However, due to the limited number of amino acid molecules encoded by natural genes, their applications in food, medicine and materials are greatly limited. Therefore, it is an urgent problem to develop a methodology to modify amino acids. This paper is devoted to the study of aromatization of amino acids on D- 伪 -phenylglycine substrate by PD catalysis of 2-pyridine amide, aryl iodine reagent as coupling agent, and the arylation of C ~ (2 +) sp _ (2) O _ (-H) on the side chain phenyl of the substrate. Small amino acid molecules containing natural chiral centers were successfully synthesized to modify the side chain of natural amino acids.
【学位授予单位】：南京理工大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O621.251

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