钯催化双齿导向基团辅助的C-H键活化官能化及应用研究

发布时间：2018-04-23 10:21

本文选题：碳氢键活化 + 双齿导向基团　；参考：《浙江工业大学》2017年博士论文

【摘要】：过渡金属催化导向基团辅助的C-H活化官能化反应具有区域选择性好,原子利用率高等优点成为有机合成领域的研究热点之一。相比单齿导向基团,双齿导向基团能够实现低活性的C(sp3)-H活化官能反应。发展新型的高活性和易移除的双齿导向基团是目前研究C-H活化领域的一大研究方向。本论文主要研究了钯催化双齿导向基团辅助的C-H键活化官能化反应及其应用,主要内容如下:1.醋酸钯催化三氮唑导向的氨基酸底物C-H键活化芳基化近年来,Click反应生成的三氮唑基团在药物开发、催化剂固载等领域获得了广泛的关注,同时三氮唑基团展示出了较强的配位能力。基于此我们发展了一种新型的Click-三氮唑双齿导向基团,实现了醋酸钯催化的氨基酸衍生物的β-位C(sp~3)-H活化芳基化反应。反应体系表现出较好的官能团兼容性,对含各种取代基的碘苯均可以顺利参与实现芳基化反应,将底物放大至克级规模时反应也可顺利进行,导向基团移除后依旧能够保持底物的高光学纯度。2.钯/碳催化三氮唑导向的C-H键活化芳基化为了实现催化剂的回收利用,我们以商业化的钯/碳为催化剂,二苯基高碘摀盐[Ar_2I]BF_4作氧化剂和芳基化试剂,成功实现了三氮唑导向芳香酰胺邻位C(sp~2)-H键活化芳基化反应。这也是首次将钯/碳作为催化剂应用于导向基团辅助的C-H活化芳基化反应的报道。钯/碳催化剂回收套用两次后依旧保持着一定的催化活性。3.钯催化导向基团辅助的C-H活化官能化的应用为了发展C-H活化方法的实际应用价值,我们将钯催化导向基团辅助的C-H活化官能化的思路运用到药物中间体合成中,实现了醋酸钯催化沙坦类抗高血压药关键中间体2-氰基-4'-甲基联苯的合成,相比以前的工作,具有反应路线短,三废污染少等优点。同时我们运用钯/碳作催化剂实现了杀虫剂氟虫双酰胺关键中间体碘代双酰胺的合成,具有产品收率高,异构体少,路线简单等优点。
[Abstract]:Transition metal catalytic guided group assisted C-H activation functionalization with good regioselectivity and high atomic utilization rate has become one of the research hotspots in the field of organic synthesis. Compared with the monodentate guided group, the bidentate guided group can achieve the low activity of C(sp3)-H activation functional reaction. The development of novel bidentate guided groups with high activity and easy removal is a major research direction in the field of C-H activation. In this paper, palladium catalyzed didentate guided group assisted C-H bond activation functionalization and its application are studied. The main contents are as follows: 1. Palladium Acetate catalyzed Activation of Triazole-directed Amino Acid substrate C-H Bond arylation in recent years, triazolyl groups generated by the Click reaction have attracted extensive attention in the fields of drug development, catalyst immobilization, and so on. At the same time, the triazole group showed strong coordination ability. Based on this, we have developed a new type of Click-triazole didentate guiding group, which has realized the 尾 -site C(sp~3)-H activation arylation of palladium acetate catalyzed amino acid derivatives. The reaction system showed good functional group compatibility and could participate in the arylation reaction of iodobenzene containing various substituents, and the reaction could be carried out successfully when the substrate was enlarged to the scale of g. The guided group is still able to maintain the high optical purity of the substrate. Palladium / carbon Catalytic Triazole-oriented C-H Bond Activation arylation in order to realize the recovery of Catalysts, we used commercial palladium / carbon as catalyst and diphenyl high iodide [Ar_2I] BF_4 as oxidant and arylation reagent. A triazole-oriented C(sp~2)-H bond activation arylation reaction was successfully achieved. It is also the first time that palladium / carbon is used as catalyst for C-H activated arylation. The palladium / carbon catalyst was recovered and applied twice, and the catalytic activity of PD / C catalyst was still maintained. 3. Application of Palladium catalyzed guided Group assisted C-H Activation Functionalization in order to develop the practical application value of C-H activation method, we applied the palladium catalyzed guided group assisted C-H activation functionalization to the synthesis of pharmaceutical intermediates. Palladium acetate was used to catalyze the synthesis of 2-cyano-4cy-methylbiphenyl, the key intermediate of sartan antihypertensive drugs. Compared with the previous work, it has the advantages of shorter reaction route and less pollution from three wastes. At the same time, we used palladium / carbon as catalyst to synthesize the key intermediate of fluorobenzamide, which has the advantages of high yield, less isomers and simple route.
【学位授予单位】：浙江工业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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