羧酸脱羧酰胺化及三氟甲基化反应研究

发布时间：2018-05-29 15:06

本文选题：酮酸 + β-酮酸　；参考：《合肥工业大学》2017年博士论文

【摘要】：竣酸作为一种廉价易得的化合物在有机合成中一直被研究人员广泛研究。近来报道了一种用芳基羧酸作为底物的脱羧反应,得到产物与Heck反应的产物一样,这种脱羧反应被报道以后,利用过渡金属作为催化剂的脱羧偶联反应逐渐引起了人们的兴趣,并慢慢成为目前的一个研究热点。在合成具有非平面结构的有机分子时,过渡金属催化的烷基偶联反应具有重要的意义,所以过渡金属催化的烷基羧酸的脱羧偶联反应也得到了科学家们的广泛重视。光催化的偶联反应近年来得到了广泛的关注,可见光催化的反应体系也为脱羧偶联反应提供了新的思路,最近很多利用光催化的脱羧偶联反应被报道出来。在第一章中,我们分别从过渡金属和光催化的脱羧偶联反应对前人的工作进行了总结。酰胺键作为蛋白质的基本构建骨架,在生命中扮演着重要角色,同时大量存在于各种生物质材料和药物活性分子中。目前公认最常用的策略就是胺的乙酰化反应。虽然制备酰胺最普遍简单的方法是通过羧酸与胺的缩合。但是这个最理想的策略需要极其苛刻的条件,比如高温条件,并且在形成酰胺键过程中不可避免的经过羧酸铵盐副反应。在第二章中我们介绍了一种Ag催化的羧酸脱酸酰胺化的反应。反应在空气条件下进行,反应条件也很温和,用α-酮酸作为底物与胺发生脱羧酰胺化合成酰胺。反应的产率较好,而且显示出优异的官能团耐受性。而且将底物的胺换成二氨基化合物以后可以进一步得到杂环化合物如苯并咪唑的产物。药物分子中含有三氟甲基可以有效改善其亲脂性、可吸收性以及代谢稳定性。因此,在有机分子中引入三氟甲基引起了人们的广泛关注。三氟甲基引入到有机分子中的方法有很多报道。然而,C(sp3)上引入三氟甲基与C(sp2)-CF3和C(sp)-CF3相比明显研究较少。近期在这个领域中用烷基卤化物、烷基硅烷、炔烃和烷基硼酸作为底物的三氟甲基化反应已经被报道。最近,过渡金属催化的三氟甲基化反应得到了快速发展。其中,Cu作为一种廉价且活性较高的催化剂能够实现多种三氟甲基化反应。在第三章中我们开发了一种有效的β-酮酸脱羧三氟甲基化得到α-三氟甲基酮的方法。这个反应使用Cu盐作为过渡金属催化剂,在室温下就可以进行,而且得到的产物产率较好。此外这个脱羧三氟甲基化的反应体系兼容性也很好,很多富电子和缺电子的底物都能顺利参与反应,得到相应的α-三氟甲基酮。
[Abstract]:As a cheap and readily available compound, dioxic acid has been widely studied in organic synthesis. Recently, a decarboxylation reaction using aryl carboxylic acid as substrate has been reported. The product is similar to that of Heck reaction. After this decarboxylation reaction is reported, the decarboxylation coupling reaction using transition metal as catalyst has gradually attracted people's interest. And gradually become a research hotspot. In the synthesis of organic molecules with non-planar structure, transition metal-catalyzed alkyl coupling reaction is of great significance, so transition metal-catalyzed decarboxylation of alkyl carboxylic acids has been paid more and more attention by scientists. Photocatalytic coupling reactions have been paid more and more attention in recent years. The visible photocatalytic reaction system has also provided a new way of thinking for decarboxylation. Recently, many photocatalytic decarboxylation coupling reactions have been reported. In the first chapter, we summarized the previous work from transition metal and photocatalytic decarboxylation coupling reaction. As the basic framework of protein, amide bond plays an important role in life, and it also exists in a variety of biomaterials and pharmaceutical active molecules. The most commonly used strategy is the acetylation of amines. Although the simplest way to prepare amides is by condensation of carboxylic acids with amines. However, this optimal strategy requires extremely harsh conditions, such as high temperature conditions, and the formation of amide bonds is inevitable through carboxylate side reactions. In chapter 2, we introduce a Ag-catalyzed deacidification and amidation of carboxylic acid. The reaction was carried out in air, and the reaction conditions were very mild. 伪 -ketoic acid was used as substrate to decarboxylation with amine to synthesize amides. The yield of the reaction was good and showed excellent functional group tolerance. The heterocyclic compounds such as benzimidazole can be further obtained by replacing the amines of the substrate with diamino compounds. Trifluoromethyl can effectively improve lipophilic, absorbability and metabolic stability. Therefore, the introduction of trifluoromethyl in organic molecules has attracted widespread attention. The introduction of trifluoromethyl into organic molecules has been widely reported. However, compared with C(sp2)-CF3 and C(sp)-CF3, the study of introducing trifluoromethyl into Cesp 3 is much less. Recently, trifluoromethylation of alkyl halides, alkyl silanes, alkynes and alkyl boric acids has been reported in this field. Recently, transition metal catalyzed trifluoromethylation has developed rapidly. Cu as a cheap and highly active catalyst can realize various trifluoromethylation reactions. In Chapter 3, we developed an effective method for the synthesis of 伪 -trifluoromethyl ketone by decarboxylation of 尾 -ketoic acid with trifluoromethyl methylation. This reaction can be carried out at room temperature using Cu salt as transition metal catalyst and the yield of the product is better. In addition, the reaction system of decarboxyltrifluoromethylation is also very compatible, and many electron-rich and electron-deficient substrates can participate in the reaction successfully to obtain the corresponding 伪 -trifluoromethyl ketones.
【学位授予单位】：合肥工业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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