基于羧酸及其衍生物的光催化脱羧偶联反应研究

发布时间：2018-04-10 11:30

本文选题：脱羧偶联 + 光催化　；参考：《中国科学技术大学》2017年博士论文

【摘要】：脱羧偶联反应为碳-碳键和碳-杂键的构建提供了强有力的方法。本论文在第一章综述了脱羧偶联反应的发展历史和现状,主要包括过渡金属催化的脱羧偶联反应以及可见光促进的光催化脱羧偶联反应。传统过渡金属催化的脱羧偶联经过近15年的发展,已经建立了 Pd、Cu、Ag、Au、Rh等单金属催化体系以及Pd/Cu、Pd/Ag等双金属催化体系,实现了脱羧构建C-C键、C-N键、C-S键以及C-P键等。然而该类型反应的条件相对苛刻,常需要很高的反应温度来满足脱羧所需要的能量,例如Pd催化的脱羧偶联反应温度一般在120摄氏度以上,这阻碍了脱羧偶联反应的发展和应用。且反应主要集中在活化的芳基羧酸、烯基羧酸、炔基羧酸等非脂肪类羧酸上,而对于来源广泛的脂肪类羧酸的研究相对较少。因此急需发展新的催化体系来解决这些问题。近年来发展的可见光促进的脱羧偶联反应条件十分温和,反应利用光照下激发态的光催化剂与羧酸负离子的单电子转移成功实现了自由基脱羧。将光催化引入脱羧偶联将会为脱羧偶联反应的发展提供新的机遇。光催化的脱羧偶联反应不仅条件温和、兼容性强,还可以通过和过渡金属催化相结合解决此前难以解决的问题。在第二章中,我们将光催化引入Pd催化的脱羧偶联反应中,通过利用光催化和Pd催化相结合的双催化体系在温和条件下实现了 α-羰基羧酸脱羧芳基化。反应既利用了光催化的脱羧能力,又结合了 Pd催化的成键能力。反应解决了传统的Pd催化脱羧偶联需要高温的问题。反应具有很好的兼容性,能够为酮和酰胺类化合物的合成提供有效方法。N-杂环芳烃的C-H活化烷基化是N-杂环芳烃衍生化的重要手段。传统的Minisci反应可以实现这一过程,然而传统的Minisci反应依赖于强氧化体系来实现脱羧,反应兼容性差,且会诱发自由基副反应。在第三章中,我们结合光催化利用烷基羧酸作为亲电试剂在氧化还原中性条件下实现了脱羧Minisci反应,反应为N-杂环芳烃的C-H活化烷基化提供了温和的有效策略。反应通过光催化实现自由基脱羧,不需要外加氧化剂。反应条件温和,可以兼容醛基、硫醚、烯烃等易被氧化的官能团。传统的Minisci反应难以实现N-杂环芳烃C-H活化α-氨基烷基化。因为强氧化性条件下脱羧形成的α-氨基烷基自由基很容易被过渡氧化,形成亚胺正离子,从而失去亲核性。第四章中,我们利用氨基酸或多肽的活性羧酸酯作为α-氨基烷基化试剂,结合光催化和有机磷酸催化成功实现了 N-杂环芳烃C-H活化α-氨基烷基化。反应能够兼容各种天然和非天然氨基酸,多肽也是该反应合适的底物类型。同时温和的反应条件能够实现各类复杂N-杂环芳烃的衍生化。我们通过结合光催化部分解决了脱羧偶联反应中的难点问题,丰富了脱羧偶联反应类型,推动了光催化在脱羧偶联反应中的应用。当然,一些难题依然存在,比如更丰富的脱羧转化类型。这些问题将是我们需要继续研究和克服的难点。
[Abstract]:Decarboxylation coupling provides a powerful method for the construction of carbon carbon and carbon heteroatom bond. In this paper, the first chapter summarizes the decarboxylation reaction development history and current situation, including the decarboxylation coupling reaction catalyzed by transition metal and visible light to promote the photocatalytic decarboxylation coupling reaction. The traditional transition metal catalyzed decarboxylative coupling after nearly 15 years of development, has established the Pd, Cu, Ag, Au, Rh and Pd/Cu single metal catalysts, Pd/Ag bimetallic catalyst system, realized the decarboxylative C-C bond, C-N bond, C-S bond and C-P bond. However, this type of reaction relatively harsh conditions, often require high reaction temperature to meet the decarboxylation of the energy needed, such as temperature decarboxylation coupling reaction catalyzed by Pd is generally more than 120 degrees Celsius, which hinders the development and application of the decarboxylation reaction. The reaction is mainly concentrated in the aryl carboxylic acid activation, ene Carboxylate alkynyl carboxylic acid, non fatty carboxylic acid, and for the study of fatty carboxylic acid extensive source is relatively small. An urgent need for the development of new catalytic systems to solve these problems. In recent years the development of visible light and promote conditions carboxyl coupling reaction was mild, the reaction using single electron transfer light photocatalyst with the anion of carboxylic acid under the excitation of the successful implementation of the free carboxyl based photocatalytic decarboxylation. The coupling will provide new opportunities for the development of the decarboxylation reaction. The photocatalytic decarboxylation coupling not only mild conditions, good compatibility, can also solve the previous problem difficult to solve by transition metal catalysis combined. In the second chapter, we will introduce the photocatalytic Pd catalyzed decarboxylation coupling, dual catalyst system by utilizing photocatalytic and Pd catalytic phase realized a-Oxo decarboxylation under mild conditions Acid decarboxylation arylation reaction. Both the use of sodium removal capability of photocatalysis, and the combination of the bonding ability of Pd. To solve the Pd catalytic reaction catalyzed decarboxylation coupling to traditional high temperature. The reaction has good compatibility, can ketone and amide compounds to provide an effective method for.N- synthesis of heterocyclic the activation of C-H alkylation of aromatic heterocyclic aromatics is an important means of N- derivatization. Traditional Minisci reaction can be achieved in this process, however, the traditional Minisci reaction depends on the strong oxidation system to achieve the decarboxylation reaction, poor compatibility, and will induce free radical reactions. In the third chapter, we combine photocatalysis using alkyl carboxylic acids as electrophiles in redox neutral conditions the decarboxylation reaction of Minisci reaction, provides an effective strategy for mild N- heterocyclic aromatic C-H alkylation reaction activation. The photocatalytic achieve radical decarboxylation, Do not need additional oxidant. The reaction condition is mild, can be compatible with aldehyde, ether, olefin and other easily oxidized functional groups. The traditional Minisci reaction is difficult to achieve N- C-H activation of alpha amino heterocyclic aromatic alkylation. Because of strong oxidizing conditions the decarboxylation of alpha amino alkyl radicals can easily be oxidized transition and the formation of an imine positive ions, thus losing the nucleophilicity. In the fourth chapter, we use the activity of carboxylic acid esters of amino acids or peptides as alpha amino alkylation reagent combined with photocatalysis and organic phosphoric acid catalyst for the successful implementation of the N- activation of C-H alpha amino heterocyclic aromatic alkylation reaction. Compatible with a variety of natural and non natural amino acids. The reaction peptides are also suitable substrate types. At the same time the mild reaction conditions to realize all kinds of complicated N- heterocyclic aromatic derivative. We combined photocatalysis partly solves the difficulties and questions in the coupling reaction of carboxyl The problem has enriched the type of decarboxylation coupling reaction, and promoted the application of photocatalysis in decarboxylation coupling reactions. Of course, some problems still exist, such as richer decarboxylation conversion types. These problems will be difficult for us to continue to study and overcome.

【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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