若干饱和碳碳键构筑反应的催化机理研究

发布时间：2018-05-23 23:40

本文选题：碳碳键形成 + 碳氢键活化　；参考：《中国科学技术大学》2017年博士论文

【摘要】：碳碳键的形成是有机合成中产生分子复杂性的最根本方式之一。这一领域从一开始便得到了化学家们的广泛关注,从而发展出了众多不同的转化方法以构筑碳碳键。以碳(sp3)为中心的饱和碳-碳键在工业原材料,药物以及天然产物中的存在较为广泛。因此发展饱和碳-碳键构筑方法显得尤为重要。推进反应发展的重要前提是对催化反应机理具备深入了解。掌握反应机理有助于不断提升现有催化反应效率,理性设计新反应及新催化体系。随着计算机技术的发展,以及量子理论新方法的不断创新,理论计算方法已经成为获取机理信息的重要方式。本论文采用理论计算方法,针对若干饱和碳碳键构筑反应的机理展开系统研究。论文第一部分综述了有机合成领域构筑饱和碳碳键的主要方法。第一类为过渡金属催化的偶联反应,分为交叉偶联、氧化偶联和还原偶联。第二类为基于过渡金属催化碳(sp3)-氢键活化的碳碳键形成,详细介绍了通过该方法构筑碳(sp3)-碳(sp2)键、碳(sp3)-碳(sp3)键和碳(sp3)-碳(sp)键的研究进展。第三类为过渡金属催化烯烃双官能团化构筑碳碳键,这里主要介绍了通过金催化剂实现的分子内和分子间的双官能化。第四类属于非金属催化领域,主要介绍通过卡宾催化剂实现的高烯醇化反应构筑碳碳键。最后对研究上述反应机理所需的理论方法,包括密度泛函方法、基组和溶剂化模型进行介绍。论文第二部分介绍了钯催化胺甲酰氯选择性碳(sp3)-氢键活化酰基化构筑碳(sp3)-碳(sp2)键的机理研究结果。研究表明反应经历的是"氧化加成/碳氢键活化/还原消除"机理。碳氢活化是反应的选择性决定步骤。发现添加剂能够提高反应速率,但不决定选择性。苄基碳氢键酸性高于芳基碳氢键,因此碳氢键酸性是选择性的决定因素。论文第三部分介绍了光-金双催化的烯烃氧芳基化反应的机理研究结果。研究发现光催化循环经历氧化淬灭历程。金催化循环中"自由基氧化/单电子氧化/底物络合/环化/还原消除"机理最为优势。上述机理优势的原因在于:Au(Ⅲ)络合物的环化有利(降低了烯烃的LUMO轨道能量);苯基自由基向Au(Ⅰ)中心转移一部分电子的过程使得自由基加成-SET的机理顺序有利。论文第四部分介绍了卡宾催化αα,β-不饱和酮与硝基烯烃高烯醇化反应的机理研究结果。结果表明反应经历"Breslow中间体形成/对硝基烯烃的亲核进攻/分子内质子转移/HOAc参与的质子化/协同的OEt对羰基的亲核进攻/卡宾解离"的机理过程。高烯醇化路径优于Stetter路径的原因是关键中间体的热力学稳定性,以及分子内质子转移和OEt对羰基亲核进攻的动力学优势。另外,高烯醇化路径的立体选择性决定步骤是Breslow中间体对硝基烯烃的进攻。其中位阻效应和氢键决定了 syn构型的立体选择性。
[Abstract]:The formation of carbon-carbon bond is one of the most fundamental ways to produce molecular complexity in organic synthesis. This field has been widely concerned by chemists from the beginning, and many different conversion methods have been developed to construct carbon and carbon bonds. The saturated carbon-carbon bond with carbon sp3 as its center is widely used in industrial raw materials, drugs and natural products. Therefore, the development of saturated carbon-carbon bond construction is particularly important. An important prerequisite for promoting the development of reaction is to have a thorough understanding of the mechanism of catalytic reaction. Mastering the reaction mechanism is helpful to improve the efficiency of existing catalytic reactions and to rationally design new reactions and new catalytic systems. With the development of computer technology and the innovation of new methods of quantum theory, theoretical calculation method has become an important way to obtain mechanism information. In this paper, the theoretical calculation method is used to study the mechanism of some saturated carbon bond construction reactions. In the first part, the main methods of constructing saturated carbon bond in organic synthesis are reviewed. The first type is transition metal catalyzed coupling reaction, which is divided into cross coupling, oxidative coupling and reduction coupling. The second kind is the formation of carbon bond based on transition metal catalyzed carbon sp3-hydrogen bond. The progress in the construction of carbon sp3tium-carbon sp2 bond, carbon sp3tium-carbon sp3 bond and carbon sp3- carbon sp3 bond by this method is introduced in detail. The third is transition metal catalyzed bifunctional alkenes to form carbon-carbon bonds. In this paper, intramolecular and intermolecular difunctionalization by gold catalysts is introduced. The fourth category belongs to the field of non-metallic catalysis. It mainly introduces the formation of carbon bond by the high-enolization reaction of carbene catalyst. Finally, the theoretical methods needed to study the above reaction mechanism, including density functional method, basis group and solvation model, are introduced. In the second part of this paper, the mechanism of palladium catalyzed activation and acylation of carbamoyl chloride selective carbon-sp3a-hydrogen bond to form carbon-sp3- carbon-sp2 bond is introduced. It has been shown that the reaction goes through the mechanism of "oxidation addition / carbon bond activation / reduction elimination". Hydrocarbon activation is the selective determining step of the reaction. It was found that the additive could increase the reaction rate but not determine the selectivity. The acidity of benzyl hydrocarbon bond is higher than that of aryl hydrocarbon bond, so the acidity of hydrocarbon bond is the determinant of selectivity. In the third part of this paper, the mechanism of photo-gold-catalyzed olefin arylation is introduced. It is found that the photocatalytic cycle goes through the process of oxidation quenching. The mechanism of "free radical oxidation / single electron oxidation / substrate complexation / cyclization / reduction elimination" is the most advantageous mechanism in the gold catalytic cycle. The above mechanism advantage lies in the favorable cyclization of the 1: Au3 complex (which reduces the LUMO orbital energy of olefins), and the transfer of some electrons from the phenyl radical to the center of Au1 (I), which makes the mechanism of radical addition-SET favorable. In the fourth part of the paper, the mechanism of 伪, 尾 -unsaturated ketones catalyzed by carbene for high enolefin reaction with nitroolefins was introduced. The results show that the reaction goes through the mechanism of "Breslow intermediate formation / nucleophilic attack of p-nitroolefin / intramolecular proton transfer / protonation / synergistic OEt nucleophilic attack on carbonyl group / carbene dissociation". The high enolation path is superior to the Stetter path because of the thermodynamic stability of the key intermediates and the kinetic advantages of intramolecular proton transfer and OEt on the nucleophilic attack of carbonyl groups. In addition, the step of stereoselectivity determination of high enolefin pathway is the attack of Breslow intermediate p-nitroolefin. The stereoselectivity of syn configuration is determined by steric resistance and hydrogen bonding.
【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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