过渡金属催化的若干重要有机反应C-H活化机理的理论研究

发布时间：2018-04-23 05:20

本文选题：过渡金属络合物 + C-H活化　；参考：《山东大学》2017年博士论文

【摘要】：金属有机化学是有机化学和无机化学的交叉学科,作为一门新兴交叉学科,金属有机化学的发展引起了人们广泛关注。过渡金属有机化合物作为金属有机化学发展的核心,因所具有的高度选择性、高活性、高稳定性等特点,成为有机合成领域里一个新的研究热点。与实验研究相比,过渡金属有机化合物的理论研究发展滞后,实验过程中观察到的某些特别现象无法用常规的化学知识来解释。另外,有关的分子机理也不明确,反应的中间体无法用实验检测,这些问题必然会限制金属有机催化剂的应用和新型过渡金属有机催化剂的开发。因此对有机反应进行理论研究,探索宏观反应背后的微观本质,对金属有机化学的发展具有深远意义。C-H活化是有机合成新目标。研究发现C-H活化所用底物范围广,且通常不需要官能团预活化,有高的原子经济效率,所以通过底物C-H活化方法可以大大简化药品、天然产品、农用化学品、聚合物等化学品的合成过程。尽管C-H活化取得了较大进步,但这些反应所用催化剂为贵金属催化剂,如铑、钌、钯、铱、铂、镍,成本较高。另外这类反应需加入外部氧化剂,在反应过程中会导致副产物的形成。为了克服这些弊端,人们开始寻找合适的内部氧化剂以及C-H活化的新型催化剂。本论文在相关实验背景的基础上,选择几种代表性过渡金属络合物催化的有机反应进行研究。通过理论计算,探讨若干重要有机反应机理,揭示了催化反应的微观本质,给出了反应的基元步骤和反应的热力学和动力学性质。分析了取代基以及溶剂化对反应的影响,找到反应区域选择性根源,并给出合理解释,理论计算结果加深了人们对相关化学反应及其现象的认识和理解,为新型有机反应的设计以及新型有机反应催化剂开发提供了重要理论指导。本论文研究内容和创新点概括如下:一、研究了钌原子簇三核钌羰基化合物N-甲基官能团上C-H键活化反应。Cabeza课题组报道了一类关于氮杂环卡宾金属配合物甲基发生C-H活化反应,反应在温和条件下完成。他们提出了 C-H键活化的分子机理,并进行了相关的理论计算,发现总能垒超过80.0kcal/mol,并且反应吸热近40.0kcal/mol,这些结果与实验现象(实验温度低于100 ℃)明显不符。为理解这类C-H键活化机理,合理解释实验现象,我们对该反应重新进行了研究,提出了新的反应机理,反应步骤如下:氮杂环配体重排、脱CO、第一个C-H活化、脱CO、第二个C-H活化。反应物转化为产物自由能变为14.7kcal/mol,总能垒为35.1kcal/mol。计算结果验证了 C-H活化反应在实验条件容易发生,常温下往反应体系通入一氧化碳会使产物向反应物转化。二、研究了三核钌羰基化合物-氮杂环卡宾络合物中N-甲基和亚甲基官能团上C-H键活化反应,给出详细反应机理,并分析了烃基选择性活化的原因。(1)理论研究了三核钌羰基化合物与磷相连的N-亚甲基上C-H活化机理。理论计算表明该反应具有以下特点:第一个C-H活化发生在磷与金属重新配位之前,CO消除是第二个C-H活化必经过程,磷与金属配位模式在反应物和产物中保持不变,第一个C-H活化为反应的决速步,需要克服能垒37.9 kcal/mol。C-H活化涉及两个CO配体消除,由于反应为敞开体系,CO配体消除具有不可逆性,并且实验中不断用惰性气体净化释放的CO气体,因此尽管总能垒相对高,但是CO不可逆的释放驱使反应顺利进行。(2)研究了含有磷配体的钌原子簇羰基化合物氮杂环N-甲基C-H活化反应机制以及反应热力学和动力学性质。计算表明磷迁移过程优先于C-H活化过程发生,且反应过程中磷配体与金属配位位置发生变化,第一个C-H活化是反应决速步,总能垒为39.0kcal/mol。通过NBO电荷分析发现,与氮杂环相连甲基上的C1原子电子密度大于亚乙基C2原子电子密度,表明C1具有更强的亲核性。因此甲基Cl-H更容易活化。三、研究了辅助酸协助的甲酸脱氢反应。运用密度泛函理论分别计算了一分子辅助酸和两分子辅助酸条件下,Fe催化甲酸脱氢反应可能路径,结果表明两分子辅助酸参与反应,金属Fe中心脱氢更有利于甲酸分解。两分子辅助酸参与反应的主要步骤为:H_2脱出、CO_2脱出、催化剂再生。决速步为CO_2脱出,总能垒为23.5 kcal/mol。辅助酸协助甲酸脱氢的主要原因是其可以有效增加碳酸盐上的正电荷,使原子重排过渡态以及氢键合甲酸盐中间体更加稳定,从而有利于CO_2脱出。四、研究了氧化还原中性条件CoⅢ催化N-N键断裂合成吲哚的反应机理。首先计算了文献中提出的C-H活化炔烃插入路径,发现炔烃插入过渡态能量高出反应入口55.0 kcal/mol,这一较高能垒无法合理解释实验现象(实验温度80 ℃)。通过计算提出了新的反应机理,涉及C-H键活化、酯基相连N原子脱质子、炔烃插入、氮原子质子转移、N-C还原消除、N-N氧化加成、质子化等过程。计算结果表明,酯基相连N原子脱质子形成的稳定中间体在反应过程中起着重要作用,可有效降低炔烃插入过渡态的能量。理论结果与同位素标记实验结果(C-H是决速步骤)吻合较好。理论结果阐明了详细的反应机理,加深了我们对氧化还原中性条件下钴催化联氨和炔烃合成吲哚反应的理解,为相关实验提供了一定的理论指导。五、研究了 RhⅢ催化NH-亚砜亚胺和二氮化合物合成1,2-苯并硫氮反应。计算结果表明,实验预测的反应机理,即先N-H/C-H活化、再脱氮气,不能合理解释实验现象。我们提出了新的反应机理:即氮气消除、N-H/C-H活化、卡宾插入、质子化、脱水等过程。反应的决速步为C-H活化,总能垒37.2kcal/mol。另外,研究了 NH-亚砜亚胺取代基(甲氧基,硝基)对反应的影响以及反应选择性C-H活化。发现由电子效应是产物产率不同主要原因。反应的区域选择性主要与电子效应以及非键相互作用有关,而空间位阻影响较小。理论结果合理地解释了实验观察现象。
[Abstract]:Organometallic chemistry is an interdisciplinary subject of organic chemistry and inorganic chemistry. As a new interdisciplinary subject, the development of organometallic chemistry has aroused widespread concern. As the core of the development of metal organic chemistry, transition metal organic compounds have become organic synthesis because of their high selectivity, high activity, high stability and so on. A new research hotspot in the field. Compared with experimental research, the theoretical research of transition metal organic compounds is lagging behind. Some special phenomena observed in the experiment can not be explained by conventional chemical knowledge. In addition, the related molecular mechanism is not clear, the intermediates of the reaction can not be tested by experiments. These problems are bound to be inevitable The application of metal organic catalysts and the development of a new type of transition metal organic catalysts. Therefore, the theoretical study of organic reactions and the exploration of the microscopic nature behind the macro reaction have far-reaching significance for the development of the organic chemistry of metals..C-H activation is a new target for organic synthesis. Without the need of functional group pre activation and high atomic economic efficiency, the synthesis process of drugs, natural products, agrochemicals, polymers and other chemicals can be greatly simplified by the activation of substrate C-H. Although great progress has been made in the activation of C-H, these reactions are used as noble metal catalysts, such as rhodium, ruthenium, palladium, iridium, platinum, nickel, and so on. In addition, this kind of reaction needs to be added to the external oxidizer and lead to the formation of the by-products during the reaction. In order to overcome these disadvantages, people began to look for the appropriate internal oxidant and the new catalyst for C-H activation. Based on the relevant experimental background, this paper chooses several representative transition metal complexes to catalyze the catalytic agent. The mechanism of some important organic reactions was discussed by theoretical calculation. The microscopic nature of the catalytic reaction was revealed. The basic steps of the reaction and the thermodynamic and kinetic properties of the reaction were given. The influence of the substituent and solvent on the reaction was analyzed, and the selective root of the reaction was found. The rational explanation was given and the theory was given. The results of the calculation deepen the understanding and understanding of the related chemical reactions and their phenomena, and provide important theoretical guidance for the design of new organic reactions and the development of new organic reaction catalysts. The contents and innovations of this paper are summarized as follows: first, the C-H bond on the ruthenium cluster three nuclear ruthenium carbonyl compound N- methyl functional group is studied. The group of activation reaction.Cabeza reports on a class of nitrogen heterocyclic CABBEEN metal complexes methyl C-H activation reaction. The reaction was completed under mild conditions. They proposed the molecular mechanism of the activation of C-H bonds, and the related theoretical calculations were carried out to find that the total energy barrier was over 80.0kcal/mol and the reaction endothermic was nearly 40.0kcal/mol. In order to understand the activation mechanism of this kind of C-H bonds and explain the experimental phenomena reasonably, we restudied the reaction and proposed a new reaction mechanism. The reaction steps are as follows: nitrogen heterocyclic ligand rearrangement, deactivation of CO, the first C-H activation, deactivation of CO, and activation of C-H. The reactant is transformed into product self. From the energy change to 14.7kcal/mol, the total energy barrier is 35.1kcal/mol. calculation results verifying that the activation reaction of C-H is easy to occur in the experimental conditions. The carbon monoxide in the reaction system at normal temperature can convert the product into the reactant. Two, the activation of the C-H bond on the N- methyl and methylene functional group of the three nuclear ruthenium carbonyl compound nitrogen heterocyclic complex is studied. The reaction mechanism is given and the reasons for the selective activation of alkyl groups are analyzed. (1) the mechanism of C-H activation of N- methylene on the three nuclear ruthenium carbonyl compounds with phosphorus is theoretically studied. The theoretical calculation shows that the reaction has the following characteristics: the first C-H activation occurs before the redistribution of phosphorus and gold, and the elimination of CO is the second C-H activation must. Through the process, the mode of phosphorus and metal coordination remains unchanged in the reactants and products. The first C-H is activated as a quick step of the reaction. It is necessary to overcome the elimination of the energy barrier 37.9 kcal/mol.C-H activation involving two CO ligands, because the reaction is open system, the CO ligand eliminates the irreversibility, and the CO gases released by the inert gas in the experiment are continuously purified. Therefore, although the total energy barrier is relatively high, the CO irreversible release drives the reaction to proceed smoothly. (2) the mechanism of the activation reaction of the Ru atomic cluster carbonyl compound nitrogen heterocyclic N- methyl C-H, which contains phosphorus ligands, and the thermodynamic and kinetic properties are studied. The calculation shows that the phosphorus migration process is preceded by the C-H activation process and the phosphorus is in the process of reaction. The coordination position of ligand and metal is changed, the first C-H activation is the quick step of the reaction. The total energy barrier is 39.0kcal/mol. through the NBO charge analysis. The electron density of the C1 atom on the methylated methyl on the nitrogen heterocycle is greater than the electron density of the ethyl C2 atom, indicating that the C1 has a stronger nucleophilic activity. Therefore, the methyl Cl-H is more easily activated. Three, studies the auxiliary The possible path of dehydrogenation of formic acid catalyzed by Fe is calculated by density functional theory. The results show that the two molecular auxiliary acid is involved in the reaction, and the Fe center dehydrogenation is more favorable for the decomposition of formic acid. The main step of the two molecular auxiliary acid reaction is: H The main reason for dehydrogenation of formic acid with a total barrier of 23.5 kcal/mol. assisted acid to assist the dehydrogenation of formic acid is that it can effectively increase the positive charge on the carbonate, which makes the transition state of the rearrangement of the atom and the intermediate of the hydrogen bond formate more stable, which is beneficial to the release of CO_2. Four, the oxidation reduction is studied. The main reason for the 23.5 kcal/mol. auxiliary acid to assist the dehydrogenation of formic acid is that it can effectively increase the dehydrogenation of formic acid. The neutral condition Co III catalyzes the reaction mechanism of N-N bond breaking into indole. First, the insertion path of C-H activated alkynes proposed in the literature is calculated. It is found that the insertion of the transition state of alkynes into the transition state is 55 kcal/mol. This high energy barrier can not explain the experimental phenomenon reasonably (the experimental temperature is 80 degrees C). The new reaction mechanism is proposed by calculation. C-H bond activation, ester group connecting N atom deprotons, alkyne insertion, nitrogen atom proton transfer, N-C reduction elimination, N-N oxidation addition, and protonation process. The results show that the stable intermediate of ester based N atom deprotonates plays an important role in the reaction process, which can effectively reduce the energy of the insertion of Alkynes into the transition state. The results are in good agreement with the results of the isotope labeling experiment (C-H is a quick step). The theoretical results illustrate the detailed reaction mechanism, which deepens our understanding of the synthesis of indole by cobalt catalyzed hydrazine and alkynes under the oxidation-reduction neutral condition, and provides some theoretical guidance for the related experiments. Five, Rh III catalyzes the catalytic NH- sulfoxide imide and two. The reaction mechanism of 1,2- benzo sulfur nitrogen is synthesized by nitrogen compounds. The results show that the reaction mechanism predicted by the experiment, namely N-H/C-H activation first, and then nitrogen removal, can not explain the experimental phenomena reasonably. We put forward a new reaction mechanism: nitrogen removal, N-H/C-H activation, CABBEEN insertion, protonation, dehydration and so on. The reaction speed step is C-H activation, total energy barrier 37.2 Kcal/mol. also studied the effect of NH- sulfoimide substituent (methoxy, nitro) on the reaction and the activation of selective C-H. It is found that the electron effect is the main reason for the difference in the yield of the products. The regional selectivity of the reaction is mainly related to the electron effect and the non bond interaction, but the effect of the space hindrance is less. The theoretical results are reasonable. The phenomenon of experimental observation was explained.

【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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