通过直接活化芳香环碳氢键实现官能化或分子偶联是有机合成的研究热点之一。一般认为，过渡金属羧酸盐催化的碳氢键活化反应会按照协同金属化-去质子化机理进行。向底物中引入羰基、酰胺基等导向基团可以使其与过渡金属形成配位，催化剂就能从底物的特定位置接近而产生反应位点的选择性。在一定的反应条件下，导向基团还有可能与底物通过成环反应生成各种二环或螺环产物。本文选取了钌（Ⅱ）催化的体系进行理论计算，以完整的催化机理为基础，对催化剂物种和配位位点的选择、底物结合构象对后续反应的影响、导向基团不发生成环反应的原因和溶剂效应等进行了讨论。

本论文主要内容为钌（Ⅱ）催化酰胺基导向的邻位碳氢键活化反应的理论研究：以N-甲基苯甲酰胺与马来酰亚胺的邻位碳氢键活化反应为例，对酰胺基作为导向基团且在反应后得到保留的机理进行了B3LYP+IDSCRF/TZP-DKH(-dfg)理论计算研究。

机理表明，催化剂在此反应中以离子型参与，和通常认为的分子型催化反应相比，离子型的自由能在373.15 K下低7.7 kcal·mol^-1。催化剂与酰胺基的氧进行配位和与酰胺基的氮配位相比，生成五元钌杂环中间体的自由能垒低15.9 kcal·mol^-1，反应进行更为有利。以分子型催化剂为活性催化剂时，无论与氧还是与氮进行配位，配位自由能垒都超过了50 kcal·mol^-1，在实验温度373.15 K下反应无法进行。

当底物2a以指向分子内侧或指向分子外侧两种构象进行结合时，反应决速步的自由能垒分别为37.1 kcal·mol^-1和30.3 kcal·mol^-1，因此底物采取指向分子外侧的构象是可能的反应路径。在底物以指向分子内侧进行反应时，也存在醋酸以二聚形式从分子外侧进行质子化的路径，但其反应自由能垒为51.4 kcal·mol^-1，据此认为该路径不可行。在整个反应路径中，酰胺基的氮氢键和马来酰亚胺的碳氢键均远离反应中心，因此虽然体系中加入了氧化剂，但导向基团难以发生成环反应而得到保护。

在该反应的条件优化过程中，将溶剂DCE替换为DMF后没有得到预期产物，因此对该反应也进行了B3LYP+IDSCRF/TZP-DKH(-dfg)理论计算研究。结果表明，银盐酸根离子由BF₄^-替换为SbF₆^-后，反应决速步自由能垒由30.3 kcal·mol^-1变为31.3 kcal·mol^-1，对反应的影响较小。在换用极性溶剂DMF后，极性溶剂会与离子型催化剂结合成溶剂化分子型催化剂，该物种的自由能降低8.4 kcal·mol^-1。以溶剂化分子型催化剂为活性催化剂时，醋酸根活化邻位碳氢键的氢迁移过程变得困难， 其反应自由能垒由21.3 kcal·mol^-1提升至38.3 kcal·mol^-1，而返回到离子型催化剂为活性催化剂会使[2+2]环加成的自由能垒提升至33.6 kcal·mol^-1, 在实验温度373.15 K下反应很难进行，由此可以解释在实验中以DMF为溶剂的反应无法检测到预期产物。

Direct aryl C-H activation has been a focus on molecule functionalization and coupling. C-H activation with a transition-metal carboxylate catalyst generally follows concerted metalation–deprotonation (CMD) mechanism. A carbonyl or amide group, also known as a directing group, can coordinate with the catalyst and limit its position to provide the regioselectivity. Under some circumstances, directing group may undergo a cyclization step with the reactant, producing a bicyclic or spirocyclic product. In this thesis, we selected a Ru(II)-catalyzed system to proceed theoretical calculations, and discussed the complete catalysis mechanism and some effects on this reaction.

The main contents include theoretical study on Ru(II)-catalyzed amide-directed ortho C-H activation: taking the reaction of N-methylbenzamide and N-ethylmaleimide for example, DFT calculations based on B3LYP+IDSCRF/TZP-DKH(-dfg) have been employed to investigate the reaction mechanism, in order to explain why the directing group does not undergo cyclization to form bicyclic structure.

Calculation result shows that Ru(II) catalyst participates in the reaction with the ion structure, which has a lower free energy of 7.7 kcal·mol^-1, at the temperature of 373.15 K, than the commonly considered molecule structure. The catalyst coordinates with amide O atom, rather than amide N atom, can lower the free energy barrier of the formation of Ru-heterocyclic intermediate by 15.9 kcal·mol^-1, which is conducive to the follow-up steps. Molecule structure catalyst has a free energy barrier of more than 50 kcal·mol^-1 during coordination whether to amide O atom or to amide N atom.

Maleimide may insert to Ru-heterocycle with inward or outward conformation. The rate determining steps have a free energy barrier of 37.1 kcal·mol^-1 and 30.3 kcal·mol^-1, respectively, indicating that the outward insertion is a feasible pathway. We also considered a pathway that acetic acid dimer protonates maleimide group from the opposite side of Ru(II). The free energy barrier of this protonation step is 51.4 kcal·mol^-1, which is too high for the reaction to carry out. In the outward insertion pathway, N-H of amide group and C-H of maleimide group are distant from Ru(II) center, preventing the amide group from cyclization.

During the optimization of reaction condition, experiments result in no expected product when the non-polar solvent DCE is replaced with polar solvent DMF, thus we employed DFT calculations based on B3LYP+IDSCRF/TZP-DKH(-dfg) to investigate the derivative reaction. Calculation results shows that replacing BF₄^- ion with SbF₆^- ion raises the free energy barrier of the rate determining step from 30.3 kcal·mol^-1 to 31.3 kcal·mol^-1, which has little influence on the reaction. Polar solvent DMF is able to coordinate with ion catalyst to generate solvated catalyst, which has a free energy drop by 8.4 kcal·mol^-1. Solvated catalyst raises the difficulty for acetate to activate aryl C-H. Free energy barrier of the H-transfer is raised to 38.3 kcal·mol^-1 from 21.3 kcal·mol^-1. Moreover, the free energy barrier of [2+2] cyclization is raised to 33.6 kcal·mol^-1 when solvated catalyst decomposes to participate in the reaction as ion catalyst. These high barriers may explain why no yield of expected product in DMF solvent under the experiment temperature of 373.15 K.