钌催化间位磺化反应机理的DFT研究

DFT Study on Mechanism of Ruthenium-catalyzed meta Sulfonation

导向过渡金属催化反应是实现区域选择性芳环碳氢活化/衍生化的一种重要手段.本文使用DFT理论(M06//B3LYP)对Frost小组的钌催化2-芳基吡啶间位磺化反应机理进行了研究.通过计算,我们发现该机理主要包括邻位C—H活化、亲电取代、还原消除及催化剂再生四个步骤.其中导向邻位C—H活化是速率决定步,亲电取代为区域选择决定步.Ru与导向基邻位碳原子成键使苯环电子密度分布发生变化,同时与位阻作用相结合引导亲电取代发生在Ru—C键的对位(即导向基间位).在此基础上,我们还研究了K2CO3和溶剂极性对反应的影响.

The transition metal catalyzed direct C--H functionalization reaction is an important strategy for selective activa- tion of aromatic C--H bond and its functionalization. In the present study, DFT method （M06//B3LYP） has been used for mechanistic study on the Ruthenium-catalyzed meta-sulfonation of 2-phenylpyridines reported by Frost and co-workers. All calculations involved in this study were performed using Gaussian09 suite of program. The proposed mechanism consists of four main steps： pyridine directed ortho C--H activation, electrophilic substitution, reductive elimination and catalyst regen eration. It is found that the ortho C-H activation is the rate-determing step of overall catalytic cycle, At 298.15 K and stan- dard pressure, the KIE ofortho C--H activation step was calculated for the model reaction. Good agreement has been gained between the calculations （KIE=4.8） and the experimental observed primary isotope effect （KIE----3.0）. The regioselectivity determining step of the catalytic cycle is found to be the electrophilic substitution. With the coordination of Ru center to the ortho carbon atom, the electron density distribution on the benzene ring of cycloruthenium intermediate changes accordingly. The charge distribution and the steric hindrance around the Ru center then make the electrophilic substitution occur favorably at the para-position of Ru--C bond （the para-position of directing group） in preference to the chelating-C or the ortho of the chelating group. In one word, regioselectivity was determined by electrophilic substitution, rather than the directed C--H activation. In the process of reaction, K2CO3 played an important role in promoting the reaction. K2CO3 first participates in the ortho C--H activation, and then it stabilizes the TsC1 dissociating intermediates. In the electrophilic substitution step, K2CO3 directly engages in the cleavage of C--H bonds. Finally K2CO3 takes part in the generation of ortho C--H. As to the solvent effect, we found that the rate determining step changes with the changes of solvent polarity. When the solvent changes from acetonitrile to toluene （or dioxane）, the rate determining step would vary from ortho C--H activation to the TsCI dissociation and the reaction activation energy would increase accordingly. This trend is consistent with the experimen tal yields renorted by Frost et al. All these consistency verify the calculation results nrovided in this study.