School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing 210093, People's Republic of China.
Office of Science and Technology, Nanjing Xiaozhuang University , Nanjing 211171, People's Republic of China.
J Org Chem. 2017 Mar 17;82(6):2984-2991. doi: 10.1021/acs.joc.6b03050. Epub 2017 Mar 7.
The reaction mechanism of the C-H bond activation of toluene promoted by the hypervalent iodine compound TIPP-I(OH)OTs was investigated in detail by density functional theory calculations. Our calculations show that a plausible reaction pathway of the C-H bond activation of toluene contains two stages: (1) the ligand exchange process on TIPP-I(OH)OTs, involving the substitution of the hydroxyl group and tosyloxyl group with TfOH, and (2) the C-H bond activation of toluene promoted by the hypervalent iodine center with the assistance of the triflate anion. The second step is the rate-limiting step with a relatively low free energy barrier of 19.6 kcal mol in acetonitrile, which is in accord with the experimental fact that the reaction takes place at room temperature. Frontier molecular orbits and natural population analysis show that partial electron transfer from the toluene to the hypervalent iodine moiety occurs in the charge-transfer complex, resulting in the activation of the C-H bond at the para position of toluene. Further calculations show that this hypervalent iodine compound promoted C-H bond activation reaction will be effective if the substrate is electron-rich and a strong Brønsted acid is used.
详细的密度泛函理论计算研究了高价碘化合物 TIPP-I(OH)OTs 促进的甲苯 C-H 键活化的反应机理。我们的计算表明，甲苯 C-H 键活化的一个可能反应途径包含两个阶段：（1）TIPP-I(OH)OTs 上的配体交换过程，涉及羟基和对甲苯磺酰氧基与 TfOH 的取代，（2）高价碘中心在三氟甲磺酸根阴离子协助下促进甲苯的 C-H 键活化。第二步是速率限制步骤，在乙腈中的自由能垒相对较低，为 19.6 kcal/mol，这与反应在室温下进行的实验事实相符。前沿分子轨道和自然布居分析表明，在电荷转移配合物中，部分电子从甲苯转移到高价碘部分，导致甲苯对位的 C-H 键活化。进一步的计算表明，如果底物是富电子的并且使用强布朗斯特酸，这种高价碘化合物促进的 C-H 键活化反应将是有效的。
