Zhou Mei-Juan, Yang Ti-Long, Dang Li
Department of Chemistry, South University of Science and Technology of China , Shenzhen 518055, People's Republic of China.
J Org Chem. 2016 Feb 5;81(3):1006-20. doi: 10.1021/acs.joc.5b02571. Epub 2016 Jan 26.
DFT calculations have been carried out to investigate the reaction mechanism for Pd(II)-mediated enantioselective C-H iodination. Iodination of the aryl ortho C-H bond of benzylamines catalyzed by Pd(II) diacetate complexes in the presence of the L-MPAA ligand experiences three main steps: first, C-H bond activation; second, oxidative addition of iodine on Pd(II) and reductive elimination of iodobenzene; third, catalyst regeneration through ligand exchange. The C-H bond activation is found to be the rate-determining step of the overall iodination due to higher activation energy. The reaction barrier for the formation of iodinated (R)-benzylamine is lower than that of (S)-benzylamine, which confirms the R enantioselectivity in iodination at room temperature. The retainment of the coordination of one acetic acid on Pd(II) and the chelating MPAA ligand during the catalyzed reaction are suggested to give space economy to facilitate the C-H bond activation. The NHTf functional group on the substrate is found to be very important for ortho C-H iodination at ambient condition. Our calculated results are consistent with the experimental observations.
已进行密度泛函理论（DFT）计算以研究钯（II）介导的对映选择性C-H碘化反应机理。在L-MPAA配体存在下，由二乙酸钯配合物催化的苄胺芳基邻位C-H键的碘化经历三个主要步骤：首先，C-H键活化；其次，碘在钯（II）上的氧化加成和碘苯的还原消除；第三，通过配体交换进行催化剂再生。由于较高的活化能，发现C-H键活化是整个碘化反应的速率决定步骤。碘化（R）-苄胺形成的反应势垒低于（S）-苄胺，这证实了室温下碘化反应中的R对映选择性。有人认为，在催化反应过程中，钯（II）上一个乙酸的配位以及螯合的MPAA配体的保留可提供空间经济性，以促进C-H键活化。发现底物上的NHTf官能团对于环境条件下的邻位C-H碘化非常重要。我们的计算结果与实验观察结果一致。
