Key Lab of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, P. R. China.
Chemistry. 2020 Apr 24;26(24):5459-5468. doi: 10.1002/chem.202000079. Epub 2020 Apr 15.
This work presents a DFT-based computational study on the regio- and enantioselective C-H functionalization of pyridines with alkenes at the relatively unreactive C4-position, which was successfully achieved by Shi et al. [J. Am. Chem. Soc. 2019, 141, 5628-5634] using Ni /N-heterocyclic carbene (NHC) catalysis under the assistance of an aluminum-based Lewis acid additive (2,6-tBu -4-Me-C H O) AlMe (MAD). The calculations indicate that the selective functionalization involves a three-step mechanism in which a unique H-migration assisted oxidation metalation (HMAOM) step is identified as the rate- and enantioselectivity-determining step. The newly proposed mechanism can well rationalize the experimental observation that the preferred product is the endo-type (vs. exo-type), R-configuration (vs. S-configuration) product at the C4 (vs. C2) position, and also unveil the reasons that the NHC ligand and the MAD additive can facilitate the reaction.
这项工作提出了一项基于密度泛函理论的计算研究，研究了 Shi 等人[J. Am. Chem. Soc. 2019, 141, 5628-5634]使用镍/N-杂环卡宾（NHC）催化，并在铝基路易斯酸添加剂（2,6-tBu-4-Me-C H O）AlMe（MAD）的辅助下，对吡啶在相对惰性的 C4 位与烯烃进行区域和对映选择性 C-H 官能化的反应。计算表明，选择性官能化涉及一个三步机制，其中确定了一个独特的 H-迁移辅助氧化金属化（HMAOM）步骤，该步骤是速率和对映选择性决定步骤。新提出的机制可以很好地解释实验观察到的结果，即优先得到内型（相对于外型）、C4（相对于 C2）位的 R-构型（相对于 S-构型）产物，也揭示了 NHC 配体和 MAD 添加剂可以促进反应的原因。
