Graduate School of Pharmaceutical Sciences , The University of Tokyo , 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-0033 , Japan.
Advanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science, and Elements Chemistry Laboratory , RIKEN , 2-1 Hirosawa , Wako-shi, Saitama 351-0198 , Japan.
J Org Chem. 2018 Nov 2;83(21):13498-13506. doi: 10.1021/acs.joc.8b02397. Epub 2018 Oct 22.
The reaction pathways of lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-mediated deprotonative metalation of methoxy-substituted arenes were investigated. Importantly, it was experimentally observed that, whereas TMEDA has no effect on the course of the reactions, the presence of more than the stoichiometric amount of LiCl is deleterious, in particular without an in situ trap. These effects were corroborated by the DFT calculations. The reaction mechanisms, such as the structure of the active species in the deprotonation event, the reaction pathways by each postulated LiTMP complex, the stabilization effects by in situ trapping using zinc species, and some kinetic interpretation, are discussed herein.
研究了锂 2,2,6,6-四甲基哌啶（LiTMP）介导的甲氧基取代芳基去质子化金属化的反应途径。重要的是，实验观察到，尽管 TMEDA 对反应过程没有影响，但过量的化学计量的 LiCl 是有害的，特别是在没有原位捕获剂的情况下。这些影响通过 DFT 计算得到了证实。本文讨论了反应机制，例如去质子化事件中活性物种的结构、每个假定的 LiTMP 配合物的反应途径、使用锌物种进行原位捕获的稳定化效应以及一些动力学解释。
