Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India.
Angew Chem Int Ed Engl. 2019 Sep 23;58(39):13808-13812. doi: 10.1002/anie.201907544. Epub 2019 Aug 14.
Distal C-H bond functionalization of heterocycles remained extremely challenging with covalently attached directing groups (DG). Lack of proper site for DG attachment and inherent catalyst poisoning by heterocycles demand alternate routes for site selective functionalization of their distal C-H bonds. Utilizing non-productive coordinating property to hold the heterocycle into the cavity of a template system in a host-guest manner, we report distal C-H alkylation (C-5 of quinoline and thiazole, C-7 of benzothiazole and benzoxazole) of heterocycles. Upon complexation with heterocyclic substrate, nitrile DG in template directs the metal catalyst towards close vicinity of the specific distal C-H bond of the heterocycles. Our hypothesized pathway has been supported by various X-ray crystallographically characterized intermediates.
杂环的远端 C-H 键官能团化一直极具挑战性，因为需要共价连接的导向基团 (DG)。由于缺乏合适的 DG 连接位置，并且杂环本身会使催化剂中毒，因此需要通过其他途径对其远端 C-H 键进行选择性官能团化。我们利用非生产性配位性质，以主客体方式将杂环固定在模板系统的空腔中，从而实现了杂环的远端 C-H 烷基化（喹啉和噻唑的 C-5、苯并噻唑和苯并恶唑的 C-7）。在与杂环底物络合后，模板中的腈 DG 将金属催化剂引导至杂环特定远端 C-H 键的附近。我们的假设途径得到了各种通过 X 射线晶体学表征的中间体的支持。
