School of Chemical Science and Engineering, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, 1239 Siping Road, Shanghai 200092, China.
J Am Chem Soc. 2021 Mar 31;143(12):4524-4530. doi: 10.1021/jacs.0c13057. Epub 2021 Mar 22.
A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of -substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of KCO as a base, iodoarenes are dimethylated at the - and -positions of the iodo group, which represents a novel strategy for -C-H methylation. With KOAc as the base, subsequent oxidative C(sp)-H/C(sp)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.
甲基可以对有机分子的药理学性质产生深远影响。因此，在药物化学中，开发甲基化方法和甲基化试剂是至关重要的。我们报告了一种钯催化的碘代芳烃的 - 位二甲基化反应，使用碳酸二甲酯作为甲基源。在 KCO 作为碱的存在下，碘代芳烃在碘原子的 - 和 - 位上被二甲基化，这代表了一种新的 -C-H 甲基化策略。当 KOAc 作为碱时，随后会发生氧化 C(sp)-H/C(sp)-H 偶联；在这种情况下，总转化实现了三重 C-H 活化，形成了三个新的 C-C 键。这些反应可以方便地得到 2,6-二甲基苯酚、2,3-二氢苯并呋喃和茚满，它们是广泛存在的结构基元和生物和药理学活性化合物的重要合成中间体。
