Remote site-selective C-H activation directed by a catalytic bifunctional template.
Remote site-selective C-H activation directed by a catalytic bifunctional template.
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DOI：
10.1038/nature21418
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发表时间：
2017-03-23
期刊：
影响因子：
64.8
通讯作者：
Yu JQ
中科院分区：
文献类型：
--
作者：
Zhang Z;Tanaka K;Yu JQ
将 C-H 键直接转化为碳-碳和碳-杂原子键可以通过提供传统官能团操作的替代断开方式来显着提高合成的步骤经济性。在这种背景下，定向 C-H 激活反应已被广泛探索用于区域选择性功能化。尽管其适用性可能会因与导向基团的距离和分子的形状而受到严重限制，但已经开发了许多方法来克服这一限制。例如，最近利用对现有官能团和多个 C-H 键之间的远端和几何关系的识别，通过使用共价连接的 U 形模板来实现元选择性 C-H 激活。然而，在没有适当的官能团手柄的情况下，模板的化学计量安装是不可行的。在这里，我们报告了一种催化双功能模板的设计，该模板通过可逆配位而不是共价键结合杂环底物，从而允许杂环的远程位点选择性C-H烯化。与该模板协调的两个金属中心发挥着不同的作用；将底物锚定在催化剂附近并分别裂解远端的 C-H 键。使用这种策略，我们演示了杂环底物的远程位点选择性 C-H 烯化，这些底物不具有用于共价连接模板的官能团手柄。
Converting C–H bonds directly into carbon-carbon and carbon-heteroatom bonds can significantly improve step-economy in synthesis by providing alternative disconnections to traditional functional group manipulations. In this context, directed C–H activation reactions have been extensively explored for regioselective functionalization. Though applicability can be severely curtailed by distance from the directing group and the shape of the molecule, a number of approaches have been developed to overcome this limitation. For instance, recognition of the distal and geometric relationship between an existing functional group and multiple C–H bonds has recently been exploited to achieve meta-selective C–H activation by use of a covalently attached U-shaped template. However, stoichiometric installation of the template is not feasible in the absence of an appropriate functional group handle. Here we report the design of a catalytic, bifunctional template that binds heterocyclic substrate via reversible coordination instead of covalent linkage, allowing remote site-selective C–H olefination of heterocycles. The two metal centers coordinated to this template play different roles; anchoring substrates to the proximity of catalyst and cleaving the remote C–H bonds respectively. Using this strategy, we demonstrate remote site-selective C–H olefination of heterocyclic substrates which do not have functional group handles for covalently attaching templates.