Ligand-enabled meta-C-H activation using a transient mediator

Article

关键词: PALLADIUM;    ARYLATION;    OLEFINATION;    2-ALKYLATION;    ALKYLATION;    C(SP(3))-H;    MECHANISM;    INDOLES;    PD;   

DOI  :  10.1038/nature14214

来源: SCIE

【 摘 要 】

Achieving site selectivity in C-H functionalization reactions is a significant challenge, especially when the target C-H bond is distant from existing functional groups(1-5). Coordination of a functional group to a metal is often a key driving force and control element in many important reactions including asymmetric hydrogenation(6), epoxidation(7,8) and lithiation(9). Exploitation of this effect has led to the development of a broad range of directed C-H activation reactions(10-14). However, these C-H activation methods are limited to proximal C-H bonds, which are spatially and geometrically accessible from the directing functional group. The development of meta-selective C-H functionalizations remains a significant challenges(1-5,15-17). We recently developed a U-shaped template that can be used to overcome this constraint and have shown that it can be used to selectively activate remote meta-C-H bonds(1,2). Although this approach has proved to be applicable to various substrates and catalytic transformations(3-5), the need for a covalently attached, complex template is a substantial drawback for synthetic applications. Here we report an alternative approach employing norbornene as a transient mediator to achieve meta-selective C-H activation with a simple and common orthodirecting group. The use of a newly developed pyridine-based ligand is crucial for relaying the palladium catalyst to the meta position by norbornene after initial ortho-C-H activation. This catalytic reaction demonstrates the feasibility of switching ortho-selectivity to metaselectivity in C-H activation of the same substrate by catalyst control.

【 授权许可】

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