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Nature. 2015 Mar 19;519(7543):334-8. doi: 10.1038/nature14214. Epub 2015 Mar 9.

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

Author information

1
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.

Abstract

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. Coordination of a functional group to a metal is often a key driving force and control element in many important reactions including asymmetric hydrogenation, epoxidation and lithiation. Exploitation of this effect has led to the development of a broad range of directed C-H activation reactions. 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 challenge. 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. Although this approach has proved to be applicable to various substrates and catalytic transformations, 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 ortho-directing 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 meta-selectivity in C-H activation of the same substrate by catalyst control.

PMID:
25754328
PMCID:
PMC4368492
DOI:
10.1038/nature14214
[Indexed for MEDLINE]
Free PMC Article

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