Publication Date:
2015-03-11
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368492/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiao-Chen -- Gong, Wei -- Fang, Li-Zhen -- Zhu, Ru-Yi -- Li, Suhua -- Engle, Keary M -- Yu, Jin-Quan -- 1R01 GM102265/GM/NIGMS NIH HHS/ -- R01 GM102265/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Mar 19;519(7543):334-8. doi: 10.1038/nature14214. Epub 2015 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25754328" target="_blank"〉PubMed〈/a〉
Keywords:
Alkylation
;
Amides/chemistry
;
Carbon/*chemistry
;
Catalysis
;
Halogens/chemistry
;
Hydrogen/*chemistry
;
Ligands
;
Norbornanes/chemistry
;
Palladium/chemistry
;
Pyridines/chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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