Publication Date:
2012-06-29
Description:
Functionalization of unactivated carbon-hydrogen (C-H) single bonds is an efficient strategy for rapid generation of complex molecules from simpler ones. However, it is difficult to achieve selectivity when multiple inequivalent C-H bonds are present in the target molecule. The usual approach is to use sigma-chelating directing groups, which lead to ortho-selectivity through the formation of a conformationally rigid six- or seven-membered cyclic pre-transition state. Despite the broad utility of this approach, proximity-driven reactivity prevents the activation of remote C-H bonds. Here we report a class of easily removable nitrile-containing templates that direct the activation of distal meta-C-H bonds (more than ten bonds away) of a tethered arene. We attribute this new mode of C-H activation to a weak 'end-on' interaction between the linear nitrile group and the metal centre. The 'end-on' coordination geometry relieves the strain of the cyclophane-like pre-transition state of the meta-C-H activation event. In addition, this template overrides the intrinsic electronic and steric biases as well as ortho-directing effects with two broadly useful classes of arene substrates (toluene derivatives and hydrocinnamic acids).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386562/" 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/PMC3386562/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leow, Dasheng -- Li, Gang -- Mei, Tian-Sheng -- Yu, Jin-Quan -- 1 R01 GM084019-03/GM/NIGMS NIH HHS/ -- R01 GM084019/GM/NIGMS NIH HHS/ -- R01 GM084019-03/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Jun 27;486(7404):518-22. doi: 10.1038/nature11158.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Scripps Research Institute, 10550 North 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/22739317" target="_blank"〉PubMed〈/a〉
Keywords:
Alkenes/chemistry
;
Carbon/*chemistry
;
Chemistry Techniques, Synthetic/*methods
;
Ethers, Cyclic/chemistry
;
Hydrogen/*chemistry
;
Nitriles/chemistry
;
Phenylpropionates/chemistry
;
Piperidines/chemistry
;
Toluene/chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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