title: Activation of remote meta-C-H bonds assisted by an end-on template.
abstract: 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 σ-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).
authors: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors: Dasheng
authors: D
authors: Leow
authors: Gang
authors: G
authors: Li
authors: Tian-Sheng
authors: TS
authors: Mei
authors: Jin-Quan
authors: JQ
authors: Yu
mesh_terms: D000475:Alkenes / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D004988:Ethers, Cyclic / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D009570:Nitriles / Q000737:chemistry; D010666:Phenylpropionates / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D014050:Toluene / Q000737:chemistry
chemical_list: D000475:Alkenes; D004988:Ethers, Cyclic; D009570:Nitriles; D010666:Phenylpropionates; D010880:Piperidines; D014050:Toluene; C035253:3-phenylpropionic acid; D002244:Carbon; D006859:Hydrogen