title: Ligand-enabled meta-C-H activation using a transient mediator.
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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Wang
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Fang
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Ru-Yi
authors.initials: RY
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Suhua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Keary M
authors.initials: KM
authors.lastname: Engle
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D006219:Halogens / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D008024:Ligands; D009636:Norbornanes / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry
chemical_list: D000577:Amides; D006219:Halogens; D008024:Ligands; D009636:Norbornanes; D011725:Pyridines; D010165:Palladium; D002244:Carbon; D006859:Hydrogen; C023666:pyridine