title: Conformation-induced remote meta-C-H activation of amines.
abstract: Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a long-standing challenge in organic chemistry. The small differences in intrinsic reactivity of C-H bonds in any given organic molecule can lead to the activation of undesired C-H bonds by a non-selective catalyst. One solution to this problem is to distinguish C-H bonds on the basis of their location in the molecule relative to a specific functional group. In this context, the activation of C-H bonds five or six bonds away from a functional group by cyclometallation has been extensively studied. However, the directed activation of C-H bonds that are distal to (more than six bonds away) functional groups has remained challenging, especially when the target C-H bond is geometrically inaccessible to directed metallation owing to the ring strain encountered in cyclometallation. Here we report a recyclable template that directs the olefination and acetoxylation of distal meta-C-H bonds--as far as 11 bonds away--of anilines and benzylic amines. This template is able to direct the meta-selective C-H functionalization of bicyclic heterocycles via a highly strained, tricyclic-cyclophane-like palladated intermediate. X-ray and nuclear magnetic resonance studies reveal that the conformational biases induced by a single fluorine substitution in the template can be enhanced by using a ligand to switch from ortho- to meta-selectivity.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Ri-Yuan
authors.initials: RY
authors.lastname: Tang
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry; D001596:Benzylamines / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D015195:Drug Design; D006859:Hydrogen / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry
chemical_list: D000475:Alkenes; D000588:Amines; D000814:Aniline Compounds; D001596:Benzylamines; D011804:Quinolines; D002244:Carbon; D006859:Hydrogen; C030796:benzylamine; C542964:1,2,3,4-tetrahydroquinoline; C021313:methylaniline