biostudies-literatureChu LNational Institute of General Medical SciencesNIGMS NIH HHS394-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC4827496biostudies-literatureUnknown1(7)The pyridyl group has been extensively employed to direct transition-metal-catalyzed C-H activation reactions in the past half-century. The typical cyclic transition states involved in these cyclometalation processes have only enabled the activation of ortho-C-H bonds. Here, we report that pyridine is adapted to direct meta-C-H activation of benzyl and phenyl ethyl alcohols through engineering the distance and geometry of a directing template. This template takes advantage of a stronger σ-coordinating pyridine to recruit Pd catalysts to the desired site for functionalization. The U-shaped structure accommodates the otherwise highly strained cyclophane-like transition state. This development illustrates the potential of achieving site selectivity in C-H activation via the recognition of distal and geometric relationship between existing functional groups and multiple C-H bonds in organic molecules.ACS central scienceRemote Meta-C-H Activation Using a Pyridine-Based Template: Achieving Site-Selectivity via the Recognition of Distance and Geometry.PMC4827496R01 GM1022651R01 GM102265Yu JQStreckfuss EChen QShang MTanaka KPissarnitski NChu LfalseRemote Meta-C-H Activation Using a Pyridine-Based Template: Achieving Site-Selectivity via the Recognition of Distance and Geometry.The pyridyl group has been extensively employed to direct transition-metal-catalyzed C-H activation reactions in the past half-century. The typical cyclic transition states involved in these cyclometalation processes have only enabled the activation of ortho-C-H bonds. Here, we report that pyridine is adapted to direct meta-C-H activation of benzyl and phenyl ethyl alcohols through engineering the distance and geometry of a directing template. This template takes advantage of a stronger σ-coordinating pyridine to recruit Pd catalysts to the desired site for functionalization. The U-shaped structure accommodates the otherwise highly strained cyclophane-like transition state. This development illustrates the potential of achieving site selectivity in C-H activation via the recognition of distal and geometric relationship between existing functional groups and multiple C-H bonds in organic molecules.2015-01-01T00:00:00Z2015 Oct2024-11-20T00:22:44.853Z2019-03-27T03:11:44ZS-EPMC48274962716299710.1021/acscentsci.5b00312