title: Remote Meta-C-H Activation Using a Pyridine-Based Template: Achieving Site-Selectivity via the Recognition of Distance and Geometry.
abstract: 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Chu
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Shang
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Keita
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Process Chemistry and Department of Discovery Chemistry, Merck & Co. Inc. , 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States.
authors.forename: Qinghao
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Process Chemistry and Department of Discovery Chemistry, Merck & Co. Inc. , 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States.
authors.forename: Natalya
authors.initials: N
authors.lastname: Pissarnitski
authors.affiliation: Department of Process Chemistry and Department of Discovery Chemistry, Merck & Co. Inc. , 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Streckfuss
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu