title: Ligand-accelerated enantioselective methylene C(sp3)-H bond activation.
abstract: Effective differentiation of prochiral carbon-hydrogen (C-H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C-H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of β-methylene C-H bonds in aliphatic amides. Using bidentate ligands to accelerate C-H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C-H activation is also demonstrated by enantioselective β-C-H arylation of simple carboxylic acids without installing directing groups.
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Michal S
authors.initials: MS
authors.lastname: Andrä
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Yan-Qiao
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569, USA.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Yang
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu