title: Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical relay.
abstract: Direct methods for stereoselective functionalization of sp3-hybridized carbon-hydrogen [C(sp3)-H] bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C-H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp3)-CN bond formation upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90 to 99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C-H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways.
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: McCann
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Dinghai
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Pinhong
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. stahl@chem.wisc.edu gliu@mail.sioc.ac.cn.
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Stahl
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. stahl@chem.wisc.edu gliu@mail.sioc.ac.cn.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Liu