title: Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity.
abstract: We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.
authors.affiliation: Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde , Glasgow G1 1XL, United Kingdom.|GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom.
authors.forename: Julien C
authors.initials: JC
authors.lastname: Vantourout
authors.affiliation: School of Chemistry, WestCHEM, University of Glasgow , Glasgow G12 8QQ, United Kingdom.
authors.forename: Haralampos N
authors.identifier: 0000-0002-0086-5173
authors.initials: HN
authors.lastname: Miras
authors.affiliation: GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom.
authors.forename: Albert
authors.initials: A
authors.lastname: Isidro-Llobet
authors.affiliation: School of Chemistry, WestCHEM, University of Glasgow , Glasgow G12 8QQ, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sproules
authors.affiliation: Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde , Glasgow G1 1XL, United Kingdom.
authors.forename: Allan J B
authors.identifier: 0000-0002-1582-4286
authors.initials: AJ
authors.lastname: Watson