title: Bond-weakening catalysis: conjugate aminations enabled by the soft homolysis of strong N-H bonds.
abstract: The ability of redox-active metal centers to weaken the bonds in associated ligands is well precedented, but has rarely been utilized as a mechanism of substrate activation in catalysis. Here we describe a catalytic bond-weakening protocol for conjugate amination wherein the strong N-H bonds in N-aryl amides (N-H bond dissociation free energies ∼100 kcal/mol) are destabilized by ∼33 kcal/mol upon by coordination to a reducing titanocene complex, enabling their abstraction by the weak H-atom acceptor TEMPO through a proton-coupled electron transfer process. Significantly, this soft homolysis mechanism provides a method to generate closed-shell, metalated nucleophiles under neutral conditions in the absence of a Brønsted base.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
authors.forename: Kyle T
authors.initials: KT
authors.lastname: Tarantino
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Miller
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Callon
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Knowles
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000586:Amination; D002384:Catalysis; D015394:Molecular Structure
chemical_list: D000577:Amides