title: Iron-Catalyzed Cα-H Oxidation of Tertiary, Aliphatic Amines to Amides under Mild Conditions.
abstract: De novo syntheses of amides often generate stoichiometric amounts of waste. Thus, recent progress in the field has focused on precious metal catalyzed, oxidative protocols to generate such functionalities. However, simple tertiary alkyl amines cannot be used as starting materials in these protocols. The research described herein enables the oxidative synthesis of amides from simple, noncyclic tertiary alkyl amines under synthetically useful, mild conditions through a biologically inspired approach: Fe-catalyzed Cα-H functionalization. Mechanistic investigations provide insight into reaction intermediates and allow the development of a mild Cα-H cyanation method using the same catalyst system. The protocol was further applied to oxidize the drug Lidocaine, demonstrating the potential utility of the developed chemistry for metabolite synthesis.
authors.affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA (USA).
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Legacy
authors.affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA (USA).
authors.forename: Anqi
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA (USA).
authors.forename: Brian J
authors.initials: BJ
authors.lastname: O'Day
authors.affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA (USA). mhemmert@wpi.edu.
authors.forename: Marion H
authors.initials: MH
authors.lastname: Emmert
keywords: CH functionalization; iron catalysis; metabolite synthesis; oxidation; reaction mechanism