title: Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization.
abstract: Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 2034 Becker Drive, Lawrence, KS 66047 (USA).|Present address: Division of Chemical Biology and Medicinal Chemistry and the Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, North Carolina, 27599, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Frankowski
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 2034 Becker Drive, Lawrence, KS 66047 (USA).
authors.forename: Ruzhang
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Saint Martin's University, 5000 Abbey Way, Lacey, WA 98503 (USA).
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Milligan
authors.affiliation: Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63130 (USA).
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Moeller
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 2034 Becker Drive, Lawrence, KS 66047 (USA). jaube@unc.edu.|Present address: Division of Chemical Biology and Medicinal Chemistry and the Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, North Carolina, 27599, USA. jaube@unc.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
mesh_terms: D055664:Electrochemical Techniques / Q000379:methods*; D004566:Electrodes; D007769:Lactams / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D007769:Lactams
keywords: N-acyliminium ions; anodic oxidation; diversity-oriented synthesis; heterocycles; lactams