Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2015-09, Vol.54 (36), p.10555-10558
Main Authors: Frankowski, Kevin J., Liu, Ruzhang, Milligan, Gregory L., Moeller, Kevin D., Aubé, Jeffrey
Format: Article
Language:English
Subjects:
Amides
anodic oxidation
Anodizing
Complement
Derivatives
Dichloromethane
diversity-oriented synthesis
Electrochemical Techniques - methods
Electrochemistry
Electrodes
heterocycles
Intermediates
lactams
Lactams - chemistry
Lewis acid
N-acyliminium ions
Nuclear electric power generation
Oxidation
Oxidation-Reduction
Regeneration
Strategy
Synthesis
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Summary: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. An improvised electrochemical apparatus was constructed and utilized for the anodic oxidation of complex lactam substrates. Combining synthetic electrochemistry with the azido‐Schmidt/lactam disconnection has enabled the synthesis of novel lactam derivatives by N‐acyliminium ion diversification. This mild, late‐stage functionalization strategy complements the methods for heterocycle synthesis.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201504775