Electrochemical Aminoxyl-Mediated α-Cyanation of Secondary Piperidines for Pharmaceutical Building Block Diversification

Alastair J. J. Lennox, Shannon L. Goes, Matthew P. Webster, Hannes F. Koolman, Stevan W. Djuric, Shannon S. Stahl

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Secondary piperidines are ideal pharmaceutical building blocks owing to the prevalence of piperidines in commercial drugs. Here, we report an electrochemical method for cyanation of the heterocycle adjacent to nitrogen without requiring protection or substitution of the N–H bond. The reaction utilizes ABNO (9-azabicyclononane N-oxyl) as a catalytic mediator. Electrochemical oxidation of ABNO generates the corresponding oxoammonium species, which promotes dehydrogenation of the 2° piperidine to the cyclic imine, followed by addition of cyanide. The low-potential, mediated electrolysis process is compatible with a wide range of heterocyclic and oxidatively sensitive substituents on the piperidine ring and enables synthesis of unnatural amino acids.
Original languageEnglish
Pages (from-to)11227-11231
Number of pages5
JournalJournal of the American Chemical Society
Volume140
Issue number36
Early online date24 Aug 2018
DOIs
Publication statusPublished - 12 Sep 2018

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