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

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.

SUBMITTER: Lennox AJJ

PROVIDER: S-EPMC6178801 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Lennox Alastair J J AJJ Goes Shannon L SL Webster Matthew P MP Koolman Hannes F HF Djuric Stevan W SW Stahl Shannon S SS

Journal of the American Chemical Society 20180831 36

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 t ...[more]

PMID: 30141925

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