Oxidation of azacycloalkanes

Troyanskii, E. I.; Ioffe, V. A.; Nikishin, G. I.

doi:10.1007/bf00956799

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…The synthesis of the cyanomethyl substituted derivative 33 in 78% yield by adding formalin and potassium cyanide to a methanol solution of piperidine 23 confirmed this conclusion (Scheme ). The Boc protection group could smoothly be transferred to the azacyclic amino functionality of the diamines 23 and 24 in high yields (Scheme ). Reduction of the carbamate function in 25e led to a slightly increased overall yield of methylated 25a (89% starting from 21b ).…”

Section: Resultsmentioning

confidence: 99%

Preparation of Enantiopure 3-Aminopiperidine and 3-Aminoazepane Derivatives from Ornithine and Lysine. Consecutive Syntheses of Pharmacologically Active Analogs, Such as Besifloxacin

Schiffers

Frings

Kübber

et al. 2022

Org. Process Res. Dev.

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In recent years, 3-aminopiperidine and 3-aminoazepane have been identified as important pharmacophores that led to the development of drugs having several billion dollar global revenues. Although the number of protocols for the resolution of suitable racemic derivatives is steadily increasing, there is an ongoing demand for new synthetic methods to prepare enantiomerically pure analogs from readily available starting materials. Herein, we report the cyclization of methyl esters derived from natural ornithine and lysine as well as their enantiomeric counterparts. Lactam synthesis was regularly performed on a lab scale of up to 150 mmol per batch. Protection and subsequent reduction to enantiopure 3-(tritylamino)piperidine and 3-(tritylamino)azepane allowed the selective derivatization of the heterocyclic nitrogen. Deprotection gave access to a set of building blocks that were applied to the synthesis of eight molecules reported to be pharmacologically active in drug research. For example, besifloxacin was prepared in only a few steps starting from D-lysine.

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Section: Resultsmentioning

confidence: 99%

Preparation of Enantiopure 3-Aminopiperidine and 3-Aminoazepane Derivatives from Ornithine and Lysine. Consecutive Syntheses of Pharmacologically Active Analogs, Such as Besifloxacin

Schiffers

Frings

Kübber

et al. 2022

Org. Process Res. Dev.

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“…Synthetically useful precedents, however, are limited to activated substrates (e.g., tetrahydroisoquinolines) and the 3° amine/amide derivatives noted above. No general methods are available for analogous cyanation of 2° piperidines, reflecting the susceptibility of cyclic imines to undergo decomposition. , …”

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confidence: 99%

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

et al. 2018

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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.

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N,N′-Bisazaheterocycles: Synthesis and Importance

Reddy

Bhavani

2015

Advances in Heterocyclic Chemistry

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Oxidation of azacycloalkanes

Cited by 5 publications

References 9 publications

Preparation of Enantiopure 3-Aminopiperidine and 3-Aminoazepane Derivatives from Ornithine and Lysine. Consecutive Syntheses of Pharmacologically Active Analogs, Such as Besifloxacin

Preparation of Enantiopure 3-Aminopiperidine and 3-Aminoazepane Derivatives from Ornithine and Lysine. Consecutive Syntheses of Pharmacologically Active Analogs, Such as Besifloxacin

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

N,N′-Bisazaheterocycles: Synthesis and Importance

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