Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the...

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Autores principales: Vargová, Denisa, Baran, Rastislav, Šebesta, Radovan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2018
Materias:
Full Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852648/
https://www.ncbi.nlm.nih.gov/pubmed/29623117
http://dx.doi.org/10.3762/bjoc.14.42
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author Vargová, Denisa
Baran, Rastislav
Šebesta, Radovan
author_facet Vargová, Denisa
Baran, Rastislav
Šebesta, Radovan
author_sort Vargová, Denisa
collection PubMed
description Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er.
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spelling pubmed-58526482018-04-05 Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure Vargová, Denisa Baran, Rastislav Šebesta, Radovan Beilstein J Org Chem Full Research Paper Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er. Beilstein-Institut 2018-03-05 /pmc/articles/PMC5852648/ /pubmed/29623117 http://dx.doi.org/10.3762/bjoc.14.42 Text en Copyright © 2018, Vargová et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Vargová, Denisa
Baran, Rastislav
Šebesta, Radovan
Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
title Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
title_full Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
title_fullStr Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
title_full_unstemmed Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
title_short Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
title_sort investigations towards the stereoselective organocatalyzed michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852648/
https://www.ncbi.nlm.nih.gov/pubmed/29623117
http://dx.doi.org/10.3762/bjoc.14.42
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