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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Main Authors:	Denisa Vargová, Rastislav Baran, Radovan Šebesta
Format:	Article
Language:	English
Published:	Beilstein-Institut 2018-03-01
Series:	Beilstein Journal of Organic Chemistry
Subjects:	kinetic resolution Michael addition organocatalysis pregabalin squaramide
Online Access:	https://doi.org/10.3762/bjoc.14.42

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spelling	doaj-d9b4b3abdee24ba8a791fc85fd02b6732021-02-02T04:39:10ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972018-03-0114155355910.3762/bjoc.14.421860-5397-14-42Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structureDenisa Vargová0Rastislav Baran1Radovan Šebesta2Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, SK-842 15 Bratislava, SlovakiaDepartment of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, SK-842 15 Bratislava, SlovakiaDepartment of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, SK-842 15 Bratislava, SlovakiaChiral 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.https://doi.org/10.3762/bjoc.14.42kinetic resolutionMichael additionorganocatalysispregabalinsquaramide
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Denisa Vargová Rastislav Baran Radovan Šebesta
spellingShingle	Denisa Vargová Rastislav Baran Radovan Šebesta Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure Beilstein Journal of Organic Chemistry kinetic resolution Michael addition organocatalysis pregabalin squaramide
author_facet	Denisa Vargová Rastislav Baran Radovan Šebesta
author_sort	Denisa Vargová
title	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_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_sort	investigations towards the stereoselective organocatalyzed michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
publisher	Beilstein-Institut
series	Beilstein Journal of Organic Chemistry
issn	1860-5397
publishDate	2018-03-01
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.
topic	kinetic resolution Michael addition organocatalysis pregabalin squaramide
url	https://doi.org/10.3762/bjoc.14.42
work_keys_str_mv	AT denisavargova investigationstowardsthestereoselectiveorganocatalyzedmichaeladditionofdimethylmalonatetoaracemicnitroalkenepossibleroutetothe4methylpregabalincorestructure AT rastislavbaran investigationstowardsthestereoselectiveorganocatalyzedmichaeladditionofdimethylmalonatetoaracemicnitroalkenepossibleroutetothe4methylpregabalincorestructure AT radovansebesta investigationstowardsthestereoselectiveorganocatalyzedmichaeladditionofdimethylmalonatetoaracemicnitroalkenepossibleroutetothe4methylpregabalincorestructure
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Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

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