Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives

An efficient stereoselective strategy for the synthesis of chiral bisspiro barbituric acid–oxindole derivatives was developed. The asymmetric Michael addition/cyclization tandem reaction between benzylidene barbituric acids and oxindolylmalonitriles was catalyzed by squaramide catalyst, and the corr...

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Main Authors: De-Jun Qiao, Da-Ming Du
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/30/9/2000
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author De-Jun Qiao
Da-Ming Du
author_facet De-Jun Qiao
Da-Ming Du
author_sort De-Jun Qiao
collection DOAJ
description An efficient stereoselective strategy for the synthesis of chiral bisspiro barbituric acid–oxindole derivatives was developed. The asymmetric Michael addition/cyclization tandem reaction between benzylidene barbituric acids and oxindolylmalonitriles was catalyzed by squaramide catalyst, and the corresponding spirocyclic products were obtained in good-to-high yields (up to 97%) with excellent stereoselectivities (up to >99% ee, >20:1 dr). At the same time, the practicality of the reaction was verified by the gram-scale preparation reaction.
format Article
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institution Kabale University
issn 1420-3049
language English
publishDate 2025-04-01
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series Molecules
spelling doaj-art-d8a6bfa8d7e34b8d87d6c914aee2794b2025-08-20T03:52:57ZengMDPI AGMolecules1420-30492025-04-01309200010.3390/molecules30092000Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole DerivativesDe-Jun Qiao0Da-Ming Du1Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, ChinaAn efficient stereoselective strategy for the synthesis of chiral bisspiro barbituric acid–oxindole derivatives was developed. The asymmetric Michael addition/cyclization tandem reaction between benzylidene barbituric acids and oxindolylmalonitriles was catalyzed by squaramide catalyst, and the corresponding spirocyclic products were obtained in good-to-high yields (up to 97%) with excellent stereoselectivities (up to >99% ee, >20:1 dr). At the same time, the practicality of the reaction was verified by the gram-scale preparation reaction.https://www.mdpi.com/1420-3049/30/9/2000organocatalysisasymmetric catalysisbarbituric acidoxindoleMichael addition
spellingShingle De-Jun Qiao
Da-Ming Du
Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives
Molecules
organocatalysis
asymmetric catalysis
barbituric acid
oxindole
Michael addition
title Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives
title_full Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives
title_fullStr Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives
title_full_unstemmed Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives
title_short Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric Acid–Oxindole Derivatives
title_sort squaramide catalyzed asymmetric michael addition cyclization reaction for the synthesis of chiral bisspiro barbituric acid oxindole derivatives
topic organocatalysis
asymmetric catalysis
barbituric acid
oxindole
Michael addition
url https://www.mdpi.com/1420-3049/30/9/2000
work_keys_str_mv AT dejunqiao squaramidecatalyzedasymmetricmichaeladditioncyclizationreactionforthesynthesisofchiralbisspirobarbituricacidoxindolederivatives
AT damingdu squaramidecatalyzedasymmetricmichaeladditioncyclizationreactionforthesynthesisofchiralbisspirobarbituricacidoxindolederivatives