A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water

Abstract A simple and highly chemoselective heteroannulation protocol for the synthesis of polysubstituted heterocycles is reported. In this work, various oxa-aza[3.3.3]propellanes were synthesized via a sequential one-pot reaction of ninhydrin, malononitrile and nitroketene acetal or nitroketene am...

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Main Authors: Zahra Rahimi, Mohammad Bayat, Hajar Hosseini
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-13577-0
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author Zahra Rahimi
Mohammad Bayat
Hajar Hosseini
author_facet Zahra Rahimi
Mohammad Bayat
Hajar Hosseini
author_sort Zahra Rahimi
collection DOAJ
description Abstract A simple and highly chemoselective heteroannulation protocol for the synthesis of polysubstituted heterocycles is reported. In this work, various oxa-aza[3.3.3]propellanes were synthesized via a sequential one-pot reaction of ninhydrin, malononitrile and nitroketene acetal or nitroketene aminals in water at ambient temperature. This successive Knoevenagel condensation/Michael addition/cyclization sequence features high atom economy, excellent efficiency, and the use of water as a solvent without the need for metal catalysts or external activators. This method can be presented as a good example of group-assisted purification (GAP), in which traditional purification techniques such as recrystallization and column chromatography are avoided and pure products are obtained simply by washing the crude products.
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spelling doaj-art-e87bac459d83408fb7dfa0dd8ff5b4e12025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-13577-0A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in waterZahra Rahimi0Mohammad Bayat1Hajar Hosseini2Department of Chemistry, Faculty of Science, Imam Khomeini International UniversityDepartment of Chemistry, Faculty of Science, Imam Khomeini International UniversityDepartment of Chemistry, Faculty of Science, Imam Khomeini International UniversityAbstract A simple and highly chemoselective heteroannulation protocol for the synthesis of polysubstituted heterocycles is reported. In this work, various oxa-aza[3.3.3]propellanes were synthesized via a sequential one-pot reaction of ninhydrin, malononitrile and nitroketene acetal or nitroketene aminals in water at ambient temperature. This successive Knoevenagel condensation/Michael addition/cyclization sequence features high atom economy, excellent efficiency, and the use of water as a solvent without the need for metal catalysts or external activators. This method can be presented as a good example of group-assisted purification (GAP), in which traditional purification techniques such as recrystallization and column chromatography are avoided and pure products are obtained simply by washing the crude products.https://doi.org/10.1038/s41598-025-13577-0[3.3.3]propellaneNitroketene aminalMulticomponent reaction
spellingShingle Zahra Rahimi
Mohammad Bayat
Hajar Hosseini
A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water
Scientific Reports
[3.3.3]propellane
Nitroketene aminal
Multicomponent reaction
title A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water
title_full A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water
title_fullStr A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water
title_full_unstemmed A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water
title_short A highly chemo- and regioselective synthesis of heterocyclic [3.3.3]propellanes via sequential multicomponent reactions in water
title_sort highly chemo and regioselective synthesis of heterocyclic 3 3 3 propellanes via sequential multicomponent reactions in water
topic [3.3.3]propellane
Nitroketene aminal
Multicomponent reaction
url https://doi.org/10.1038/s41598-025-13577-0
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