Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes

Abstract Calix[4]arenes display inherent chirality, with broad applications in synthetic and medicinal chemistry and in materials sciences. However, their use is hindered by their limited synthetic accessibility, primarily due to the lack of enantioselective methods for preparing chiral calix[4]aren...

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Main Authors: Vojtěch Dočekal, Ladislav Lóška, Adam Kurčina, Ivana Císařová, Jan Veselý
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59781-4
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author Vojtěch Dočekal
Ladislav Lóška
Adam Kurčina
Ivana Císařová
Jan Veselý
author_facet Vojtěch Dočekal
Ladislav Lóška
Adam Kurčina
Ivana Císařová
Jan Veselý
author_sort Vojtěch Dočekal
collection DOAJ
description Abstract Calix[4]arenes display inherent chirality, with broad applications in synthetic and medicinal chemistry and in materials sciences. However, their use is hindered by their limited synthetic accessibility, primarily due to the lack of enantioselective methods for preparing chiral calix[4]arenes with an ABCC substitution pattern. Here, we address this challenge by presenting a simple, efficient, and metal-free protocol for organocatalytic desymmetrisation of prochiral diformylcalix[4]arenes. Through this highly effective and sustainable approach, we synthesize structurally unique products in gram-scale reactions. Accordingly, this method facilitates extensive post-functionalisations of the carbonyl groups, including for organocatalyst development. Furthermore, our experimental mechanistic studies demonstrate that desymmetrisation determines enantiocontrol in esterification reactions catalysed by N-heterocyclic carbenes. These findings underscore the broad potential of this method for providing versatile access to inherently chiral calix[4]arenes with an ABCC substitution pattern while offering a valuable platform for asymmetric molecular recognition and catalysis.
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issn 2041-1723
language English
publishDate 2025-05-01
publisher Nature Portfolio
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series Nature Communications
spelling doaj-art-cf3d4bef77884f62a6deb8ee002fffc62025-08-20T03:48:06ZengNature PortfolioNature Communications2041-17232025-05-0116111010.1038/s41467-025-59781-4Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenesVojtěch Dočekal0Ladislav Lóška1Adam Kurčina2Ivana Císařová3Jan Veselý4Department of Organic Chemistry, Faculty of Science, Charles UniversityDepartment of Organic Chemistry, Faculty of Science, Charles UniversityDepartment of Organic Chemistry, Faculty of Science, Charles UniversityDepartment of Inorganic Chemistry, Faculty of Science, Charles UniversityDepartment of Organic Chemistry, Faculty of Science, Charles UniversityAbstract Calix[4]arenes display inherent chirality, with broad applications in synthetic and medicinal chemistry and in materials sciences. However, their use is hindered by their limited synthetic accessibility, primarily due to the lack of enantioselective methods for preparing chiral calix[4]arenes with an ABCC substitution pattern. Here, we address this challenge by presenting a simple, efficient, and metal-free protocol for organocatalytic desymmetrisation of prochiral diformylcalix[4]arenes. Through this highly effective and sustainable approach, we synthesize structurally unique products in gram-scale reactions. Accordingly, this method facilitates extensive post-functionalisations of the carbonyl groups, including for organocatalyst development. Furthermore, our experimental mechanistic studies demonstrate that desymmetrisation determines enantiocontrol in esterification reactions catalysed by N-heterocyclic carbenes. These findings underscore the broad potential of this method for providing versatile access to inherently chiral calix[4]arenes with an ABCC substitution pattern while offering a valuable platform for asymmetric molecular recognition and catalysis.https://doi.org/10.1038/s41467-025-59781-4
spellingShingle Vojtěch Dočekal
Ladislav Lóška
Adam Kurčina
Ivana Císařová
Jan Veselý
Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
Nature Communications
title Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
title_full Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
title_fullStr Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
title_full_unstemmed Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
title_short Desymmetric esterification catalysed by bifunctional chiral N-heterocyclic carbenes provides access to inherently chiral calix[4]arenes
title_sort desymmetric esterification catalysed by bifunctional chiral n heterocyclic carbenes provides access to inherently chiral calix 4 arenes
url https://doi.org/10.1038/s41467-025-59781-4
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