Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions

This work presents a detailed mechanistic study of a quininium‐catalyzed aza‐Michael reaction, providing essential information for advancing chiral proton catalysis (CPC). The use of cinchona derivatives as chiral proton catalysts demonstrates their potential beyond their conventional roles as base‐...

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Autores: Auria-Luna, Fernando, Marqués-López, Eugenia, Gimeno, M. Concepción, Alegre-Requena, Juan V., Pérez Herrera, Raquel
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2025
País:España
Institución:Universidad de Zaragoza
Repositorio:Zaguán. Repositorio Digital de la Universidad de Zaragoza
OAI Identifier:oai:zaguan.unizar.es:156591
Acceso en línea:http://zaguan.unizar.es/record/156591
Access Level:acceso abierto
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spelling Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael AdditionsAuria-Luna, FernandoMarqués-López, EugeniaGimeno, M. ConcepciónAlegre-Requena, Juan V.Pérez Herrera, RaquelThis work presents a detailed mechanistic study of a quininium‐catalyzed aza‐Michael reaction, providing essential information for advancing chiral proton catalysis (CPC). The use of cinchona derivatives as chiral proton catalysts demonstrates their potential beyond their conventional roles as base‐promoted and phase‐transfer catalysts. Competitive reaction pathways are explored using density functional theory (DFT), wavefunction theory, and microkinetic simulations. Theoretical analyses are complemented with experimental titration and kinetic techniques to verify the intrinsic details of the reaction. This study reveals an intricate hydrogen bond network formed in the rate‐ and selectivity‐determining step, involving four noncovalently attached components that favor a stronger substrate⋅⋅⋅catalyst interaction in the R transition state. Significantly, this research emphasizes the pivotal role of carboxylate anions as nucleophile‐activating bases impacting reaction yield and enantioselectivity. Therefore, this work introduces cinchonium derivatives as new options for CPC and provides a thorough mechanistic analysis significant in expanding this underdeveloped catalytic domain.2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://zaguan.unizar.es/record/156591reponame:Zaguán. Repositorio Digital de la Universidad de Zaragozainstname:Universidad de ZaragozaInglésinfo:eu-repo/grantAgreement/ES/AEI/PID2020-117455GB-I00info:eu-repo/grantAgreement/ES/DGA/E07-23Rinfo:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136861NB-I00info:eu-repo/grantAgreement/ES/MICINN/PID2022-140159NA-I00info:eu-repo/grantAgreement/ES/MICINN/PID2023-147471NB-I00info:eu-repo/semantics/openAccessoai:zaguan.unizar.es:1565912026-05-29T13:59:51Z
dc.title.none.fl_str_mv Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
title Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
spellingShingle Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
Auria-Luna, Fernando
title_short Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
title_full Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
title_fullStr Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
title_full_unstemmed Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
title_sort Understanding Chiral Proton Catalysis Using Cinchonium Derivatives in aza‐Michael Additions
dc.creator.none.fl_str_mv Auria-Luna, Fernando
Marqués-López, Eugenia
Gimeno, M. Concepción
Alegre-Requena, Juan V.
Pérez Herrera, Raquel
author Auria-Luna, Fernando
author_facet Auria-Luna, Fernando
Marqués-López, Eugenia
Gimeno, M. Concepción
Alegre-Requena, Juan V.
Pérez Herrera, Raquel
author_role author
author2 Marqués-López, Eugenia
Gimeno, M. Concepción
Alegre-Requena, Juan V.
Pérez Herrera, Raquel
author2_role author
author
author
author
description This work presents a detailed mechanistic study of a quininium‐catalyzed aza‐Michael reaction, providing essential information for advancing chiral proton catalysis (CPC). The use of cinchona derivatives as chiral proton catalysts demonstrates their potential beyond their conventional roles as base‐promoted and phase‐transfer catalysts. Competitive reaction pathways are explored using density functional theory (DFT), wavefunction theory, and microkinetic simulations. Theoretical analyses are complemented with experimental titration and kinetic techniques to verify the intrinsic details of the reaction. This study reveals an intricate hydrogen bond network formed in the rate‐ and selectivity‐determining step, involving four noncovalently attached components that favor a stronger substrate⋅⋅⋅catalyst interaction in the R transition state. Significantly, this research emphasizes the pivotal role of carboxylate anions as nucleophile‐activating bases impacting reaction yield and enantioselectivity. Therefore, this work introduces cinchonium derivatives as new options for CPC and provides a thorough mechanistic analysis significant in expanding this underdeveloped catalytic domain.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://zaguan.unizar.es/record/156591
url http://zaguan.unizar.es/record/156591
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/ES/AEI/PID2020-117455GB-I00
info:eu-repo/grantAgreement/ES/DGA/E07-23R
info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136861NB-I00
info:eu-repo/grantAgreement/ES/MICINN/PID2022-140159NA-I00
info:eu-repo/grantAgreement/ES/MICINN/PID2023-147471NB-I00
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv
publisher.none.fl_str_mv
dc.source.none.fl_str_mv reponame:Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname:Universidad de Zaragoza
instname_str Universidad de Zaragoza
reponame_str Zaguán. Repositorio Digital de la Universidad de Zaragoza
collection Zaguán. Repositorio Digital de la Universidad de Zaragoza
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