The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation

The Michael addition of activated methylenes to β-substituted α,β-unsaturated aldehydes (enals) via iminium catalysis takes place following reactivity and enantioselectivity patterns which depend on the electronic nature of the substituent in the β position (β-aryl or β-alkyl). Application of the sa...

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Autores: Duce, Sara, Alonso Montero, María Inés, Lamsabhi, Al Mokhtar, Rodrigo, Eduardo, Morales, Sara, García Ruano, José Luis, Poveda, Ana, Mauleón Pérez, Pablo, Cid de la Plata, María Belén
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/681765
Acceso en línea:http://hdl.handle.net/10486/681765
https://dx.doi.org/10.1021/acscatal.7b02806
Access Level:acceso abierto
Palabra clave:Acidity
Asymmetric organocatalysis
Enals
Iminium activation
Michael addition
Química
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spelling The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium ActivationDuce, SaraAlonso Montero, María InésLamsabhi, Al MokhtarRodrigo, EduardoMorales, SaraGarcía Ruano, José LuisPoveda, AnaMauleón Pérez, PabloCid de la Plata, María BelénAcidityAsymmetric organocatalysisEnalsIminium activationMichael additionQuímicaThe Michael addition of activated methylenes to β-substituted α,β-unsaturated aldehydes (enals) via iminium catalysis takes place following reactivity and enantioselectivity patterns which depend on the electronic nature of the substituent in the β position (β-aryl or β-alkyl). Application of the same reaction conditions to both families of enals may result in erratic levels of asymmetric induction in the reactions of β-aryl enals or low reactivity with β-alkyl enals. A systematic analysis of this behavior using phenylacetic acid derivatives as case studies has led us to find a general trend: the different problems found for β-aryl and β-alkyl enals depend on the acidity of the nucleophile, and the outcome of the reaction for both types of enals can be improved substantially by careful choice of catalyst, solvent, and additive. Furthermore, this study has allowed us to understand subtle aspects of this transformation and has enabled the formulation of a general and reliable protocol to obtain high yields and enantioselectivities consistently, regardless of the acidity of the nucleophile and the nature of the substituent (aromatic or aliphatic) at the β positionWe thank CTQ-2009-12168, CAM (AVANCAT CS2009/PPQ-1634), UAM-CAM (CCG10-UAM/PPQ-5769), CTQ-2012-35957, CTQ2015-63997-C2-1-P, CTQ2016-78779-R and FOTOCARBON-CAM S2013/MIT-2841 for financial support. S.D. thanks the Comunidad Autónoma de Madrid (CAM), and E.R. and S.M. thank MICINN, for predoctoral fellowships. P.M. thanks MICINN for a Ramón y Cajal contract and the EU for a Marie Curie grant (CIG: HYPERCAT-304228American Chemical SocietyDepartamento de Química OrgánicaDepartamento de QuímicaFacultad de Ciencias20172017-11-08research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/681765https://dx.doi.org/10.1021/acscatal.7b02806reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6817652026-06-23T12:46:27Z
dc.title.none.fl_str_mv The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
title The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
spellingShingle The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
Duce, Sara
Acidity
Asymmetric organocatalysis
Enals
Iminium activation
Michael addition
Química
title_short The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
title_full The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
title_fullStr The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
title_full_unstemmed The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
title_sort The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
dc.creator.none.fl_str_mv Duce, Sara
Alonso Montero, María Inés
Lamsabhi, Al Mokhtar
Rodrigo, Eduardo
Morales, Sara
García Ruano, José Luis
Poveda, Ana
Mauleón Pérez, Pablo
Cid de la Plata, María Belén
author Duce, Sara
author_facet Duce, Sara
Alonso Montero, María Inés
Lamsabhi, Al Mokhtar
Rodrigo, Eduardo
Morales, Sara
García Ruano, José Luis
Poveda, Ana
Mauleón Pérez, Pablo
Cid de la Plata, María Belén
author_role author
author2 Alonso Montero, María Inés
Lamsabhi, Al Mokhtar
Rodrigo, Eduardo
Morales, Sara
García Ruano, José Luis
Poveda, Ana
Mauleón Pérez, Pablo
Cid de la Plata, María Belén
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Química Orgánica
Departamento de Química
Facultad de Ciencias
dc.subject.none.fl_str_mv Acidity
Asymmetric organocatalysis
Enals
Iminium activation
Michael addition
Química
topic Acidity
Asymmetric organocatalysis
Enals
Iminium activation
Michael addition
Química
description The Michael addition of activated methylenes to β-substituted α,β-unsaturated aldehydes (enals) via iminium catalysis takes place following reactivity and enantioselectivity patterns which depend on the electronic nature of the substituent in the β position (β-aryl or β-alkyl). Application of the same reaction conditions to both families of enals may result in erratic levels of asymmetric induction in the reactions of β-aryl enals or low reactivity with β-alkyl enals. A systematic analysis of this behavior using phenylacetic acid derivatives as case studies has led us to find a general trend: the different problems found for β-aryl and β-alkyl enals depend on the acidity of the nucleophile, and the outcome of the reaction for both types of enals can be improved substantially by careful choice of catalyst, solvent, and additive. Furthermore, this study has allowed us to understand subtle aspects of this transformation and has enabled the formulation of a general and reliable protocol to obtain high yields and enantioselectivities consistently, regardless of the acidity of the nucleophile and the nature of the substituent (aromatic or aliphatic) at the β position
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-11-08
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/681765
https://dx.doi.org/10.1021/acscatal.7b02806
url http://hdl.handle.net/10486/681765
https://dx.doi.org/10.1021/acscatal.7b02806
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
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repository.mail.fl_str_mv
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