The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation
Entity
UAM. Departamento de Química; UAM. Departamento de Química OrgánicaPublisher
American Chemical SocietyDate
2017-11-08Citation
10.1021/acscatal.7b02806
ACS Catalysis 8.1 (2018): 22-34
ISSN
2155-5435DOI
10.1021/acscatal.7b02806Funded by
We 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-304228Project
Gobierno de España. CTQ-2009-12168; Comunidad de Madrid. CS2009/PPQ-1634/AVANCAT; Gobierno de España. CTQ-2012-35957; Gobierno de España. CTQ2015-63997-C2-1-P; Gobierno de España. CTQ2016-78779-R; Comunidad de Madrid. S2013/MIT-2841/FOTOCARBON-CAM; info:eu-repo/grantAgreement/EC/FP7/304228Editor's Version
http://doi.org/10.1021/acscatal.7b02806Subjects
Acidity; Asymmetric organocatalysis; Enals; Iminium activation; Michael addition; QuímicaRights
© 2017 American Chemical SocietyAbstract
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
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Google Scholar:Duce, Sara
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Alonso Montero, María Inés
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Lamsabhi, Al Mokhtar
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Rodrigo, Eduardo
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Morales, Sara
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García Ruano, José Luis
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Poveda, Ana
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Mauleón Pérez, Pablo
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Cid de la Plata, María Belén
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