Electrooxidative C(sp3)−H Cyanation of Sparteine and Lupanine in Undivided Batch and Continuous-Flow Cells
Raquel M. Durão
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
These authors contributed equally to this work.
Search for more papers by this authorDuarte B. Clemente
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
These authors contributed equally to this work.
Search for more papers by this authorAbdullahi A. Muiz
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorSara Lima
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorDaniel F. Carvalho
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorStijn De Vos
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorRita de Jesus
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
Current address: Otto-Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany
Search for more papers by this authorAndreia Fortuna
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
Current address: BioISI–BioSystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorCorresponding Author
Carlos A. M. Afonso
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
Search for more papers by this authorCorresponding Author
Jaime A. S. Coelho
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorRaquel M. Durão
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
These authors contributed equally to this work.
Search for more papers by this authorDuarte B. Clemente
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
These authors contributed equally to this work.
Search for more papers by this authorAbdullahi A. Muiz
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorSara Lima
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorDaniel F. Carvalho
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorStijn De Vos
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorRita de Jesus
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
Current address: Otto-Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany
Search for more papers by this authorAndreia Fortuna
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
Current address: BioISI–BioSystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorCorresponding Author
Carlos A. M. Afonso
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon, 1649-003 Portugal
Search for more papers by this authorCorresponding Author
Jaime A. S. Coelho
Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, 1749-016 Portugal
Search for more papers by this authorGraphical Abstract
A selective electrochemical α-cyanation of sparteine-type bis-quinolizidine alkaloids enables the efficient synthesis of valuable α-aminonitrile derivatives. The method employs controlled electrochemical oxidation in aqueous media with sodium cyanide and operates under both batch and continuous-flow conditions without requiring additional supporting electrolytes, delivering high yields and preventing overoxidation reactions.
Abstract
Sparteine is widely used as a chiral ligand in asymmetric synthesis, but methods for providing efficient access to functionalized sparteine derivatives are still limited. Herein, we describe an electrochemical α-cyanation of sparteine-type bis-quinolizidine alkaloids. This method features commercially available setups for batch and single-pass continuous flow conditions, enabling easy gram scale synthesis of valuable racemic and enantiopure products. Moreover, insights into the selectivity of the reaction and overoxidation mechanisms are disclosed. This allows for the development of divergent oxidation pathways depending on the electrolysis conditions.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| cssc202401305-sup-0001-Cartesian_coordinates_and_energies_SI_AK.txt46.6 KB | Supporting Information |
| cssc202401305-sup-0001-misc_information.pdf4.1 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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