Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds

Abstract Alkylidenecyclopropanes (ACPs) can work as versatile 3 C partners in a range of [3+n] cycloadditions with unsaturated carbon partners. We now demonstrate that they can also be harnessed for inter‐ and intramolecular palladium‐catalyzed [3+2] formal cycloadditions with imines, offering a str...

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Main Authors: Ricardo Rodiño, Felipe Verdugo, José L. Mascareñas, Fernando López
Format: Article
Language:English
Published: Wiley-VCH 2025-05-01
Series:ChemistryEurope
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Online Access:https://doi.org/10.1002/ceur.202500005
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author Ricardo Rodiño
Felipe Verdugo
José L. Mascareñas
Fernando López
author_facet Ricardo Rodiño
Felipe Verdugo
José L. Mascareñas
Fernando López
author_sort Ricardo Rodiño
collection DOAJ
description Abstract Alkylidenecyclopropanes (ACPs) can work as versatile 3 C partners in a range of [3+n] cycloadditions with unsaturated carbon partners. We now demonstrate that they can also be harnessed for inter‐ and intramolecular palladium‐catalyzed [3+2] formal cycloadditions with imines, offering a straightforward approach to constructing a diverse array of pyrrolidine scaffolds. The best results for the intermolecular variants are obtained using electron deficient imine partners, while the use of oxime ethers proved to be key for the intramolecular cases, which produce bicyclic pyrrolidine scaffolds. We also report preliminary results on enantioselective variants using palladium complexes bearing chiral phosphoramidite ligands. Finally, a DFT analysis provides relevant mechanistic insights, suggesting that the reactions proceed via pallada‐ene type of processes between initially generated palladacyclobutane and the C=N double bond of the imine partner.
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spelling doaj-art-5ecff662efa34c978d1bc8aef69527bd2025-08-20T02:30:32ZengWiley-VCHChemistryEurope2751-47652025-05-0133n/an/a10.1002/ceur.202500005Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine ScaffoldsRicardo Rodiño0Felipe Verdugo1José L. Mascareñas2Fernando López3Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química Orgánica Universidade de Santiago de Compostela (Spain) 15782 Santiago de Compostela SpainCentro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química Orgánica Universidade de Santiago de Compostela (Spain) 15782 Santiago de Compostela SpainCentro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química Orgánica Universidade de Santiago de Compostela (Spain) 15782 Santiago de Compostela SpainCentro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química Orgánica Universidade de Santiago de Compostela (Spain) 15782 Santiago de Compostela SpainAbstract Alkylidenecyclopropanes (ACPs) can work as versatile 3 C partners in a range of [3+n] cycloadditions with unsaturated carbon partners. We now demonstrate that they can also be harnessed for inter‐ and intramolecular palladium‐catalyzed [3+2] formal cycloadditions with imines, offering a straightforward approach to constructing a diverse array of pyrrolidine scaffolds. The best results for the intermolecular variants are obtained using electron deficient imine partners, while the use of oxime ethers proved to be key for the intramolecular cases, which produce bicyclic pyrrolidine scaffolds. We also report preliminary results on enantioselective variants using palladium complexes bearing chiral phosphoramidite ligands. Finally, a DFT analysis provides relevant mechanistic insights, suggesting that the reactions proceed via pallada‐ene type of processes between initially generated palladacyclobutane and the C=N double bond of the imine partner.https://doi.org/10.1002/ceur.202500005AlkylidenecyclopropanesCycloadditionImine palladiumPyrrolidines
spellingShingle Ricardo Rodiño
Felipe Verdugo
José L. Mascareñas
Fernando López
Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds
ChemistryEurope
Alkylidenecyclopropanes
Cycloaddition
Imine palladium
Pyrrolidines
title Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds
title_full Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds
title_fullStr Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds
title_full_unstemmed Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds
title_short Palladium‐Catalyzed [3+2] Cycloadditions of Alkylidenecyclopropanes to Imines: A Direct Approach to Pyrrolidine Scaffolds
title_sort palladium catalyzed 3 2 cycloadditions of alkylidenecyclopropanes to imines a direct approach to pyrrolidine scaffolds
topic Alkylidenecyclopropanes
Cycloaddition
Imine palladium
Pyrrolidines
url https://doi.org/10.1002/ceur.202500005
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