In contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)−C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic β-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.

Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes / Bonciolini, S.; Pulcinella, A.; Leone, M.; Schiroli, D.; Ruiz, A. L.; Sorato, A.; Dubois, M. A. J.; Gopalakrishnan, R.; Masson, G.; Della Ca', N.; Protti, S.; Fagnoni, M.; Zysman-Colman, E.; Johansson, M.; Noel, T.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 15:1(2024). [10.1038/s41467-024-45804-z]

Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes

Schiroli D.;Della Ca' N.;
2024-01-01

Abstract

In contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)−C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic β-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.
2024
Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes / Bonciolini, S.; Pulcinella, A.; Leone, M.; Schiroli, D.; Ruiz, A. L.; Sorato, A.; Dubois, M. A. J.; Gopalakrishnan, R.; Masson, G.; Della Ca', N.; Protti, S.; Fagnoni, M.; Zysman-Colman, E.; Johansson, M.; Noel, T.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 15:1(2024). [10.1038/s41467-024-45804-z]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2982933
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