Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes
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.
Citation
Bonciolini , S , Pulcinella , A , Leone , M , Schiroli , D , Ruiz , A L , Sorato , A , Dubois , M A J , Gopalakrishnan , R , Masson , G , Ca' , N D , Protti , S , Fagnoni , M , Zysman-Colman , E , Johansson , M & Noël , T 2024 , ' Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes ' , Nature Communications , vol. 15 , 1509 . https://doi.org/10.1038/s41467-024-45804-z
Publication
Nature Communications
Status
Peer reviewed
ISSN
2041-1723Type
Journal article
Description
Authors are grateful to have received generous funding from the European Union H2020 research and innovation program under the Marie S. Curie Grant Agreement (PhotoReAct, No 956324, S.B., M.L., A.L., G.M., E.Z.C., T.N.; CHAIR, No 860762, A.P., M.J., T.N.)Collections
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