Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38374079.
- Also identified by DOI 10.1038/s41467-024-45804-z and PMC identifier 10876646.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
In contemporary drug discovery, enhancing the sp<sup>3</sup>-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(sp<sup>3</sup>)-C(sp<sup>3</sup>) 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.