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.

在当代药物发现中，增强分子结构的 sp ³杂化特征至关重要，因此需要创新的合成方法。在此，我们介绍了一种脱氧交叉亲电子偶联技术，该技术在可见光照射下使用曙红 Y 作为有机光催化剂，将易于获得的羧酸衍生的氧化还原活性酯与醛磺酰腙配对。这种方法作为一种多功能、无金属的 C(sp ³ )−C(sp ³ ) 交叉耦合平台。我们证明了其作为更安全、广泛适用的羧酸 C1 同系物的合成价值，提供了传统 Arndt-Eistert 反应的替代方案。此外，我们的方法可以使用多种醛衍生的磺酰腙直接获得环状和无环 β-芳基乙胺。值得注意的是，该方法被证明与固相肽的后期功能化兼容，简化了复杂肽的修饰，而无需彻底的从头合成。