Fu Xiaoyang, Tian Jiarui, Zhang Mingjun, Jing Yue, Liu Yuxiu, Song Hongjian, Wang Qingmin
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, P. R. China.
Adv Sci (Weinh). 2025 Jan;12(2):e2411744. doi: 10.1002/advs.202411744. Epub 2024 Nov 18.
Allylic amide moieties are commonly encountered in natural products and are privileged structures in pharmaceuticals and agrochemicals. Moreover, because allylic amide can be to converted into an array of high-value motifs, they have been widely employed in organic synthesis. However, the development of catalytic systems for intermolecular allylic amidation of olefins, particularly branched α-olefins, has proven to be challenging. Here, a biomimetic, synergistic catalytic method is reported that combines photoredox, cobalt, and Brønsted base catalysis for the synthesis of substituted allylic amides from branched α-olefins and simple imides without using oxidants. This low-cost, operationally simple method features a broad substrate scope and excellent functional group compatibility. Moreover, it is successfully used for the functionalization of several structurally complex molecules demonstrating the method's potential utility for medicinal chemistry applications. Mechanistic studies revealed that C(sp)─N bond formation is mediated by a nitrogen-centered radical intermediate, which is generated via a sequence involving deprotonation and single-electron oxidation.
烯丙基酰胺部分在天然产物中普遍存在，并且是药物和农用化学品中的优势结构。此外，由于烯丙基酰胺可以转化为一系列高价值的基团，它们已被广泛应用于有机合成中。然而，开发用于烯烃分子间烯丙基酰胺化反应的催化体系，尤其是支链α-烯烃的分子间烯丙基酰胺化反应，已被证明具有挑战性。在此，报道了一种仿生协同催化方法，该方法结合了光氧化还原、钴和布朗斯特碱催化，用于从不使用氧化剂的支链α-烯烃和简单酰亚胺合成取代的烯丙基酰胺。这种低成本、操作简单的方法具有广泛的底物范围和优异的官能团兼容性。此外，它成功地用于几种结构复杂分子的官能团化反应，证明了该方法在药物化学应用中的潜在效用。机理研究表明，C(sp)─N键的形成由以氮为中心的自由基中间体介导，该中间体通过涉及去质子化和单电子氧化的序列生成。
