Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Rd, Sanmin District, Kaohsiung City, 807, Taiwan.
Department of Medical Research, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Sanmin District, Kaohsiung City, 807, Taiwan.
Nat Commun. 2022 Apr 29;13(1):2345. doi: 10.1038/s41467-022-30001-7.
The radical chemistry of ynamides has recently drawn the attention of synthetic organic chemists to the construction of various N-heterocyclic compounds. Nevertheless, the ynamide-radical chemistry remains a long-standing challenge for chemists due to its high reactivity, undesirable byproducts, severe inherent regio- and chemoselective problems. Importantly, the ynamide C(sp)-N bond fission remains an unsolved challenge. In this paper, we observe Photoinduced radical trigger regio- and chemoselective ynamide bond fission, structural reshuffling and functionalization of 2-alkynyl-ynamides to prepare synthetically inaccessible/challenging chalcogen-substituted indole derivatives with excellent step/atom economy. The key breakthroughs of this work includes, ynamide bond cleavage, divergent radical precursors, broad scope, easy to handle, larger-scale reactions, generation of multiple bonds (N-C(sp), C(sp)-C(sp), C(sp)-SOR/C-SR, and C-I/C-Se/C-H) in a few minutes without photocatalysts, metals, oxidants, additives. Control experiments and C-labeling experiments supporting the conclusion that sulfone radicals contribute to ynamide structural reshuffling processes via a radical pathway.
炔酰胺的自由基化学最近引起了合成有机化学家的关注，使其能够构建各种杂环化合物。然而，由于炔酰胺-自由基的高反应性、不理想的副产物以及固有区域和化学选择性问题严重，其化学仍然是化学家面临的一个长期挑战。重要的是，炔酰胺 C(sp)-N 键的断裂仍然是一个未解决的挑战。在本文中，我们观察到光诱导自由基引发的区域和化学选择性炔酰胺键断裂、2-炔基炔酰胺的结构重排和官能化，以制备具有优异的步骤/原子经济性的难以合成/具有挑战性的含硫、硒和碘取代吲哚衍生物。这项工作的关键突破包括炔酰胺键的断裂、不同的自由基前体、广泛的适用范围、易于操作、更大规模的反应、在几分钟内通过无光照催化剂、金属、氧化剂、添加剂生成多个键（N-C(sp)、C(sp)-C(sp)、C(sp)-SOR/C-SR 和 C-I/C-Se/C-H）。控制实验和 C 标记实验支持了这样的结论，即砜自由基通过自由基途径参与炔酰胺的结构重排过程。
