Shi Shao-Qing, Cui Chen-Chang, Xu Lin-Lin, Zhang Jin-Peng, Hao Wen-Juan, Wang Jianyi, Jiang Bo
School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou, 221116, China.
Key Laboratory of Human Genetics and Environmental Medicine, College of Public Health, Xuzhou Medical University, Xuzhou, 221004, China.
Nat Commun. 2024 Oct 1;15(1):8474. doi: 10.1038/s41467-024-52823-3.
Inherently chiral medium-ring derivatives have important applications in many research fields, such as materials science, molecular recognition, and asymmetric catalysis. However, the enantioselective assembly of these molecules, especially by organocatalytic strategies, remains a formidable challenge, and few methods are available. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) formal high-order (5 + 3) annulation of 1-(2-indolyl)naphthalen-2-ols with ynals. In the presence of an NHC pre-catalyst, base, Lewis acid and oxidant, this protocol enables the catalytic formation of C-C and C-O bonds, providing practical and facile access to an array of inherently chiral saddle-shaped eight-membered lactones featuring an oxocin-2-one scaffold with structural diversity in good efficiency and excellent enantiocontrol. Moreover, the scale-up preparation and representative late-stage transformations of the eight-membered lactones further demonstrate the application potential of this synthetic technology.
具有固有手性的中环衍生物在材料科学、分子识别和不对称催化等许多研究领域有着重要应用。然而，这些分子的对映选择性组装，尤其是通过有机催化策略进行的组装，仍然是一项艰巨的挑战，可用的方法很少。在此，我们报道了N-杂环卡宾（NHC）催化的1-(2-吲哚基)萘-2-醇与烯醛的对映选择性形式高阶（5 + 3）环化反应。在NHC预催化剂、碱、路易斯酸和氧化剂存在下，该反应能够催化形成C-C键和C-O键，以高效和出色的对映选择性提供了一种实用且简便的方法来制备一系列具有固有手性的鞍形八元内酯，这些内酯具有结构多样的氧杂环辛-2-酮骨架。此外，八元内酯的放大制备和代表性的后期转化进一步证明了这种合成技术的应用潜力。
