Liu Jun, Liu Hainai, Zhou Meijuan, Yu Xiaolong, Zhao Gang, Wang Hongyu
Key Laboratory of Marine Drugs, Ministry of Education, Molecular Synthesis Center, and School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, P. R. China.
Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, 266237, P. R. China.
Nat Commun. 2025 Jul 1;16(1):5488. doi: 10.1038/s41467-025-60660-1.
The catalytic asymmetric dearomatization of naphthalenes is a pivotal strategy for generating enantioenriched three-dimensional aliphatic polycycles from flat aromatic precursors. However, achieving such transformations involving electronically unbiased naphthalenes remains a long-standing challenge. Here, we describe a silver-mediated enantioselective aza-electrophilic dearomatization approach that couples readily accessible vinylnaphthalenes in conjunction with azodicarboxylates to afford chiral polyheterocycles via formal [4 + 2] cycloaddition reactions, yielding up to 99% yield and 99 : 1 e.r. Central to the method is the formation of an aziridinium intermediate that facilitates the subsequent dearomatization of naphthalenes. A 100 mmol-scale reaction and the divergent transformation of the products into enantioenriched aliphatic polycycles highlight their synthetic utility. Mechanistic experiments and DFT calculations offer insights into the reaction mechanism and the origin of the observed enantiocontrol outcome.
萘的催化不对称去芳构化是一种从平面芳香前体生成对映体富集的三维脂肪族多环化合物的关键策略。然而,实现涉及电子中性萘的此类转化仍然是一个长期存在的挑战。在此,我们描述了一种银介导的对映选择性氮杂亲电去芳构化方法,该方法将易于获得的乙烯基萘与偶氮二羧酸酯相结合,通过形式上的[4 + 2]环加成反应生成手性多杂环化合物,产率高达99%,对映体比例为99 : 1。该方法的核心是形成氮杂环丙烷鎓中间体,它促进了随后萘的去芳构化。100 mmol规模的反应以及产物向对映体富集的脂肪族多环化合物的多样化转化突出了它们的合成效用。机理实验和密度泛函理论计算为反应机理以及所观察到的对映体控制结果的起源提供了见解。