Diversification of Nucleophile-Intercepted Beckmann Fragmentation (NuBFr) Products and Related DFT Studies
Diversification of Nucleophile-Intercepted Beckmann Fragmentation (NuBFr) Products and Related DFT Studies
复制标题
亲核试剂截获的贝克曼断裂 (NuBFr) 产品的多样化及相关 DFT 研究
DOI：
10.1021/acs.joc.0c01486
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Wu, Jimmy
中科院分区：
文献类型：
--
作者：
Lowder, Leah;Zhao, Fengyue;Vaughan, Mathes M.;Houk, K. N.;Liu, Fang;Wu, Jimmy
亲核截留的Beckmann裂解(NuBFr)具有广泛应用于合成吲哚类生物碱类天然产物的潜力。然而，该反应没有被广泛采用，部分原因是与合适的启动子-尿素剂的可用性相关的限制。我们设计了一种立体专一性的Ag(I)促进反应，用于使NuBFr产物功能化，从而得到可能在合成和药物化学中有用的物质的新成分。与不受阻碍的胺类亲核试剂一起，生成结构独特的[2.2.2]-双环胺。我们还首次公开了详细的密度泛函理论研究，这些研究揭示了NuBFr和Ag促进的取代反应的机理，该反应支持一个不寻常的氮杂环丙烷离子作为关键中间体。
The nucleophile-intercepted Beckmann fragmentation (NuBFr) has the potential to be broadly applicable to the synthesis of indoline alkaloid-based natural products. However, the reaction has not been widely adopted, in part, because of limitations associated with the availability of appropriate promoter–Nureagents. We have devised a stereospecific Ag(I)-promoted reaction for functionalizing NuBFr products to give novel compositions of matter that may be useful in synthesis and medicinal chemistry. With unhindered amine nucleophiles, structurally unique [2.2.2]-bicycloamidines are generated. We also disclose for the first time detailed density functional theory studies, which shed light on the mechanism of the NuBFr and Ag-promoted substitution reaction that supports an unusual aziridinium ion as a key intermediate.