Department of Chemistry , University of Minnesota-Twin Cities , 207 Pleasant St. SE , Minneapolis , Minnesota 55455 , United States.
J Am Chem Soc. 2018 Mar 7;140(9):3331-3338. doi: 10.1021/jacs.8b01330. Epub 2018 Feb 21.
An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported. Importantly, the need for a rigid tether in these reactions has been obviated. The ease-of-synthesis and viability of substrates bearing flexible backbones has permitted for diastereoselective variants as well. We demonstrated the utility of this methodology with the formation of pyrrolidones, piperidinones, isoindolinones, and sultams. Furthermore, subsequent transformation of these motifs into medicinally relevant molecules is also demonstrated. A double crossover C-labeling experiment is consistent with a fully intramolecular cyclization mechanism. Deuterium labeling experiments support a mechanism involving syn-addition across the alkene.
本文报道了一种通过非活化烯烃的分子内氨腈化反应来拓展方法学以形成多功能有机腈的方法。重要的是，这些反应中不再需要刚性连接基团。具有柔性骨架的底物易于合成且具有可行性，因此也可以实现非对映选择性变体。我们通过形成吡咯烷酮、哌啶酮、异吲哚啉酮和吗啉来证明该方法的实用性。此外，还证明了这些结构单元转化为具有医学相关性的分子的用途。双交叉 C 标记实验与完全分子内环化机制一致。氘标记实验支持涉及烯烃顺式加成的反应机制。
