Kelgokmen Yilmaz, Zora Metin
Department of Chemistry , Middle East Technical University , 06800 Ankara , Turkey.
J Org Chem. 2018 Aug 3;83(15):8376-8389. doi: 10.1021/acs.joc.8b01029. Epub 2018 Jul 5.
An efficient, general, and unprecedented methodology for the synthesis of 2-methylene-2,3-dihydro-1,4-thiazepines from N-propargylic β-enaminones is described. Initially, N-propargylic β-enaminones were thionated with Lawesson's reagent in good to high yields, and then the resulting N-propargylic β-enaminothiones were subjected to electrophilic cyclization. When treated with zinc chloride in refluxing chloroform, N-propargylic β-enaminothiones underwent electrophilic cyclization to yield 2-methylene-2,3-dihydro-1,4-thiazepines in good to high yields. A general trend was observed for all N-propargylic β-enaminothiones, and the cyclization proceeded with high efficiency and large functional group tolerance. This process is also applicable to the cyclization of internal alkyne-tethered N-propargylic β-enaminothiones. This operationally simple and facile method may represent a very rapid entry to a library of functionalized 1,4-thiazepines in the area of pharmaceuticals.
描述了一种从N-炔丙基β-烯胺酮合成2-亚甲基-2,3-二氢-1,4-硫氮杂䓬的高效、通用且前所未有的方法。首先，用劳森试剂对N-炔丙基β-烯胺酮进行硫代反应，产率良好至高。然后，将所得的N-炔丙基β-烯胺硫酮进行亲电环化反应。当在回流的氯仿中用氯化锌处理时，N-炔丙基β-烯胺硫酮发生亲电环化反应，以良好至高的产率生成2-亚甲基-2,3-二氢-1,4-硫氮杂䓬。观察到所有N-炔丙基β-烯胺硫酮都有一个普遍趋势，环化反应高效进行且对官能团耐受性大。该过程也适用于内部炔烃连接的N-炔丙基β-烯胺硫酮的环化反应。这种操作简单且简便的方法可能代表了在药物领域快速构建功能化1,4-硫氮杂䓬库的一种途径。
