Synthesis of 1,4-Thiazepines


Kelgokmen Y. , Zora M.

JOURNAL OF ORGANIC CHEMISTRY, vol.83, pp.8376-8389, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 83
  • Publication Date: 2018
  • Doi Number: 10.1021/acs.joc.8b01029
  • Title of Journal : JOURNAL OF ORGANIC CHEMISTRY
  • Page Numbers: pp.8376-8389

Abstract

An efficient, general, and unprecedented methodology for the synthesis of 2-methylene-2,3-dihydro-1,4-thiazepines from N-propargylic beta-enaminones is described. Initially, N-propargylic beta-enaminones were thionated with Lawesson's reagent in good to high yields, and then the resulting N-propargylic beta-enaminothiones were subjected to electrophilic cyclization. When treated with zinc chloride in refluxing chloroform, Npropargylic beta-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 beta-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 beta-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.