Synthesis of cis-thiiranes as diastereoselective access to epoxide congeners via 4 pi-electrocyclization of thiocarbonyl ylides

Abstract

Thiirane, the sulfur congener of oxirane, has been hard to access in a stereodefined form. Here, the authors accomplished a highly stereoselective synthesis of cis-diarylthiiranes through the stereospecific sulfurization of E,E-aldazine N-oxides. Organochalcogen heterocycles are ubiquitously present and widely utilized in various fields. Among them, oxirane has been extensively studied, and all of the stereoisomeric forms are readily available. In contrast, synthetic studies on thiirane were rarely reported, and thus the useful sulfur-congener of oxirane has been difficult to access in a stereodefined form. In this research, a general stereoselective synthesis of cis-thiiranes is accomplished by taking advantage of stereospecific electrocyclization of trans-thiocarbonyl ylides, which are generated in situ from readily available E,E-aldazine N-oxides upon treatment with Lawesson's reagent. This newly developed practical method provides a variety of cis-1,2-diarylthiiranes as essentially single diastereomers in high yields under mild reaction conditions. The intermediacy of trans-thiocarbonyl yilde is confirmed by mechanistic experiments, and the excellent stereocontrol is rationalized by DFT calculation.