Part Ⅰ: Study on Stereoselective Alkene Synthesis via 4π-Electrocyclization of Aldazines and Aldazine N-Oxides Part Ⅱ: Diastereoselective Synthesis of cis-Thiiranes via 4π-Electrocyclization of Thiocarbonyl Ylides

Abstract

Part I. Geometrically defined alkene is one the most important subunit in natural products and pharmaceuticals. We investigated stereoselective alkene synthesis via 4π-electrocyclization of aldazines or aldazine N-oxides with various additives. The HBD-catalyzed 4π-electrocyclization of aldazine N-oxide was examined using thiosquaramide, which provided trans-stilbene in a moderate yield. However, thiirane was serendipitously observed in the crude mixture, and the generation of thiirane could not be prevented in the presence of thiosquaramide. Other HBDs were inefficient in producing trans-stilbene. On the other hand, phosphonium salt, oxenium, Vilsmeier’s reagent, and ammoniumyl salt were employed to polarize aldazines or aldazine N-oxides, but all reactions were unsuccessful. The optimization of unusual loss of methylene unit during the cyclization of aliphatic aldazine was performed, but all attempts using Brønsted acid and base were unsuccessful. Part II. Synthetic studies on thiirane were rarely reported, and thus the useful sulfur-congener of oxirane has been difficult to access in a stereodefined form. 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. Subsequently, synthesis of other three-membered heterocycles containing group 15–16 elements were examined, and the use of Woolins' reagent successfully provided cis-selenirane. Diastereoselective access to trans-thiirane was performed under several conditions, and trans-thiirane was serendipitously obtained upon the treatment with silyl sulfides. LR-Mediated synthesis of thiirane was also expanded to skeletal editing of phthalazine N-oxide, but deoxygenation remained a major side reaction.