Computational insights into cycloadditions of thioisomuenchnones with acetylenes: how does sulfur escape from cycloadducts?

• Published in: Tetrahedron Vol. 72; no. 31; pp. 4665 - 4670
• Main Authors: de la Concepcion, Juan Garcia, Avalos, Martin, Babiano, Reyes, Cintas, Pedro, Jimenez, Jose L, Light, Mark E, Palacios, Juan C
• Format: Journal Article
• Language: English
• Published: 04.08.2016
• Subjects: Cycloaddition; Isocyanates; Mathematical analysis; Pathways; Spontaneous; Sulfur; Tetrahedrons; Thiophenes
• ISSN: 0040-4020
• DOI: 10.1016/j.tet.2016.06.041

The spontaneous loss of sulfur or isocyanate from transient 7-thia-2-azabicyclo[2.2.1]hept-5-en-3-ones, which are initially formed by 1,3-dipolar cycloadditions of thioisomuenchnones with acetylenic dipolarophiles, is the key step in the chemoselective syntheses of pyridin-2-ones or thiophenes. The way by which sulfur is released has been the subject of previous studies pointing to a concerted retro-cheletropic mechanism as a more favorable route than the alternative stepwise pathway. The latter however, is apparently prevalent for elimination of isocyanate. Working with a conformationally-restricted bicyclic thioisomuenchnone that undergoes facile cycloaddition with acetylenes, sulfur elimination has now been interrogated by experiment and theoretical calculations at the M06-2X and M11 methods in combination with the 6-311++G(d,p) basis set, which unveil rather a sigmatropic shift via the intermediacy of thiirane species. These results provide new vistas and synthetic opportunities in mesoionic cycloadditions.