Synthesis of Highly Functionalized 1,3-Oxathioles via an Unusual [4+1] Annulation of α,α'-Dioxothione with 1,2-Diaza-1,3-dienes

Abstract

The present method provides highly functionalized 1,3-oxathioles through an unusual base-promoted [4+1] annulation between α,α'-dioxothione, generated in situ from a phthalimide precursor, and 1,2-diaza-1,3-dienes. An intriguing scaffold comprised of spiro-fused oxathiole and pyrazolone components was also obtained in moderate yield.

Formal [4+1] Annulation Reactions in the Synthesis of Carbocyclic and Heterocyclic Systems

“…Recently, the Glorius group developed an interesting sequential N -heterocyclic carbene-catalyzed Stetter reaction of the enal-derived acyl anion to the in situ-formed 1,2-diaza-1,3-dienes and the TsOH-mediated intramolecular cyclization, which furnished useful formal [4+1] annulation products, the styryl pyrazoles, in moderate yields with a high functional group tolerance . In addition to serving as the four-atom fragment, the highly active 1,2-diaza-1,3-dienes with electron-withdrawing groups can serve as the C1 fragment to participate in an unusual formal [4+1] annulation with α,α′-dioxothione, which is derived in situ from phthalimide, to provide an efficient entry to the α,α′-disubstituted oxathioles with reasonable yields …”

“…225 In addition to serving as the four-atom fragment, the highly active 1,2-diaza-1,3-dienes with electron-withdrawing groups can serve as the C1 fragment to participate in an unusual formal [4+1] annulation with α,α′-dioxothione, which is derived in situ from phthalimide, to provide an efficient entry to the α,α′-disubstituted oxathioles with reasonable yields. 226 The indole moiety is a privileged heterocyclic scaffold that is common to a large family of biologically active natural products and pharmaceuticals. 227 Therefore, the search for more practical and efficient processes for the synthesis of the indole moiety remains a research area of considerable interest.…”