3+3] Annulation of Diazoenals and α-Mercapto Ketones via Protic Sulfonium Ylides: Direct Synthesis of 2H-Thiopyrans, Innovative Progenitors for Unstudied 2H-Thiopyran-2-ones and 4H-Thiopyran-4-ones.

Abstract

Herein, we report a new Rh(II)/Sc(III)-catalyzed [3+3] annulation between diazoenals and α-mercapto ketones for the direct synthesis of 4-formyl-2H-thiopyrans. The reaction proceeds via protic sulfonium ylides derived from highly electrophilic Rh-enalcarbenoids, followed by regioselective intramolecular aldol condensation. Further studies revealed that 4-formyl-2H-thiopyrans are novel precursors for unstudied 2H-thiopyran-2-ones and 4H-thiopyran-4-ones. The 4H-thiopyran-4-ones were obtained via a novel O2/Et3N-mediated oxidative deformylation. This methodology was applied to the short synthesis of structurally complex pyrimidine-fused 2H-thiopyran via cascade Schmidt, Ritter, and intramolecular cyclization reactions.