Synthesis of Functionalized Allylic Sulfoxides and Their Use in the Construction of 2,3,4-Trisubstituted Furans via a [3 + 2] Annulation

A route to 2,3,4-trisubstituted furan derivatives based on a [3 + 2] annulation of functionalized allylic sulfoxides and aldehydes is described. In this strategy, the precursors of allylic sulfoxides 4, allylic sulfides 3, were synthesized via a thiomethylation reaction of an α-EWG ketene-S,S-acetal 1 (EWG: electron-withdrawing group), formaldehyde, and a thiol 2 in high to excellent yields. Allylic sulfoxides 4 were prepared by a highly regioselective oxidation of 3, using m-chloroperoxybenzoic acid as oxidant. Thus, starting from these readily available sulfoxides 4, 2-alkylthio-3,4-disubstituted furans 6 were efficiently constructed via the [3 + 2] annulation reaction of 4 with aldehydes 5 under mild conditions. Further replacement of the 2-alkylthio group of 6 with amines led to the formation of 2-amino-3,4-disubstituted furan derivatives 7.