C2-hydroxyglycosylation with glycal donors. Probing the mechanism of sulfonium-mediated oxygen transfer to glycal enol ethers

Article abstract of DOI:10.1021/ja025639c

The C2-hydroxyglycosylation reaction employing the reagent combination of a diaryl sulfoxide and triflic anhydride offers a novel method for glycal assembly whereby a hydroxyl functionality is stereoselectively installed at the C2-position of a glycal donor with concomitant glycosylation of a nucleophilic acceptor. Mechanistic investigations into this reaction revealed a novel process for sulfonium-mediated oxidation of glycal enol ethers in which the sulfoxide oxygen atom is stereoselectively transferred to the C2-position of the glycal. ¹⁸O-labeling studies revealed that the S-to-C2 oxygen-transfer process involves initial formation of a C1-O linkage followed by O-migration to C2, leading to the generation of an intermediate glycosyl 1,2-anhydropyranoside that serves as an in situ glycosylating agent. These findings are consistent with the initial formation of a C2-sulfonium-C1-oxosulfonium pyranosyl species upon activation of the glycal donor with Aryl₂SO·Tf₂O.