Probing the mechanism of sulfoxide-catalyzed hemiacetal activation in dehydrative glycosylation.
The concept of sulfoxide-covalent catalysis has been established in the context of a versatile hemiacetal hydroxyl activation/substitution reaction for the formation of anomeric linkages. Mechanistic studies focused on the hemiacetal activation process show that this transformation proceeds in the presence of a sulfonic anhydride and an acid scavenger through the intermediacy of a glycosyl sulfonate species (10), which serves as a resting state prior to the addition of an external nucleophile and subsequent glycosidic bond formation. Successful determination of the proportion of (18)O incorporation in 10 as a function of its formation, via the technique of dynamic monitoring of (13)C-(16/18)O isotopic chemical shift perturbations, provides strong evidence that hemiacetal activation proceeds through initial nucleophilic addition of the hemiacetal hydroxyl to the S(IV)-center of putative sulfonium sulfonate 6. Further confirmation was obtained through the independent synthesis, structure verification, and (1)H NMR detection of glycosyl oxosulfonium 11 during the sulfoxide-catalyzed conversion of hemiacetal 3 to glycosyl sulfonate 10.
Boebel
Timothy A
TA
Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Gin
David Y
DY
D000080:Acetals / Q000737:chemistry*; D000812:Anhydrides / Q000737:chemistry; D002384:Catalysis; D006031:Glycosylation; D017665:Hydroxyl Radical / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D012451:Safrole / Q000031:analogs & derivatives* / Q000737:chemistry; D013451:Sulfonic Acids / Q000737:chemistry; D013452:Sulfonium Compounds / Q000737:chemistry; D013997:Time Factors
D000080:Acetals; D000812:Anhydrides; D013451:Sulfonic Acids; D013452:Sulfonium Compounds; D017665:Hydroxyl Radical; D012451:Safrole; C005746:sulfoxide