A Novel Mechanism of Glycoside Anomerization
Berven, L.A., David Dolphin, and Withers, S.G.
J. Am. Chem. Soc.
The mechanism of carbonate-catalyzed anomerization of peracetylated 2,4-dinitrophenyl β-D-glucopyranoside in Me2SO was investigated using a variety of techniques. A mechanism involving proton abstraction at C(1) is disproved by the absence of proton exchange at that center and the measurement of a secondary deuterium isotope effect for the 1-deuterio substrate. A mechanism involving phenolate departure and recombination is rendered unlikely on the basis firstly of remote substituent effects on the reaction rate and secondly the absence of any exchange of the Ph moiety with added phenolate. A mechanism involving nucleophilic aromatic substitution initiated by attack of the dimethylsulfinyl anion and generating a glucosyl oxyanion intermediate that anomerizes and recombines with the reactive aryl intermediate is consistent with these observations. This mechanism is further supported by the observation of a purple Meisenheimer complex intermediate and by the exchange observed between substrate containing a labeled sugar moiety and added unlabeled 2,3,4,6-tetra-O-acetylglucose.