Computational Study of the Formation of α and β O-Unsaturated Glycosides via Ferrier Rearrangement

We studied the formation of new 2,3-unsaturated O-glycosides via Ferrier rearrangement using electronic structure calculations at the B3LYP/6-31g level. Using the Gibbs free energy variation, it was possible to indicate the formation of an intermediate stabilized by the anchimeric assistance at C3, which explains the preferred formation of the α-anomer. The calculations show that there is also the possibility of the formation of an anchimeric assistance intermediate at C4, which also favors the formation of the intermediate at C3. We analyzed the hypothesis of the repulsion of the aglycone with the acetoxy group at C6, and the results showed that there is less repulsion from the top of the oxonium ion, which corroborates the thermodynamic data. We propose a transition state starting from the C3 intermediate that explains the formation of the alpha anomer. The effect of the hyperconjugation present in the anomeric effect was studied using the NBO model, and according to the calculations compared to the literature, this factor did not prove to play a fundamental role in explaining the preferential formation of the α-anomer. Thus, the main factor favoring the preferential formation of the α-anomer is the spontaneous formation of the intermediate at C3, which prevents the formation of the β-anomer.