Theoretical study of 1,6-anhydrosugar formation from phenyl D-glucosides under basic condition: reasons for higher...

Degradation of anomeric phenyl d-glucosides to levoglucosan under basic condition is theoretically studied. MP4(SDQ)//DFT(B3LYP)-computational results indicate that the degradation of phenyl α-glucoside (R(α)) occurs via the S(N)icB mechanism. In this mechanism, the oxyanion at the C6, which is formed through deprotonation of the OH group, directly attacks the anomeric carbon. On the other hand, the degradation of phenyl β-glucoside (R(β)) occurs via the S(N)icB(2) mechanism. In this mechanism, the oxyanion at the C2 attacks the anomeric carbon in a nucleophilic manner to afford 1,2-anhydride intermediate and then the oxyanion at the C6 attacks the anomeric carbon to afford levoglucosan. The activation barrier is much lower in the reaction of R(β) (ΔG(0++) = 25.6 kcal/mol and E(a) = 26.5 kcal/mol) than in the reaction of R(α) (ΔG(0++) = 38.1 kcal/mol and E(a) = 37.2 kcal/mol), which is consistent with the experimental observation that β-glucoside is generally much more reactive than the corresponding α-glucoside. The lower activation barrier of the reaction of R(β) arises from the stereoelectronic effect, which is induced by the charge transfer from the ring oxygen to the anomeric carbon, and the staggered conformation around the C1-C2 bond. When the stereoelectronic effect is absent, the degradation needs larger activation energy; for instance, the degradation of phenyl 5a-carba-β-d-glucoside (R(Cβ)) occurs with large ΔG(0++) and E(a) values like those of α-glucosides, because the methylene group of R(Cβ) does not contribute to the stereoelectronic effect. Also, the conformation around the C1-C2 bond is staggered in the transition state of the R(β) reaction but eclipsed in that of the R(α) reaction, which also leads to the larger reactivity of R(β).