REACTIONS OF ANIONIC NUCLEOPHILES WITH ALPHA-D-GLUCOPYRANOSYL FLUORIDE IN AQUEOUS-SOLUTION THROUGH A CONCERTED, A(N)D(N) (S(N)2) MECHANISM

The first-order rate constants for the disappearance of alpha-D-glucopyranosyl fluoride in the presence of anionic nucleophiles show a linear dependence on the concentration of the nucleophile in water at 30.0-degrees-C and ionic strength 2.0 M, maintained with KCl. The products from the reactions with azide and acetate anions, identified by H-1 NMR, show complete inversion of stereochemistry. These results provide evidence for a concerted bimolecular S(N)2 (or A(N)D(N)) reaction of anionic nucleophiles at the anomeric carbon atom of alpha-D-glucosyl fluoride. The second-order rate constants for the nucleophiles follow the Swain-Scott correlation with a slope of s = 0.18, indicating a small sensitivity of the displacement reaction to the nature of the nucleophile. No reaction is observed with uncharged amine nucleophiles, which do not provide electrostatic stabilization to the carbocation-like transition state for substitution. The solvolysis of alpha-D-glucosyl fluoride in mixtures of H2O, EtOH, and CF3CH2OH, and in H2O and MeOH, has a high selectivity for reaction with water. The lifetime of the glucosyl cation is probably too short to allow diffusion, so that this suggests that the rate of formation of the unstable glucosyl oxocarbenium ion is increased in the presence of water molecules that stabilize the cationic transition state. These results are consistent with the conclusion that the glucosyl oxocarbenium ion exists for a short time in water but has no significant lifetime when it is in contact with a strong nucleophile, so that the reaction mechanism is forced to become concerted. They also suggest that glycosides may undergo concerted displacement reactions by anionic groups at the active sites of enzymes.