Transition-State Structure for the Quintessential SN2 Reaction of a Carbohydrate: Reaction of α-Glucopyranosyl Fluoride with Azide Ion in Water

We report that the S(N)2 reaction of alpha-D-glucopyranosyl fluoride with azide ion proceeds through a loose (exploded) transition-state (TS) structure. We reached this conclusion by modeling the TS using a suite of five experimental kinetic isotope effects (KIEs) as constraints for the calculations. We also report that the anomeric C-13-KIE is not abnormally large (k(12)/k(13) = 1.024 +/- 0.006), a finding which is at variance with the previous literature value (Zhang et al. J. Am. Chem. Soc. 1994, 116, 7557).