1 research outputs found
C2-Oxyanion Neighboring Group Participation: Transition State Structure for the Hydroxide-Promoted Hydrolysis of 4‑Nitrophenyl α‑d‑Mannopyranoside
The hydroxide-catalyzed
hydrolysis of aryl 1,2-<i>trans</i>-glycosides proceeds
through a mechanism involving neighboring group
participation by a C2-oxyanion and rate-limiting formation of a 1,2-anhydro
sugar (oxirane) intermediate. The transition state for the hydroxide-catalyzed
hydrolysis of 4-nitrophenyl α-d-mannopyranoside in
aqueous media has been studied by the use of multiple kinetic isotope
effect (KIE) measurements in conjunction with <i>ab initio</i> theoretical methods. The experimental KIEs are C1-<sup>2</sup>H
(1.112 ± 0.004), C2-<sup>2</sup>H (1.045 ± 0.005), anomeric
1-<sup>13</sup>C (1.026 ± 0.006), C2-<sup>13</sup>C (0.999 ±
0.005), leaving group oxygen 2-<sup>18</sup>O (1.040 ± 0.012),
and C2-<sup>18</sup>O (1.044 ± 0.006). The transition state for
the hydrolysis reaction was modeled computationally using the experimental
KIE values as constraints. Taken together, the reported kinetic isotope
effects and computational modeling are consistent with the reaction
mechanism involving rate-limiting formation of a transient oxirane
intermediate that opens in water to give α-d-mannopyranose.
The transition state has significant nucleophilic participation by
the C2-alkoxide, an essentially cleaved glycosidic bond, and a slight
shortening of the endocyclic C1–O5 bond. The TS is late, consistent
with the large, normal C2-<sup>18</sup>O isotope effect