C2-Oxyanion Neighboring Group Participation: Transition State Structure for the Hydroxide-Promoted Hydrolysis of 4-Nitrophenyl alpha-D-Mannopyranoside

Abstract

The hydroxide-catalyzed hydrolysis of aryl 1,2-trans-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 ab initio theoretical methods. The experimental KIEs are C1-2H (1.112 ± 0.004), C2-2H (1.045 ± 0.005), anomeric 1-13C (1.026 ± 0.006), C2-13C (0.999 ± 0.005), leaving group oxygen 2-18O (1.040 ± 0.012), and C2-18O (1.044 ± 0.006). The transition state for t..