Conversely, for the formation of the glucosyl dioxanium ion expulsion of the anomeric triflate presents the highest overall barrier on the potential energy surface. To understand the differences in barrier height for TSIII man/glu, we examined the structures surrounding the transition states: RCII, TSIII, PC and P. From the computed reaction profiles the relative Gibbs free energy RCII-glu is sightly higher than of RCII-man, while the energy of PC-man and PC-glu are very different. Thus, the difference in energy between TSIII-man and TSIII-glu develops in going towards the transition state. When the conformations of RCII, TSIII, PC and P are compared we note that the conformations of the glucose and mannose stationary points are virtually identical (i.e. B2,5-like) in this part of the reaction profiles, and that during the transitioning between these points only minimal conformational changes occur. As the energy difference does not originate from deviating ring conformations we compared the interactions of the ring substituents in the gluco and manno systems. In the B2,5 conformers, flagpole interactions of the axial C-2 and C-5 substituents are a major contributor of the ring strain. For the mannoside this represents an interaction between two protons, while the in glucoside it is a more severe oxygenhydrogen interaction. In going to TSIII the C-2 and C-5 substituents are brought closer together (See Figure ), to forge the bond between C-1 and the benzoyl carbonyl, increasing the flagpole interactions, leading to a significantly higher energy penalty for the glucoside than for the mannoside because. In addition, the triflate leaving group in the mannoside can be positioned in a more favorable orientation, allowing interaction between the triflate and the H-2 and H-5 protons. For the glucoside this orientation would lead to unfavorable electrostatic repulsion between the pseudo axial triflate and the C-2 oxygen substituent. Instead, the glucose triflate avoids this steric clash through a different orriention, in which there is less interaction with the O-2. As a result the transition state for the glucose system is significantly later with the triflate further away from the positive charge, leading to an increase in energy. To corroborate the effect of the C-2 substituent, the reaction profile of the C-2-deoxy system was generated in a similar manner. The potential energy surface for the formation of the 1,3-dioxanium ion from the 2deoxy-3-O-benzoyl-4,6-O-ethylidene glucosyl triflate was indeed shown to be very similar, in terms of both structure and energy, to that of its mannosyl counterpart (Supplementary figure ).