Curtin energy barrier

The theory was tested in simple tetrahydropyranyl acetal systems, which exist in the axial conformation [92], but can be constrained to adopt the equatorial conformation [93] by building in appropriate structural features. It was found, for example, that the equatorial isomers of the oxadecalin acetals [94] are actually more reactive than the axial compounds [95], although only the latter have a lone pair on the donor ring oxygen antiperiplanar to the C-OAr bond (Kirby, 1984, 1987). This and other similar observations do not disprove the theory of stereoelectronic control because any stereoelectronic barrier can be got round if there is sufficient conformational flexibility. In other words, these are Curtin-Hammett systems, with free energy barriers between conformations much smaller than... 

Curtin-Hammett Principle. The idea that reactive conformer in a Kinetically-Controlled Reaction is not necessarily the lowest-energy conformer. The rationale is that the energy barriers separating conformers are typically much smaller than barriers to chemical reaction, and that any reactive conformers will be replenished. 

According to the Curtin-Hammett principle, the ratio of the distribution between two products depends only on their rates offormation (Figure 9.1). If the two products are conformers, the energy barrier between the two states tends to be small and the ratio between the two products is an indicator of the free enthalpies of the transition states. The Curtin-Hammett principle can be applied when two conformations, tautomers, or isomers of a starting material are in rapid equilibrium compared to the rate of a reaction. In this case, the product ratio provides no information about which conformation, tautomer, or isomer was present in the starting material. 

This interpretation could be complicated by the conformational equilibrium Hs/ H4 which gives to 3,4,6-tri-O-acetyl-D-glucal 10, for instance, a 40% contribution of the (d) conformer with all its substituents axial. A vinylogous anomeric effect could explain this unusual distribution [28]. However, assuming a lower energy barrier for this conformer equiUbrium in comparison to the subsequent reactions, the Curtin-Hammett principle can be apphed and the product ratio will be governed by the activation energy of the electrophilic addition, rather than by the actual concentration of conformers. 

In both of these situations, the reaction actually observed does not occur from the lowest-energy conformation of the reactants. That this need not be the case is a direct consequence the Curtin-Hammett principled This recognizes that some higher-energy reactive conformation , will be in rapid equilibrium with the global minimum and, assuming that any barriers which separate these conformations are much smaller than the barrier to reaction, will be replenished throughout the reaction. 

FIGURE 7.8 Potential curves for Curtin-Hammett/Winstein-Holness kinetics limiting cases (a) LI limit where the free energy difference between barriers dictates product distribution and (b) L2 limit where the free energy difference between equilibrating intermediates dictates the product distribution. 

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