Stereoselective Processes and Kinetic Control

The chemical reaction is kinetically controlled when its rate is determined by the energy of the transition state. When two reactions are competing, the faster is the one with a lower transition state energy. A practical consequence of this kinetic relation is the larger quantity of stereoisomer formed via the reaction with the lower transition state. To illustrate the control of enantioselectivity by the kinetic parameters, we use the relation of their Gibbs activation energies (Fig. 3.4). 

In this scheme the effect of the chiral catalyst on the transition state energy of the reaction of the prochiral substrate to enantiomers is presented. A stronger interaction of the chiral catalyst, presented as a scalene triangle (the chiral object in two-dimensional space ) with a prochiral substrate along the reaction coordinate, is indicated by sidewise interaction and on the route to the minor enantiomer by a point-wise interaction. In the absence of the chiral catalyst, the transition state energies will be equal on the route to either enantiomer resulting in the racemate. 

The ratio between two enantiomers is expressed as the enantiomeric excess (e.e. %) by a simple equation  

As already stated, the direction of enantioselectivity is diflhcult to anticipate. The main reason resides in the subtle difference between structures of the two transition 

The enantiomeric excess is exponentially correlated with AAG and it is worth illustrating the practical consequence of this exponential correlation. Thus, ca. 10 % e.e is available at the AAG of ca. 1.5 kJ/mol, ca. 70 % e.e., when the difference in TS energies is above ca. 5 kJ/mol and approaches 100 % e.e. at the AAG of ca. 8-9 kJ/mol. We can understand how small this energy difference is by comparison with the energy barrier for the rotation around the C-C bond in ethane of ca. 8 kJ/mol—this process is defined as free rotation  

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