The application of No Barrier Theory to the aldol addition reaction

Abstract

No Barrier Theory asserts that any reaction can be analyzed as the result of a set of simple processes, where simple is defined as one having a quadratic dependence of energy on some suitable progress variable. The idea leads to a simple qualitative way of thinking about relative rates of reactions and can be used quantitatively to calculate the free energy of activation for a reaction. This method has now been applied to the aldol addition reaction for a set of simple examples involving acetaldehyde, acetone, and acetophenone enolates, and formaldehyde, acetaldehyde, benzaldehyde, acetone, acetophenone, and trifluoroacetophenone as carbonyl compound undergoing addition. The calculated values are in good agreement with experimental values (11 cases, rmse = 1.68), and with additional values estimated by means of Marcus Theory.