DFT-Based Regioselectivity Criteria for Cycloaddition Reactions

Local softness and the local HSAB principle, as defined within DFT, have attracted considerable interest since they can be used to predict regioselectivity from the electronic properties of the isolated reactants only. This approach proved successful in predicting the regioselectivity of several cycloaddition reactions. However, the employed prediction criteria are only loosely derived from the local HSAB. In this paper the atomic grand potential variation is introduced as a quantitative measure of the stabilization induced by bond-forming interactions. Using this as a uniform figure of merit, regioselectivity criteria are obtained for two widespread reaction classes. By expressing the criteria in terms of the local softnesses, it is shown when they agree with the criteria used in the literature, thus ensuring the validity of this approach to regioselectivity prediction on a rigorous theoretical basis.