A Fukui function overlap method for predicting reactivity in sterically complex systems

摘要

A tormahsm IS given for predicting reactivity of complex systems by combining electronic calculations with forcefield calculations within a transition state theory framework. The 1 employed in combination with the Fukui function to produce a simulation method capab ensemble sampling needed to examine sterically complex systems. An important linkage reactivity information and energetic quantities is provided by introduction of the Fukui integral. This spatial overlap integral measUres the coincidence of electron donating regii nucleophile with electron accepting regions on the corresponding electrophilic reactant. ~ that configurations with high values of this overlap integral tend to have lowerdensity-ft theory energies. Thus, Fukui functions calculated once on single isolated reactants can be quickly estimate the reactivity of configurations generated using conventional forcefie simulations. The correlation between energies and high overlap integrals can also be used to initia[ guess configurations for transition state searches. However, in the present impleml real transition states are not accessible because intramolecular geometry relaxation is not The proposed method is tested on electrophilic aromatic alkylation reactions. Simulatiol successfully reproduce experimental substituent effects in a series of variously sui aromatics. Especially encouraging is the ability of the simulations to predict steric effecl reaction of toluene with a series of electrophiles of varying bulkiness. Further appl previously inaccessible to simulation, are expected in systems where steric effects playa d role in determining reaction selectivity.