A novel partitioning scheme for the application of the distortion/interaction - activation strain model to intramolecular reactions

The distortion/interaction or activation strain model, developed by Houk and Bickelhaupt, relates chemical reactivity to the reagents deformations and reciprocal electronic influences. However, in its original formulation, it struggles to elucidate the mechanistic insights of intramolecular reactions, those unimolecular processes in which two parts of a molecule, the reaction centers, linked by a connector, are brought together to yield a different chemical species. Here we present a modification of the distortion/interaction procedure for its application on intramolecular reactions. This new procedure allows the calculation of the influence exerted by the connector over the reaction pathway in an indirect way, from the distortions of the two reaction centers and their interaction energy. This procedure does not include additional, undesired interactions and offers the possibility of calculating very large connectors in a computationally inexpensive way. We applied this methodology in the normal electron-demand Diels-Alder reaction of 1,3,8-nonatriene derivatives, with different functionalizations and connector lengths. In-depth analysis of the IRC showed that the reaction pathway can be subdivided in three main regions, what we called the oncoming, conversion and relaxation phases, each of them characterized by different evolutions of the distortion and interaction energies, and with clear geometry changes. We suggest that this new formulation can provide additional information for intramolecular reactions, especially to those processes for which the connector is said to play a crucial role in the observed reaction rates.Funding Agencies|Ministerio de Ciencia e Innovacion of SpainSpanish Government [PGC2018-094644-B-C21]