Density functional studies on the Nazarov reaction involving cyclic systems.

Density functional theory (DFT) has been used to define the energy profiles of the Nazarov reaction involving cyclic systems. The calculations were carried out at the B3LYP/6-311G** level of theory and the solvent (dichloromethane) contribution was estimated by using the recently developed SM5.43R solvation model. DFT calculations were first carried out to determine the energy profiles associated with the electrocyclization reactions of 3-hydroxy- and 3-ethoxypentadienyl cations in which one of the double bonds is embedded in O-heterocyclic and carbocyclic systems. In particular, the effects on the reaction rate of modifications to the substrate, as well as the presence of the heteroatom in the cycle, have been investigated. The torquoselectivity of the electrocyclization reaction was then explored with substituted O-heterocycles to understand the factors that control the stereochemical outcome of the process that preferentially provides 2,5-trans-disubstituted products. These DFT-based results rationally explain most of the experimental observations related to the Nazarov reaction of the substrates herein investigated and could be useful in the rational interpretation, and likely in the prediction, of the outcome of Nazarov reactions involving other cyclic systems.