The calculated effects of substitution on intramolecular cyclization of 2,5-hexadienyl radicals

The effects of substituents on the rate of intramolecular cyclization of the 2,5-hexadienyl radicals have been investigated computationally with DFT theory, using the UB3LYP functional. Various substituents - CN, NO₂, CH₃, NH₂, and t-butyl - at various positions - C₁, C₅ and C₆ - were considered in the calculations. An electron-donating substituent on the C₁ position raises the radical SOMO energies to increase the interaction with the alkene LUMO, whereas an electron-withdrawing counterpart lowers the SOMO and increases the interaction with the alkene HOMO. Both interactions decrease the activation energies, by 0.9-10.2 kcal/mol, and increase the rate of reaction rate, from 3 to 2.7 × 10⁷ times. Similar results were obtained for the substituents at the C₆ position, and the activation energies for the intramolecular cyclization were decreased by 0.2-4.8 kcal/mol and the reaction rate increased from 2 to 2.8 × 10³ times. The substituent at the C₅ position favors the formation of a 6-endo product because of a steric effect. The effects of disubstituents at both C₁ and C₆ positions were also investigated; the results showed that the electron-withdrawing groups decrease most effectively the activation energies. The so-called captodative effect was also investigated.