Impact of Conjugation and Hyperconjugation on the Radical Stability of Allylic and Benzylic Systems: A Theoretical Study

Abstract

Resonantly stabilized radicals are some of the most investigated chemical species due to their preferential formation in a wide variety of chemical environments. Density functional theory and post-Hartree-Fock calculations were utilized to elucidate the chemical interactions that contribute to the stability of two ubiquitous, resonantly stabilized radicals, allyl and benzyl radicals. The relative stability of these radical species was quantified through bond dissociation energies and relative rotational energy barriers, with a difference of only 0.1 kcal/mol. To clarify and contextualize the energetic results, natural bond orbitals were used to evaluate the atomic spin density distribution in the given molecules. The benzyl radical was found to be ∼3 kcal/mol less stable than the allyl radical, which was attributed to the inability to efficiently delocalize the spin on a phenyl unit, starkly contrary to general chemistry knowledge. Increasing the degree of π-conjugation and hyperconjugation was shown to benefit allyl radicals to a greater degree than benzyl radicals, again due to more efficient radical delocalization in allyl radicals. This work highlights that more resonance structures do not always lead to a more stabilized radical species, and provides fundamental knowledge about how conjugation and hyperconjugation impact the stabilization of nonbonding electrons in these systems.

1,2-H Atom Rearrangements in Benzyloxyl Radicals

“…Once the reaction has proceeded to the product complex, the excess alpha spin is in three major positions, C1, O1, and Ph-R. Of these three, C1 has the largest amount of radical character with ∼54% of the excess alpha spin located on this center, with less significant amounts of alpha spin density, ∼13% and ∼35% on the oxygen and phenyl ring system, respectively. This shows that the phenyl ring does not equally share the unpaired spin with the benzylic carbon due to the presence of three resonance structures which is in agreement with our previous calculations . The degree of radical localization or delocalization in the RC, TS, and the PC of these atomic centers or fragments can change significantly upon the introduction of substituents.…”

“…Unrestricted DFT methods utilized in this work did not suffer from significant spin contamination, nevertheless, unrestricted post-HF and double hybrid methods were observed to be prone to spin contamination, making them an unsuitable choice for the system under study. We heed our previous calculations on benzyl radicals, with which we came to similar conclusions concerning unrestricted post-HF composite methods and spin contamination . The results of ROCBS-QB3 calculations on the three cases shown in Table did not significantly differ from our chosen method (superscript c, Table ), especially when comparing the Gibbs free energy barrier for two-water-assisted 1,2-H atom rearrangements.…”

“…We heed our previous calculations on benzyl radicals, with which we came to similar conclusions concerning unrestricted post-HF composite methods and spin contamination. 43 The results of ROCBS-QB3 calculations on the three cases shown in Table 1 did not significantly differ from our chosen method (superscript c, Table 1), especially when comparing the Gibbs free energy barrier for two-water-assisted 1,2-H atom rearrangements. Furthermore, calculations at the ROCBS-QB3 level for the unassisted case is surprisingly close to the activation barrier predictions by previous work, 21.1 kcal/mol for the one-waterassisted rearrangement contrasted to 21.9 kcal/mol in the unassisted case.…”

“…This shows that the phenyl ring does not equally share the unpaired spin with the benzylic carbon due to the presence of three resonance structures which is in agreement with our previous calculations. 43 The degree of radical localization or delocalization in the RC, TS, and the PC of these atomic centers or fragments can change significantly upon the introduction of substituents.…”

Spontaneous Stereoselective Oxidation of Crystalline Avermectin B1a to Its C-8a-(S)-Hydroperoxide

“…The proposed pathway for this transformation is shown in Figure . The key feature of this pathway is the stabilization of the formed radical by the close proximity of conjugated double bonds at C-8C-9 and C-10C-11 positions. , Such peroxidation reactions are rare in the literature, although they have been reported for example for ezlopitant, for which an isopropyl peroxide derivative forms upon storage …”