A molecular electron density theory study of the mechanism, chemo- and stereoselectivity of the epoxidation reaction of R-carvone with peracetic acid

Abstract

The epoxidation reaction of R-carvone 8 with peracetic acid 9 has been studied within the molecular electron density theory at the B3LYP/6-311(d,p) computational level. The chemo- and stereoisomeric reaction paths involving the two C-C double bonds of R-carvone 8 have been studied. DFT calculations account for the high chemoselectivity involving the C-C double bond of the isopropenyl group and the low diastereoselectivity, in complete agreement with the experimental outcomes. The Baeyer-Villiger reaction involving the carbonyl group of R-carvone 8 has also been analysed. A bonding evolution theory analysis of the epoxidation reaction shows the complexity of the bonding changes taking place along this reaction. Formation of the oxirane ring takes place asynchronously at the end of the reaction by attack of anionic oxygen on the two carbons of the isopropenyl C-C double bond.

Scheme 1. Epoxidation reactions of alkenes mediated by peracids.

Scheme 2. Epoxidation of carene 1 with perfomic acid 2.

Scheme 3. Epoxidation of micheliolide 5 with m-CPBA 6.

Scheme 4. Reactions of R-carvone 8 with peracetic acid 9 studied by Murphy.

Scheme 5. Competitive reaction paths associated to the epoxidation reaction of R-carvone 8 with peracetic acid 9. B3LYP/6-311G(d,p) relative enthalpies and Gibbs free energies, in parentheses, at 25 °C in DCM, are given in kcal mol⁻¹.

Fig. 1. Three-dimensional (3D) representations of the Mulliken atomic spin densities of the radical cation of R-carvone 8 and the radical anion of peracetic acid 9 together with the nucleophilic P_k⁻ Parr functions for 8, and the electrophilic P_k⁺ Parr functions for 9.

Scheme 6. BV reaction of R-carvone 8 with peracetic acid 9. B3LYP/6-311G(d,p) relative enthalpies and Gibbs free energies, in parentheses, at 25 °C in DCM, are given in kcal mol⁻¹.

Fig. 2. B3LYP/6-311G(d,p) geometries in DCM of the TSs involved in the epoxidation reaction of R-carvone 8 with peracetic acid 9. Distances are given in Angstroms.

Fig. 3. B3LYP/6-311G(d,p) geometries in DCM of the TSs involved in the BV reaction of R-carvone 8 with peracetic acid 9. Distances are given in Angstroms.

Scheme 7. Competitive reaction paths associated with the epoxidation reaction of α,β-conjugated ketone 10 with peracetic acid 9. B3LYP/6-311G(d,p) relative enthalpies and Gibbs free energies, in parentheses, in at 25 °C DCM, are given in kcal mol⁻¹.

Fig. 4. B3LYP/6-311G(d,p) geometries in DCM of the TSs involved in the epoxidation reaction of α,β-conjugated ketone 10 with peracetic acid 9. Distances are given in Angstroms.

Fig. 5. Gibbs free energy profiles, ΔG in kcal mol⁻¹, for the competitive reaction paths associated with the reaction of R-carvone 8 with peracetic acid 9, computed at 25 °C in DCM. (A) Reaction of R-carvone 8 with 1 equivalent of peracetic acid 9 in blue; (B) BV reaction of R-carvone 8 with peracetic acid 9; and reaction of epoxide 10 with 1 equivalent of peracetic acid 9 in green. The stationary points associated with the chemo- regio- and stereoisomeric reaction paths are given in grey.

Fig. 6. B3LYP/6-311G(d,p) ELF localisation domains of the structures S12, S13, S15 and S14 involved in the formation of the two oxiranic C–O single bonds along the most favourable reaction path associated with the monoepoxidation of R-carvone 8 with peracetic acid 9, represented at an isosurface value of ELF = 0.75.