Fission of the epoxide ring in 6,8-dioxabicyclo[5.1.0]octa-2,4-diene (epoxyoxepin) and in 8-oxabicyclo[5.1.0]octa-2,4-diene: An ab initio molecular orbital study

As part of our investigation of the role of 6,8-dioxabicyclo[5.1.0]octa-2,4-diene (6,8-dioxaBCOD; epoxyoxepin) as the precursor of muconaldehyde in the metabolic oxidation of benzene, we have carried out ab initio molecular orbital calculations on the fission of the three-membered (epoxide) ring in 6,8-dioxaBCOD and 8-oxaBCOD in which cyclic enol structures are formed. Electronic energies have been calculated at the MP2/6-31G* (frozen core, valence orbitals active) level with full geometry optimization at the RHF/6-31G* level. With the inclusion of thermal energies derived from vibrational frequencies obtained at the RHF/6-31G*//RHF/6-31G* level, reaction energies and activation energies that would correspond to gas phase data at 298 K have been evaluated. Syn and anti conformers of the enol structures have been identified. The syn conformer from 8-oxaBCOD is more stable than the anti by 2.0 kcal mol(-1), in common with other enols, whereas the anti conformer from 6,8-dioxaBCOD is more stable than the syn by 1.9 kcal mol(-1) a difference attributable to a hydrogen bonding interaction with O-6 in the seven-membered ring. The ketone formed by the tautomeric shift is 8.4 kcal mol(-1) lower in energy than the syn-enol from 8-oxaBCOD, whereas the lactone formed by the corresponding shift in the anti-enol from 6,8-dioxaBCOD is 27.4 kcal mol(-1) lower in energy; an enhanced energy difference mainly attributable to the well-known stabilization in an acyl grouping. Transition states for the ring fission have been characterized and found to lead to the syn conformers of the enol structures. The activation energy for the fission in 6,8-dioxaBCOD is far larger than that for the cooperative fission of both rings; 32.7 compared with 16.5 kcal mol(-1). Hence, competition with the formation of eZzZz-muconaldehyde in the latter reaction is negligible. The energy barriers for the two fission processes in 8-oxaBCOD, however, favor the former; 33.7 compared with 41.5 kcal mol(-1). These results have established that the fission of the epoxide ring giving enol structures is an extremely unfavorable process, due apparently to an inherent difficulty in effecting the requisite 1,2 H-shift and the lack of any driving force that might originate in changes in the bonding in the seven-membered ring. In contradistinction, the fission of both rings, which in the case of 6,8-dioxaBCOD results in the formation of muconaldehyde, is characterized by a profound alteration in the bonding between the heavy atoms: all the bonds but one change from double to single, or vice versa, notably the bonding to the oxygen atoms.