Rearrangement of vinyl allene oxide geometric isomers to cyclopentenones. Further computational insights with biologically relevant model systems

Abstract

Pathways for the rearrangement of the E and Z isomers of allyl- and methyl-substituted vinyl allene oxides to stereodefined cyclopentenones have been studied by DFT computations. Regardless of the reactant geometry, cis-configured cyclopentenones are found to be formed in a stepwise cascade comprising as key steps the ring opening of the oxirane to give an oxidopentadienyl diradical, its isomerization, and electrocyclization. An allyl substituent at the C atom of the starting vinyl allene oxide induces opposite effects on the activation energies for ring opening: a decrease owing to assistance by homoconjugation for the out motion and an increase due to the stereoelectronic stabilization of the reactant. As a result, allyl- and methyl-substituted vinyl allene oxides exhibit comparable activation energies. Only model systems with crotyl substituents afford lower activation energies than the methyl counterparts due to the additional stabilization of the forming charge deficiency at a secondary carbon by homoconjugation. Moreover, upon homoconjugative interaction reactants of Z geometry are predicted to undergo cyclization more readily than the E isomers. The results with Z-crotyl substituent are congruent with the spontaneous rearrangement of natural vinyl allene oxide derived from α-linolenic acid to a racemic cis-cyclopentenone (12-oxo-PDA).

Biosynthesis of Jasmonates from Linoleic Acid by the Fungus Fusarium oxysporum. Evidence for a Novel Allene Oxide Cyclase

“…As reported here, fungal AOC transform 12,13 S ‐EOD, but may nevertheless use the same reaction mechanism. Fungal AOC may, therefore, catalyze homolytic cleavage of the epoxide of 12,13 S ‐EOD with formation of an oxyallyl radical, which rearranges to 9 S ,13 S ‐12‐OPEA (González‐Pérez et al, ; Hebert et al, ). An outline of the transformation of 12,13 S ‐EOD into 9 S ,13 S ‐12‐OPEA by AOC and then into 9,10‐dihydro‐(+)‐7‐ iso ‐JA‐Ile is shown in Fig.…”

Computational studies on the formation of aza‐oxypentadienyl intermediates from alkylidene oxaziridines and keteneimine oxides and their conversion to 1,5‐dihydropyrrolones

“…for a complete description of the manifold). Similarly to other pentadienyl zwitterions/diradicals, three isomeric aza‐oxypentadienyl species named U , s (sickle) and W are possible for the intramolecular reactivity of the nitrogen‐containing functional group . The computed mechanisms for their interconversions are described in the S.I.…”

“…On the other hand, a thorough exploration of the PES allowed the characterization of a lower energy pathway for the interconversion of isomeric aza‐oxypentadienyl species (Figure ). This involves an initial disrotatory ring closure to aziridinone 2a‐ R ‐t ( R refers to the configuration of the N from the selected enantiomer of 1a ) followed by rotation of the vinyl group and ring opening of the aziridinone conformer 2a‐ R ‐c leading to aza‐oxypentadienyl intermediate 4a‐ Z ‐U . This isomer could only be characterized when a restricted formalism (RDFT) was used, which was taken as an indication of its closed‐shell configuration and zwitterionic nature.…”

“…20 kcal/mol lower in energy) in the aza case because of the stabilization of diradicals/zwitterions by the nitrogen atom . For vinyl allene oxide (a similar system as the substrate studied previously, with the methyl group located at the vinyl terminus as the only difference) more similar energies of both reactants and intermediates were computed (the differences range from −2 to 9 kcal/mol) . In contrast, the Gibbs free energies of activation for the isomerization processes are comparable in both systems.…”

“…Intermediate IVb also affords vinyl cyclopropanone IIb but the activation energy for the one‐step rearrangement of the latter intermediate to cyclopentenone IIIb is higher and thus this pathway was considered noncompetitive with the cyclization of IVb to IIIb . Additional studies on the effects of substituents with different structures and double bond geometries (allyl, E ‐crotyl, and Z ‐crotyl) on the energetics of the process more recently provided a rationale for the exquisite diastereoselectivity in the rearrangement of natural vinyl allene oxides with Z ‐crotyl groups to afford cis ‐cyclopentenones …”