Rearrangements of Germacrane sesquiterpenoids – An ab initio investigation

A number of germacrane sesquiterpenoids have been reported to undergo facile Cope rearrangement to their corresponding elemane derivatives. Thus, for example, germacrene A leads to β-elemene, germacrene B to γ-elemene, and germacrene C to δ-elemene. Gas chromatographic analyses of essential oils generally show that germacrane sesquiterpenoids are often accompanied by their corresponding elemane Cope rearrangement products, and there has been some concern about whether one or the other may be an artifact due to the high temperatures encountered during the hydrodistillation or the gas chromatographic analysis. The energetics of the Cope rearrangement of seventeen germacrane sesquiterpenoids to their respective elemane forms have been calculated using both density functional theory (B3LYP/6–31G*) and post Hartree-Fock (MP2/6–31G**) ab initio methods. The calculations are in qualitative agreement with experimentally observed Cope rearrangements, but the two methods do give slightly different results. MP2 calculations generally show more favorable elemene energies compared to the respective germacrenes by around 3–4kcal/mol and smaller activation energies by 2–3kcal/mol.

It is generally observed that essential oils containing large concentrations of the sesquiterpene germacrene D are typically accompanied by cadinane and muurolane sesquiterpenoids and germacrene D has been suggested to serve as biogenetic precursor to a number of different sesquiterpenoid skeletons. The acid-catalyzed cyclization of germacrene D to give cadinane, muurolane, and amorphane sesquiterpenes has been computationally investigated using both density functional (B3LYP/6–31G*) and post Hartree-Fock (MP2/6–31G**) ab initio methods. The calculated energies are in general agreement with experimentally observed product distributions, both from acid-catalyzed cyclizations as well as distribution of the compounds in essential oils.