Synthesis of cubebane-type sesquiterpenoids and the stereochemistry of cubebol

Abstract

The total synthesis of cubebane-type sesquiterpenoids, i.e.α- and β-cubebenes (II) and (III), and cubebol (I), from (–)-trans-caran-2-one (IX), has been accomplished. Pyrolytic cleavage of carane-2-spiro-2′-tetrahydrofuran-5′-one (XII)(having a trans-carane structure) led to methyl 3-(trans-p-mentha-2,8-dien-2-yl)propionate (XV), which was converted into the corresponding diazo-ketone (XVI). Copper-catalysed decomposition of the diazo-ketone resulted in the formation of a mixture of intramolecular addition products, one of which, upon hydrogenation, gave trans-7-isopropyl-10-methyltricyclo[4,4,0,0^1,5]decan-4-one (norcubebanone)(XVIIIa), the key intermediate of this synthesis. Cubebenes and cubebol were synthesised from norcubebanone, and the stereoselective course of the synthesis provided a synthetic proof for the stereochemistry of these sesquiterpenoids.