Synthetic studies on terpene compounds. Part 13. Total synthesis of fraxinellone

Abstract

The total synthesis of fraxinellone (1), the simplest example of a degraded limonoid, via the 6-formyl-2,6-dimethyl-cyclohex-2-enecarboxylates (2) is described. In the initial approach the C-6 methylation of ethyl 6-formyl-2-methylcyclohex-2-enecarboxylate (7) was carried out by cyclopropanation and ring cleavage which unexpectedly gave the bicyclo[2.2.1]heptene compound (20), with a poor yield of the desired product. Subsequently, the key intermediate (2) was synthesized effectively by the Diels–Alder reaction between ethyl 3-methylpenta-2,4-dienoate and methacrolein. The reaction of the aldehyde ester (2) with furyl-lithium followed by double-bond isomerization with base afforded (±)-fraxinellone, together with the corresponding diastereoisomer.