Total synthesis of (±)-β-bulnesene via intramolecular cycloaddition of a 2-substituted 3-oxidopyrylium

Abstract

A route to the sesquiterpene (±)-β-bulnesene is described which starts with the substituted furan, 2-(1-hydroxy-4-methylhex-5-enyl)furan. Oxidation of the latter generates a precursor of a 2-substituted 3-oxidopyrylium, which undergoes smooth intramolecular cyclisation to generate a highly functionalised perhydroazulene intermediate. Further chemical manipulation of the latter readily generates the desired natural product. In order to control the relative geometry of the pendent 4-methyl group in the target molecule, a method involving the stereoselective reduction of an exocyclic methylene group is employed; the means for introducing such methylene groups are detailed.