Preparation of a bicyclic analogue of qinghao (artemisinic) acid via a Lewis acid catalyzed ion Diels-Alder reaction involving a hydroxy diene and cyclic enone and facile conversion into (±)-6,9-desdimethylqinghaosu

Article abstract of DOI:10.1021/jo00096a015

Treatment of 6-methylcyclohex-2-enone (8) and hexa-3,5-dien-1-ol (14) either in dichloromethane at -20 to 0°C with aluminum chloride (1 equiv) or in acetonitrile at -20°C with Cu(II) trifluoromethanesulfonate (1 equiv) rapidly provides in a highly stereoselective reaction the hemiacetal Diels-Alder adduct 15, which with a trans ring junction and anti methyl group is considered to arise via an ionic Gassman-type Diels-Alder reaction involving prior formation of a hemiacetal between the alcohol and enone followed by generation of an allylic cation from the hemiacetal mediated by the Lewis acid. The adduct 15 is then converted in straightforward fashion into the methyl ester of the desdimethyl analogue of qinghao (artemisinic) acid, which upon sequential photosensitized oxygenation and then Fe(phen)₃(PF₆)₃/copper(II) triflate catalyzed cleavage-oxygenation provides (±)-6,9-desdimethylqinghaosu.