TY - JOUR
T1 - Preparation of a Bicyclic Analog of Qinghao (Artemisinic) Acid via a Lewis Acid Catalyzed Ionic Diels-Alder Reaction Involving a Hydroxy Diene and Cyclic Enone and Facile Conversion into (±)-6,9-Desdimethylqinghaosu
AU - Haynes, Richard K.
AU - King, Geoffrey R.
AU - Vonwiller, Simone C.
PY - 1994/8/1
Y1 - 1994/8/1
N2 - 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.
AB - 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.
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U2 - 10.1021/jo00096a015
DO - 10.1021/jo00096a015
M3 - Article
AN - SCOPUS:0028037751
SN - 0022-3263
VL - 59
SP - 4743
EP - 4748
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 17
ER -