An improved preparation of the desmethyl qinghao acid precursor of (+/-)-6,9-desmethylqinghaosu

The trimethylsilyl triflate catalysed DA reaction of the 3,5-hexadien-1-ol TMS ether with (+/-)-6-methylcyclohexenone efficiently gives the trans-fused adduct acetal, whose controlled hydrolysis converts it into (3aRS,6aSR,9SR,9aSR,9bRS)-9a-hydroxy-9-,3a6,6a,7,8,9,9a,9b-decahydro-1ox a-1-H-phenalene. An efficient sequence involving hydrogenation, stereoselective reduction with lithium tri-tert-butoxyaluminohydride to the alcohol, selective protection of the primary hydroxyl group with tert-butyldimethylsilyl chloride, dehydration of the secondary alcohol to the alkene, deprotection and oxidation of the primary alcohol group to the carboxylic acid provides the desmethyl qinghao acid analogue which has been converted previously into (+/-)-6,9-desmethylqinghaosu. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.