TOTAL SYNTHESIS OF -13-ETHYL-3-METHOXYGONA-1,3,5,9(11)-TETRAEN-17-ONEVIA THE TANDEM CLAISEN-ENE STRATEGY())

A total synthesis of the title compound 2, a potential precursor of th e progestagens desogestrel and 3-ketodesogestrel, is described. The ba ckbone of the steroid was assembled by condensation of 1,2-dihydro-4,7 -dimethoxynaphthalene (12) and [S-(Z)]-8,9-dihydroxy-7-ethyl-6-nonen-2 -ynoic acid methyl ester 9-(tert-butyldimethyl)silyl ether (11), prepa red from [R-(+)]-glyceraldehyde acetonide (4), and subsequent Claisen rearrangement. Heating of the resulting disecosteroid (14) at 170-degr ees-C gave a 1:1 mixture of 9,11-secosteroids, 15 and 16, having the 8 alpha,13beta,14alpha- and 8alpha,13alpha,14alpha-configuration, respec tively. The 13beta-epimer 15 was converted into -methoxy-9,11-secogona -1,3,5(10)-triene-9,17-dione (21), which reacted with triphenylphosphi ne under high pressure conditions (12 kbar, 55-degrees-C) to give the corresponding phosphonium salt 22. The intramolecular Wittig reaction of 22 proceeded with epimerization at C-8 to give exclusively -13-ethy l-3-methoxygona-1,3,5,9(11)-tetraen-17-one (23) which, upon treatment with acid, isomerized to the title compound 2.