Total synthesis of (+)‐13‐ethyl‐3‐methoxygona‐1,3,5,9(11)‐tetraen‐17‐one via the tandem Claisen‐ene strategy

A total synthesis of the title compound 2, a potential precursor of the progestagens desogestrel and 3‐ketodesogestrel, is described. The backbone 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), prepared from [R‐(+ )]‐glyceraldehyde acetonide (4), and subsequent Claisen rearrangement. Heating of the resulting disecosteroid (14) at 170°C gave a 1:1 mixture of 9,11‐secosteroids, 15 and 16, having the 8α, 13β, 14α‐ and 8α, 13α, 14α‐configuration, respectively. The 13β‐epimer 15 was converted into 11‐bromo‐13‐ethyl‐3‐methoxy‐9,11‐secogona‐1,3,5(10)‐triene‐9,17‐dione (21), which reacted with triphenylphosphine under high pressure conditions (12 kbar, 55°C) to give the corresponding phosphonium salt 22. The intramolecular Wittig reaction of 22 proceeded with epimerization at C‐8 to give exclusively (8α)‐13‐ethyl‐3‐methoxygona‐1,3,5,9(11)‐tetraen‐17‐one (23) which, upon treatment with acid, isomerized to the title compound 2.