A Convenient Synthesis of Estrone and 11-Methylequilenines based on the Thermal Elimination of β-Ketosulfoxides

Abstract

The thermal elimination of β-ketosulfoxides (3, 4, 5) derived easily from methyl 4-(3-methoxyphenyl) butyrate (1) gave 6-(3-methoxyphenyl) hex-1-en-3-one (6), which was condensed with 2-methylcyclopentane-1, 3-dione (8) to yield the triketone (7), one of key intermediates of Smith's estrone synthesis. Compound 7 was cyclized to the unsaturated diketone (9), which was converted to estrone methyl ether (13) by the established procedures. When the mixture of 3 (or 4) and 8 was heated, 7 was directly formed in a good yield. Moreover, heating of 5 and 8 gave 9, though in less satisfactory yield. The over-all yield of this simple and short cut synthesis of estrone methyl ether (13) from the starting material (1) was 34%, nearly twice of the original Smith method. This method also applied for the synthesis of 11α-methylequilenine methyl ether (20) and 11α-methylisoequilenine methyl ether (19) via the prior introduction of a methyl group to 3 yielding the β-ketosulfoxide (14) in 40% over-all yield.