Acid-mediated rearrangements of 14,17-ethenoestra-1,3,5(10)-trien-17-ols: synthesis of 14,16-ethano-19-norsteroids

Abstract

3-Methoxy-17¹-methyl-l 4,17α-ethenoestra-1,3,5(10)-trien-17β-ol 1 undergoes a 16(17 → 17¹)abeo-rearrangement in the presence of boron trihalides, to give the corresponding 16α-methyl-14β,16β-ethano 17-ketone. Similar rearrangements are described for epimeric 14,17-bridged estradiol analogues, leading to 16β-methyl-14α,16α-ethano 17-ketones. By contrast, acid-mediated reactions of 3-methoxy-14,17α-ethenoestra-1,3,5(10)-trien-17β-ol 11 display reagent dependence, leading to products of competing 16(17 →r;17¹)abeo-and 15(14 → 17²)abeo-rearrangements. Conversion of certain rearrangement products into 14,16-ethano analogues of estradiol and 19-nortestosterone are described, and X-ray crystallographic structure determinations are reported for three ring-D-bridged compounds, and a novel spiro compound arising from rearrangement of the 14α,17α-etheno 17β-alcohol 11.