Hydration and related reactions of 14,17-ethenoestradiol methyl ethers: a comparative study in selectivity

Hydroboration-oxidation of 3-methoxy-14,17-ethenoestra-1,3,5(10)-trien-17 beta-ol 1 furnishes all of the four possible 17 beta,17(1-) and 17 beta,17(2)-diols arising from addition to the etheno bridge. Although the product distribution reveals moderate endo-selectivity (similar to 3:1), the process lacks synthetically useful regioselectivity, an outcome which is not noticeably influenced by incorporation of bridgehead functionality designed to facilitate intramolecular participation during hydroboration. A comparative study on 3-methoxy-14,17 alpha-ethanoestra-1,3,5(10),15-tetraen-17 beta-ol 17 reveals similar endo-selectivity, but with a regioselective bias toward hydration adjacent to the bridgehead hydroxy group. Osmylation of 17 lacks stereoselectivity, in contrast to that of the derived 17 beta-acetate 18, in which addition is predominantly exo-directed. These results are compared and interpreted, and an attempt to develop a hydroformylation-mediated method for conversion of 1 into 14 alpha-allyl-3-methoxyestra-1,3,5(10)-trien-17-one is described.