Regioselective synthesis of 2-chloromercurio-estradiol and -estrone derivatives: A novel approach to A-ring substituted estrogens

The following derivatives of estradiol and estrone, 3-methoxyestra-1,3, 5(10)-trien-17β-yl acetate (3a), 3-methoxyestra-1,3,5(10)-trien-17-one (3b), estra-1,3,5(10)-triene-3,17β-diyl diacetate (1f), and 3-acetoxyestra-1,3,5(10)-trien-17-one (1g), can be regioselectively mercuriated at the less hindered position 2. The 2-mercurio derivative (4a), prepared from (3a), can be used as the starting material for the synthesis of some 2-substituted estrogens, such as 2-halogeno- and 2-hydroxy-estrogens. Additionally, the 2-chloromercurio-4-bromo derivative (5c) can be obtained from 4-bromo-3-methoxyestra-1,3,5(10)-trien-17β-yl acetate (2f), whereas from 3-methoxyestra-1,3,5(10)-triene-2,17β-diyl diacetate (3g) the 4-chloromercurio derivative (5d) can also be obtained. An explanation of the regioselectivity shown by some electrophiles towards the aromatic A-ring of estrogens is presented.