Oxidative chemistry of 2-nitro and 4-nitroestradiol: Dichotomous behavior of radical intermediates and novel potential routes for oxyfunctionalization and B-ring fission of steroidal scaffolds

Oxidn. of 4-nitro-17β-estradiol with the peroxidase/H2O2 system gave the sym. C2-linked dimer through phenoxy radical coupling. Similar oxidn. of 2-nitro-17β-estradiol (I), in which the nitro group is coplanar with the arom. ring, yielded 9α- and 9β-hydroxy-2-nitro-17β-estradiol, (17β)-2-nitroestra-1(10),2,4,9(11)-tetraene-3,17-diol, and (12α,17β)-2-nitroestra-1(10),2,4,9(11)-tetraene-3,12,17-triol. With higher concns. of H2O2, the novel secoestra-1(10),2,4-trien-9-one deriv. was obtained from I. Theor. calcns. suggested that the peculiar behavior of I may be due to the generation of a relatively stable radical intermediate at C9, which would then be converted to the reactive quinone methide. The chem. described in this paper appears to be an intriguing example of control of the site of substitution over evolution of phenoxy radicals, and opens new vistas toward selective oxyfunctionalization of the estrane skeleton.