Synthesis of 4-hydroxyestrogens from steroid 4,5-epoxides: thermal rearrangement of 4-chloro-4,5-epoxides

Abstract

The synthesis of 4-hydroxyestrone and 4-hydroxyestradiol from estr-4-ene-3,17-dione through the 4,5-epoxyestra-3,17-diones is described. Thermolysis of 4-chloro-4,5-epoxyestra-3,17-diones also gives 4-hydroxyestrone, but in lower yield, together with 4-hydroxyestra-4,6-diene-3,17-dione and the B ring aromatic product, estra-5,7,9-triene-4,17-dione. Structures have been established by NMR methods except for the structure of 4β-chloro-4,5-epoxy-5α-estra-3,17-dione which has been determined by X-ray crystallographic analysis.