Preparative chemical methods for aromatization of 19-nor- Δ4-3-oxosteroids

Abstract

Two preparative chemical methods for aromatization of 19-nor- Δ 4-3-oxosteroids are described. The first method consist of an oxidative aromatization of 19-nor- Δ 4-3-oxosteroids with iodine-ceric ammonium nitrate in methanol to give a mixture of 3-methoxy ring-A aromatized derivatives consisting of the desired product, the Δ 9,11 derivative, the 6-oxo derivative as well as some ring-A iodinated material. Conversion of this material to a mixture of the 3-methoxy ring-A aromatized derivative and its 6-oxo derivative was achieved by catalytic hydrogenation. Finally, reduction of the 6-oxo function with triethylsilane in trifluoroactive acid gave the 3-methoxy-17-trifluoroacetate ring-A aromatized derivative as a single product. In the second method, reaction of 19-nor- Δ 4-3-oxosteroids with copper (II) bromide in acetonitrile at room temperature resulted in aromatic steroids in a single in excellent yields. The second method was used in the first practical synthesis of a 6-dehydroestrogen from a 19-nor- Δ 4,6-3-oxosteroid.