PREPARATIVE CHEMICAL METHODS FOR AROMATIZATION OF 19-NOR-DELTA(4)-3-OXOSTEROIDS

Two preparative chemical methods for aromatization of 19-nor-Delta(4)-3-oxosteroids are described. The first method consists of an oxidative aromatization of 19-nor-Delta(4)-3-oxosteroids with iodine-eerie ammonium nitrate in methanol to give a mixture of 3-methoxy ring-A aromatized derivatives consisting of the desired product, the Delta(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 trifluoroacetic acid gave the 3-methoxy-17-trifluoroacetate ring-A aromatized derivative as a single product. In the second method, reaction of 19-nor-Delta(4)-3-oxosteroids with copper(II) bromide in acetonitrile at room temperature resulted in aromatic steroids in a single step in excellent yields. The second method was used in the first practical chemical synthesis of a 6-dehydroestrogen from a 19-nor-Delta(4,6)-3-oxosteroid.