Photoinduced molecular transformations. 107. A versatile substitution of a carbonyl group of steroidal ketones by a heteroatom. The synthesis of aza-, oxa-, thia-, selena-, and tellurasteroids

Article abstract of DOI:10.1021/jo00294a035

A new method is described for transforming steroidal six-membered cyclic ketones into steroidal cyclic amines, cyclic sulfides, cyclic tellurides, and cyclic selenides with the same ring size via five to six steps. Baeyer-Villiger oxidation of a steroidal ketone to the corresponding lactone followed by reduction with DIBAL gives the corresponding lactol. Irradiation of the hypoiodite, generated in situ by a reaction of the lactol with mercury(II) oxide-iodine in benzene, gives iodo formates arising from regiospecific β-scission. The transformation of these iodo formates into the corresponding diiodides with trimethylsilyl iodide followed by treatment of the resulting diiodides with either primary amines, sodium sulfide, or sodium telluride readily affords aza-, thia-, or tellurasteroids, respectively. Treatment of the diiodides with potassium selenocyanate, on the other hand, gives rise to monoselenocyanates, which can be readily converted into selenasteroids with sodium borohydride. The iodo formates can also by converted into cyclic sulfides through reductive hydrolysis with diisobutyl aluminum hydride (DIBAL) to iodo alcohols followed by mesylation and reaction of the resulting mesylates with sodium sulfide. 3-Thia-, 3-aza-, 3-tellura-, and 3-selena-5α-cholestanes, the corresponding 2,2,4,4-tetradeuterio derivatives, 6-thia-5β-cholestane, 11-thia-5β,9β-pregnan-3α-ol, and 16-thia-, 16-aza-, and 16-selena-5α-androstanes were thus synthesized from the corresponding steroidal ketones in fair to good yields. The synthesis of 11-oxa-5β-pregnan-3α-ol by our previously reported method is also described.