Synthetic steroids. Part XI. Stereochemistry of the Tiffeneau—Demjanov ring expansion of 5α-cholestan-3-one

Abstract

The reaction of 5α-cholestan-3-one with acetone cyanohydrin has been shown to give a mixture of epimers (II and III; R = H) containing at least 80% of the epimer with the axial cyano-group. Each of these cyanohydrins has been converted into its acetate and then, by reduction, into the corresponding amino-alcohol, both of which have been deaminated with nitrous acid. Epimer (II; R = H) gives as the sole product of rearrangement the A-homo-ketone (VI), whereas the epimer (III; R = H) furnishes the same ketone (VI) along with an exocyclic epoxide by-product (X). Each of the intermediate amino-alcohols (IV and VII; R = NH₂) has been synthesised independently from the appropriate epoxide (IX or X) and the stereochemistry of the deamination reactions is discussed.