Production of 16beta-(acetoxy)acetoxy derivatives by reaction of 17-keto steroid enol acetates with lead (IV) acetate.

Abstract

Treatment of enol acetates of 3beta-acetoxyandrost-5-en-17-one and its 5alpha-reduced analog, 5alpha-androstan-17-one, and estrone acetate, 1-4, with Pb(OCOCH(3))(4) in acetic acid and acetic anhydride gave the previously unreported products, 16beta-(acetoxy)acetoxy-17-ketones 8-10 and 12, in 9-15% yields along with the known major products, 16beta-acetoxy-17-ketones 5-7 and 11. Similar treatment of the 16beta-acetoxy-17-ketones with the lead reagent did not yield the corresponding (acetoxy)acetates. Reaction of the enol acetate 3 with Pb(OCOCD(3))(4) in CD(3)COOD yielded principally the labeled (acetoxy)acetate 10-d(3), which had a CD(3)COOCH(2)COO moiety at C-16beta. In contrast, when the deuterated enol acetate 3-d(3), which was obtained by treatment of the 17-ketone 14 with (CD(3)CO)(2)O in the presence of LDA and which had a CD(3)COO moiety at C-17, was reacted with Pb(OCOCH(3))(4), the resulting product was the labeled compound 10-d(2). This product had a CH(3)COOCD(2)COO function at C-16beta. Based on these results, along with further isotope-labeling experiments, it seems likely that the (acetoxy)acetate is produced through a lead (IV) acetate-catalyzed migration of the 17-acetyl function of the enol acetate to the C-16beta-position followed by attack of an acetoxy anion of the lead reagent.