Preparation of the Steroidal 1, 4, 11-Trien-3-ones and a Surprisingly Rapid Dienone-phenol Rearrangement

Abstract

25D-Spirosta-1, 4, 11-trien-3-one (5a) and androsta-1, 4, 11-trien-17β-ol-3-one acetate (16b) were prepared from hecogenin and 5β-androstane-3α, 12α, 17β-triol, respectively. The dienone-phenol rearrangements of these compounds were carried out and the structures of all reaction products were clarified. Rates of the rearrangement of 16b were determined in a 95 : 5 (w/w) mixture of acetic acid and acetic anhydride containing p-toluenesulfonic acid at 20° and varying acidity function H₀. Comparison with a reference compound, androsta-1, 4-dien-17β-ol-3-one acetate (36), indicated for 16b a reactivity enhanced by a factor of 180 at 20°and H₀=0. Products were found to be four kinds of the A-aromatic B-seco allyl acetates (at 20°and H₀=-0.80 ; Δ⁹⁽¹¹⁾-12α-OAc (25c) 75%, Δ⁹⁽¹¹⁾-12β-OAc (25d) 2%, and Δ¹¹⁽¹²⁾-9 (α and β)-OAc (26c) 23%) with the A-aromatic B/C cis Δ¹¹⁽¹²⁾-steroid (27c) (3%). The results suggest important participation of the C-11 (12) double bond in the rearrangement of 16b. Treatment of the B-seco Δ⁹⁽¹¹⁾-12α-allyl alcohol (25b) with the acid of H₀=-1.86 at 80° led to the B/C cis steroid (27c) with a concurrent isomerization to an intermediate, B-seco Δ⁹⁽¹¹⁾-12β-allyl acetate (25d), which is interpreted as a result of electrophilic aromatic substitution of an allyl cation formed from the B-seco Δ⁹⁽¹¹⁾-12α-allyl alcohol.