Bridged-ring steroids. V. The total synthesis of 1,4-methano steroids by a modified Torgov sequence

The Diels–Alder adduct, 17, of cyclopentadiene and 2-methoxy-5-methyl-1,4-benzoquinone was reduced with sodium borohydride to the ketol 18, whose acetate 19 was further reduced with zinc amalgam to the monoketone 20. Reaction of 20 with vinyllithium gave the allylic alcohol 21, which underwent very ready dehydration with rearrangement to give the tricyclic enol ether 27, which was hydrolyzed to ketone 28a. Hydrogenation of 19 gave the dihydro product 30, which was reduced with zinc amalgam to the ketone 31. Treatment of the latter with vinyllithium gave the allylic alcohol 32. This was more stable than its analogue 21, but underwent hydrolysis and dehydration to the dienone 33. Treatment of 32 with 2-methyl-1,3-cyclo-pentanedione (5) in the presence of Triton B gave the tricyclic intermediate 35, its hydrolysis product 36, and the hydroxy derivative of the latter, 37. In the absence of base, 32 and 5 gave largely product 36. Hydrogenation of 36 gave the dihydro product 38, which on treatment with methanolic potassium hydroxide gave (±)-(1β,4β,5β,8α,9β,10β,13β,14β)-14-hydroxy-1,4-methanoandrostane-7,17-dione (39). Dehydration of 39 with p-toluenesulfonic acid gave first (±)-(1β,4β,5β,9β,10β,13β)-1,4-methanoandrost-8(14)-ene-7,17-dione (40), which was converted in turn to (±)-(1β,4β,5β,8α,9β,10β,13β,14β)-1,4-methanoandrost-15-ene-7,17-dione (41). Similar dehydration of 36 gave (±)-(1β,4β,5β,10β,13β,14β)-1,4-methanoandrosta-8,15-diene-7,17-dione (45).