The biomimetic cyclization of I,3-dimethyl-2-(trans-trans-7,II-dimethyl-3,7,II-dodecatrienyl)-2-cyclohexenol to give the d-homosteroid nucleus (I)

The cyclization of tetraenols 3 and 4 has been studied. The tetraenols were prepared as follows: alkylation of the lithium salt of 1-benzyloxy-3-butyne with the previously known trans-tosylates 19 and 20 gave the dienynes 21 and 22. Reduction with sodium in ammonia gave the trans,trans-trienols 25 and 26, which were used to alkylate, via the tosylates 27 and 28, the sodio salt of Hagemann's ester 7. Decarbethoxylation gave the tetraenones 29 and 30 which were converted with methyllithium to 3 and 4. Treatment of tetraenol 3 with trifluoroacetic acid in pentane at −78°C to −10°C gave tetracyclic diene 5 stereoselectively in 45% yield, along with 5% tricyclic triene 32 and a mixture of esters. The esters were reduced and eliminated, giving a mixture (25% yield based on 3) of 66% diene 5 and 34% triene 32. Tetraenol 3 was cyclized with stannic chloride in nitromethane at 22°C giving a 77% yield of a 4:1 mixture of 5 and 32. Treatment of tetraenol 4 with anhydrous formic acid followed by cleavage of the formate esters gave tetracyclic alcohol 6 (isolated in 9% yield) and a mixture of tricyclic trienes 36 and alcohols 37. Cyclization of 4 in trifluoroacetic acid led to larger amounts of tetracyclic diene 40. The structure and configuration (anti,trans,anti,trans) of the cyclization products, 5 and 6, were established by conversion of 6 into the dl ketone 38 and comparison with authentic d-38. Also d-38 was converted into authentic d-5 which was compared with the synthetic dl-5. The comparison substances were prepared as follows. Testosterone benzoate (41) was methylated at C-4, and the C-3 carbonyl group was removed by conversion to the acetate 44, followed by reductive cleavage of the allylic acetate with lithium in ethylamine. Oxidation of the C-17 alcohol gave the ketone 46, which was converted to the carbinolamine 49 by epoxidation with dimethylsulfonium methylide, followed by conversion to the hydroxyazide and reduction with lithium aluminum hydride. Nitrous acid deamination led to the d-homoketone d-38. Treatment of d-38 with methyllithium followed by dehydration led to a mixture of dienes from which d-5 was isolated.