Biomimetic Polyene Cyclizations. Participation of the Methylacetylenic Terminator and Nitroalkanes. A Synthesis of Testosterone

Article abstract of DOI:10.1021/ja00522a060

The aim of this study was to examine nitroalkanes as trapping agents for the presumed intermediary vinyl cation formed in the acid-catalyzed cyclization of allylic alcohols 1, 5, and 8.Treatment of a solution of the allylic alcohols 1, 5, and 8 with excess trifluoroacetic acid in nitroethane resulted in the formation of the isomeric oxime ethers 3, 7, and 10.Confirmation of the trans-fused hydrindan skeleton of 3 was established by oxidative degradation to the known dione 4.The use of nitroethane as the cyclization solvent allows for the formation of syn and anti forms of the oxime ethers, thereby increasing the complexity of the products formed.This problem was eliminated by using 2-nitropropane as the cyclization solvent.Cyclization of 8 in 2-nitropropane with trifluoroacetic acid yielded the oxime ether 12 which was readily converted to diol 13 with lithium aluminuim hydride in refluxing THF.The stereoisomeric mixture of diols was converted, by two different synthetic pathways (see Schemes I and V), into the 17-hydroxypregnan-20-ones 15 and 16 and dl-testosterone benzoate (34).Catalytic reduction of the Δ¹ olefinic bond in diol 13, followed by oxidation of the secondary hydroxyl group with N-bromosuccinimide, afforded dl-17α-hydroxy-5β,17β-pregnan-20-one (15) and dl-17β-hydroxy-5β,17α-pregnan-20-one (16).Alternatively, treatment of the diol 13 with periodic acid gave ketone 28 which upon reduction with sodium borohydride and esterification of the resulting hydroxyl group with benzoyl chloride afforded the benzoate 30.Oxidation of 30 with tert-butyl chromate, followed by reduction of the Δ¹ olefinic bond, gave ketone 32.Enol acetylation of ketone 32, followed first by bromination, then dehydrobromination, and cleavage of the resulting semicarbazone, resulted in the completion of a facile synthesis of dl-testosterone benzoate (34) in 18percent overall yield from trienynol 8.