Application to the Synthesis of Steroids

Stoichiometric amounts of a titanium(II) reagent regioselectively produced benzyltitanium intermediate 34 in the reaction between the propargyl bromide 32 and the alkyne ester 33 to give the five-membered-ring annotated benzene 35 after protonation. However, an additional five synthetic steps were necessary to complete of the total synthesis of 36. 

As little as 3 to 5 mol % of RhCl(PPh3) induced the intramolecular cyclotrimerization reaction of triyne 43 to provide the tricyclic benzocylobutane 44. After attachment 

The synthesis of linearly and angular fused tetracyclines, an important class of natural antibiotics showing a broad spectrum of biological activities, has also been 

Cyclization of triyne 63 was mediated by the CpCo(C2H4)2 complex and resulted in formation of the tetrahydrobenz[a]anthracene 64 (80% yield) after acidic workup. However, a stoichiometric amount of the more reactive but quite sensitive CpCo(C2H4)2 complex was necessary to execute this intramolecular [2 - - 2 - - 2] cycloaddition within reasonable chemical yields. Other cobalt reagents, such as the CpCo(CO)2 or the CpCo(cod) complexes, were less effective. Anthracene 64 was then oxidized to give the tetrahydrobenz[a]anthraquinone 65, which after deprotection and a regioselective photooxidation provided (-)-8-0-methyltetrangomycin (59). 

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This cyclization has obvious applications to the synthesis of steroids and indeed Johnson et al. applied this reaction to a synthesis of dZ-progcsterone. The key step in the synthesis involves the cyclization of (3) to give (4). This reaction was carried out with trifluoroacetic acid as above, but ethylene carbonate was added to the reaction to trap the vinyl cation. After cyclization potassium carbonate was added to hydrolyze the enol complex. In this way (3) was converted into (4) in 71 % yield. The tetracyclic ketone (4) was converted into progesterone (6) by ozonization followed by intramolecular aldol condensation. Nole that (4) is a 5 1 mixture of the 17/7- and 17a-epimeric ketones. The mixture was converted into (6) and then separated by fractional crystallization. 

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