Norsteroids epoxidation

An alternative to fluorohydrin formation is observed with the 6/ -methyl-5a,6a-epoxide (30), which rearranges, possibly in a concerted reaction, to the A-homo-B-norsteroid (31) (cf, chapter 14, Vol. II). 

In the course of synthetic efforts aimed at obtaining 6j5-fluoro steroids, Kirk and Petrow treated a 3)5-acetoxy-6-raethyl-5a,6a-epoxide with boron trifluoride etherate and unexpectedly obtained a fluorine-free acetoxy ketone." Later transformations established that the product was the A-homo-B-norsteroid (104). 

High yields of A-homo-B-norsteroids are also obtained on rearrangement of the 5a,6a-epoxides from 3)3-hydroxy-6-methylandrost-5-en-17-one and Sp, 17)5-diacetoxy-6-methylandrost-5-ene. 

In a typical Knof procedure, 3jS-hydroxyandrost-5-en-17-one acetate is epoxidized with perbenzoic acid (or m-chloroperbenzoic acid ) to a mixture of 5a,6a- and 5)5,6)5-epoxides (75) in 99 % yield. Subsequent oxidation with aqueous chromium trioxide in methyl ethyl ketone affords the 5a-hydroxy-6-ketone (76) in 89% yield. Baeyer-Villiger oxidation of the hydroxy ketone (76) with perbenzoic acid (or w-chloroperbenzoic acid ) gives keto acid (77) in 96% yield as a complex with benzoic acid. The benzoic acid can be removed by sublimation or, more conveniently, by treating the complex with benzoyl chloride and pyridine to give the easily isolated )5-lactone (70) in 40% yield. As described in section III-A, pyrolysis of j5-lactone (70) affords A -B-norsteroid (71). Knof used this reaction sequence to prepare 3)5-hydroxy-B-norandrost-5-en-17-one acetate, B-noran-... 

Epoxide (88) is converted to C-norpregnane (89) in 60% yield by methyl-magnesium iodide in refluxing ether-benzene. No rearrangement to the C-norsteroid occurs with dimethylmagnesium. 

The stereochemistry of the epoxidation of A-norsteroids is less predictable than that of the corresponding steroids in view of the flattened nature of ring A and the preferred cis fusion of the hydrindane it has been shown that epoxidation with peroxy acids proceeds predominantly from the fi-face in some norsteroids294. 

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