C(10)-methylation of steroidal synthesis intermediate BCD-tricyclic 9-en-5-ones.

A literature survey indicated that stereospecific non-reductive β-face methylation at C(10) of steroidal synthesis intermediate BCD-tricyclic 9-en-5-ones had never been effected. An attempt to define the factors controlling the β/α product ratio in such alkylations was made. The course of methylation is significantly affected by the temperature. In the best case, methylation of the sodium enolate of 17 β-t-butoxy-19-(3,5-dimethyl-4-isoxazolyl)-deA-androst-9-en-5-one (18) in tetrahydrofuran at − 78° gave a β/α product ratio of > 5:1. The reaction mixture contained no unalkylated or dialkylated materials, indicating that enolate exchange probably did not occur at this temperature. The 10β-methylated product 23, isolated in 78% yield, was converted to Δ9(ll)-dehydrotestosterone (29). Compounds 23 and 29 are potential intermediates for the synthesis of 11-oxygenated steroids.

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