Conformational studies. Part 5. Functionalisation of methyl groups in 4,4-dimethyl steroids

Abstract

Hydroboration of 3,3-ethylenedioxy-4,4-dimethylandrost-5-ene (6; R¹= Me, R²= H₂) gave (a) the 5α-androstan-6α-ol (9; R¹= Me, R²= H), (b) the 5β-androstan-6β-ol (10; R¹= Me, R²= H), and (c) the 5α-androstan-7α-ol (7). Oxidation of 3,3-ethylenedioxy-4,4-dimethyl-5α-androstan-6α-ol (9; R¹= Me, R²= H) furnished the 5α-6-ketone (12; R = Me), which on reduction with lithium aluminium hydride gave the 6β-ol (11; R¹= Me, R²= H). Oxidation of 3,3-ethylenedioxy-4,4-dimethyl-5β-androstan-6β-ol (10; R¹= Me, R²= H) afforded the corresponding 5β-6-ketone (13). Deacetalisation of (12; R = Me) and of (13) gave 4,4-dimethyl-5α-androstane-3,6-dione (15; R = Me) and 4,4-dimethyl-5β-androstane-3,6-dione (16), respectively, which were interconverted by acid.

Oxidation of 3,3-ethylenedioxy-4,4-dimethyl-5α-androstan-7α-ol (7) gave the 7-ketone (17), which was also synthesised from 3,3-ethylenedioxy-4,4-dimethylandrost-5-ene (6; R¹= Me, R²= H₂) as starting material.

3,3-Ethylenedioxy-4,4-dimethyl-19-norandrost-5-ene (6; R¹= H, R²= H₂) was hydroborated to afford the 19-nor-5α-androstan-6α-ol (9; R¹= R²= H) in high yield; this alcohol was oxidised to the 5α-6-ketone (12; R = H), reduction of which gave the corresponding 6β-ol (11; R¹= R²= H).

The nitrites of 6α- and 6β-hydroxy-3,3-ethylenedioxy-4,4-dimethyl-5α-androstane, of 4,4-dimethyl-3-oxo-5α-androstan-6α-ol, of 6α- and 6β-hydroxy-3,3-ethylenedioxy-4,4-dimethyl-19-nor-5α-androstane, and of 6α- and 6β-hydroxy-4,4-dimethyl-3-oxo-19-nor-5α-androstane were irradiated (u.v.) and the products characterised. The results are interpreted in terms of the conformations of the substrates.