Steroid analogues. Part 5. Synthesis of Δ9-6,7-dinor-5,8-seco-steroids viaΔ3-1,3,4-thiadiazolines

Abstract

A general synthesis of symmetrical bi(cycloalkylidene)s is reported, involving successive reaction of an azine with hydrogen sulphide to give a 1,3,4-thiadiazolidine, oxidation to a Δ³-1,3,4-thiadiazoline, pyrolysis to a thiiran, and desulphurisation. The stereochemistry of the products and intermediates was elucidated by ¹H n.m.r. spectroscopy with reference to the Woodward–Hoffmann rules and to conformation theory. The intermediate thiadiazolidines may also be prepared by direct condensation of a cycloalkanone with hydrazine and hydrogen sulphide, with different stereochemical consequences.

A novel synthesis of mixed azines by oxidation of carboxyhydrazones with lead dioxide is described. Combined with the above process, this constitutes a general synthesis of unsymmetrical bicycloalkylidenes. This method has been used to prepare 3,17-disubstituted Δ⁹-6,7-dinor-5,8-secoestrenes. The stereochemistry at C-3 in these olefins and in the intermediate episulphides was assigned by correlation with known compounds, and the orientation of the sulphur atom in the episulphides was elucidated by ¹H n.m.r. spectroscopy with reference to conformation theory and the Woodward–Hoffmann rules. Unexplained differences in the ¹H n.m.r. spectra of secosteroidal epoxides and episulphides are described.