Collect. Czech. Chem. Commun. 2001, 66, 1797-1808

Stereochemistry of Cuprate-Mediated Conjugate Additions of a 17-Iodoandrost-16-ene to E- and Z-6-Methylhept-2-en-4-one

Denise L. Andersen and Thomas G. Back*

Department of Chemistry, University of Calgary, Calgary, Alberta, T2N 1N4, Canada


(3S,15R)-15-(Benzyloxy)-3-[(tert-butyldimethylsilyl)oxy]-17-iodoandrosta-5,16-diene (3) was prepared from the corresponding 17-hydrazone 9 with iodine in the presence of tetramethylguanidine. The vinyl iodide 3 was converted into the corresponding organocuprate and conjugate additions of the latter were performed with both (E)- and (Z)-6-methylhept-2-en-4-one (4a and 4b, respectively). In each case, the resulting adduct 5a was obtained exclusively with the unnatural 20S configuration. (3S,15R)-15-(Benzyloxy)-3-[(tert-butyldimethylsilyl)oxy]androsta-5,16-diene (13) and the corresponding 17,17' homocoupling product 14 were obtained as byproducts. When the addition to the E-enone was repeated in the presence of chloro(trimethyl)silane, the yield of the conjugate addition product improved, but the stereochemistry at C-20 remained the same.

Keywords: Vinyl iodides; Cuprates; Conjugate additions; Steroids; Total syntheses; Antibiotics; A25822 B.

References: 44 live references.