Radical C-C bond formation in cobalt-propargyl complexes: Stereoselective access to novel nonsteroidal hormones

ORGN 82

Gagik G. Melikyan, Arthur Florut, and Christopher Wild. Department of Chemistry, California State University Northridge, 18111 Nordhoff str, Northridge, CA 91330
Novel radical C-C bond forming reactions – spontaneous and THF-mediated dimerization of cobalt-complexed propargyl systems (Org.Lett. 2003, 5, 3395; J.Organomet.Chem. 2003, 683, 324) – were used, as a key step, in the stereoselective assembling of novel nonsteroidal hormones. The topology of polyphenolic structures having a D,L-3,4-disubstituted 1,5-hexadiyne backbone was designed based on the anticipated biological activity and the most conceivable metabolic pathways. The typical synthetic scheme includes the preparation of dicobalthexacarbonyl-propargyl alcohol complex, followed by the generation of carbocationic and radical centers in alpha-position to the metal core. The efficacy of radical coupling reactions is found to be dependent upon the substrate structure and an electronic nature, disposition and a number of substituents at aromatic nuclei. The intramolecular variant of the parent reaction will also be presented, along with the preliminary data on antiestrogenic activity of lead compounds.