Regiocontrolled Coupling of (π-Allylic)palladium Complexes with Organozirconium Species

A carbon-carbon bond-forming reaction has been developed involving coupling between an alkenylzirconium(IV) complex, prepared by hydrozirconation of the corresponding terminal acetylene, and (η³-allylic)palladium chloride dimers, prepared from olefins, to give 1,4 dienes. A stereospecific synthesis of 20(R)-cholestan-3-one is described. Bis(η⁵-cyclo-pentadienyl)chloro(4′-methylpent-1′-en-1′-yl)zirconium reacts with di-μ-chloro-bis[η³-16,17,20-(3-oxopregn-17(20)(Z)-en-16-yl ethylene ketal)]dipalladium in the presence of maleic anhydride. A mixture is obtained consisting of 1,4 dienes produced by addition of the alkenyl group to either the C(20) or C(16) terminus, respectively, of the allylic system. Hydrogenation of the C(20)-coupled product and deketalization yielded 20(R)-cholestanone exclusively. Transfer of the organic group from zirconium to palladium precedes carbon-carbon bond formation; this result is shown to be valid both in the presence and in the absence of added ligand. Coupled product thus obtained has stereochemistry opposite to that formed by stabilized anion attack on η³-allylic complexes of palladium. The analogous sequence, starting from the epimeric di-μ-chloro-bisη³-16,17,20-(3-oxopregn-17(20)(E)-en-16-yl ethylene ketal)]dipalladium, yielded 20(S)-cholestanone exclusively. It was observed that regioselectivity of coupling depends on the nature of palladium ligands present. This phenomenon is rationalized by postulating the intermediacy of isomeric square-planar (η³-allyl)palladium(alkenyl)(ligand) complexes, which subsequently reductively eliminate allyl-alkenyl (1,4 diene) with concomitant extrusion of palladium(0).