A new C-C bond forming reaction involving palladium enolates will be discussed. This reaction involves an alpha-halocarbonyl-alkene coupling, which will be studied using a diverse set of substrates including alpha- haloketones, -esters, and -amides. The synthesis of an array of carbocyclic and heterocyclic architectures will be examined. Applications towards the synthesis of bridged cycloalkenones, constituting the core architectures of the anticancer molecules N-methyl welwitindolinone C isothiocyanate, Taxol, and CP-263,114 will be a focus of these investigations. The potential for asymmetric induction in the coupling process will also be assessed. Detailed studies will be performed on catalytically relevant palladium enolates to identify preferred catalyst systems for the coupling process, particularly with respect to minimizing enolate decomposition via beta-hydride elimination. The synthesis and characterization of relevant substituted palladium enolate complexes will be performed. The thermodynamic stability of these substituted enolates will be assessed under thermolytic conditions, and the mechanism of-decomposition via beta-hydride elimination will be identified via detailed kinetic analysis. ? ? ?
| Alexanian, Erik J; Hartwig, John F (2008) Mechanistic study of beta-hydrogen elimination from organoplatinum(II) enolate complexes. J Am Chem Soc 130:15627-35 |
