Nickel-catalyzed arylation of iminium ion intermediates to synthesize 3-aryl-isoindolinones

Abstract

Chemical reactions in which achiral or racemic starting material is converted to an enantioenriched product is called asymmetric or enantioselective synthesis. Such synthesis is a powerful tool in modern chemistry particularly in the field of pharmaceuticals because the different enantiomers of a compound often have different biological activity. Stereoselectivity can be controlled by biocatalysts such as enzymes, chiral auxiliary groups, organocatalysts, or metal catalysts. However, because most transition metal catalysts are utilized at low concentrations, transition metal catalysis in general is particularly favored in industrial scale synthesis due to its cost-effectiveness. Previously, M. Watson group has demonstrated a novel process for nonasymmetric synthesis of 3-aryl-isoindolinones. This thesis presents my progress toward establishing an asymmetric synthesis of 3-aryl-isoindolinones using a nickel catalyst. The first chapter overviews the developments of various isoindolinone syntheses including the discussion of the previous work on asymmetric synthesis of isoindolinones using chiral auxiliaries, chiral base, chiral acid, or metal catalysts. The second chapter describes my studies toward Ni-catalyzed Suzuki-type arylation of iminium ion intermediates to synthesize 3-aryl-isoindolinones. Specifically, it introduces the preliminary results on an asymmetric synthesis of 3-phenyl-isoindolinone using a chiral bidentate ferrocene ligand.