Part 1: The Direct Arylation of Azine N-Oxides with Aryl Triflates Part 2: The Site-Selective Direct Arylation of Substituted Indoles

Abstract

Part 1: The Direct Arylation of Azine N -Oxides with Aryl Triflates. Two sets of conditions for the palladium-catalyzed direct arylation of azine N-oxides with aryl triflates have been developed. Using palladium(II) acetate, a trialkylphosphine ligand, a carbonate base and pivalic acid, both mono- and diarylated azine N-oxides could be synthesized in good to excellent yields.* The reaction regioselectivity was examined for 3-substituted pyridine N-oxides, with arylation at C2 being favoured. The methodology was applied to the efficient formal synthesis of a biologically active diaryl pyridine. Part 2: The Site-Selective Direct Arylation of Substituted Indoles. Initial studies into the site selectivity of the direct arylation reaction were conducted. Several competition studies were performed using various methodologies to determine the selectivity, if any, between two arenes capable of undergoing direct arylation. It was found that selectivity was greatest when competition was between one electron-rich and one electron-poor arene.* From these results a substituted indole was synthesized and subsequently derivatized at three different positions. It was demonstrated that site selectivity on a complex molecule could be achieved through careful selection of reaction conditions. *Please refer to dissertation for diagrams.