| Palladium complexes are currently the most general catalysts for transforming C-H bonds into other functional groups. In this thesis, general reaction conditions for arylation of electron-rich heterocycles with aryl chlorides were optimized for a large scale palladium-catalyzed phenylation reaction of 2-isobutylthiazole for submission to Organic Synthesis. The reaction requires smaller amounts of ligand and base compared with the earlier procedure, and proceeds with an excellent yield of 92-96%. The reaction can be assembled outside the glovebox.;Also, a new method for intermolecular C-H arylation of indoles has been developed. Moderately sterically hindered 1,3-disubstituted indoles can be arylated utilizing catalytic palladium(II) acetate, 2-(dicyclohexylphosphino)biphenyl ligand, sodium carbonate base, and an aryl chloride coupling partner. 1-Methylindole, 1-phenylpyrrole and furan can be monoarylated under slightly modified conditions. Careful optimization of reaction conditions is required for every electron-rich heterocycle. Mechanistic investigations are necessary to understand the reaction mechanism for further rational improvement of arylation reactions. |
