Transition metal ligands for Suzuki-Miyaura cross-coupling reactions and the coordination of radionuclides - studies towards aurora kinase inhibition for PET imaging

Abstract

This thesis is wide-ranging covering disparate areas of synthetic organic and metalorganic chemistry, unified by the general use of these projects in medicinal chemistry. Two organometallic palladium complexes 2.3 and 2.4, the 2-methyl-4-phenyl-1,3- thiazole and the 4-phenyl-1,3-thiazol-4-ylamine ligand respectively were synthesized and characterized using NMR, mass spectrometry, IR, and X-ray crystallography. These catalysts were tested with various substrates to understand the influence of these catalysts on substrates with electron-withdrawing groups or electron-donating groups in the Suzuki- Miyaura cross-coupling reaction. Several aryl halides and different boronic acid pairs were studied yielding a conversion rate between 27-97 % when 5 mol % of each palladium catalyst was used at 60 oC for 8 hours. The relative rate of electron poor aryl halides was faster than electron rich aryl halides with catalyst 2.4 (amine substituted catalyst) showing preference for electron-withdrawing group (EWG > EDG). The relative rates of the electron rich aryl halides were faster than the electron poor aryl halides when the catalyst with the methyl substituted ligand (catalyst 2.3) was used and we get the opposite preference for electron-donating group (EDG > EWG). The latter behavior is unique in Suzuki-Miyaura coupling reactions, which makes catalyst 2.3 a useful addition to the family of Suzuki-Miyaura catalytic systems. [...]