Synthesis, Coordination Chemistry and Reactivity of 1H-pyridin-(2E)-ylidenes and Application of Their Transition Metal Complexes

This thesis describes the synthesis of 1H-pyridin-(2E)-ylidenes (PYE) ligands, their coordination chemistry with late transition metals and the application of their metal complexes in selected catalytic reactions and anticancer activity.
The preparation of mono- and bidentate PYE ligands was achieved from reactions between pyridinium salts and primary amines in the presence of a base. A variety of PYE ligands including chiral and bulky examples were fully characterised by a number of techniques, including single crystal X-ray diffraction.
A range of transition metal precursors were tested with PYE ligands and the resulting metal complexes including Rh(I), Pd(II), Ni(II) and Ru(II) were characterised by methods including single-crystal X-ray diffraction and NMR spectroscopy to examine metal-ligand bonding and ligand dynamics. Data comparison of the solid-state structures, NMR spectroscopy and DFT calculations with respect to neutral ligands, protonated salts and metal complexes indicates that charge redistribution occurs within the PYE heterocyclic ring to give a contribution from a pyridinium-amido-type resonance structure. Strong donor character of PYE ligands was supported by IR spectroscopy and supplemented by DFT calculations.
Selective cyclopalladation, directed by various ligand structural motifs was studied and steric effects were found to be dominant. A series of cationic derivatives were prepared from coordination of small molecules, e.g. CO, NH3 and pyridine and it was found that steric hindrance from the PYE N-methyl group prevents side-on coordination of ligands such as alkenes and alkynes.
Application of PYE ligands in the Suzuki-Miyaura cross-coupling and enantioselective addition of diethylzinc to aldehydes was carried out. A reasonable yield (88%) was obtained for the coupling of 4-bromotoluene with phenylboronic acid using one chelating PYE derivative. Enantioselectivities of up to 21% ee for the ethyl addition of benzaldehyde were also obtained.
The biological activity of two types of Ru(II) complexes derived from alkyl and aryl linked di-PYE ligands and a cationic palladacycle 31 were tested against three cancer cell lines. Complexes 31 and 40 showed promising cytotoxicity results compared with cis-platin.
Overall it has been found that PYE ligands are amongst the strongest donors and that the lack of rotation about the formally exocyclic imine bond locates the N-methyl group in the vicinity of the metal. Whilst this allows the steric environment to be controlled, there other consequences such as cyclometallation and a weakening of the M-PYE bond due to steric pressure.