The effect of fluorine substituents on intramolecular C–H bond activation reactions at transition metals

This thesis describes an investigation into the effects of fluorine substituents on the regioselectivity of intramolecular C–H activation reactions at different transition metals, including Pd, Ir, Rh and Ru. A range of mono- and di-fluorinated N,N-dimethylbenzylamines were synthesised initially and their behaviour towards cyclometallation at Pd was studied (Chapter 2), revealing an unprecedented difference in the regioselectivity of the C–H activation between the formation of acetate- and chloro-bridged palladacycles. The spectroscopic and crystallographic properties of all of these palladacycles are described and analysed in detail. Acetate-bridged palladacycles present a “clam-shell” structure, which shows a dramatic variation with the number and the position of the fluorine atoms on the aromatic ring of the ligand. Conversely the planar chloride-bridged palladacycles do not show any structural variation. Biological assays have been performed on two of the fluorinated amino-derived palladacycles against ovarian cancer cells, revealing promising activity. A series of fluorinated diphenylbenzylphosphines and their corresponding chloride-bridged phosphapalladacycles have also been synthesised (Chapter 3), and a similar regioselectivity observed to that seen for the corresponding amino-derived palladacycles. Various successful attempts at cyclometallation reactions using the fluorinated amines as substrates at Rh, Ir and Ru demonstrate a preference for C–H activation ortho to fluorine (Chapter 4). Finally the synthesis of a novel pentafluorobenzyl phosphine, and some preliminary work towards C–F activation reactions using this substrate at Pt is described (Chapter 5).