A Mechanistic Investigation into Mn(I)-Catalysed C-H Bond Functionalisation: from Pre-Catalyst Activation to Substrate Coordination and Transformation

This thesis describes mechanistic investigations into Mn(I)-mediated C–H bond activation and functionalisation processes, with an additional focus on the factors influencing the reactivity of the manganese complexes. Initially, an investigation into Mn(I)-catalysed C–H bond alkenylation of 2-phenylpyridines was performed, utilising the distinct IR bands of the manganese carbonyl species to monitor the catalyst in situ (Chapter 2). The mechanistic studies allowed for a comprehensive reaction mechanism to be derived, where pre-catalyst activation was found to be substrate-dependent, leading to two distinct pathways. Furthermore, two new catalytic cycles (involving protonation by the 2-phenylpyridine and water) were discovered, in addition to the confirmation of the previously proposed cycle.
Time-Resolved InfraRed (TRIR) spectroscopy provided an opportunity to study the processes underpinning C–C bond formation in further detail, observing short-lived (0.5 ps – 1 ms) reaction intermediates and their respective kinetic behaviour (Chapter 3). Photochemical initiation led to the utilisation of a range of manganese complexes and unsaturated substrates. The uni- and bimolecular behaviour of the intermediates and their kinetics were probed from experiments diluted in toluene.
Carboxylic acid additives were employed to increase the efficiency of Mn(I)-catalysis using terminal alkynes, while inhibiting reactions with acrylates (Chapter 4). Mechanistic studies revealed that a change in catalyst resting-state explains the different effects. TRIR spectroscopy allowed for the observation of the protonation by carboxylic acids, leading to an observation of the steps underpinning the CMD/AMLA-6 mechanism.
Investigation into the fluorine-induced regioselectivity of Mn(I)-mediated C–H bond functionalisation of 2-phenylpyridines showed that the cyclomanganation reaction is kinetically driven and irreversible. Addition of benzoic acid led to a reversible mechanism, where the regioselectivity is thermodynamically controlled. It was additionally revealed that the regioselectivity likely arises from the relative thermodynamic stability of the manganacycles, where the trend follows the order: ortho>meta>para (with respect to the fluorine substituent).