Palladium and manganese catalysis in C-H activation

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Mackey, Katrina
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University College Cork
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Direct arylation via C-H activation has emerged as a powerful tool for the construction of new aryl-aryl bonds and provides an alternative to classical cross coupling procedures. Double C-H activation in particular, represents a more sustainable approach in terms of waste, cost and atom economy. 2-Pyrone and 2-coumarin analogues represent privileged biological scaffolds and possess broad spectrum biological activity. Importantly, there have been limited reports of catalytic methods involving the C-H activation of 2-pyrones and 2-coumarins. The cyclisation of 2-pyrones and 2-coumarins via double C-H activation is described in Chapter 2 of this thesis. The synthesis of a library of 2-pyrone and 2-coumarin substrates was achieved using this methodology. Excellent yields were achieved for the 2-coumarin substrates and some good regioselectivity was obtained for both the 2-pyrone and 2-coumarin analogues. The developed double C-H activation reaction conditions also facilitated a three step synthesis of flemichapparin C. The application of this methodology was then transferred to the synthesis of meta-substituted dibenzofurans. A variety of mono- and di-substituted diarylethers were efficiently cyclised in good to excellent yields. In Chapter 3, the cyclisation of mono-halogenated diarylethers via single C-H activation to produce dibenzofurans is discussed. Previous methods for the synthesis of dibenzofurans via transition metal-mediated catalysis suffer from a number of drawbacks. Thus, focus was targeted at addressing many of the limitations existing with the current protocols for the intramolecular direct arylation of diarylethers. Substrates with electron withdrawing groups were particularly well tolerated and yields of up to 99% were observed. The final section of this thesis involved the synthesis and application of a number of carbonyl manganese phosphine complexes. The vast majority of C-H activation protocols involve the use of precious 4d or 5d transition metal catalysts. However, many of these metals are now classed as ‘finite raw materials’. Clearly, there is an urgent need to alleviate the worldwide reliance on precious metals, especially palladium. The cost effective and sustainable nature of earth abundant first row transition metals, renders the development of C-H activation protocols using inexpensive 3d metal catalysts a particularly attractive alternative. In recent years, Mn catalysed C-H activation has gained considerable momentum as a more environmentally benign and economically attractive alternative to typically used transition XIII metal based catalysts. Despite this, most reports on Mn catalysed C-H activation utilise the commercially available MnBr(CO)5 and Mn2CO10 pre-catalysts. The CO ligand cannot be optimised, and this represents the bottle-neck for the expansion of Mn catalysis. In contrast to more commonly studied metals such as Pd, there has yet to be widespread study of the influence of ligands in Mn(I)-catalysis, in many reaction types including C−H bond activation. This represents a significant gap in the State-of-the Art. Thus, the future of Mn catalysed C-H activation requires the development of new tuneable ligands for Mn, analogous to the past developments in Pd catalysis. The work in Chapter 5 involved the synthesis of a range of tetracarbonyl- and tricarbonyl Mn phosphine complexes. The complexes were fully characterised by spectroscopic, single crystal structure X-ray analysis and elemental analysis and applied in a number of C-H activation reactions. Critically, it was demonstrated that these carbonyl Mn phosphine complexes are catalytically competent in a proof-of-principle reaction; the hydroarylation of N-(2-pyridyl)indole with ethyl trifluoropyruvate.
C-H activation , Palladium and manganese catalysis
Mackey, K. 2020. Palladium and manganese catalysis in C-H activation. PhD Thesis, University College Cork.