Synthesis of pyridone building blocks for biomimetic complexes of mono-iron hydrogenase
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Hydrogen gas is a promising alternative to conventional fuels like coal or gasoline because it can be produced from water. The most effective catalysts for the reduction of water to hydrogen are based on palladium and platinum—precious, expensive metals—but the search for catalysts based on the more abundant transition metals (e.g. Co, Fe, and Ni) is ongoing. Chemists have turned to biological catalysts—enzymes like mono-iron hydrogenase—for guidance in the design of transition metal-based hydrogen activation catalysts. Mono-iron hydrogenase activates H2 by cleaving it heterolytically, resulting in H+ and a hydride (H.) which is transferred to a hydride carrier molecule called methenyltetrahydromethanopterin (methylene-H4MPT). The mono-iron hydrogenase active site contains an iron center complexed to two carbonyls and an acyl-pyridone ligand conjugated to a guanine nucleotide by a phosphodiester bond. The iron cofactor is connected to the enzyme by only one covalent association: the cysteine amino acid ligand. The work described in this thesis relates to the synthesis and characterization of a series of pyridone compounds to be used in ligands that mimic the chemical environment of the mono-iron hydrogenase active site in small-molecule iron complexes. Biomimetic iron complexes synthesized using these ligands may shed some light on the catalytic mechanism of the mono-iron hydrogenase enzyme and may themselves be capable of useful catalysis. A series of 3-Br, N- and O-protected pyrone and pyridone coupling partners and a collection of trifluoromethylated pyridone derivatives have been synthesized, and the synthesis of an unreported 5-methyl pyridone is proposed.