First-row Transition Metal Catalysed Synthesis of Organophosphorus Compounds

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Organophosphorus compounds are of considerable importance due to their many applications as medicines, agrochemicals, fire retardants and ligands.1 Classical synthetic methodologies to synthesise these compounds using heat, light or radical initiators suffer significantly from the use of stoichiometric additives, the use of protecting groups, poor functional group tolerance and the formation of regiochemical mixtures of organophosphorus products.2 The need for a less wasteful and more regioselective and stereoselective method of organophosphorus synthesis has promoted the use of metal catalysts to form P-C bonds; by addition of a P-H unit to an unsaturated carbon-carbon double bond.3 This methodology is ideal because it presents the potential to be a 100% atom economic process, in line with one of 12 Principles of Green Chemistry.4 However, a significant proportion of the metal catalysts commonly used in these reactions are precious metal catalysts, mainly palladium and to a lesser extent early lanthanides.2 Additionally, the majority of recent literature has focused on P-H addition using secondary phosphines to unfunctionalised alkenes and alkynes, due to a lack of suitable catalysts that can tolerate heteroatom functionality. This is problematic as the secondary phosphines used are originally derived from PCl3, which is classified as very toxic and corrosive under EU Directive 67/548/EEC. To circumvent these issues, more environmentally benign phosphorus precursors and earth-abundant robust transition metal catalysts are needed to make this methodology more sustainable. Previous research by the Kays group has shown that low co-ordinate iron complexes can catalyse P-H addition to heteroatom-functionalised substrates such as isocyanates (R-N=C=O). Significantly these complexes have also been shown to catalyse novel diinsertion pathways for this reaction, which are exceedingly rare and typically difficult to control (e.g. Scheme 1). Building on this work the project will utilise low coordinate first-row transition metal complexes to catalyse the addition of a range of P-H and P(O)-H derivatives to heterocumulenes containing C=X (X = O, N, S) bonds, to introduce a heteroatom functionality efficiently into organophosphorus compounds with novel motifs relevant to pharmaceutical and agrochemical industries. A key part of the project will be to use more sustainable and benign organophosphorus derivatives which can present more challenge to the catalysis as a much broader pKa range and more functional groups compared will be used compared to typical hydrophosphination reactions. Expansion of the reactivity to other additions will allow us to explore the applicability of the first-row transition metal precatalysts. Reaction mechanisms will be investigated using detailed kinetic experiments and will help inform future reaction development at the gram scale with green solvents.