Phosphorus-Carbon Bond Formation Using Phosphorus Electrophiles

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Organophosphorus compounds are defined as those having a bond between phosphorus and carbon. They have many applications, including ligands for catalysis, anticancer drugs, and materials. The key step in their formation is the creation of the phosphorus-carbon bond. The purpose of this proposal is to develop new methodologies for the synthesis of phosphorus-carbon bonds using metal mediated reactions. The primary tool will be a phosphenium ion, a positively charged phosphorus fragment with two attached groups. Because of their electron deficiency and positive charge, phosphenium ions can undergo electrophilic addition reactions to organic molecules. However, their electron deficiency means that they are typically unstable. They can be stablilized using pi donor groups, but this limits their versatility in organophosphorus synthesis because the P-bound groups are then limited to pi donors. An alternative way of stabilizing phosphenium ions is by coordinating them to metals. Not only does this stabilize them, but it also facilitates their reactions with organic substrates. We will therefore examine the generation and reactivity of transition metal coordinated phosphenium ions, and their applicability to organophosphorus synthesis. Metal-coordinated phosphenium ions will be generated by abstraction of chloride, amino groups or alkoxy groups from metal coordinated phosphines. The corresponding phosphine triflate complexes, which are in equilibrium with phosphenium ions and show similar reactivity, will be generated using silver triflate or triflic anhydride. The reactivity of the phosphenium ion complexes, and their triflate analogs, will be tested with a wide range of organic nucleophiles, including arenes, aromatic heterocycles, alkenes, alkynes, and ketones. The resulting electrophilic substitution reactions will lead to new P-C bonds, resulting in a wide range of organophosphorus products with applications as ligands for catalysis, functional materials precursors, and pharmaceuticals. These electrophilic additions will provide improved regioselectivity, yields, and functional group tolerance compared to traditional P-C bond forming reactions as a result of enhanced electrophilicity and protection of the phosphorus lone pair. The methodologies described here represent a powerful new technique to form P-C bonds. The metal-mediated reactions are uniquely facile, regioselective, and very functional group tolerant compared with many established P-C bond forming reactions.