Phosphorus-carbon bond formation using metal coordinated 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 key tool will be a phosphenium ion, a cationic phosphorus fragment with two attached groups. Because of their electron deficiency and positive charge, phosphenium can undergo electrophilic additions 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 via metal coordination. Not only does this stabilize them, but it also enhances their electrophilicity. 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 from metal coordinated chlorophosphines. Factors that determine phosphenium ions stability will be assessed experimentally and computationally. The corresponding phosphine triflate complexes will be generated using silver triflate. We have shown that the triflates are in equilibrium with the phosphenium ions and react in the same way, but provide greater functional group tolerance. 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. 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. Metal complexes can also be used for templated reactions. Coordination of a reactive substrate cis to the phosphenium ligand can provide additional control over the regioselectivity of the electrophilic addition reaction.  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 to many established P-C bond forming reactions. As a result, they will find many applications in the synthesis of organophosphorus compounds.