Expanding the scope and utility of DalPhos-based catalyst systems

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Modern chemical synthesis makes use of catalysts to promote chemical transformations that would otherwise prove challenging or impossible. Catalysts based on transition metals have proven to be particularly effective in enabling the transformation of simple substrate molecules into more complex, value-added products (e.g. pharmaceuticals) under mild experimental conditions, and in some cases without the formation of waste by-products. Indeed, transition metal catalysis is employed broadly in both industrial and academic settings for the construction of C-C, C-N and related bonds, and there is significant interest in the establishment of increasingly effective catalysts for such bond-forming reactions. While the behavior of transition metal catalysts can be attributed primarily to the metal employed, the coordination of ancillary ligands to the metal provides a powerful control element in tuning the reactivity profile of the metal, thereby affording catalytic processes with high levels of selectivity and efficiency. In this vein, the design of new transition metal catalysts for increasingly challenging substrate transformations relies heavily on the design of new ancillary ligands. My research group has developed a family of ancillary ligands (named "DalPhos" - DALhousie PHOSphine) that have proven to be particularly effective in combination with late transition metals for the construction of C-C and C-N bonds. For example, we have demonstrated that Mor-DalPhos/Pd mixtures are capable of promoting unprecedented cross-coupling reactions involving ammonia and hydrazine, which are of widespread interest to synthetic chemists in the pharmaceutical industry as well as in academia. Having secured patent protection for this DalPhos ligand family, and in an effort to accelerate the development of this promising technology in order to promote commercialization, this proposal seeks to carry out key R&D work that will allow us to: (a) broaden our patent claims regarding composition of matter; (b) expand the DalPhos ligand library and optimize the ligand synthesis; (c) expand the scope of DalPhos-based catalysts; and (d) evaluate the stability of DalPhos ligands/catalysts under commonly encountered laboratory conditions.