Preparation and Applications of New Highly Active P-Chiral Phosphine Oxide Catalysts

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The manufacturing processes that lead to high value fine chemicals used in pharmaceutical and related industrial applications require low-cost, efficient and safe technologies that have minimal environmental impact. Catalytic processes are especially attractive in this respect, and the area of catalytic asymmetric reduction, where the elements of hydrogen gas are added across a suitable substrate with suitable control of the selectivity, has been dominated by the use of transition metal catalysts in conjunction with hydrogen gas. This field is now fairly mature, and although employed in many applications, still suffers from the safety issues associated with using hydrogen gas and the cost and recovery of transition metal catalysts and ligands. In recent years, alternative processes which employ organic molecules as catalysts have become increasingly attractive, using alternatives to hydrogen gas, such as isopropanol and trichlorosilane. Catalysts for the latter are usually classified as Lewis bases and are typically easily accessible, low molecular weight species. Usually just 10% of a catalyst is required to efficiently produce the desired product, usually in excellent yield and selectivity for one isomer over another, although a few catalysts of this class are active enough for only 1% to be employed.Recent research from our laboratories has developed a catalyst that may be used routinely with only 1% of the active species being employed. More recent work has established an improved catalyst that is two orders of magnitude more active, and with only 0.01% needed, represents the most active catalytic species in the world for this type of transformation. Our unique understanding of the activity of this new catalyst has allowed us to develop new catalyst architectures based on phosphine oxides, a hitherto unexplored class of catalyst for this reaction. This proposal aims to develop efficient chemical methods to prepare these catalysts and then evaluate, optimise and exemplify their use in the preparation of chiral amines, a class of molecule found in around a third of all active pharmaceutical ingredients. In parallel with our current ventures, this new technology could offer an exciting low cost manufacturing solution for the pharmaceutical industry, at the same time reducing the cost and risk of using hydrogen gas and transition metal species. The use of environmentally acceptable solvents, with little waste, further accentuate the benefits of this process.In parallel with this, we aim to apply these new catalyst species in a selection of varied chemical transformations, thus exemplifying their use as an emerging new class of catalyst.