New strategy for ruthenium olefin metathesis catalysts using dianionic tridentate ligands

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Olefin metathesis has become a formidable tool for synthetic chemists to create carbon-carbon double bonds. This transformation, made possible by the use of metal carbene catalysts, has had a remarkable influence of the development of new materials (polymers/plastics) and organic compounds, including those with biological activity (drugs). The importance of this reaction is reflected in the 2005 Nobel Prize in Chemistry awarded to Chauvin, Schrock and Grubbs. Although remarkable progress has been made in the past decades, the thermal stability of ruthenium-based catalysts and their ability to achieve good selectivity for a wide range of reactants (also known as substrates) and transformations still remain an issue. For instance, poor thermal stability results in decomposition of these catalysts over the course of the reaction with a decrease in productivity. Furthermore, poor selectivity of the catalyst leads to mixtures of products that can be difficult to isolate in their pure form. This is especially concerning for biologically-active compounds where side-product contaminants can cause severe undesired side effects. A strategy to develop new catalysts capable of mediating olefin metathesis is presented in the proposal. The approach leverages observations made by the Lavoie group and by others in the field. Catalysts with building blocks that can easily be modified are proposed and used to modulate the performance of these catalysts in olefin metathesis. The initial focus of the research is aimed at producing thermally robust catalysts that can be used in several types of olefin metathesis transformations with a wide range of substrates. Studying the effects of the building blocks on the catalysts will give us fundamental knowledge to further enhance their performance through structure-activity relationships. In addition to research done in conventional synthetic laboratories, new advances in computational chemistry will be incorporated in the research program to gain further insight into the catalysis. The development of catalyst systems with excellent thermal stability, activity, and substrate scope will greatly benefit from this multi-prong approach. The chemical structure of these new systems will be further tailored at a later stage (5 to 10-year timeframe) to address other complex issues, including that of selectivity. In the long term, this research program will lead to easy and controlled ways to make carbon-carbon double bonds, giving access to materials and organic compounds with new and enhanced properties, including drugs with potent biological activity.