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Enantioselective Transition Metal Catalysis for Efficient Chemical Synthesis

Final Report Summary - ETMCECS (Enantioselective Transition Metal Catalysis for Efficient Chemical Synthesis)

This ERC-funded project was based around the development of new catalytic methods to prepare organic compounds that might be used as building blocks for the development of new medicines, agrochemicals, or other functional molecules. Many of these building blocks are “chiral” – that is, they are non-superimposable on their mirror images. When preparing these compounds, controlling which particular mirror image is formed is often critical. For example, opposite mirror images of compounds can possess different biological properties when interacting with biological systems (which are themselves chiral).
Of the different ways in which chiral organic building blocks can be prepared, the use of transition metal catalysts is particularly powerful because:
• The use of small quantities of a catalyst to accelerate and control the outcome of reactions can be highly efficient, often reducing the quantities of waste generated.
• Transition metal catalysis enables new ways to break and form chemical bonds, allowing more concise synthetic routes to target molecules.
• The use of a chiral ligand (an organic compound bound to the transition metal center) in the catalyst can enable the selective preparation of one mirror image form, in which case the reaction is termed “enantioselective”.
• Varying the chiral ligand in the catalyst can lead to fine-tuning of chemical reactions, allowing optimization for greater efficiency. In some cases, changing the ligand can alter the outcome of the reaction entirely, enabling different chemical building blocks to be accessed.
In this project, we have developed several new organic reactions using various transition metal catalysts to access valuable chiral building blocks with high enantioselectivities:
- Copper-catalyzed addition of compounds containing alkenes (carbon–carbon double bonds) adjacent to nitrogen-containing cyclic structures called “azaarenes” (which are extremely common structures in biologically active pharmaceuticals, agrochemicals, and natural products) to ketones (compounds containing carbon–oxygen double bonds).
- Copper-catalyzed addition of a boron-based functional group to compounds containing two alkenes adjacent to each other.
- Rhodium-catalyzed additions of compounds containing carbon–boron bonds to imines (compounds containing carbon–nitrogen double bonds).
- Palladium-catalyzed additions of azaarene-containing compounds to imines.
Furthermore, we have developed a range of different reactions that involve the functionalization of normally unreactive carbon–hydrogen bonds, using catalysts based upon palladium, rhodium, or iridium. These "C-H functionalization" reactions have the conceptual advantages of shorter routes to target compounds and the generation of less chemical waste.
The outcomes of this project have therefore been very successful. At the end of the project, 17 papers have been published and ongoing work arising from this project is anticipated to lead to >5 additional publications.