Back to Basics: Investigating Structure, Reactivity and Catalysis of Organolithium-Diamine Complexes

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This project is concerned with developing a deeper insight into a fundamental process in organic chemistry, namely deprotonation of a weak carbon acid using a strong base. Acid-base interactions and deprotonation is a concept first met in school chemistry classes (acid-base titrations). Deprotonation using a strong base composed of a reactive organolithium reagent complexed to a diamine has become one of the most powerful tools in organic synthesis in recent times. It is also possible to use a chiral diamine (of which naturally occurring (/)-sparteine is the most famous) to control the stereochemistry (or handedness) of the products. Unfortunately, despite their widespread use in synthesis, very little structural and mechanistic information is known about these organolithium-diamine complexes. In this project, collaboration between two groups (O'Brien, York, UK) and (Hilmersson, Goteborg, Sweden) with complementary areas of expertise will be established to unravel the complexities of organolithium-diamine-mediated deprotonation processes. The research will investigate the kinetics and thermodynamics of complexing diamines to organolithiums as well as the solution structures and stoichiometry of the complexes that are formed. This project will also deliver a considerable body of kinetic data on reactivity of organolithiums complexed to diamines which will inform the synthetic chemists and allow organolithium reactions to be optimised (in industry and academia). All of these results will be combined to understand and rationalise one-ligand and two-ligand catalytic asymmetric deprotonation processes, an under-developed research area, which has received no mechanistic attention thus far. This project is of much importance and use to Process R & D groups of, for example, pharmaceutical companies and Astra-Zeneca are specifically supporting the research.