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

Lead Research Organisation: University of York
Department Name: Chemistry

Abstract

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.
 
Description This project focused on the area of synthetic organic chemistry. In particular, some fundamental studies on the reactions of strong organolithium bases were explored. Two key findings were: (i) a new type of reactivity of an organolitihum diamine complex and (ii) the ability to functionalise piperidines. Piperidines are common features in pharmaceuticals and this advance could be very useful for the synthesis of the drugs of the future.
Exploitation Route Methodology may be used in the pharmaceutical industry for the synthesis of drug molecules.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

 
Description AstraZeneca
Amount £22,500 (GBP)
Organisation AstraZeneca 
Sector Private
Country United Kingdom
Start 09/2010 
End 09/2013
 
Description Pfizer
Amount £22,800 (GBP)
Organisation Pfizer Ltd 
Sector Private
Country United Kingdom
Start 09/2010 
End 09/2013