Details of Grant 

EPSRC Reference:	EP/J001872/1
Title:	Chiral Concepts in s-Block Metal Amide Chemistry
Principal Investigator:	O'Hara, Dr C
Other Investigators:
Researcher Co-Investigators:
Project Partners:	AstraZeneca
Department:	Pure and Applied Chemistry
Organisation:	University of Strathclyde
Scheme:	Career Acceleration Fellowship
Starts:	01 October 2011	Ends:	30 September 2016	Value (£):	907,993
EPSRC Research Topic Classifications:	Chemical Structure Chemical Synthetic Methodology Co-ordination Chemistry
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:	Panel Date Panel Name Outcome 14 Jun 2011 Fellowships 2011 Interview Panel B Announced
Summary on Grant Application Form
Organolithium reagents (i.e., compounds that contain a direct bond between a lithium and a carbon atom) are extremely important reagents in chemical synthesis. It has been estimated that 95% of all pharmaceuticals rely upon the use of these cornerstone reagents at some point in their preparation. In general, organolithium compounds are very reactive; however, this is sometimes coupled with the compounds exhibiting a lack of selectivity even when the reactions are carried out at very low, cryogenic temperatures. This is a massive hurdle to the synthetic chemist! To overcome this situation, less reactive, but more selective compounds [such as organomagnesium (e.g., Grignard) or organozinc (e.g., Reformatsky) reagents] are often used; however, these reagents are often too inert. Recent research has shown that by combining a lithium reagent with a magnesium (or zinc) one, a whole new and in many cases surprising chemistry can be produced. Fascinatingly, in these cases the reactivity cannot be replicated using the monometallic compounds on their own! Another important theme of this work is the generation of organic molecules (i.e., molecules which contain no metal atoms) which can be used as building blocks for key pharmaceuticals. Just as human beings have a left and a right hand, certain organic molecules (known as chiral compounds) can also be considered left- or right-handed. In medicine, it is common that only one handed form of an organic molecule has the required therapeutic effect; it is also usual for the other handed form to induce nasty side effects. Therefore it is critical that the synthetic chemist can easily produce only one handed form of a specific organic compound. In chemistry this is known as enantioselective synthesis. This research will systematically investigate the two aforementioned topics and combine them for the first time - that is enantioselective synthesis using alkali metal-magnesium or alkali metal-zinc complexes. During the first part of this research many new mixed-metal compounds which contain chiral molecules will be prepared. Various analytical techniques will be used to determine their structure, both in solution and in the solid state. Then a systematic study of how these compounds react with organic molecules will be conducted. It is envisaged that in the near future these new "bimetallics" will be used to complement the well known organolithium reagents that presently corner the market in the pharmaceutical industry. Another area which will be explored is the chemistry of alkali metal amides. Despite their widespread usage, the structural chemistry of alkali metal amides and their complexes continues to spring many fascinating surprises. We have recently observed that molecular rings of various sizes - consisting only of alkali metal cations and amide anions - can capture anions (such as hydroxide and chloride) in the presence of chiral diamine ligands. This new direction in s-block macrocyclic chemistry turns conventional crown ether chemistry on its head and opens the door for simple alkali metal amide/diamine compositions to be utilised in anion recognition chemistry. Results from this new direction within synergic chemistry will undoubtedly appeal to a broad spectrum of academics, including inorganic, organometallic and organic chemists, as well as to supramolecular chemists due to the strong structural and coordination chemistry nature of the area. This new methodology in enantioselective synthesis will also be of considerable interest to researchers in the chemical industry (fine chemicals, pharmaceutical, agrochemical etc.) who strive to produce chiral molecules (new and old!) in a facile manner.
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Organisation Website:	http://www.strath.ac.uk