Details of Grant 

EPSRC Reference:	EP/G005206/1
Title:	The Primary Phosphine Renaissance
Principal Investigator:	Higham, Dr LJ
Other Investigators:
Researcher Co-Investigators:
Project Partners:	Rhodia
Department:	School of Chemistry
Organisation:	Newcastle University
Scheme:	Career Acceleration Fellowship
Starts:	01 March 2009	Ends:	30 April 2014	Value (£):	919,531
EPSRC Research Topic Classifications:	Catalysis & Applied Catalysis Chemical Synthetic Methodology Co-ordination Chemistry
EPSRC Industrial Sector Classifications:	Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 26 Jun 2008 Fellowship Allocation Panel Meeting Announced 09 Jun 2008 Fellowships 2008 Interviews - Panel A Excluded
Summary on Grant Application Form
My research interests focus on novel organophosphorus compounds with applications in catalysis, materials and medicine. Our most recent breakthrough came with asymmetric primary phosphines; these contain a chiral carbon-based backbone attached to a phosphorus atom, which is also bonded to two hydrogens. In overly simplistic terms, we describe the phosphorus centre as also possessing a 'lone pair of electrons', through which it can bind to metals and behave as a ligand. The reactivity of the P-H bonds make them ideal starting materials for the synthesis of tertiary phosphines, a crucial class of ligand used in making products as diverse as mint flavourings and anti-Parkinson's drugs. However primary phosphines (unlike their nitrogen counterparts) have a fearsome reputation for being spontaneously flammable, occasionally explosive and often toxic; phenylphosphine is no longer sold in the UK by a major chemical manufacturer due to its hazardous nature. Primary phosphines are so reactive because they can form strong P=O bonds with dioxygen from the air. However the P-H bond is also highly reactive, which means we can convert these bonds into highly useful P-C, P-Cl, P-OR or P-N functionality with ease.Our research has discovered chiral primary phosphines which are air-stable, white solids. Of the very few known air-stable primary phosphines, sterics and negative hyperconjugation from a heteroatom (O or N) elsewhere in the molecule have been used to account for this stability. Our compounds often don't possess these features so another factor must be responsible for their stability; instead we have accumulated significant evidence to propose that increasing conjugation also leads to a greater resistance to oxidation.We have been fortunate enough to get some 'firsts'; an X-ray crystal structure of an optically pure primary phosphine; the first electrochemical study, which revealed that the removal of an electron is more difficult when the extent of conjugation is greater (the first step in P oxidation by aerobic oxygen); we were also the first to bubble dioxygen through bench chloroform solutions of our stable phosphines and found that they were still resistant to oxidation.To exploit these early findings we will elucidate the rules about what degree of conjugation in necessary to afford air-stability. If we lower the resonance stability by incorporating heteroatoms (whose p orbitals don't overlap so well with the pi system on the rings), do we see a breakdown in oxidative resistance? Can electron withdrawing groups similarly offer enhanced stability? We will use molecular modelling to understand and predict why the sensitivity to dioxygen is related to conjugation, and back this up with synthetic studies. We will also look beyond phosphorus to see if we can extend the principle of conjugative stabilisation to primary arsines, other hydrides and carbenes.Whilst we predict these properties for new molecules, we will also prepare new chiral ligands from these unique starting materials. We will synthesise new phosphonite, phospholane and phosphoramidite ligand libraries. Industry use sensitive primary phosphines in manufacturing important phosphine ligands; can we design safer variants with built in conjugation to reduce these hazards? Water-soluble phosphines will be made by hydrophosphination of formaldehyde to yield catalysts capable of operating under aqueous and biphasic conditions; the latter allows for the recovery of expensive, toxic transition metals from the products.We will also study low oxidation state rhenium coordination chemistry using phosphines built from the primary compounds. This is an understudied area of highly interesting chemistry as it allows us to make new imaging agents for disease. We will functionalise the phosphines with biomolecules and fluorescent tags and then substitute in radioactive technetium and rhenium isotopes (with our Oxford collaborators) to study in vitro and in vivo imaging.
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Organisation Website:	http://www.ncl.ac.uk