A New Iron Age: Atom efficient P-C bond forming reactions with simple, designed iron catalysts

Catalysis is the process by which chemical reactions are made to run faster at lower temperature. The vast majority of chemical industries rely on developing catalysis therefore making vital industrial processes, fundamental to the pharmaceutical, agrochemical and fine chemical industries, easier and more cost efficient. Catalysis allows us to precisely modify chemical structure through the ability to make and break specific chemical bonds. Catalyst design is therefore an incredibly important and vital undertaking: the key to unlocking new reactivity and new bond forming methods.

This project looks into the design of catalysts which contain staggeringly simple motifs along with abundant and inexpensive iron centre. Iron is also biocompatible and non-toxic providing a strong foundation for our targeted reaction: hydrophosphination. These reactions allow the synthesis of carbon-phosphorus bonds using efficient reaction conditions, forming key motifs or new architectures with ease. The preparation of phosphorus-containing motifs cannot be underestimated, allowing the preparation of new ligands, organocatalysts and biologically relevant motifs vital to a host of crucial manufacturing sectors. Beyond this we will develop this carbon-phosphorus bond forming chemistry for the preparation of new building blocks to construct non-burning plastics (high value materials used in advanced electronic devices and as commodity chemicals in the flame retardants industries).

The aim:
* Investigate their potential in 100% atom-economic processes which make molecules relevant to the pharmaceutical and agrochemical industries.
* Generate high value chemicals by developing a new route to the building blocks for phosphorus-containing plastics; this new route gives access to new plastics.

Society:
In the medium to long term society will benefit from this research because it is envisaged that the development of new ligands will allow more efficient syntheses of important organic motifs (lower loading of pre-catalyst, lower reaction temperature means reduced production cost of chemicals). Catalyst design gives us the potential to undertake new reactions, generate new motifs or make and break bonds that have never been achieved before. This has the potential to open up new avenues in molecular space, the importance of this lies firmly in the pharmaceutical/ agrochemicals sector where the drug pipeline has started to dry up due to limitations on the areas of chemical space that can be accessed through standard synthetic transformations: new drug molecules means better healthcare.

The focus of this research is on simple ligands complexed to iron: if we can start to undertake industrially important synthesis of phosphorus-containing molecules in such a way, replacing the need for the use of the Platinum Group Metals (PGMs), then these expensive and rare metals can be used for other applications were there are currently no alternatives. As a result the development of new processes which utilise an alternative to the PGMs is of fundamental importance. Therefore the overarching impact from these outcomes will also be economic: cleaner, greener, cheaper syntheses along with new drug molecules.

A new route to phosphaalkenes would allow the development of new phosphorus-containing polymers. With access to new materials we envisage new or improved properties/ applications, benefiting industry and thus society as a whole.


People:
The PDRA will become highly trained in all aspects of synthetic inorganic chemistry, organic chemistry and polymer science, leaving them well-positioned to continue to pursue a career in academia or industry. The impact activities incorporated into the proposal will also leave the PDRA with a strong network in industry and with softer skills related to public engagement and the promotion of synthetic chemistry, thus having a positive impact on society.


Business:
In addition to the collaborators, this research will impact upon the wider chemical industries, most notably pharmaceutical, biomedical, agrochemical and fine chemicals manufacturers. Presentation of our research at the CatScI industry conference (Spring 2016) as well as hosting an open forum session at the conference will help to engage attendees from industry (in the past this has included Astra Zeneca, Bayer CropScience, Chiral Quest, Dr Reddy's Laboratories Inc., EcoSynth, Jansene Pharmaceutica, Johnson Matthey, PhosphonicS to name but a few) and help influence future research plans. Industry will benefit from first-hand experience of accessible, tuneable, inexpensive catalysts derived from simple precursors and an abundant metal. Abundant metal catalysis is gathering momentum in academia, but the uptake within industry lags behind: presenting research at leading industry conferences will help to deliver high impact science to its key market.

Malonic acid (one of our ligand precursors), although useful in biological treatments, has limited use in synthetic chemistry. Malonic acid can be prepared from the fermentation of biomass and either hydrogenated to form 1,3-propanediol (for the synthesis of step growth polymers) or transformed into simple organic motifs. Although much effort is being placed on the fermentation route to malonic acid, the potential uses are limited: by transforming malonic acid into the malonamide ligand, and proving its use in synthetically desirable catalytic transformations, we can expose a new market for malonic acid. Thus, bio-derived malonic acid has a new use. This will benefit the producers of biomass (large scale agriculture) and companies specialising in fermentation of biomass by facilitating a new customer base for their product (i.e. pharmaceutical industry).