Cast iron catalysis: New catalytic protocols for carbon-phosphorus bond synthesis

Lead Research Organisation: University of Bath


The importance of catalysis cannot be underestimated; it is responsible for 35% of the world's Gross Domestic Product and is one of the key processes needed to tackle some of the world's grand challenges. For example, catalysis is a fundamental tool for the efficient preparation of modern pharmaceuticals and agrochemicals, vital for a rapidly expanding world population. Catalysis also contributes to our future energy needs by enabling new methods of energy capture, storage and release. It is essential for a sustainable future not least because of the inherent ability to make chemicals in a more environmentally benign manner, allowing chemical reactions to run faster at lower temperature making the preparation of key chemicals easier and more cost efficient. While the Platinum Group Metals dominate this landscape, development of abundant Base Metal alternatives is urgently required to maintain and advance global development.

This fellowship will specifically deliver new catalytic strategies for the preparation of phosphines. Phosphorus-containing motifs are crucial to a host of manufacturing sectors where they constitute the vast majority of ligands used by the fine chemicals and pharmaceutical industries. Phosphines are excellent organocatalysts, constitute a range of biologically relevant motifs and since antiquity, have been central to the agrochemical industry. Traditional methods of making phosphines are inadequate by modern standards of innovative research; they often generate vast amounts of chemical waste and are limited in the types of chemical architectures that can be accessed both through a restricted pool of 'reactive' phosphines and by the small number of classical phosphine-tolerant reactions available to the synthetic chemist. We therefore need new and efficient methods to make phosphines that will overcome these technological barriers. I seek to develop novel catalytic protocols that are atom economic, use inexpensive phosphorus sources and/or exploit some of the simplest forms of phosphorus, using them in a new way to build up large amounts of molecular complexity from the simplest possible starting materials. In order to achieve this I will use mechanistic investigations to unravel the finer details of the catalytic cycles involved and thus inform future reaction development. By using iron, the fourth most abundant element in the earth's crust, these new processes will have sustainability built-in from first principles. The challenge is clear; few examples of using iron in this way exist. I aim to change this.

The aim:
-Investigate iron catalysts in atom-economic phosphine synthesis, making molecules relevant to the pharmaceutical and agrochemical industries.

-Use iron catalysis for the activation and subsequent controlled delivery of the simplest phosphines.

-Develop iron photocatalysis for completely novel reactivity, complementary to traditional thermal processes.

Planned Impact

The importance of this research lies firmly in the pharmaceutical/ agrochemicals sector, while there will be significant environmental and economic impact within the manufacturing sector concerned with the production of phosphorus containing materials.
For example, the agrochemical glyphosate with a forecasted market value of $9.5 billion (by 2020) is the world's bestselling herbicide. Since 1974, 8.6 billion kg of this product has been synthesised using stoichiometric and wasteful transformations. The work proposed herein employs an environmentally benign catalyst, with visible light using catalytic hydrophosphination, avoiding the need for pre-functionalisation and vastly reduces the amount of salt waste generated. Furthermore, using this system will allow us to easily explore analogues of glyphosate, test their properties and begin to combat the global problem of herbicide resistant weeds, an issue threating the world's ability to feed itself.
A new route to phosphaalkenes would allow the development of new phosphorus-containing polymers with applications ranging from drug delivery, dentistry and materials. Indeed, organophosphorus materials are essential for the production of flame-retardants where their non-burning low-charring properties make them ideal for use in household products. The sustainable methodologies proposed will not only dramatically reduce this industry's environmental footprint but also provide entirely new classes of phosphine enabling the production of the next generation of safer flame-retardants
In the medium to long term, trickle down effects from this research will benefit society across a range of avenues. For example, catalyst design will unlock new reactions, generate new structures and make or break bonds previously deemed impossible. This has the potential to generate new chemical shapes with unusual properties, key to helping the beleaguered pharmaceutical drug pipeline.
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 unsustainable metals can be used for other applications were there are currently no alternatives.

The PDRAs 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 PDRAs with a strong industrial network and with softer skills related to public engagement and the promotion of synthetic chemistry, thus having a positive impact on society and its perception of the chemical industry.

It is clear that functionalisation of the more challenging phosphorus targets can only lead to publication in the highest profile journals, surpassing our early proof-of-concept work. Long term, these results will have a transformative effect on the fine chemicals, pharmaceutical and agrochemicals industries where new practical and efficient routes to P-C bonds and the development of new molecular architectures is fundamental to their continued growth.
Hosting roundtable events will help to engage these key sectors in our research and in the future of homogeneous catalysis. By using established contacts within the Centre for Sustainable Chemical Technologies, which includes Astra Zeneca, Johnson Matthey and Syngenta, we will engage in two-way discussions which will also help inform our future research plans. Industry will benefit from first-hand experience of accessible, tuneable, inexpensive catalysts derived from simple precursors and an abundant metal, the uptake of which lags behind academia. Presenting research to leading industrialists will help to deliver high impact science to its key market.


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Description Very selective hydrogenation and dehydrogenation reactions can be undertaken using this catalyst and a range of E-H compounds, this has also led to unprecedented mono-deuteration reactions.
Exploitation Route Our mono-deuteration chemistry might be of interest to the pharmaceutical industry.
Sectors Chemicals