Asymmetric Catalysis Using Novel Iron Complexes.

There is a continual and ongoing requirement to prepare new and more complex molecules, for example as pharmaceutical candidates, agrochemical products and novel materials. In addition, pressures on dwindling resources and energy supplies make it imperative for more efficient routes to be found to known molecules. To achieve these objectives in a sustainable manner, it is necessary to continue to develop more selective and efficient catalysts. These will reduce waste and side-product formation, and have lower energy requirements during use and for subsequent product isolation.

This proposal is concerned with the development and evaluation of a series of catalysts for the precise control of the way in which hydrogen atoms are added to specific bonds within a molecule during certain transformations. This process is often an important component of the synthetic approaches to a large proportion of pharmaceutical products and intermediates, agrochemicals and materials. This transformation can often be achieved efficiently using existing catalysts however a drawback of these catalysts is that they are all based on expensive metals, most typically rhodium, ruthenium, iridium and palladium. In addition, the long term security of these very expensive metals is by no means secure and each of them exhibit significant toxicity. For these reasons, there is an increasingly compelling need to reduce the use of precious-metal catalysts in industrial use and to ideally eliminate them fully.

In order to address this challenge, this project will focus on the development of catalysts based upon complexes of the transition metal iron, which is known to be a very active for the control of hydrogen addition reactions. Some preliminary related results have already been obtained, which confirm that the proposed synthetic approach to the catalysts is a valid one. The applicant is now set to prepare further extended iron complex derivatives and to test them in hydrogenation reactions. The project will involve the preparation of a broad range of iron-based catalysts with a diverse structure, and these will be tested extensively against a wide range of substrates. Through this process, we shall determine what structural features are most valuable, and which should be avoided. In addition a range of valuable, pharmaceutically-active target molecules will be prepared in order to demonstrate the value of the catalysts.

In summary, this project will result in the development of a new class of environmentally friendly, inexpensive and selective catalysts for hydrogen addition to a broad range of substrate classes, thus significantly extending the synthetic power and value of this already pivotal synthetic transformation.

The economic and societal beneficiaries, and how they will benefit, will be described in this section.

i) Economic.
Every molecule that is prepared, be it a pharmaceutical, and agrochemical, a polymer, a material or any other type of product, usually requires a number of synthetic steps. Ideally, each of these would be 100% atom efficient, use inexpensive and non-toxic materials, generate no waste or side products, require minimal energy and generate no waste materials. Achieving these demanding requirements must be the ultimate aim of the synthetic chemist. Each time synthetic chemists improve a process, we get closer to these ideals and also create a more economical (as well as environmentally-friendly) process. UK companies which are involved with catalysis can generate economic benefits in the form of increased profits by reducing their costs and overheads and can also sell or license the technology to buyers outside the UK.

Good catalytic processes can not only generate incremental improvements, they can also deliver great forward steps in progress.
Taking these requirements in turn, the work in this project will contribute positively in the following ways:

Atom efficiency; hydrogenation reactions (the subject of this proposal) are 100% atom efficient in terms of the reaction, and close to 100% if the catalyst loading can be minimised and/or recycled and reused, which is

Inexpensive and non-toxic; iron is substantially cheaper and less toxic than commonly used precious metals such as ruthenium, rhodium, Iridium and palladium.

Energy; significantly less energy is required to refine iron than precious metals, and the catalysts will work at low temperatures.

Waste and side product generation; the efficient catalysts will be used at low loadings to facilitate product purification. Their lower toxicity will reduce the need for complex purifications to reduce the metal to less than 1 ppm as is required for precious metals. Precious metal refining creates very large amounts of side and waste products. Hydrogenation reactions are very selective and typically generate few side products.

Hence there are many potential positive economic impacts from the project.

ii) Societal.
Without repeating the discussion above, all of the benefits described above will have a positive effect on our society. Elimination of the need for toxic metals will contribute to improving our health, as there will be fewer pollutants in the environment. Reduction of energy requirements means less demand for dwindling resources so that what we have will last longer and sustainable energy sources will be able to fill the gap (without that gap continuing to get wider). Reduction of waste is a benefit for all of society, as landfill space is limited, and the environmental impact of the waste is reduced. All of these changes help to lead to a healthier and more sustainable society.

Every time we can improve a chemical step, we can improve the economy and the environment we live and work in.