Asymmetric Catalysis Using Novel Iron Complexes.
Lead Research Organisation:
University of Warwick
Department Name: Chemistry
Abstract
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.
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.
Planned Impact
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.
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.
People |
ORCID iD |
Martin Wills (Principal Investigator) |
Publications
Hodgkinson R
(2016)
Iron cyclopentadienone complexes derived from C2-symmetric bis-propargylic alcohols; preparation and applications to catalysis.
in Dalton transactions (Cambridge, England : 2003)
Del Grosso A
(2017)
Strained alkynes derived from 2,2'-dihydroxy-1,1'-biaryls; synthesis and copper-free cycloaddition with azides.
in Organic & biomolecular chemistry
Knighton R
(2018)
Asymmetric transfer hydrogenation of acetophenone derivatives using 2-benzyl-tethered ruthenium (II)/TsDPEN complexes bearing ?6-(p-OR) (R = H, iPr, Bn, Ph) ligands
in Journal of Organometallic Chemistry
Vyas VK
(2018)
Combining Electronic and Steric Effects To Generate Hindered Propargylic Alcohols in High Enantiomeric Excess.
in Organic letters
Del Grosso A
(2018)
Synthesis and applications to catalysis of novel cyclopentadienone iron tricarbonyl complexes.
in Dalton transactions (Cambridge, England : 2003)
Mistry A
(2018)
Synthesis and cycloaddition reactions of strained alkynes derived from 2,2'-dihydroxy-1,1'-biaryls.
in Organic & biomolecular chemistry
Knighton RC
(2019)
Synthesis and Reactivity of a Bis-Strained Alkyne Derived from 1,1'-Biphenyl-2,2',6,6'-tetrol.
in ACS omega
Forshaw S
(2019)
A strained alkyne-containing bipyridine reagent; synthesis, reactivity and fluorescence properties
in RSC Advances
Del Grosso A
(2019)
Asymmetric ruthenium tricarbonyl cyclopentadienone complexes; synthesis and application to asymmetric hydrogenation of ketones
in Inorganica Chimica Acta
Forshaw S
(2023)
Increasing the versatility of the biphenyl-fused-dioxacyclodecyne class of strained alkynes.
in Organic & biomolecular chemistry
Description | We have been able to prepare and test a large number of iron complexes as proposed in the original proposal. Many of these have given good results and have improved our understanding of the area, and two papers have arisen from this work. In addition, alongside this work we also discovered a new class of strained alkyne which has been the subject of a patent and one research paper to date. Follow-on funding has also been awarded for work in this area and new collaborations have been established. This represents a very good 'bonus' finding. |
Exploitation Route | A collaboration with AstraZeneca will fund a project student to 2021. This student will work on the synthesis of strained alkynes as reagents for biolabelling studies. |
Sectors | Chemicals,Environment,Pharmaceuticals and Medical Biotechnology |
URL | https://warwick.ac.uk/fac/sci/chemistry/research/wills/willsgroup/publications/ |
Description | The discovery of a strained alkyne with the potential to be used in bioconjugations and labeling studies of biomolecules has let to a patent being filed and further collaboration within Warwick University and with AstraZeneca. |
First Year Of Impact | 2017 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Royal Society Newton International Fellowship to Vijesh Vyas Nov 2018-Nov 2020 |
Amount | £85,000 (GBP) |
Funding ID | NIF\R1\180142 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2018 |
End | 11/2020 |
Description | Visiting Fellowship for J Chew |
Amount | £100,000 (GBP) |
Funding ID | SE/AIF/16/001 |
Organisation | Agency for Science, Technology and Research (A*STAR) |
Sector | Public |
Country | Singapore |
Start | 08/2017 |
End | 07/2019 |
Description | Warwick Impact Fund |
Amount | £30,644 (GBP) |
Organisation | University of Warwick |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2016 |
End | 03/2017 |
Description | Collaboration with AstraZenca on Strained Alkynes |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | AstraZeneca (Macclesfield) financially support a PhD student from Oct 2017 - Sept 2021 through a National Productivity Studentship in collaboration with Warwick University. |
Collaborator Contribution | Financial and in kind through access to facilities etc. |
Impact | Just started and in progress |
Start Year | 2017 |
Title | COMPLEXES AND METHODS FOR THEIR PREPARATION |
Description | The invention provides methods for the preparation of ligands for complexes, methods for preparing complexes and complexes having those ligands. Also provided is the use of a complex as a catalyst in a method of synthesis. |
IP Reference | WO2016042298 |
Protection | Patent application published |
Year Protection Granted | 2016 |
Licensed | No |
Impact | Filed by Johnson Matthey, who sell the catalysts. |
Title | Synthesis of a class of strained alkyne for use as bioconjugation agents |
Description | New strained alkynes with potential for bioconjusgation. |
IP Reference | GB1701151.1 |
Protection | Patent application published |
Year Protection Granted | 2017 |
Licensed | No |
Impact | further funding secured. |
Description | Invited lecture at Queens University Belfast 31/1/2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited lecture given on my research work |
Year(s) Of Engagement Activity | 2020 |
Description | Invited lecture at YorkUniversity |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited lecture given on my research work |
Year(s) Of Engagement Activity | 2019 |
Description | LEcture at Chiral India 29-30th October 2015, Mumbai, India |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A lecture on my research 29-30th October 2015, Mumbai, India |
Year(s) Of Engagement Activity | 2015 |
Description | Participation in EUCHEMS conference Liverpool 26-30 August 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation of talk and poster at the August 2018 EUCHEMS conference at Liverpool 26-30th August 2018. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.euchems2018.org/ |
Description | Submitted lecture at Dalton Conference 2018 at Warwick University April 3-5th 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Submitted lecture at Dalton Conference 2018 at Warwick University April 3-5th 2018 |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.rsc.org/events/detail/27854/dalton-2018 |
Description | Submitted lecture at the UK Catalysis Hub Annual Conference at Loughborough 9-11th Jan 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Submitted lecture at the UK Catalysis Hub Annual Conference at Loughborough 9-11th Jan 2019 |
Year(s) Of Engagement Activity | 2019 |
URL | http://events.manchester.ac.uk/event/event:e4y-jhjab6we-q9k8yc/uk-catalysis-conference-2019 |
Description | Workshop at Federal University of MInas Gerais, Brazil |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A group of four academics visited the Workshop at Federal University of MInas Gerais, Brazil to establish and continue collaborations. This led to further exchanges and scientific interactions. |
Year(s) Of Engagement Activity | 2017 |
Description | Workshop at Federal University of Minas Gerais, BRazil |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Participated in workshops with UFMG Brazil, 6-7th Feb 2017 (at Warwick) and Sept 2017 (in Brazil). And in a half day meeting on Catalysis at UFMG in 19-24th Sept 2017. |
Year(s) Of Engagement Activity | 2017 |