Artificial photosynthesis strategies for synthesis: Combined photoredox and transition metal-catalysed transfer hydrogenation of C-C multiple bonds
Lead Research Organisation:
University of Greenwich
Department Name: Pharm., Chem. & Environmental Sci., FES
Abstract
The feasibility of chemical reactions is generally governed by the existence of a sufficient thermodynamic driving force pushing them. When performing sequences of reactions to prepare compounds of interest, this driving force is ensured by using in each step highly reactive small molecule reactants with a high energy contents, and the availability and procedence of such reactants determine the limits of how practical and sustainable a chemical process can be. Illustrative examples are oxidations and reductions, two of the main categories in which we classify chemical reactions. In the case of oxidation reactions, molecular oxygen can be used an ideal oxidant, since it is abundant and innocuous and in ideal conditions it can be consumed to produce only water as a by-product. Similarly, we could conceive using water as an ideal reductant, which would result in production of only oxygen as by-product. However, this faces the problem of water not being a good reductant or, in other words, lacking the thermodynamic driving force needed to push the reaction. Instead, the most common reductant used for organic compounds is molecular hydrogen, which is not found in nature and is instead produced in an overwhelming majority from fossil fuels in a process that releases enormous amounts of carbon dioxide.
Remarkably, photosynthetic organisms use water as the reductant in the fixation of carbon dioxide to form carbohydrates and release molecular oxygen, with sunlight providing the required energy. Taking inspiration from this, in this proposal we aim to develop an 'artificial photosynthesis' approach for the reduction of certain types of organic compounds of industrial importance -namely, alkenes and alkynes. To do this, we will need to develop systems where two catalysts operate in a concerted manner, with one using the energy from light to oxidise water (forming oxygen and providing the 'reductive power') and the other reducing the organic compound. Catalysts are already known capable of performing the first of these roles, and in this project we will develop the second, thus bridging the key gap to enable true artificial photosynthesis reactions in organic chemistry.
This investigation will result in more sustainable methods for reduction of alkenes and alkynes which, importantly, are among the largest scale organic reactions performed in chemical industry. Thus, success in this project will contribute towards the development of a more sustainable chemical industry in general, reducing its dependence on the use of fossil sources of carbon. Also, this investigation will produce valuable information on the mechanistic manifolds involved, thus providing facilitating the discovery of other efficient and sustainable reactions in the future.
Remarkably, photosynthetic organisms use water as the reductant in the fixation of carbon dioxide to form carbohydrates and release molecular oxygen, with sunlight providing the required energy. Taking inspiration from this, in this proposal we aim to develop an 'artificial photosynthesis' approach for the reduction of certain types of organic compounds of industrial importance -namely, alkenes and alkynes. To do this, we will need to develop systems where two catalysts operate in a concerted manner, with one using the energy from light to oxidise water (forming oxygen and providing the 'reductive power') and the other reducing the organic compound. Catalysts are already known capable of performing the first of these roles, and in this project we will develop the second, thus bridging the key gap to enable true artificial photosynthesis reactions in organic chemistry.
This investigation will result in more sustainable methods for reduction of alkenes and alkynes which, importantly, are among the largest scale organic reactions performed in chemical industry. Thus, success in this project will contribute towards the development of a more sustainable chemical industry in general, reducing its dependence on the use of fossil sources of carbon. Also, this investigation will produce valuable information on the mechanistic manifolds involved, thus providing facilitating the discovery of other efficient and sustainable reactions in the future.
| Description | As a result of the work in this grant we have made several important findings that have shaped the research in our team for the next years. We have discovered several new reactions that were unkonwn and that we believe will be useful for organic synthesis and, therefore, scientific and technological areas that depend on it such as medicinal chemistry, agrochemistry and pharmaceutical science. Although these new reactions are different, they share as a common characteristic that they result in the coupling of two organic molecules into a larger, more complex molecule containing all the atoms from the two starting ones, in such a way that no waste is produced in the process. Thus, our new reactions will help chemists in other areas produce molecules in a cheaper and greener way. |
| Exploitation Route | As mentioned above, the main outcomes from our research are new methods to assemble molecules. These methods will be used by chemists in areas such as medicinal chemistry, agrochemistry and pharmaceutical science, who need to produce new molecules in their search of new, useful bioactive compounds. They will be applied by chemists working in both academic research and industry, both in research and manufacturing. |
| Sectors | Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology |
| Description | A modular platform for regio- and stereoselective photocatalytic C-H functionalisation reactions: Oxidative alkylation of pyridines as a case study |
| Amount | £20,000 (GBP) |
| Funding ID | RGS\R2\212051 |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 08/2023 |
| Description | SUPRAMOLECULAR CONTROL OF SELECTIVITY IN HAT CATALYSIS - TARGETED FUNCTIONALISATION OF SP3 C-H BONDS |
| Amount | £32,000 (GBP) |
| Organisation | GlaxoSmithKline (GSK) |
| Sector | Private |
| Country | Global |
| Start | 11/2022 |
| End | 11/2026 |
| Title | Methods for fast and efficient synthesis of P2N2 ligands |
| Description | P2N2 ligands are central to the project and, although they have been known for some time, methods for their synthesis were complex and lacked generality. We have developed a general method based on the one-pot reduction of dichlorophosphines and subsequent condensation of the formed primary phosphines with formaldehyde. The method simplifies the purification process and allows the preparation of a range of differently substituted P2N2 ligands in a modular manner. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | The main impact is on allowing us to synthesise the named ligands in a fast and reliable manner, thus accelerating our work on reaction discovery. Upon publication, we expect the method will be use by other groups in the area, leading to discovery/optimisation of other catalytic reactions. |
| Description | An artificial intelligence for prediction of selectivity in photocatalytic C-H functionalisation |
| Organisation | University of Greenwich |
| Department | School of Science Greenwich |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | As a result of my EPSRC-funded research I discovered new, simple photocatalysts for C-H functionalisation reactions of aliphatic compounds. This is an exciting reaction, which would be perfectly suited to enable late-stage functionalisation strategies for synthesis, a synthetic strategy with enormous potential to streamline research in medicinal chemistry and drug discovery but which has not been fulfilled to date. However, aliphatic C-H functionalisation is limited by the enormous challenge of systematically controlling or predicting the reaction regioselectivity. Starting from the discoveries in my group, we developed a new research project on using machine learning to develope a computational model for selectivity, and enrolled into the project Dr Jiayun Pang, a computational chemist with expertise in machine learning applied to prediction of physicochemical properties of compounds. |
| Collaborator Contribution | Dr Jiayun Pang is an expert in computational chemistry and machine learning. She has helped design a strategy for the application of machine learning to the problem of predicting selectivity in photocatalytic C-H functionalisation. Together we have secured funding from the University of Greenwich for this project, through a PhD studentship. We have recruited a student who started recently and we are supervising him jointly. |
| Impact | The collaboration is multidisciplinary, involving synthetic chemistry (photocatalysis) and computation (machine learning). No outputs have been generated yet, besides the recruitment and onboarding of the PhD student |
| Start Year | 2022 |
| Description | Mechanism of the spontaneous photochemical C-H functionalisation of ethers |
| Organisation | State University of Campinas |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | During our EPSRC-funded research, we discovered a reaction between ethers and alkenes promoted by visible light but not requiring a photocatalyst. Besides a potentially useful transformation itself, this reaction was mechanistically puzzling. Thus, we devised a plan for a detailed mechanistic study through both experimental and computational methods. My team has performed the experimental studies, specifically showing that the process is likely a radical chain reaction initiated by oxygen and light. |
| Collaborator Contribution | We enrolled into this project Prof. Atahualpa Braga from the State University of Campinas whose team is performing computational studies on the reaction. They have confirmed that a radical chain mechanism fits our experimental observations and are currently working on detemining the light-mediated initiation step. |
| Impact | No publications yet, but a significant amount of data has been produced that we expect to publish shortly. The collaboration is somewhat interdisciplinary, involving experimental and computational chemistry. |
| Start Year | 2022 |
| Description | Photocatalytic synthesis of difluoromethyl-substituted compounds |
| Organisation | Queen Mary University of London |
| Department | Department of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | As a result of my EPSRC-funded work, I was approached by Dr Stellios Arseniyadis to collaborate on one of his projects dealing with the preparation of difluoromethyl-substituted compounds. I have been performing computational and mechanistic studies on the reaction developed by his team, while one of my PhD students has contributed to experimental reaction optimisation. I have created a computational model that successfully explains the reaction mechanism and stereoselectivity. |
| Collaborator Contribution | The team of Dr Arseniyadis performed most of the reaction development, optimisation and scope. |
| Impact | We are preparing a publication together at the moment. Also, a member of my team presented our research at the RSC Sustainable Synthesis and Catalysis in London in November 2022. |
| Start Year | 2021 |
| Title | Parallel photoreactor for reaction discovery |
| Description | As a part of our research, we have developed a new parallel photoreactor to use for reaction discovery, in synthetic chemistry. The reactor is based on a 3D printed structure and some easily assembled electronic components, with the aim of making it available to researchers as an open source design. Final adjustments to the design for incorporation of safety measures and underway and it will soon be released in a publication. |
| Type Of Technology | Physical Model/Kit |
| Year Produced | 2022 |
| Impact | The parallel reactor has already contributed to accelerate reaction discovery and optimisation work in my group, and we expect it to lead to several publications further down the line. Upon public release we expect two areas of impact: - Use by other research groups will accelerate reaction discovery and optimisation beyond our own team. - We have made initial contacts with potential distributors to offer an assembly service, allowing those without ability or time to build the reactor themselves to buy it from us directly. This will be done in conjunction with the University of Greenwich. |
| Description | Lecture at U3A Eltham |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | A lecture at the U3A Eltham Science group, as part of their regular sessions, attended by around 30 people. It sparked questions and a very lively discussion afterwards and the coordinator reported very positive feedback and an increased appreciation of the importance of organic chemistry research |
| Year(s) Of Engagement Activity | 2021 |
| Description | Stall at the Medway Rapture Festival |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | We installed a stall at the Medway Rapture Festival were we carried out hands-on activities on photochemistry with visitors. The festival was a two-day event attended mostly by young adults and families with children. Visitors could see the photoreactors we use in our research and discuss the research we do, as well as do themselves several experiments making cyanotype prints, studying how sunscreen works and preparing a chemoluminescent compound. |
| Year(s) Of Engagement Activity | 2022 |