Recent developments in photoredox catalysis have led to much interest in academic research as well as in pharmaceutical, agrochemical and fine chemical industries. Photoredox-catalysed reactions proceed by free radical mechanisms. Mild reaction conditions, excellent functional group tolerance, high selectivity and low energy consumption make them highly attractive for modern synthetic applications. However, due to short-lived nature of radical intermediates, the mechanisms of these reactions are complex and difficult to model and optimise. Many radical reactions are chain processes, and even small perturbation to the radical chain can lead to significant changes in the reaction outcome.
Improving the yields of synthetic radical reactions through mechanistic understanding requires quantitative detection of radical intermediates – but this is a challenging task, radicals are an elusive species! They are often detected indirectly following their reaction with a chemical trap. However, conventional radical trapping suffers from poor stability of adducts, poor selectivity of their detection, ubiquitous side reactions. We have recently reported a new method for indirect detection of radicals, which addresses many of the disadvantages of the conventional techniques (J. Am. Chem. Soc. 2022, 144, 15969). Our method has already made it possible to qualitatively observe a wide range of radical intermediates and assign their structures in many different systems including synthetic organic reactions. In this project, we will make our radical detection technique quantitative, and apply it to model and optimise radical reactions relevant to pharmaceutical and agrochemical industries.
- To develop methodology for quantitative detection of radical intermediates in synthetic reactions.
- Use this quantitative information to better understand and model radical chain reactions.
- Apply new technique to improve yield/selectivity of topical photoredox-catalysed reactions.
Our new radical detection method uses mass spectrometry (MS) for analysis. In order to make MS quantitative, we will synthesise a range of new cationic and isotopically-labelled radical traps. Our traps are compounds with a double bond (which the radicals will add to) and a radical leaving group (so that the product of radical trapping is no longer a radical but a stable molecule).
We use a state-of-the-art MS instrument (FT-ICR) with very high mass resolution in order to be confident in structure assignment. Analysis will be further enhanced by coupling chromatography to MS (i.e., LC-MS) and using advanced MS techniques such as tandem MS.
In order to build kinetic models of radical reactions, we will measure the rates of trapping by using competition reactions with other compounds. We use Kintecus software for kinetic modelling.
Once our quantitative methodology for radical detection has been established, we will apply it to optimise recently-reported photoredox reactions catalysed by donor-acceptor complexes. These reactions are metal-free and have excellent substrate scope.
Novelty and collaboration with industry
Our new radical trapping approach provides an unprecedented opportunity to quantitatively detect radical intermediates in complex reaction mixtures. These data will help improve our understanding and modelling of photoredox-catalysed and other radical processes, which in particularly important in process development, e.g., in pharmaceutical or agrochemical industry. The project is co-funded by Syngenta who we have had a strong collaboration with over several years. You will benefit from the interactions with our partners and fellow students at annual Syngenta Collaborative Research Conferences.
The project is multidisciplinary and you will be trained in a diverse range of synthetic and mechanistic organic methods and radical chemistry. This will include organic synthesis, advanced mass spectrometry, reaction kinetics, data analysis, kinetic modelling.
What makes a suitable candidate?
You will be interested in organic chemistry, have an open and curious mind. You will be fascinated by reaction mechanisms. You will enjoy spending a day in the lab, making new compounds and looking at NMR and MS spectra. You will be motivated by finding answers to your questions through data interpretation.
You will follow our core cohort-based training programme to support the development of scientific, transferable and employability skills, as well as training on specific techniques and equipment. Training includes employability and professionalism, graduate teaching assistant training and guidance on writing papers. https://www.york.ac.uk/chemistry/postgraduate/training/idtc/idtctraining/
There will be opportunities for networking and sharing your work both within and beyond the University. Funding is provided to enable you to attend conferences and external training. The department also runs a varied and comprehensive seminar programme.
Equality and Diversity
The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/
As part of our commitment to Equality and Diversity, and Widening Participation, we are working with the YCEDE project (https://ycede.ac.uk/) to improve the number of under-represented groups participating in doctoral study.
You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a relevant related subject. Check the entry requirements for your country: https://www.york.ac.uk/study/international/your-country/
English language requirements: https://www.york.ac.uk/study/postgraduate-research/apply/international/english/
For more information about the project, click on the supervisor's name above to email them.
For more information about the application process or funding, please click on email institution.
Guidance for applicants: https://www.york.ac.uk/chemistry/postgraduate/apply/
Submit an online PhD in Chemistry application: https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3
The start date of the PhD will be 16 September 2024