Development of photoredox catalysis in the late 2000s revolutionised the use of free radical chemistry in organic synthesis. These new radical reactions make it possible to carry out previously inaccessible transformations, often with excellent selectivity and under very mild conditions, with very good functional group tolerance. Photoredox catalysis is being actively adopted by the chemical industry. However, after rapid initial growth based on a trial-and-error approach, the field of photoredox catalysis has now reached a stage where mechanistic understanding is critical for further development and optimisation. Mechanistic understanding requires methods for detection and characterisation of short-lived free radicals (which are intermediates in all photoredox reactions). Surprisingly, there have been no major developments in this area for over 50 years. In most cases, free radicals are trapped by spin traps and studied by EPR spectroscopy. While this technique provides direct information about elusive radical intermediates, it suffers from many serious drawbacks, including limited sensitivity, limited structural information, it is prone to artefacts and often fails in complex systems due to poor stability of spin traps and their adducts. We have recently developed new chemical traps for free radical intermediates designed for mass spectrometry (MS) rather than EPR spectroscopy. In our preliminary work, these traps showed excellent results in model reactions, resolving most disadvantages of the conventional spin traps.
This projects is part-sponsored by Syngenta. It aims to apply our new methodology to photoredox radical reactions relevant to agrochemical industry. We will explore a range of reactions including trifluoromethylation, Minisci-type alkylations, mechanistically complex reactions such as Ni-catalysed decarboxylative cross-coupling or multicomponent reactions, e.g., hydroaminoalkylations. These reactions are initiated with blue (LED) light in the presence of Ir(III) or Ru(II) catalysts. We will detect, identify and quantify free radical intermediates and develop mechanistic understanding of these processes. This is unchartered territory: there have only been a few reports on the detection of free radicals in these reactions. We believe unambiguous structure assignment and quantification of radical intermediates will yield unprecedented mechanistic information which will enable us to improve yields, selectivity and substrate scope.
In the first part of the project, we will synthesise new radical traps. We have already built a small library of these compounds, and in this project we will seek to tune their structures to optimise performance in synthetic photoredox reactions. The project will then use the new traps to characterise and quantify radical intermediates in the photoredox reactions. The mechanistic understanding and kinetic modelling will be used to improve reaction yields and selectivity.
Our approach to monitoring free radicals is unprecedented; we believe that the new traps will yield previously unavailable mechanistic details. Our preliminary results proved the feasibility of the new method in liquid phase reactions and gas phase mixtures.
A significant component of the project is organic synthesis (e.g., synthesising new traps, running photoredox reactions), and you will be trained to use synthetic methods, experiment design, work-up and purification, spectroscopic characterisation techniques. In the second part of the project, you will use the traps to detect radical intermediates with ESI-MS. You will be trained to use advanced MS instrumentation in the MS Centre of Excellence at York. Mass spectra of reactions mixtures are complex, and there will be training opportunities in numerical and data analysis skills. Once the trapping of free radicals has been established, the project will explore mechanistic chemistry. You will be trained in radical mechanisms and physical organic techniques for mechanistic interrogation. Quantification of radical intermediates will enable us to carry out kinetic modelling.
All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/idtc/
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/
. This PhD project is available to study full-time or part-time (50%).
This PhD will formally start on 1 October 2020. Induction activities will start on 28 September.