Macrocyclic compounds are a promising alternative to small molecules for targeting difficult-to-treat diseases. However, challenges in their synthesis have hindered their application. This project aims to develop efficient computational methods to support sustainable and effective macrocycle synthesis. It will incorporate automated tools, high-throughput experimentation (HTE), and machine learning to design and identify novel macrocycles for biological applications.

Useful links:
Duarte research group: https://www.duartegroupchem.org

For further details please contact Fernanda Duarte (fernanda.duartegonzalez@chem.ox.ac.uk).

Whole-cell biocatalysis is emerging as a sustainable and environmentally-compatible alternative to chemical catalysis. This approach takes advantage of the metabolism of a bacterial cell for the production of valuable target molecules, with highly (enantio)selective transformations being enabled in water-containing media, under ambient conditions and by using renewable feedstocks. Despite these clear advantages, limitations associated with the transport of substrates and catalysts through cell membranes are often reducing the overall catalytic effectiveness of whole-cell setups. The aim of this project is therefore to develop suitable delivery vectors to transport the respective active components into cells. Target reactions include the production of active pharmaceutical ingredients and the selective activation of masked antimicrobial prodrugs using Ru and Pd catalysis. The work will use bio-derived components, degradable linkers, and enzymatic synthesis where possible and experiments will be performed on small scales to minimise the usage of chemicals. Catalytic performance will be assessed though product analysis by chiral HPLC, electronic absorption and fluorescence spectroscopy and via the release of antimicrobial products, as appropriate.

Key publications:
Redox-switchable siderophore anchor enables reversible artificial metalloenzyme assembly. (Nat Catal. 2018, 1, 680)
Siderophore-Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells. (Chem. Eur. J. 2023, 29, e202202536)
Coupling Photoresponsive Transmembrane Ion Transport with Transition Metal Catalysis. (J. Am. Chem. Soc. 2024, 146, 4351)

For further details please contact Anne Duhme-Klair (anne.duhme-klair@york.ac.uk).

Cyclobutanes are strained ring systems found in many medicines and natural products. Their unusual geometry offers access to new shapes and vectors in drug discovery — but they remain underused due to inefficient, non-sustainable routes for their synthesis. This project develops a greener, catalytic asymmetric cross-coupling platform that transforms simple cyclobutenes into richly functionalised, chiral cyclobutanes.
Our approach emphasises sustainability at every stage: starting from cyclobutenes that are readily accessible in 1–2 steps from feedstocks, avoiding protecting groups, and eliminating stoichiometric reagents. As well as being atom-economical, modular, and convergent, it enables rapid access to diverse products and the opportunity to discover, understand, and harness new reactivity patterns. These methods represent a step-change over current multistep approaches and align with the goals of circular chemistry.
In collaboration with J&J Innovative Medicine, we will use their High Throughput Experimentation (HTE) Centre of Excellence to accelerate catalyst development and explore the potential of these scaffolds in real-world drug discovery. Students will also investigate new reactivity patterns, such as 1,2-difunctionalisation or hydroalkylation, guided by J&J’s interest and expertise.
This project offers training in asymmetric catalysis, reaction design, and industry collaboration — while contributing to more sustainable ways of making high-value molecules for pharmaceutical applications.

Key publications:
A catalytic asymmetric cross-coupling approach to the synthesis of cyclobutanes. (Nat. Chem., 2021, 13, 880)
Rhodium-Catalyzed Asymmetric Arylation of Cyclobutenone Ketals. (Angew. Chem. 2023, 135, e202217381)
Rhodium-Catalyzed Asymmetric Suzuki and Related Cross-Coupling Reactions. (Aldrichimica Acta, 2024, 57, 1)

For further details please contact Stephen Fletcher (stephen.fletcher@chem.ox.ac.uk)

The introduction of saturation in the form of C_sp3-F into pharmaceutical candidates improves medicinal properties and increase the chance to reach the clinic. New chemistry will be developed for the conversion of alcohols into alkyl fluorides using safe and cost-effective alkali metal fluorides. Our goal is to invent a deoxyfluorination process under asymmetric phase transfer catalysis.

Key publications:
Asymmetric Nucleophilic Fluorination Under Hydrogen Bonding Phase-Transfer Catalysis. (Science 2018, 360, 638)
Hydrogen Bonding Phase-Transfer Catalysis with Alkali Metal Fluorides and Beyond. (J. Am. Chem. Soc. 2022, 144, 5200)
Impact of Multiple Hydrogen Bonds with Fluoride on Catalysis: Insight from NMR Spectroscopy. (J. Am. Chem. Soc. 2020, 142, 19731)
Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis. (Nature Catalysis 2025, 8, 107)

For further details please contact Véronique Gouverneur (veronique.gouverneur@chem.ox.ac.uk).

This project will explore methods to use earth abundant, Lewis acidic main group catalysts to catalyse organic transformations in water by exploiting micellar confinement. The student will prepare novel micellar catalysts that leverage solvent insensitive halogen and chalcogen bonding interactions, and designer functionalized (chiral) surfactants to mediate a wide range of organic transformations relevant to pharmaceutical and fine chemical synthesis in water.

Useful links:
Langton research group: https://langtonrg.web.ox.ac.uk
Shimizu research group: https://www.york.ac.uk/chemistry/people/sshimizu/
Centre for Transformation of Chemistry: https://transforming-chemistry.org/en/

For further details please contact Matthew Langton (matthew.langton@chem.ox.ac.uk).

Quaternary carbon stereocenters, particularly all carbon ones, are key structural moieties in pharmaceuticals yet remain challenging to synthetically construct as there is no general catalytic asymmetric solution. The discovery and development of efficient synthetic methods for quaternary carbon stereocenters would expand a discovery chemists’ toolbox as well as provide the basis for sustainable commercial manufacturing. Towards this goal, this proposal aims to develop new base metal-catalysed methods for the selective functionalization of C-H bonds to desymmetrize prochiral molecules. In particular, we intend to introduce quaternary carbon stereochemistry by functionalisation of one of two enantiotopic substituents of a prochiral quaternary carbon center. Base metal catalysts, including iron and cobalt, will be the focus of catalyst development in this work due to their improved sustainability and reduced toxicity compared to traditional precious metal catalysts, representing a key development towards a more sustainable synthetic future.

Key publications:
Iron-catalyzed stereoselective C–H alkylation for simultaneous construction of C–N axial and C-central chirality. (Nat. Commun. 2024, 15, 3503)

For further details please contact Michael Neidig (michael.neidig@chem.ox.ac.uk)

luorine-containing molecules are essential in a range of applications, including many pharmaceuticals and crop-protection products. This collaborative project will develop novel metal-free catalysis for the preparation of functional fluorinated molecules. Non-metal catalysts, based on earth-abundant elements, will avoid the need for expensive, toxic precious-metals. Readily available fluorinated building blocks will be upcycled through highly atom economical reactions. Overall, this will allow the preparation of functional fluorinated molecules in more sustainable ways.
The project will build on recent work in our groups to develop novel, non-metal catalysts, for the sustainable manipulation of fluorine atoms. We will take perfluoroarenes/heteroarenes as starting materials, which are readily available, but in the current push to eliminate perfluorinated molecules will benefit from partial defluorination. These will be upcycled to more valuable building blocks by C-F bond functionalisation, developing catalysis based on simple phosphines reported by Slattery and Lynam.
C-F activation liberates fluoride, which will be captured and utilised in tandem, enantioselective C-F bond formation processes. This will make use of recent advances by Gouverneur, using chiral ureas as hydrogen bonding phase-transfer catalysts. The project will involve synthesis, catalyst development and mechanistic studies and will leverage the complementary expertise in York and Oxford to provide broad training.

Key publications:
Metallomimetic C–F Activation Catalysis by Simple Phosphines. (J. Am. Chem. Soc. 2024, 146, 2005)
Asymmetric nucleophilic fluorination under hydrogen bonding phase-transfer catalysis. (Science 2018, 360, 638)

For further details please contact John Slattery (john.slattery@york.ac.uk).

This project will focus on efficient approaches to the synthesis of complex heterocyclic molecules through the development of a photochemical cycloaddition/fragmentation process. These reactions will be enabled through the design and application of sustainable photosensitizers based upon earth abundant metals and metal-free scaffolds.

For further details please contact Martin Smith (martin.smith@chem.ox.ac.uk).

Polymer manufacturing is already responsible for 1.6 Gt CO₂ equiv. emissions annually, our recent research reveals that replacing petrochemical raw materials with biomass, carbon dioxide and waste polymers can help to drive down these emissions, and provide other sustainability benefits, to reach net zero targets. This project focusses on a technology of high promise in carbon dioxide utilization: catalytic copolymerization with heterocycles to produce recyclable plastics for use in high-value areas, including electronics, transport and construction.

Key publications:
Quantifying CO₂ Insertion Equilibria for Low-Pressure Propene Oxide and Carbon Dioxide Ring Opening Copolymerization Catalysts. (J. Am. Chem. Soc. 2024, 146, 10451)
Insights into the Mechanism of Carbon Dioxide and Propylene Oxide Ring-Opening Copolymerization Using a Co(III)/K(I) Heterodinuclear Catalysts. (J. Am. Chem. Soc. 2022, 144, 17929)

Useful links:
Williams research group: https://cwilliamsresearch.web.ox.ac.uk/

For further details please contact Charlotte Williams (charlotte.williams@chem.ox.ac.uk).

Adhesives play a critical role in many technologies from construction, transportation, electronics to consumer goods. There are growing environmental concerns, legislation and customer pressure to deliver more sustainable adhesives and to ensure they maximise recycling of other components. Adhesives which can bond/de-bond on demand and which are degradable after use are particularly important. Here, we will develop new lower carbon footprint sustainable polymers, sourced from biomass and waste carbon dioxide, as debondable, recyclable and degradable adhesives.

Key publications:
Bio-based and Degradable Block Polyester Pressure-Sensitive Adhesives. (Angew. Chem. Int. Ed. 2020, 59, 23450)
Switchable Catalysis Improves the Properties of CO₂-Derived Polymers: Poly(cyclohexene carbonate-b-ε-decalactone-b-cyclohexene carbonate) Adhesives, Elastomers, and Toughened Plastics. (J. Am. Chem. Soc. 2020, 142, 4367)

Useful links:
Williams research group: https://cwilliamsresearch.web.ox.ac.uk/

For further details please contact Charlotte Williams (charlotte.williams@chem.ox.ac.uk).

Macrocyclic compounds are a promising alternative to small molecules for targeting difficult-to-treat diseases. However, challenges in their synthesis have hindered their application. This project aims to develop efficient computational methods to support sustainable and effective macrocycle synthesis. It will incorporate automated tools, high-throughput experimentation (HTE), and machine learning to design and identify novel macrocycles for biological applications.

Useful links:
Duarte research group: https://www.duartegroupchem.org

For further details please contact Fernanda Duarte (fernanda.duartegonzalez@chem.ox.ac.uk).

Cyclobutanes are strained ring systems found in many medicines and natural products. Their unusual geometry offers access to new shapes and vectors in drug discovery — but they remain underused due to inefficient, non-sustainable routes for their synthesis. This project develops a greener, catalytic asymmetric cross-coupling platform that transforms simple cyclobutenes into richly functionalised, chiral cyclobutanes.
Our approach emphasises sustainability at every stage: starting from cyclobutenes that are readily accessible in 1–2 steps from feedstocks, avoiding protecting groups, and eliminating stoichiometric reagents. As well as being atom-economical, modular, and convergent, it enables rapid access to diverse products and the opportunity to discover, understand, and harness new reactivity patterns. These methods represent a step-change over current multistep approaches and align with the goals of circular chemistry.
In collaboration with J&J Innovative Medicine, we will use their High Throughput Experimentation (HTE) Centre of Excellence to accelerate catalyst development and explore the potential of these scaffolds in real-world drug discovery. Students will also investigate new reactivity patterns, such as 1,2-difunctionalisation or hydroalkylation, guided by J&J’s interest and expertise.
This project offers training in asymmetric catalysis, reaction design, and industry collaboration — while contributing to more sustainable ways of making high-value molecules for pharmaceutical applications.

Key publications:
A catalytic asymmetric cross-coupling approach to the synthesis of cyclobutanes. (Nat. Chem., 2021, 13, 880)
Rhodium-Catalyzed Asymmetric Arylation of Cyclobutenone Ketals. (Angew. Chem. 2023, 135, e202217381)
Rhodium-Catalyzed Asymmetric Suzuki and Related Cross-Coupling Reactions. (Aldrichimica Acta, 2024, 57, 1)

For further details please contact Stephen Fletcher (stephen.fletcher@chem.ox.ac.uk)

The introduction of saturation in the form of C_sp3-F into pharmaceutical candidates improves medicinal properties and increase the chance to reach the clinic. New chemistry will be developed for the conversion of alcohols into alkyl fluorides using safe and cost-effective alkali metal fluorides. Our goal is to invent a deoxyfluorination process under asymmetric phase transfer catalysis.

Key publications:
Asymmetric Nucleophilic Fluorination Under Hydrogen Bonding Phase-Transfer Catalysis. (Science 2018, 360, 638)
Hydrogen Bonding Phase-Transfer Catalysis with Alkali Metal Fluorides and Beyond. (J. Am. Chem. Soc. 2022, 144, 5200)
Impact of Multiple Hydrogen Bonds with Fluoride on Catalysis: Insight from NMR Spectroscopy. (J. Am. Chem. Soc. 2020, 142, 19731)
Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis. (Nature Catalysis 2025, 8, 107)

For further details please contact Véronique Gouverneur (veronique.gouverneur@chem.ox.ac.uk).

This project will explore methods to use earth abundant, Lewis acidic main group catalysts to catalyse organic transformations in water by exploiting micellar confinement. The student will prepare novel micellar catalysts that leverage solvent insensitive halogen and chalcogen bonding interactions, and designer functionalized (chiral) surfactants to mediate a wide range of organic transformations relevant to pharmaceutical and fine chemical synthesis in water.

Useful links:
Langton research group: https://langtonrg.web.ox.ac.uk
Shimizu research group: https://www.york.ac.uk/chemistry/people/sshimizu/
Centre for Transformation of Chemistry: https://transforming-chemistry.org/en/

For further details please contact Matthew Langton (matthew.langton@chem.ox.ac.uk).

Quaternary carbon stereocenters, particularly all carbon ones, are key structural moieties in pharmaceuticals yet remain challenging to synthetically construct as there is no general catalytic asymmetric solution. The discovery and development of efficient synthetic methods for quaternary carbon stereocenters would expand a discovery chemists’ toolbox as well as provide the basis for sustainable commercial manufacturing. Towards this goal, this proposal aims to develop new base metal-catalysed methods for the selective functionalization of C-H bonds to desymmetrize prochiral molecules. In particular, we intend to introduce quaternary carbon stereochemistry by functionalisation of one of two enantiotopic substituents of a prochiral quaternary carbon center. Base metal catalysts, including iron and cobalt, will be the focus of catalyst development in this work due to their improved sustainability and reduced toxicity compared to traditional precious metal catalysts, representing a key development towards a more sustainable synthetic future.

Key publications:
Iron-catalyzed stereoselective C–H alkylation for simultaneous construction of C–N axial and C-central chirality. (Nat. Commun. 2024, 15, 3503)

For further details please contact Michael Neidig (michael.neidig@chem.ox.ac.uk)

This project will focus on efficient approaches to the synthesis of complex heterocyclic molecules through the development of a photochemical cycloaddition/fragmentation process. These reactions will be enabled through the design and application of sustainable photosensitizers based upon earth abundant metals and metal-free scaffolds.

For further details please contact Martin Smith (martin.smith@chem.ox.ac.uk).

Polymer manufacturing is already responsible for 1.6 Gt CO₂ equiv. emissions annually, our recent research reveals that replacing petrochemical raw materials with biomass, carbon dioxide and waste polymers can help to drive down these emissions, and provide other sustainability benefits, to reach net zero targets. This project focusses on a technology of high promise in carbon dioxide utilization: catalytic copolymerization with heterocycles to produce recyclable plastics for use in high-value areas, including electronics, transport and construction.

Key publications:
Quantifying CO₂ Insertion Equilibria for Low-Pressure Propene Oxide and Carbon Dioxide Ring Opening Copolymerization Catalysts. (J. Am. Chem. Soc. 2024, 146, 10451)
Insights into the Mechanism of Carbon Dioxide and Propylene Oxide Ring-Opening Copolymerization Using a Co(III)/K(I) Heterodinuclear Catalysts. (J. Am. Chem. Soc. 2022, 144, 17929)

Useful links:
Williams research group: https://cwilliamsresearch.web.ox.ac.uk/

For further details please contact Charlotte Williams (charlotte.williams@chem.ox.ac.uk).

Adhesives play a critical role in many technologies from construction, transportation, electronics to consumer goods. There are growing environmental concerns, legislation and customer pressure to deliver more sustainable adhesives and to ensure they maximise recycling of other components. Adhesives which can bond/de-bond on demand and which are degradable after use are particularly important. Here, we will develop new lower carbon footprint sustainable polymers, sourced from biomass and waste carbon dioxide, as debondable, recyclable and degradable adhesives.

Key publications:
Bio-based and Degradable Block Polyester Pressure-Sensitive Adhesives. (Angew. Chem. Int. Ed. 2020, 59, 23450)
Switchable Catalysis Improves the Properties of CO₂-Derived Polymers: Poly(cyclohexene carbonate-b-ε-decalactone-b-cyclohexene carbonate) Adhesives, Elastomers, and Toughened Plastics. (J. Am. Chem. Soc. 2020, 142, 4367)

Useful links:
Williams research group: https://cwilliamsresearch.web.ox.ac.uk/

For further details please contact Charlotte Williams (charlotte.williams@chem.ox.ac.uk).

Whole-cell biocatalysis is emerging as a sustainable and environmentally-compatible alternative to chemical catalysis. This approach takes advantage of the metabolism of a bacterial cell for the production of valuable target molecules, with highly (enantio)selective transformations being enabled in water-containing media, under ambient conditions and by using renewable feedstocks. Despite these clear advantages, limitations associated with the transport of substrates and catalysts through cell membranes are often reducing the overall catalytic effectiveness of whole-cell setups. The aim of this project is therefore to develop suitable delivery vectors to transport the respective active components into cells. Target reactions include the production of active pharmaceutical ingredients and the selective activation of masked antimicrobial prodrugs using Ru and Pd catalysis. The work will use bio-derived components, degradable linkers, and enzymatic synthesis where possible and experiments will be performed on small scales to minimise the usage of chemicals. Catalytic performance will be assessed though product analysis by chiral HPLC, electronic absorption and fluorescence spectroscopy and via the release of antimicrobial products, as appropriate.

Key publications:
Redox-switchable siderophore anchor enables reversible artificial metalloenzyme assembly. (Nat Catal. 2018, 1, 680)
Siderophore-Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells. (Chem. Eur. J. 2023, 29, e202202536)
Coupling Photoresponsive Transmembrane Ion Transport with Transition Metal Catalysis. (J. Am. Chem. Soc. 2024, 146, 4351)

For further details please contact Anne Duhme-Klair (anne.duhme-klair@york.ac.uk).

luorine-containing molecules are essential in a range of applications, including many pharmaceuticals and crop-protection products. This collaborative project will develop novel metal-free catalysis for the preparation of functional fluorinated molecules. Non-metal catalysts, based on earth-abundant elements, will avoid the need for expensive, toxic precious-metals. Readily available fluorinated building blocks will be upcycled through highly atom economical reactions. Overall, this will allow the preparation of functional fluorinated molecules in more sustainable ways.
The project will build on recent work in our groups to develop novel, non-metal catalysts, for the sustainable manipulation of fluorine atoms. We will take perfluoroarenes/heteroarenes as starting materials, which are readily available, but in the current push to eliminate perfluorinated molecules will benefit from partial defluorination. These will be upcycled to more valuable building blocks by C-F bond functionalisation, developing catalysis based on simple phosphines reported by Slattery and Lynam.
C-F activation liberates fluoride, which will be captured and utilised in tandem, enantioselective C-F bond formation processes. This will make use of recent advances by Gouverneur, using chiral ureas as hydrogen bonding phase-transfer catalysts. The project will involve synthesis, catalyst development and mechanistic studies and will leverage the complementary expertise in York and Oxford to provide broad training.

Key publications:
Metallomimetic C–F Activation Catalysis by Simple Phosphines. (J. Am. Chem. Soc. 2024, 146, 2005)
Asymmetric nucleophilic fluorination under hydrogen bonding phase-transfer catalysis. (Science 2018, 360, 638)

For further details please contact John Slattery (john.slattery@york.ac.uk).