Difluoromethyl-1,2,4-triazoles can act as bioisosteric replacements for acidic tetrazole rings. The applicability of substituted derivatives of this scaffold, however, is limited by lengthy syntheses and the availability of suitable starting materials. In this proposal, we want to develop tools to assemble substituted difluoromethyl-1,2,4-triazoles in a highly modular and resource-efficient fashion. This will give us a more sustainable access to the scaffold by shortening multistep synthetic procedures to essentially one single step, thereby significantly reducing waste and the consumption of solvents as well as energy. The candidate will then apply the developed methods to a medicinal chemistry project and optimise small molecule inhibitors for a hard-to-drug protein target.

Key publications:
Acidic triazoles as soluble guanylate cyclase stimulators. (Bioorg. Med. Chem. Lett., 2011, 21, 6515)

For further details please contact Paul Brennan (paul.brennan@cmd.ox.ac.uk).

Configurationally defined, partially and fully substituted vicinal amino alcohols are indispensable motifs in natural products, pharmaceuticals, and agrochemicals, and serve as critical building blocks across a range of synthetic applications. Traditional synthetic approaches predominantly rely on polar bond retrosynthetic logic and protecting group strategies, often resulting in lengthy and inefficient routes to these valuable structures. As medicinal chemistry increasingly prioritizes sp³-rich architectures, there is a pressing need for novel and efficient methodologies to access these complex motifs.
This proposal outlines a two-stage, three-component strategy that addresses this challenge by integrating cutting-edge enantioselective catalysis with stereoselective electrocatalytic decarboxylative transformations. In the first stage, chiral vicinal amino alcohol building blocks bearing redox-active ester functionalities are constructed with high stereocontrol. In the second stage, these intermediates will undergo modular and selective electrocatalytic decarboxylation, affording a broad array of enantiopure, partially and fully substituted amino alcohols.
Distinct from conventional methods, this build-and-modify approach is both general and modular, leveraging readily available starting materials such as aldehydes, ketones, and organohalides. The proposed platform enables unprecedented stereoselective and chemoselective access to structurally diverse amino alcohols, offering transformative potential for both high-throughput library generation and the synthesis of complex molecular targets.

Key publications:
Direct Catalytic Enantio- and Diastereoselective Ketone Aldol Reactions of Isocyanoacetates. (Angew. Chem. Int. Ed., 2015, 54, 4895)
A New Family of Cinchona-Derived Amino Phosphine Precatalysts: Application to the Highly Enantio- and Diastereoselective Silver-Catalyzed Isocyanoacetate Aldol Reaction. (J. Am. Chem. Soc., 2011, 133, 1710)
Bespoke and Accessible Electrochemical Reactors. (ACS Cent. Sci. 2024, 10, 2000)
Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings. (Nat. Chem., 2025, 17, 44)

For further details please contact Darren Dixon (darren.dixon@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).

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)

There is interest in 3-D heterocyclic scaffolds for medicinal chemistry. The O'Brien group has recently disclosed a modular synthetic platform for the elaboration of 2-D fragments into 3-D lead-like compounds that utilised 3-D cyclopropyl organoboron building blocks (with distinct vectors in 3-D). In terms of sustainable synthesis, there are significant limitations with the 1^st generation building blocks, namely multi-step synthesis using stoichiometric reagents and Pd-catalysed cross-coupling for aryl group attachment. To address, in a new collaborative project with Sneddon, 2^nd generation cyclopropyl N-hydroxyphthalimide (NHP) ester building blocks will be explored. This will include: (i) a one-step synthesis of the building blocks using diazo-NHP esters under Cu(I) catalysis and (ii) a reductive decarboxylative Ni-catalysed cross-electrophile coupling. The scope of the Ar-Br in the cross-coupling step will be explored as it will be necessary to demonstrate broad scope with medicinally-relevant motifs for use in the modular fragment elaboration platform. Finally, a range of cyclopropyl NHP-ester 3-D building blocks will be synthesised and cross-coupled – the building blocks will contain different 3-D vectors between the N–Boc and cyclopropane ester bonds (assessed using of the computed lowest energy conformation). In this way, a more sustainable modular synthetic platform for fragment elaboration will be developed.

Key publications:
Modular Synthetic Platform for Elaboration of Fragments in Three Dimensions for Fragment-Based Drug Discovery. (J. Am. Chem. Soc. 2025, 147, 29292)
Control of Redox-Active Ester Reactivity Enables a General Cross-Electrophile Approach to Access Arylated Strained Rings. (Angew. Chem. Int. Ed. 2022, 61, e202205673)

For further details please contact Peter O'Brien (peter.obrien@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).

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).

Difluoromethyl-1,2,4-triazoles can act as bioisosteric replacements for acidic tetrazole rings. The applicability of substituted derivatives of this scaffold, however, is limited by lengthy syntheses and the availability of suitable starting materials. In this proposal, we want to develop tools to assemble substituted difluoromethyl-1,2,4-triazoles in a highly modular and resource-efficient fashion. This will give us a more sustainable access to the scaffold by shortening multistep synthetic procedures to essentially one single step, thereby significantly reducing waste and the consumption of solvents as well as energy. The candidate will then apply the developed methods to a medicinal chemistry project and optimise small molecule inhibitors for a hard-to-drug protein target.

Key publications:
Acidic triazoles as soluble guanylate cyclase stimulators. (Bioorg. Med. Chem. Lett., 2011, 21, 6515)

For further details please contact Paul Brennan (paul.brennan@cmd.ox.ac.uk).

Configurationally defined, partially and fully substituted vicinal amino alcohols are indispensable motifs in natural products, pharmaceuticals, and agrochemicals, and serve as critical building blocks across a range of synthetic applications. Traditional synthetic approaches predominantly rely on polar bond retrosynthetic logic and protecting group strategies, often resulting in lengthy and inefficient routes to these valuable structures. As medicinal chemistry increasingly prioritizes sp³-rich architectures, there is a pressing need for novel and efficient methodologies to access these complex motifs.
This proposal outlines a two-stage, three-component strategy that addresses this challenge by integrating cutting-edge enantioselective catalysis with stereoselective electrocatalytic decarboxylative transformations. In the first stage, chiral vicinal amino alcohol building blocks bearing redox-active ester functionalities are constructed with high stereocontrol. In the second stage, these intermediates will undergo modular and selective electrocatalytic decarboxylation, affording a broad array of enantiopure, partially and fully substituted amino alcohols.
Distinct from conventional methods, this build-and-modify approach is both general and modular, leveraging readily available starting materials such as aldehydes, ketones, and organohalides. The proposed platform enables unprecedented stereoselective and chemoselective access to structurally diverse amino alcohols, offering transformative potential for both high-throughput library generation and the synthesis of complex molecular targets.

Key publications:
Direct Catalytic Enantio- and Diastereoselective Ketone Aldol Reactions of Isocyanoacetates. (Angew. Chem. Int. Ed., 2015, 54, 4895)
A New Family of Cinchona-Derived Amino Phosphine Precatalysts: Application to the Highly Enantio- and Diastereoselective Silver-Catalyzed Isocyanoacetate Aldol Reaction. (J. Am. Chem. Soc., 2011, 133, 1710)
Bespoke and Accessible Electrochemical Reactors. (ACS Cent. Sci. 2024, 10, 2000)
Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings. (Nat. Chem., 2025, 17, 44)

For further details please contact Darren Dixon (darren.dixon@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).

There is interest in 3-D heterocyclic scaffolds for medicinal chemistry. The O'Brien group has recently disclosed a modular synthetic platform for the elaboration of 2-D fragments into 3-D lead-like compounds that utilised 3-D cyclopropyl organoboron building blocks (with distinct vectors in 3-D). In terms of sustainable synthesis, there are significant limitations with the 1^st generation building blocks, namely multi-step synthesis using stoichiometric reagents and Pd-catalysed cross-coupling for aryl group attachment. To address, in a new collaborative project with Sneddon, 2^nd generation cyclopropyl N-hydroxyphthalimide (NHP) ester building blocks will be explored. This will include: (i) a one-step synthesis of the building blocks using diazo-NHP esters under Cu(I) catalysis and (ii) a reductive decarboxylative Ni-catalysed cross-electrophile coupling. The scope of the Ar-Br in the cross-coupling step will be explored as it will be necessary to demonstrate broad scope with medicinally-relevant motifs for use in the modular fragment elaboration platform. Finally, a range of cyclopropyl NHP-ester 3-D building blocks will be synthesised and cross-coupled – the building blocks will contain different 3-D vectors between the N–Boc and cyclopropane ester bonds (assessed using of the computed lowest energy conformation). In this way, a more sustainable modular synthetic platform for fragment elaboration will be developed.

Key publications:
Modular Synthetic Platform for Elaboration of Fragments in Three Dimensions for Fragment-Based Drug Discovery. (J. Am. Chem. Soc. 2025, 147, 29292)
Control of Redox-Active Ester Reactivity Enables a General Cross-Electrophile Approach to Access Arylated Strained Rings. (Angew. Chem. Int. Ed. 2022, 61, e202205673)

For further details please contact Peter O'Brien (peter.obrien@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).