Dr. Will Hartley

Prof. Paolo Melchiorre

Merging enantioselective isothiourea catalysis with visible-light photoactivation for the synthesis of biologically-relevant chiral molecules

Originally from Manchester (UK), Will studied chemistry at the University of Sheffield (UK), carrying out synthetic and theoretical research in the groups of Prof. Joe Harrity and Prof. Patrick Fowler FRS. After completing his Master’s thesis in 2016, Will joined the University of St Andrews as an EPSRC CRITICAT CDT student, undertaking a 6-month training programme in three areas of catalysis: homogeneous, heterogeneous, and enzymatic. He carried out his PhD research under the supervision of Prof. Andrew D. Smith, working on the development and mechanistic elucidation of Lewis base-catalysed enantioselective reactions, while also undertaking an industrial placement at Syngenta R&D (UK). In November 2020, he began his post-doctoral career in the group of Prof. Paolo Melchiorre. To relax, he enjoys playing football, listening to Mancunian music, and socialising over a beer.

From 01/03/2021 to



The quest for successful lead candidates in drug discovery has challenged synthetic chemists to develop innovative strategies to rapidly generate screening collections of chiral molecules. In this context, cascade processes provide a powerful tool for rapidly increasing, in one step, structural and stereochemical complexity, while fulfilling the requirements for atom and step economy. The development of asymmetric variants has mainly relied so far on ionic reactivity. PHOTO-ITU seeks to expand the synthetic potential of asymmetric cascade reactions to include the radical reactivity domain. To achieve this goal, we will combine asymmetric organocatalysis and photochemistry, two powerful strategies of modern chemical research with an extraordinary potential for the sustainable preparation of novel molecules. Specifically, we will exploit the unexplored excited-state reactivity of isothiourea-based catalytic intermediates thus merging, for the first time, tertiary amine isothiourea catalysis with asymmetric photochemistry. The resulting photochemical asymmetric radical cascades will rapidly generate, in one single step, architecturally complex chiral natural-like compounds containing biologically relevant heterocyclic scaffolds. The planned research combines perfectly the fellow’s experience in isothiourea catalysis and the host’s experience in photo-triggered asymmetric processes to develop otherwise unachievable catalytic asymmetric radical cascade reactions. The resulting strategies will be used as an ideal platform for assembling libraries comprising enantiopure chiral small molecules that, along with biological screening carried out in collaboration with an international pharma-company (Bayer AG), will increase the probability of success in identifying drug-candidate structures. The multi-cultural and intersectorial nature of this project will contribute to broaden the fellow’s competencies and will place him in a competitive position for the next career move.

This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement 101031533

Photochemical Organocatalytic Functionalization of Pyridines via Pyridinyl Radicals
Emilien Le Saux, Eleni Georgiou, Igor A. Dmitriev, Will C. Hartley, Paolo Melchiorre
J. Am. Chem. Soc. 2023, 145, 1, 47-52
DOI: 10.1021/jacs.2c12466

Enantioselective catalytic remote perfluoroalkylation of α-branched enals driven by light
Matteo Balletti, Tommy Wachsmuth, Antonio Di Sabato,Will C. Hartley, Paolo Melchiorre
Chemical Science 2023, 14, 4923-4927
DOI: 10.1039/D3SC01347B

Lewis Base-Catalysed Enantioselective Radical Conjugate Addition for the Synthesis of Enantioenriched Pyrrolidinones
Will C. Hartley, Florian Schiel, Elena Ermini, Paolo Melchiorre*
Angewandte Chemie International Edition 2022
DOI: 10.1002/anie.202204735