Computer-Aided Catalyst Design FI

Catalyst Discovery and Design

The discovery of new catalysts drives chemistry forwards, yet this is still dependent on trial-and-error experimentation. Screening large numbers of molecules, additives and solvent systems is inefficient, costly and wasteful. We explore computational approaches to understand and explore structure, mechanism and selectivity in catalytic transformations. Increasingly, this is carried out predictively, rather than retrospectively, in the design and optimization of new chiral catalysts to achieve high levels of stereocontrol. Collaborations with leading research groups in catalysis and synthetic organic chemistry have been established to pursue these goals.


Veronique Gouverneur (Oxford); Ed Anderson (Oxford); Darren Dixon (Oxford)

Key Papers

Enantioconvergent Nucleophilic Substitution of Alkyl Halides with Potassium Fluoride via Synergistic Phase-Transfer Catalysis.

Dooley, C.; Ibba, F.; Botlik, B.; Goult, C.; Gao, Y.; Lister, A.; Paton, R. S.; Lloyd-Jones, G. C.; Gouverneur, V. in revision 2024

Radical Chlorination of Non-Resonant Heterobenzylic C‒H Bonds and High-Throughput Diversification of Heterocycles.

Golden, D. L.; Flynn, K. M.; Aikonen, S.; Kalyani, D.; Krska, S. W.; Paton, R. S.; Stahl, S. S. Chem. 2024, DOI: 10.1016/j.chempr.2024.04.001.

Regiodivergent Nucleophilic Fluorination under Hydrogen Bonding Catalysis: A Computational and Experimental Study.

Horwitz, M. A.; Dürr, A. B.; Afratis, K.; Chen, Z.; Soika, J.; Christensen, K. E.; Fushimi, M.; Paton, R. S.; Gouverneur, V. J. Am. Chem. Soc. 2023, 145, 9708–9717

Mechanistic Studies Yield Improved Protocols for Base-Catalyzed anti-Markovnikov Alcohol Addition Reactions.

Luo, C.; Alegre-Requena, J. V.; Sujansky, S. J.; Pajk, S.; Gallegos, L. C.; Paton, R. S.; Bandar, J. S. J. Am. Chem. Soc. 2022, 144, 9586–9596

Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study.

Wang, J.; Horwitz, M.; Dürr, A.; Ibba, F.; Pupo, G.; Gao, Y.; Ricci, P.; Christensen, K.; Pathak, T.; Claridge, T. W.; Lloyd-Jones, G.; Paton, R. S.; Gouverneur, V. J. Am. Chem. Soc. 2022, 144, 4572–4584

Modeling catalysis in allosteric enzymes: Capturing conformational consequences.

Klem, H.; McCullagh, M.; Paton, R. S. Top. Catal. 2022, 65, 165–186

BIMP Catalyzed 1,3‐Prototropic Shift for the Highly Enantioselective Synthesis of Conjugated Cyclohexenones.

Golec, J. C.; Carter, E. M.; Ward, J. W.; Whittingham, W. G.; Simón, L.; Paton, R. S.; Dixon, D. J. Angew. Chem. Int. Ed. 2020, 59, 17417–17422

Enantiomerically enriched tetrahydropyridine allyl chlorides.

Karabiyikoglu S. I.; Brethomé, A. V.; Palacin, T.; Paton, R. S.; Fletcher, S. P. Chem. Sci. 2020, 11, 4125-4130

Hydrogen Bonding Phase-Transfer Catalysis with Ionic Reactants: Enantioselective Synthesis of beta-Fluoroamines.

Roagna, G.; Ascough, D. M. H.; Ibba, F.; Fontana, A.; Christensen, K. E.; Misale, A.; Trabanco, A. A.; Paton, R. S.; Pupo, G.; Gouverneur. V. J. Am. Chem. Soc. 2020, 142, 14045–14051

Enantioselective Rhodium-Catalysed Insertion of Trifluorodiazoethanes into Tin Hydrides.

Hyde, S.; Veliks, J.; Ascough, D. M. H.; Szpera, R.; Paton, R. S.; Gouverneur, V. Tetrahedron (invited contribution) 2019, 75, 17-25

Hydrogen Bonding Phase-Transfer Catalysis with Potassium Fluoride: Enantioselective Synthesis of Beta-Fluoroamines.

Hydrogen Bonding Phase-Transfer Catalysis with Potassium Fluoride: Enantioselective Synthesis of Beta-Fluoroamines. Pupo, G.; Vicini, A. C. Ascough, D. M. H.; Ibba, F.; Christensen, K. E.; Thompson, A. L.; Brown, J. M.; Paton, R. S.; Gouverneur, V. J. Am. Chem. Soc. 2019, 141, 2878–2883

Asymmetric Nucleophilic Fluorination Under Hydrogen Bonding Phase Transfer Catalysis.

Pupo, G.; Ibba, F.; Ascough, D. M. H.; Vicini, A. C.; Ricci, P.; Christensen, K.; Morphy, J. R.; Brown, J. M.; Paton, R. S.; Gouverneur, V. Science 2018, 360, 638–642

Bifunctional Iminophosphorane Catalysed Enantioselective Sulfa-Michael Addition of Alkyl Thiols to Alkenyl Benzimidazoles.

Formica, M.; Sorin, G.; Farley, A. J. M.; Diaz, J.; Paton, R. S.; Dixon, D. J. Chem. Sci. 2018, 9, 6969–6974

Catalytic Enantio‐and Diastereoselective Mannich Addition of TosMIC To Ketimines.

Franchino, A. Chapman, J.; Funes-Ardoiz, I.; Paton, R. S.; Dixon, D. J. Chem. Eur. J. 2018, 24, 17660–17664

Formation of quaternary centres by copper catalysed asymmetric conjugate addition to β-substituted cyclopentenones with the aid of a quantitative structure–selectivity relationship.

Ardkhean, R.; Mortimore, M.; Paton, R. S.; Fletcher. S. P. Chem. Sci. 2018, 9, 2628–2632

Selectivity in Transition Metal-Catalyzed Cyclizations: Insights from Experiment and Theory.

Anderson, E. A.; Paton, R. S. CHIMIA 2018, 72, 614–620

Stereospecific 1,3-H Transfer of Indenols Proceeds Via Persistent Ion-Pairs Anchored by NH−Pi Interactions.

Ascough, D. M. H.; Duarte, F.; Paton, R. S. J. Am. Chem. Soc. 2018, 140, 16740–16748

The True Catalyst Revealed: the Intervention of Chiral Ca and Mg Phosphates in Brønsted Acid Promoted Asymmetric Mannich Reactions.

Simón, L.; Paton, R. S. J. Am. Chem. Soc. 2018, 140, 5412–5420

Asymmetric Induction in C-Alkylation of Tropane-Derived Enamines: Congruence Between Computation and Experiment.

Li, Y.; Jackson, K. E.; Charlton, A.; Le Neve-Foster, B.; Khurshid, A.; Rudy, H.-K. A.; Thompson, A. L.; Paton, R. S.; Hodgson, D. M. J. Org. Chem. 2017, 82, 10479–10488

Enantioselective Silver and Amine Cocatalyzed Desymmetrizing Cycloisomerization of Alkyne-Linked Cyclohexanones.

Manzano, R.; Datta, S.; Paton, R. S.; Dixon, D. J. Angew. Chem. Int. Ed. 2017, 56, 5834–5838

Molecular Recognition in Asymmetric Counteranion Catalysis: Understanding Chiral Phosphate-Mediated Desymmetrization.

Duarte, F.; Paton, R. S. J. Am. Chem. Soc. 2017, 139, 8886–8896

Total Synthesis of (−)-Himalensine A.

Shi, H.; Michaelides, I.; Darses, B.; Jakubec, P.; Nguyen, Q. N.; Paton, R. S.; Dixon, D. J. J. Am. Chem. Soc. 2017, 139, 17755–17758

Catalytic Control in Cyclizations: from Computational Mechanistic Understanding to Selectivity Prediction.

Peng, Q.; Paton, R. S. Acc. Chem. Res. 2016, 49, 1042–1051

Computing Organic Stereoselectivity – from Concepts to Quantitative Calculations and Predictions.

Peng, Q.; Duarte, F.; Paton, R. S. Chem. Soc. Rev. 2016, 45, 6093–6107

Catalytic Enantioselective Synthesis of Indanes via Cation-Directed 5-Endo-Trig Cyclization.

Johnston, C. P.; Kothari, A.; Sergeieva, T.; Okovytyy, S. I.; Jackson, K. E.; Paton, R. S.; Smith, M. D. Nat. Chem. 2015, 7, 171–177

Dissecting Non-Covalent Interactions In Oxazaborolidinium Catalyzed Cycloadditions of Maleimides.

Paton, R. S. Org. Biomol. Chem. 2014, 12, 1717–1720