Computer-Aided Catalyst Design

The discovery of new catalysts drives chemistry forwards, yet this is still dependent on trial-and-error experimentation. Screening large number of molecules, additives and solvent systems is innefficient, 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.

Key papers: Science 2018 360, 638; Nat. Commun. 2016, 7, 10109; Angew. Chem. Int. Ed. 2015, 127, 4981
Collaborations: Veronique Gouverneur (Oxford); Ed Anderson (Oxford); Darren Dixon (Oxford)

asymmetric catalysis noncovalent interactions informatics

Compute Multidimensional Sterimol Parameters for Conformationally-Flexible Substituents


An automated computational workflow which computes multidimensional Sterimol parameters. For flexible molecules or substituents, the program will generate & optimize a conformational ensemble, and produce Boltzmann-weighted Sterimol parameters. It has been developed as a PyMol plugin and can be run from within the graphical user interface.

wSterimol is freely available (MIT license) from GitHub.

informatics gaussian noncovalent interactions design python

Conformational Effects on Physical-Organic Descriptors – the Case of Sterimol Steric Parameters

Brethomé, A. V.; Fletcher, S. P.; Paton, R. S. ChemRxiv Preprint 2018, DOI:10.26434/chemrxiv.7125656.v1

informatics sterimol noncovalent interactions design

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, DOI:10.1002/chem.201804099

asymmetric catalysis noncovalent interactions

Bifunctional iminophosphorane catalysed enantioselective sulfa-Michael addition of alkyl thiols to alkenyl benzimidazoles

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

asymmetric catalysis noncovalent interactions

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

asymmetric catalysis dynamics noncovalent interactions

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C−H Activation Reactions − An Experimental and Computational Study

Piou, T.; Romanov-Michailidis, F.; Romanova-Michaelides, M.; Jackson, K. E.; Semakul, N.; Taggart, T. D.; Newell, B. S.; Rithner, C. D.; Paton, R. S.; Rovis, T. J. Am. Chem. Soc. 2017, 39, 1296–1310

noncovalent interactions informatics

Computing Organic Stereoselectivity − from Concepts to Quantitative Calculations and Predictions

Peng, Q.; Duarte, F.; Paton, R. S. Chem. Soc. Rev. (Emerging Investigators Issue) 2016, 45, 6093−6107

asymmetric catalysis noncovalent interactions

Computational Ligand Design in Enantio- and Diastereoselective Ynamide [5+2] Cycloisomerization

Straker, R.; Peng, Q.; Mekareeya, A.; Paton, R. S.; Anderson, E. A. Nat. Commun. 2016, 7, 10109

asymmetric catalysis noncovalent interactions design

Enantioselective Desymmetrization of Prochiral Cyclohexanones via Organocatalytic Intramolecular Michael Additions to α,β-Unsaturated Esters

Gammack-Yamaguta, A. D.; Datta, S.; Jackson, K. E.; Stegbauer, L.; Paton, R. S.; Dixon, D. J. Angew. Chem. Int. Ed. 2015, 127, 4981−4985

asymmetric catalysis noncovalent interactions design

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, 171-178

asymmetric catalysis noncovalent interactions

A series of potent CREBBP bromodomain ligands reveals an induced fit pocket stabilized by a cation-π interaction

Rooney, T. P. C.; Filippakopoulos, P.; Fedorov, O.; Picaud, S.; Cortopassi, W. A.; Hay, D. A.; Martin,S.; Tumber, A.; Rogers, C. M.; Philpott, M.; Wang, M.; Thompson, A. L.; Heightman, T. D.; Pryde, D. C.; Cook, A.; Paton, R. S.; Müller-Knapp, S.; Knapp, S.; Brennan, P. E.; Conway, S. J. Angew. Chem. Int. Ed. 2014, 126, 6240–6244

chemical biology noncovalent interactions