Reaction Mechanism

Reaction Mechanism and Selectivity

Elucidating enzymatic mechanisms helps to explain how enzymes work and predict their behavior. Through experimental collaborations, classical and quantum modeling we explore this avenue in efforts to reveal the mechanistic underpinnings of important enzymatic reactions. Along the way, we aim to expand conceptual and methodological foundations.

Collaborators

Jon Burton (Oxford); Deb Maiti (IIT Bombay); Rich Payne (Sydney)

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. Nat. Catal. 2024, in revision.

Enantioconvergent Cross-Nucleophile Coupling: Cu-Catalyzed Deborylative Cyanation.

Vu, J.; Haug, G. C.; Zhao, C.; Chang, C. J.; Paton, R. S.; Dong, Y. Angew. Chem. Int. Ed. 2024, DOI: https://doi.org/10.1002/anie.202408745

Modular synthesis of aryl amines from 3-alkynyl-2-pyrones.

Gardner, K. E.; de Lescure, L.; Hardy, M. A.; Tan, J.; Sigman, M. S.; Paton, R. S.; Sarpong, R. S. Chem. Sci. 2024, advance article

Platinum-Catalyzed Regio- and Enantioselective Diboration of Unactivated Alkenes with (pin)B−B(dan).

Fang, H.; Manoj, N.; Popescu, M. V.; Noble, A.; Paton, R. S.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2024, DOI: 10.1002/anie.202413504

Selective Ni-Catalyzed Cross-Electrophile Coupling of Heteroaryl Chlorides and Aryl Bromides at 1:1 Substrate Ratio.

Su, Z-.M.; Poole, D. L.; Rafiee, M.; Paton, R. S.; Weix, D. J.;  Stahl, S. J. submitted 2024, DOI: https://chemrxiv.org/engage/chemrxiv/article-details/66e98b63cec5d6c142572268

Reductively Induced Aryl Transmetalation: An Alternative Catalytically Relevant Ni-Catalyzed Biaryl Coupling Mechanism.

Romero-Arenas, A.; Popescu, M. V.; Goetz, M. K.; Sanders, K. M.; Guzei, I. A.; Rafiee, M.; Weix, D. J.; Paton, R. S.; Stahl, S. S. submitted 2024, DOI: 10.26434/chemrxiv-2024-000fk

Combined Synthetic, Spectroscopic, and Computational Insights Into a General Method for Photosensitized Alkene Aziridination.

Meyer, A. R.; Popescu, M. V.; Sau, A.;  Damrauer, N. H.; Paton, R. S.; Yoon, T. P. ACS Catal. 2024, 14, 12310–12317

Dynamic Vertical Triplet Energies: A metric for predicting triplet energy transfer.

Popescu, M. V.; Paton, R. S. Chem 2024, DOI: 10.1016/j.chempr.2024.07.001

Late-Stage “Benzenoid-to-Troponoid” Skeletal Modification of the Cephalotanes: Total Synthesis of Harringtonolide and Computational Analysis.

Wiesler, S.; Sennari, G.;  Popescu, M. P.; Gardner, K. E.; Aida, K., Paton, R. S.; Sarpong. R. Nat. Commun. 2024, 15, 4125

A Deconstruction-Reconstruction Strategy for Pyrimidine Diversification.

Uhlenbruck, B. J. H.; Josephitis, C. M.; Lescure, L.; Paton, R. S.; McNally, A. Nature 2024, 631, 87–93

Harnessing triaryloxonium ions for aryne generation.

Smith, O.; Hindson, M.; Sreenithya, A.; Tataru, V.; Paton, R. S.; Burton, J. W.; Smith, M. D. Nat. Synth. 2024, 3, 58–66

Modeling conformational heterogeneity in biomolecules.

Klem, H. Colorado State University 2023

Control of stereogenic oxygen in a helically chiral oxonium ion.

Smith, O.; Popescu, M. V.; Hindson, M. J.; Paton, R. S.; Burton, J. W.; Smith, M. D. Nature 2023, 615, 430–435

Catalytic enantioselective 6𝝿 photocyclization of acrylanilides.

Jones, B.; Solon, P.; Popescu, M.; Du, J-Y.; Paton, R.; Smith, M. D. J. Am. Chem. Soc. 2023, 145, 171–178

Halogenation of the 3-position of pyridines through Zincke imine intermediates.

Boyle, B. T.; Levy, J. N; de Lescure, L.; Paton, R. S.; McNally, A. Science 2022, 378, 773–779

Expanding chemical space by para-C-H arylation of arenes.

Maiti, S.; Li, Y.; Sasmal, S.; Guin, S.; Bhattacharya, T.; Lahiri, G.K.; Paton, R. S.; Maiti, D. Nat. Commun. 2022, 13, 3963

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

[18F]Difluorocarbene for Positron Emission Tomography.

Sap, J. B. S.; Meyer, C. F.; Ford, J.; Straathof, N. J. W.; Dürr, A. B.; Lelos, M. J.; Paisey, S. J.; Mollner, T. A.; Hell, S. A.; Trabanco, A.; Genicot, C.; am Ende, C. W.; Paton, R. S.; Tredwell, M.; Gouverneur, V. Nature 2022, 606, 102–108.

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

Reading and Erasing of the Phosphonium Analogue of Trimethyllysine by Epigenetic Proteins.

Kamps, J. J. A. G.; Belle, R.; Poater, J.; Kumar, K.; Pieters, B. J. G. E.; Salah, E.; Brown, T.; Claridge, T. D. W.; Paton, R. S.; Bickelhaupt, F. M.; Kawamura, A.; Schofield, C. J.; Mecinović, J. Commun. Chem. 2022, 5, 27

Phosphorus-Mediated sp2-sp3 Couplings for Selective C–H Fluoroalkylation of Complex Azines.
Zhang, X.; Nottingham, K. G.; Patel, C.; Alegre-Requena, J. V.; Levy, J. N.; Paton, R. S.; McNally, A. Nature 2021, 594, 217–222.
Mechanistic Investigation of Rh (I)-Catalyzed Asymmetric Suzuki-Miyaura Coupling with Racemic Allyl Halides.

van Dijk, L.; Ardkhean, R.; Sidera, M.; Karabiyikoglu, S.; Sari, O.; Claridge, T. D. W.; Paton, R. S.; Fletcher, S. P. Nat. Catal. 2021, 4, 284–292

Goodvibes.

A Python program to compute quasi-harmonic thermochemical data and potential energy surface diagrams from frequency calculations at a given temperature/concentration, corrected for the effects of vibrational scaling-factors. All (electronic, translational, rotational and vibrational) partition functions are recomputed and can be correct to any temperature or concentration. The first public version of GoodVibes was released in 2016 and it has undergone several revisions since, during which time it has been used by many groups around the world. The program is described in the publication: GoodVibes: automated thermochemistry for heterogeneous computational chemistry data

[Zenodo] [GitHub]
Asymmetric Total Synthesis and Determination of the Absolute Configuration of (+)-Srilankenyne via Sequence-sensitive Halogenations Guided by Conformational Analysis.

Jang, H.; Kwak, S. Y.; Lee, D.; Alegre-Requena, J. V.; Kim, H.; Paton, R. S.; Kim, D. Org. Lett. 2021, 23, 1321–1326

pyQRC.

QRC is an abbreviation of Quick Reaction Coordinate. This provides a quick alternative to IRC (intrinsic reaction coordinate) calculations. The program will read a Gaussian frequency calculation and will create a new input file which has been projcted from the final coordinates along the Hessian eigenvector with a negative force constant. The magnitude of displacement can be adjusted on the command line. By default the projection will be in a positive sense (in relation to the imaginary normal mode) and the level of theory in the new input file will match that of the frequency calculation. A common application for pyQRC is in distorting ground state structures to remove annoying imaginary frequencies after reoptimization. This code has, in some form or other, been in use since around 2010.

[GitHub]
An Alkyne Linchpin Strategy for Drug: Pharmacophore Conjugation: Experimental and Computational Realization of a meta-Selective Inverse Sonogashira Coupling.

Porey, S.; Zhang, X.; Bhowmick, S.; Singh, V. K.; Guin, S.; Paton, R. S.; Maiti, D. J. Am. Chem. Soc. 2020, 142, 3762–3774

Cofactor-independent pinacolase directs non-Diels-Alderase biogenesis of the Brevianamides.

Ye, Y.; Du, L.; Zhang, X.; Newmister, S. A.; McCauley, M.; Alegre-Requena, J. V.; Zhang W.; Mu, S.; Minami, A.; Fraley, A. E.; Adrover-Castellano, M. L.; Carney, N.; Shende, V. K.; Oikawa, H.; Kato H.; Tsukamoto, S.; Paton, R. S.; Williams R. M.; , Sherman, D. H.; Li, S. Nat. Catal. 2020, 3, 497–506

Comparison of Molecular Recognition of Trimethyllysine and Trimethylthialysine by Epigenetic Reader Proteins.

Hintzen, J. C. J.; Poater, J.; Kumar, K.; Al Temimi, A. H. K.; Pieters, B. J. G. E.; Paton, R. S.; Bickelhaupt, F. M.; Mecinović, J. Molecules 2020, 25, 1918

Elucidating the chemical pathways responsible for the sooting tendency of 1 and 2- phenylethanol.

Etz, B. D.; Fioroni, G. M.; Messerly, R. A.; Rahimi, M. J.; St. John, P. C.; Robichaud, D. J.; Christensen, E. D.; Beekley, B. P.; McEnally, C. S.; Pfefferle, L. D.; Xuan, Y.; Vyas, S.; Paton, R. S.; McCormick, R. L.; Kim, S. Combust. Inst. 2020

Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger.

Pieters, B. J. G. E., Wuts, M. H. M., Poater, J.; Kumar, K.; White, P. B.; Kamps, J. J. A. G.; Sherman, W; Pruijn, G. J. M.; Paton, R. S.; Beuming, T.; Bickelhaupt, F. M.; Mecinović, J. Commun. Chem. 2020, 3, 69

Stereoretention in styrene heterodimerisation promoted by one-electron oxidants.

Zhang, X.; Paton, R. S. Chem. Sci. 2020, 11, 9309–9324

Unconventional Reactivity of Ethynylbenziodoxolone (EBX) Reagents and Thiols: Scope and Mechanism.

Liu, B. Alegre-Requena, J. V.; Paton, R. S.; Miyake, G. Chem. Eur. J. 2020, 26, 2386–2394

Visible light mediated heterocycle functionalization via a geometrically interrupted [2+2] cycloaddition.

Popescu, M. V.; Mekereeya, A.; Alegre-Requena, J. V.; Paton, R. S.; Smith, M. D. Angew Chem. Int. Ed. 2020, 59, 23020–23024

Kinisot.

A Python program to compute kinetic isotope effects from two Gaussian output files, one of which is a ground state and the other a transition state. The level of theory and basis set are detected from in the output files and the program will attempt to assign the appropriate scaling factor based on data from the Truhlar group. The program diagonalizes the mass-weighted Hessian matrices to obtain harmonic vibrational frequencies and Bigeleisen-Mayer Reduced Isotopic Partition Function Ratios. Kinisot is freely available (CC-BY license) from GitHub; alternatively, it can be installed from the command line with pipy: pip install kinisot.

[Zenodo] [GitHub]
A Pyridine-Pyridine Cross-Coupling Reaction via Dearomatized Radical Intermediates.

Koniarczyk, J. L.; Greenwood, J. W.; Alegre-Requena, J. V.; Paton, R. S.; McNally, A. Angew. Chem. Int. Ed. 2019, 58, 14882–14886

Biosynthesis of Providencin: Understanding Photochemical Cyclobutane Formation with Density Functional Theory.

Tang, B.; Paton, R. S. Org. Lett. 2019, 21, 1243–1247

Fungal Indole Alkaloid Biogenesis through Evolution of a Bifunctional Reductase/Diels-Alderase.

Dan, Q.; Newmister, S. A.; Klas, K. R.; Fraley, A. E.; McAfoos, T. J.; Somoza, A. D.; Sunderhaus, J. D.; Ye, Y.; Shende, V. V.; Yu, F.; Sanders, J. N.; Brown, W. C.; Zhao, L.; Paton, R. S.; Houk, K. N.; Smith, J. L.; Sherman, D. H.; Williams, R. M. Nat. Chem. 2019, 11, 972–980

Hydrogen Bond Enabled Dynamic Kinetic Resolution of Axially Chiral Amides Mediated by a Chiral Counterion.

Fugard, A.; Lahdenperä, A.; Mekareeya, A.; Tan, J.; Paton, R. S.; Smith, M. D. Angew. Chem. Int. Ed. 2019, 58, 2795-2798

Iterative Arylation of Amino Acids and Aliphatic Amines Via Delta-C(Sp3)−H Activation: Experimental and Computational Exploration.

Guin, S.; Dolui, P.; Zhang, X.; Paul, S.; Singh, V. K.; Pradhan, S.; Chandrashekar, H. B.; Anjana, S. S.; Paton, R. S.; Maiti, D.Angew. Chem. Int. Ed. 2019, 131, 5689–5694

Non‐Hydrolytic Beta‐Lactam Antibiotic Fragmentation by L,D‐Transpeptidases and Serine B‐Lactamase Cysteine Variants.

Lohans, C. T.; Chan, H. T. H.; Malla, T. R. Kumar, K.; Kamps, J. J. A. G.; McArdle, D. J. B.; van Groesen, E.; de Munnik, M.; Tooke, C. L.; Spencer, J.; Paton, R. S. Brem, J.; Schofield, C. J. Angew. Chem. Int. Ed. 2019, 131, 2012–2016

Palladium-Catalyzed Directed Meta-Selective C−H Allylation of Arenes: Unactivated Internal Olefins as Allyl Surrogates.

Achar, T. K.; Zhang, X.; Mondal, R.; Shanavas, M. S.; Maity, S.; Paul, N.; Paton, R. S.; Maiti, D. Angew. Chem. Int. Ed. 2019, 58, 10353–10360

A New Mechanism for Beta-Lactamases: Class D Enzymes Degrade 1-Beta-Methyl Carbapenems via Lactone Formation.

Lohans, C. T.; van Groesen, E.; Brem, J.; Kumar, K.; Paton, R. S.; Schofield, C. J. Angew. Chem. Int. Ed. 2018, 57, 1282–1285

Asymmetric Total Synthesis and Structure Confirmation of (+)-(3e)-Isolaurefucin Methyl Ether.

Sohn, T.-I.; Kim, B.; Kim, D.; Paton, R. S. Heterocycles 2018, 97, 179–191

Direct Sulfonylation of Anilines Mediated by Visible Light.

Johnson, T. C.; Elbert, B. L.; Farley, A. J. M.; Gorman, T. W.; Genicot, C.; Lallemand, B.; Pasau, P.; Flasz, J.; Castro, J. L.; MacCoss, M.; Dixon, D. J.; Paton, R. S.; Schofield, C. J.; Smith, M. D.; Willis, M. C. Chem. Sci. 2018, 9, 629–633

Dynamic Intermediates in the Radical Cation Diels-Alder Cycloaddition: Lifetime and Suprafacial Stereoselectivity.

Tan, J.; Hirvonen, V.; Paton, R. S. Org. Lett. 2018, 20, 2821–2825

Experimental and Theoretical Insight into the Soot Tendencies of the Methylcyclohexene Isomers.

Kim, S.; Fiorinia, M. Park, J.-W.; Robichaud, D. J.; Dhrubajyoti, D. D.; St. John, P. C.; Lu, T.; McEnally, C.; Pfefferle, L. D.; Paton, R. S.; Foust, T. D.; McCormick, R. L. Proc. Combust. Inst. 2019, 37, 1083–1090

Experimental and Theoretical Study of Oxidative Stability of Alkylated Furans Used as Gasoline Blend Components.

Christensen, E.; Fioroni, G. M.; Kim, S.; Fouts, L.; Gjersing, E.; Paton, R. S.; McCormick, R. Fuel 2018, 212, 576–585

Heterobiaryl Synthesis by Contractive C–C Coupling Via P(V) Intermediates.

Hilton, M. C.; Zhang, X.; Boyle, B. T.; Alegre-Requena, J. V.; Paton, R. S.; McNally, A. Science 2018, 62, 799–804

Post-Translational Site-Selective Protein Alpha-Deuteration.

Galan, S. R. G.; Wickens, J. R.; Dadova, J.; Ng, W.-L.; Zhang, X.; Simion, R. A.; Quinlan, R.; Pires, E.; Paton, R. S.; Caddick, S.; Chudasama, V.; Davis, B. G. Nat. Chem. Biol. 2018, 14, 955–963

Recognition of Shorter and Longer Trimethyllysine Analogues by Epigenetic Reader Proteins.

Al Temimi, A. H. K.; Belle, R.; Kumar, K.; Poater, J.; Betlem, P.; Pieters, B. J. G. E.; Paton, R. S.; Bickelhaupt, F. M.; Mecinović, J. Chem. Commun. 2018, 54, 2409–2412

Adenosine Monophosphate Binding Stabilizes the KTN Domain of the Shewanella Denitrificans Kef Potassium Efflux System.

Pliotas, C.; Grayer, S. C.; Ekkerman, S.; Chan, A. K. N.; Healy, J.; Marius, P.; Bartlett, W.; Khan, A.; Cortopassi, W. A.; Chandler, S. A.; Rasmussen, T.; Benesch, J. L. P.; Paton, R. S.; Claridge, T. D. W.; Miller, S.; Booth, I. R.; Naismith, J. H.; Conway, S. J. Biochemistry 2017, 56, 4219–4234

Construction of 6,10-Syn- and Anti-2,5-Dioxabicyclo[2.2.1]Heptane Skeletons via Oxonium Ion Formation-Fragmentation: Prediction of Structure of (E)-Ocellenyne by NMR Calculation.

Jeong, D.; Sohn, T.-I.; Kim, J. Y.; Kim, G.; Kim, D.; Paton, R. S. Org. Lett. 2017, 19, 6252–6255

Detailed Mechanistic Studies on Palladium-Catalyzed Selective C−H Olefination With Aliphatic Alkenes − a Significant Influence of Proton Shuttling.

Deb, A.; Hazra, A.; Peng, Q.; Paton, R. S.; Maiti, D. J. Am. Chem. Soc. 2017, 139, 763–775

Divergent Photocyclization/1,4-Sigmatropic Rearrangements for the Synthesis of Sesquiterpenoid Derivatives.

Gorobets, E.; Wong, N. E.; Paton, R. S.; Derksen, D. J. Org. Lett. 2017, 19, 484–487

Dual Gold‐Catalyzed Three‐Component Reaction: Efficient Synthesis of Indene‐Fused Esters.

Yu, C.; Ma, X.; Chen, B.; Tang, B.; Paton, R. S.; Zhang, G. Eur. J. Org. Chem. 2017, 11, 1561–1565

Investigating D-Lysine Stereochemistry for Epigenetic Methylation, Demethylation and Recognition.

Belle, R.; Al Temimi, A. H. K.; Kumar, K.; Pieters, B. J. G. E.; Dunford, J.; Tumber, A.; Johansson, C.; Brown, T.; Schofield, C. J.; Hopkinson, R. J.; Paton, R. S.; Kawamura, A.; Mecinović, J. Chem. Commun. 2017, 53, 13264–13267

Mechanistic Insight into Palladium-Catalyzed Cycloisomerization: a Combined Experimental and Theoretical Study.

Mekareeya, A.; Walker, P. R.; Couce-Rios, A.; Campbell, C. D.; Steven, A.; Paton, R. S.; Anderson, E. A. J. Am. Chem. Soc. 2017, 139, 10104–10114

Phosphazene Catalyzed Addition to Electron-Deficient Alkynes: the Importance of Nonlinear Allenyl Intermediates Upon Stereoselectivity.

Simón, L.; Paton, R. S. J. Org. Chem. 2017, 82, 3855–3863

Structural and Stereoelectronic Insights into Oxygenase Catalyzed Formation of Ethylene from 2-Oxoglutarate.

Zhang, Z.; Smart, T. J.; Choi, H.; Hardy, F.; Lohans, C. T.; Abboud, M. I.; Richardson, M. S. W.; Paton, R. S.; McDonough, M. A.; Schofield, C. J. Proc. Nat. Acad. Sci. 2017, 4667–4672

Visible Light Photocatalysis of 6 Pi-Heterocyclization.

Münster, N.; Parker, N. A.; van Dijk, L.; Paton, R. S.; Smith, M. D. Angew. Chem. Int. Ed. 2017, 56, 9468–9472

A Counterion-Directed Approach to the Diels-Alder Paradigm: Cascade Synthesis of Tricyclic Fused Cyclopropanes.

Kiss, E.; Campbell, C. D.; Driver, R. W.; Jolliffe, J. D.; Lang, R.; Sergieiva, T.; Okovytyy, S.; Paton, R. S.; Smith, M. D. Angew. Chem. Int. Ed. 2016, 55, 13813–13817

Furan Production from Light Oxygenates in HZSM-5.

Kim, S.; Evans, T. J.; Mukarakate, C.; Bu, L.; Beckham, G. T.; Nimlos, M. R.; Paton, R. S.; Robichaud, D. J. ACS Sustain. Chem. Eng. 2016, 4, 2615–2623

Investigations on Recyclization and Hydrolysis in Avibactam Mediated Serine B-Lactamase Inhibition.

Choi, H.; Paton, R. S.; Park, H.; Schofield, C. J. Org. Biomol. Chem. 2016, 14, 4116–4128

Mechanisms of Histone-Modifying and Reading Enzymes: the Role of the Protein Environment from a Computational Perspective.

Cortopassi, W. A.; Kumar, K.; Duarte, F.; Pimentel, A. S.; Paton, R. S. J. Mol. Graph. Model. 2016, 67, 69–84

QM/MM study on the enantioselectivity of spiroacetalization catalysed by an imidodiphosphoric acid catalyst: how confinement works.

Simón, L.; Paton, R. S. Org. Biomol. Chem. 2016, 14, 3031–3039

Synthesis of Malhamensilipin a Exploiting Iterative Epoxidation/Chlorination: Experimental and Computational Analysis of Epoxide-Derived Chloronium Ions.

Saska, J.; Lewis, W.; Paton, R. S.; Denton, R. Chem. Sci. 2016, 7, 7040–7049

Unravelling Innate Substrate Control in Site-Selective Palladium-Catalyzed C–H Heterocycle Functionalization.

Choi, H.; Min, M.; Peng, Q.; Kang, D.; Paton, R. S.; Hong, S. Chem. Sci. 2016, 7, 3900–3909

Alpha- and Alpha’-Lithiation–Electrophile Trapping of N-Thiopivaloyl and N-tert-Butoxythiocarbonyl Α-Substituted Azetidines: Rationalization of the Regiodivergence Using NMR and Computation.

Jackson, K. E.; Mortimer, C. L.; Odell, B.; McKenna, J. M.; Claridge, T. D. W.; Paton, R. S.; Hodgson, D. M. J. Org. Chem. 2015, 80, 9838–9846

Coordination Diversity in Hydrogen-Bonded Homoleptic Fluoride–Alcohol Complexes Modulates Reactivity.

Engle, K. M.; Pfeifer, L.; Pidgeon, G. W.; Giuffredi, G. T.; Thompson, A. L.; Paton, R. S.; Brown, J. M.; Gouverneur, V. Chem. Sci. 2015, 6, 5293–5302

Dioxygen Binding in the Active Site of Histone Demethylase JMJD2A and the Role of Protein Environment.

Cortopassi, W. E.; Simion, R. A.; Hornsby, C. E.; Costa Franca, T. C.; Paton, R. S. Chem. Eur. J. 2015, 21, 18983–18992

Enantioselective Desymmetrization of Prochiral Cyclohexanones via Organocatalytic Intramolecular Michael Additions To A,B-Unsaturated Esters.

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

Ethanol Dehydration in HZSM-5 Studied by Density Functional Theory: Evidence for a Concerted Processes.

Kim, S.; Robichaud, D. J.; Beckham, G. T.; Paton, R. S.; Nimlos, M. R. J. Phys. Chem. A 2015, 119, 3604–3614

Origins of Asymmetric Phosphazene Organocatalysis: Computations Reveal a Common Mechanism for Nitro- and Phospho-Aldol Additions.

Simón, L.; Paton, R. S. J. Org. Chem. 2015, 80, 2756–2766

Role of Hydrogen Bonding Acceptors in Organo-Enamine Catalysis.

Han, J.; Zhichao Lu, Z.; Flach, A. L.; Paton, R. S.; Hammond, G. B.; Xu, B. Chem. Eur. J. 2015, 21, 11687–11691

Small Molecule Inhibitors of Bromodomain-Acetyl-Lysine Interactions.

Brand, M.; Measures, A.; Wilson, B.; Cortopassi, W. A.; Alexander, R.; Hoss, M.; Hewings, D. S.; Paton, R. S.; Conway, S. J. ACS Chem. Bio. 2015, 10, 22–39

Substrate-Controlled Asymmetric Total Syntheses of Microcladallenes A, B and C.

Sohn, T.-I.; Kim, D.; Paton, R. S. Chem. Eur. J. 2015, 21, 15988–15997

Thermal and Photochemical Mechanisms for Cyclobutane Formation In Bielschowskysin Biosynthesis.

Tang, B.; Simion, R. A.; Paton, R. S. Synlett 2015, 26, 501–507

A Mechanistic Investigation of Acid-Catalyzed Cleavage of Aryl-Ether Linkages: Implications For Lignin Depolymerization In Acidic Environments.

Sturgeon, M. R.; Kim, S.; Lawrence, K.; Paton, R. S.; Chmely, S. C.; Nimlos, M. R.; Foust, T. D.; Beckham, G. T. ACS Sustain. Chem. Eng. 2014, 2, 472–485

A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced Fit Pocket Stabilized by a Cation-Pi 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

Asymmetric Total Synthesis of (+)-Bermudenynol, a C15 Laurencia Metabolite With a Vinyl Chloride-Containing Oxocene Skeleton.

Kim, G.; Sohn, T.-I.; Kim, D.; Paton, R. S. Angew. Chem. Int. Ed. 2014, 53, 272–276

Intramolecular Diels-Alder Reactions of Cycloalkenones: Stereoselectivity, Lewis Acid Influence and Halogen Effects.

Pham, H.; Paton, R. S.; Ross, A. G.; Danishefsky, S. J.; Houk, K. N. J. Am. Chem. Soc. 2014, 136, 2397–2403

Natural Product Biosynthesis: It’s All Downhill from Here.

Hornsby, C. E.; Paton, R. S. Nat. Chem. 2014, 6, 88–89

Phase‐Transfer‐Catalysed Synthesis of Pyrroloindolines and Pyridoindolines by a Hydrogen‐Bond‐Assisted Isocyanide Cyclization Cascade.

Knipe, P. C.; Gredičak, M.; Cernijenko, A.; Paton, R. S.; Smith, M. D. Chem. Eur. J. 2014, 11, 3005–3009

Quantum Mechanical Calculations Suggest That Lytic Polysaccharide Monooxygenases Employ a Copper-Oxyl, Oxygen-Rebound Mechanism.

Kim, S.; Sandgren, M.; Paton, R. S.; Beckham, G. T. Proc. Nat. Acad. Sci. 2014, 111, 149–154

C-Alkylation of Chiral Tropane- and Homotropane-Derived Enamines.

Hodgson, D. M.; Charlton, A.; Paton, R. S.; Thompson, A. S. J. Org. Chem. 2013, 8, 1508–1518

Computational Organic Chemistry.

Jackson, K.; Jaffar, S.; Paton, R. S. Annu. Rep. Prog. Chem., Sect. B, 2013, 109, 235–255

Diels-Alder Reactivities of Strained and Unstrained Cycloalkenes With Normal and Inverse-Electron-Demand Dienes: Activation Barriers and Distortion/Interaction Analysis.

Liu, F.; Paton, R. S.; Kim, S.; Liang, Y.; Houk, K. N. J. Am. Chem. Soc. 2013, 135, 15642–15649

Enhanced Reactivity In Dioxirane C-H Oxidations Via Strain Release: a Computational and Experimental Study.

Zhou, L; Paton, R. S.; Eschenmoser, A.; Newhouse, T. R.; Baran, P. S.; Houk, K. N. J. Org. Chem. 2013, 78, 4037–404

Mechanistic Investigations On the Enantioselective Conia-Ene Reaction Catalyzed by Cinchona-Derived Amino Urea Pre-Catalysts and Cu(I).

Sladojevich, F.; Fuentes de Arriba, A. L.; Yang, T.; Ferrali, A.; Paton, R. S.; Dixon, D. J. Chem. Eur. J. 2013, 19, 14286–14295

Mechanistic Study of a Ru-Xantphos Catalyst For Tandem Alcohol Dehydrogenation and Reductive Aryl-Ether Cleavage.

Chmely, S. C.; Kim, S. C.; Ciesielski, P. N.; Jiménez-Osés, G.; Paton, R. S.; Beckham, G. T. ACS Catal. 2013, 3, 963–974

Rapid Cross Metathesis For Protein Modifications Via Chemical Access To Se-Allyl Selenocysteine In Proteins.

Lin, Y. A.; Boutureira, O.; Lercher, L.; Bhushan, B.; Paton, R. S.; Davis, B. G. J. Am. Chem. Soc. 2013, 135, 12156–12159

Synthesis of Cyclic A-Aminophosphonates Through Copper Catalyzed Enamine Activation.

Han, J.; Paton, R. S.; Xu, B.; Hammond, G. B. Synthesis 2013, 45, 463–470

Concise Substrate-Controlled Asymmetric Total Syntheses of Dioxa- Bicyclic Marine Natural Products With 2,10-Dioxabicyclo-[7.3.0]Dodecene and 2,9-Dioxabicyclo[6.3.0]Undecene Skeletons.

Kim, M. J.; Sohn, T.-I.; Kim, D.; Paton, R. S.; J. Am. Chem. Soc. 2012, 34 , 20178–20188

Dinuclear Palladium Complexes – Precursors or Catalysts?.

Paton, R. S.; Brown, J. M. Angew. Chem. Int. Ed. 2012, 51, 10448–10450

Enzymatic Catalysis of Anti-Baldwin Ring-Closure in Polyether Biosynthesis.

Hotta, K.; Chen, X.; Paton, R. S.; Minami, A.; Li, H. Swaminathan, K. T.; Mathews, I. I.; Watanabe, K.; Oikawa, H.; Houk, K. N.; Kim, C. Y. Nature 2012, 483, 355–358

Unusual Base-Induced Rearrangement of Exo-9-Oxabicyclo[4.2.1]Non-7-Ene Oxide To Exo-8-Hydroxybicyclo[3.3.0]Octan-2-One.

Hodgson, D. M.; Stent, M. A. H.; Paton, R. S.; Wilson, F. X. Heterocycles (Albert Padwa Birthday Issue) 2012, 84, 625–635

A Stereoselective Total Synthesis of (±)-Tormesol.

Kim, H.; Bae, H.; Kim, S.; Kim, D.; Lee, D.; Paton, R. S. Tetrahedron (Gilbert Stork Special Issue) 2011, 67, 10017–10025

Computational Study of Bond Dissociation Enthalpies For a Large Range of Native and Modified Lignins.

Kim, S.; Chmely, S. C.; Nimlos, M. R.; Bomble, Y. J.; Foust, T. D.; Paton, R. S.; Beckham, G. T. J. Phys. Chem. Lett. 2011, 2, 2846–2852

Gold-Catalyzed Intramolecular Oxygen Transfer Reactions of 2-Alkynyl-1,5-Diketones: Expansion and Mechanistic Investigations On a Novel [4+2] Cycloaddition.

Liu, L.; Malhotra, D.; Jin, Z.; Paton, R. S.; Houk, K. N.; Hammond, G. B. Chem. Eur. J. 2011, 17, 10690–10699

Unravelling the Mechanism of Cascade Reactions of Zincke Aldehydes.

Paton, R. S.; Steinhardt, S. E.; Vanderwal, C. D.; Houk, K. N. J. Am. Chem. Soc. 2011, 133, 3895–3905

Indolyne and Aryne Distortions and Nucleophilic Regioselectivities.

Cheong, P. H. Y.; Paton, R. S.; Bronner, S. M.; Im, G. Y.; Garg, N. K.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 1267–1269

Indolyne Experimental and Computational Studies: Synthetic Applications and Origins of Selectivities of Nucleophilic Additions.

Im, G.-Y. J.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P.-H. Y.; Houk, K. N. Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933–17944

Origins of Regioselectivity of Diels−Alder Reactions For the Synthesis of Bisanthraquinone Antibiotic BE-43472B A.

Hayden, A. E.; Paton, R. S.; Becker, J.; Lim, Y. H.; Nicolaou, K. C.; Houk, K. N. J. Org. Chem. 2010, 75, 922–928

Origins of Stereoselectivity In the Trans-Diels-Alder Paradigm.

Paton, R. S.; Mackey, J. L.; Kim, W.H.; Lee, J. H.; Danishefsky, S. J.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 9335–9340

The [4+2], Not [2+2], Mechanism Occurs in the Gold-Catalyzed Intramolecular Oxygen Transfer Reaction of 2-Alkynyl-1,5-Diketones.

Liu, L.-P.; Malhotra, D.; Paton, R. S.; Houk, K. N.; Hammond, G. B. Angew. Chem. Int. Ed. 2010, 49, 9132–9135

Gold(I)-Catalyzed Intermolecular Hydroalkoxylation of Allenes: a DFT Study.

Paton, R. S.; Maseras, F. Org. Lett. 2009, 11, 2237–2240

Mechanistic Insights Into the Catalytic Asymmetric Allylboration of Ketones: Bronsted Or Lewis Acid Activation?.

Paton, R. S.; Goodman, J. M.; Pellegrinet, S. C. Org. Lett. 2009, 11, 37–40

1,5-Anti Stereocontrol In the Boron-Mediated Aldol Reactions of Beta-Alkoxy Methyl Ketones: the Role of the Formyl Hydrogen Bond.

Paton, R. S.; Goodman, J. M. J. Org. Chem. 2008, 73, 1253–1263

A DFT Study of the Asymmetric Alkenylation of Enones Catalyzed by Binapthols.

Paton, R. S.; Goodman, J. M.; Pellegrinet, S. C. J. Org. Chem. 2008, 73, 5078–5089

Enantioselectivity In the Boron Aldol Reactions of Methyl Ketones.

Goodman, J. M.; Paton, R. S. Chem. Commun. 2007, 2124–2126

Understanding the Origins of Remote Asymmetric Induction In the Boron Aldol Reactions of Beta-Alkoxy Methyl Ketones.

Paton, R. S.; Goodman, J. M. Org. Lett. 2006, 8, 4299–4302