Reaction Mechanism Graphic

Reaction Mechanism and Selectivity

We elucidate reaction mechanisms to understand how selectivity arises in complex chemical transformations. Our research spans enzymatic catalysis, organometallic reactions, biosynthetic pathways, and photochemistry. Using quantum chemical modeling, QM/MM methods, and molecular dynamics, we map reaction coordinates, identify reactive intermediates, and rationalize selectivity patterns. Our aims include explaining unusual reactivity, predicting reaction outcomes, and revealing the role of non-covalent interactions in controlling selectivity. These mechanistic insights guide synthetic strategy and expand fundamental chemical understanding.

Collaborators

Varinder Aggarwal, Jeff Bandar, Niels Damrauer, Andy McNally,
Richmond Sarpong

Recent Papers

Selectivity Emerges from Indiscriminate Photoreduction.

Edgecomb, J. M.; Sau, A.; Manoj, N.; Resmini, M. D.; Meyer, A. F.; Paton, R. S.; Damrauer, N. H.; Wickens, Z. K. Nature 2026, DOI: 10.1038/s41586-026-10897-7

Toward Sustainable Synthesis of Peptide Therapeutics via Tag-Assisted Peptide Synthesis and Aryl Selenoester Aminolysis Ligation.

Egelund, P. H. G.; Rachid, A.; Ayoub, A.; Platt, A. P.; Tang, A. H.; Sejer Pedersen, D.; Paton, R. S.; Kulkarni, S. S.; Premdjee, B.; Payne, R. J. J. Am. Chem. Soc. 2026, 148, 25050–25061.

Protecting Groups as Dispersive Directing Groups: Toward the Asymmetric Synthesis of Altemicidin.

Wang, Y.; Platt, A. P.; Gaston, R., Jr.; Paton, R. S.; Trauner, D. H. Org. Lett. 2026, 28, 7959–7964

The generation of five-membered hetarynes balanced on the edge of accessibility.

Hindson, M. J.; Popescu, M. V.; Alisauskas, E.; Fresia, M.; Holmes, S.; Petropavloskikh, D.; Paton, R. S.; Burton, J. W.; Smith, M. D. in revision 2026

TagC-RED: An Infrared-Triggered Retro-Ene Reaction for Deep-Tissue Bioconjugation.

Suh, S. M.; Ben-zvi, B.; Talbott, J. M.; Manoj, N.; Nelson, B. M.; Hughes, R. R.; Haug, G.; Koide, S.; Paton, R. S.; Raj, M.; Diao, T. J. Am. Chem. Soc. 2026, 148, 19738–19749

Enantioconvergent Chan-Evans-Lam C(sp3)–O Coupling: Cu-Catalyzed Asymmetric Benzyl- and Allylborane Oxidation.

Schubert, T. J.; Carpentier, A.; Li, Y.; Hubbell, K. C.; Oh, J.; Zheng, S.-L.; Paton, R. S.; Dong, Y. J. Am. Chem. Soc. 2026, 148, 20694–20704

Electrophilic Amination–Induced 1,2-Boronate Migration for the Modular Synthesis of β-Amino Boronic Esters.

Shen, H.-C.; Sandvoss, A.; Hughes, W. B.; Tyler, J. L.; McCormick McPherson, L. J.; Paton, R. S.; Aggarwal, V. K. Nat. Chem. 2026, accepted

Fundamental Study of Density Functional Theory Applied to Triplet State Reactivity: Introduction of the TRIP50 Dataset.

Hughes, W. B.; Popescu, M. V.; Paton, R. S. J. Chem. Theory Comput. 2026, 22, 3530–3542

Computational Chemistry Highlights: Introduction of the TRIP50 Dataset