Rob Paton is an Associate Professor in Organic Chemistry at Oxford who uses computation to understand and predict organic structure and reactivity. In 2015 he received the RSC Harrison-Meldola Memorial Prize for pioneering the rational design of catalysts and an Outstanding Junior Faculty Award from the ACS Computers in Chemistry division. Rob completed his PhD in Cambridge, followed by a Fulbright-AstraZeneca postdoctoral fellowship at UCLA and a visiting fellowship at the Institute of Chemical Research of Catalonia.
Computational design of new ligands for asymmetric transition metal catalysis
Computational chemistry provides unparalleled insight into the transition structures of catalytic reactions. This delivers new understanding of the non-covalent interactions critical for reactivity and selectivity. Alongside experimental investigatations we have explored the mode of action of asymmetric organocatalysts, where our insights into mechanism have been used to explain unusual reactivity (such as a formally disfavoured 5-endo-trig carbocyclization) and to design of more atom-efficient asymmetric catalysts.
Despite the widespread adoption of computational tools across chemistry, the prediction and design of asymmetric catalytic reactions is not yet routine. In this talk we discuss some of the inherent challenges involved in the quantitative prediction of stereoselectivities, and our ongoing approaches to overcome them. The development of bespoke transition state force fields is introduced as a means to accurately describe these species accurately and efficiently, which has led to new ways of studying conformatioanlly flexible systems in our group. We present two approaches for the design of new ligands for asymmetric transition metal catalysis, based on a mechanistic study of competing pathways in the cycloisomerizations of ynamides, and the development of quantitative structure-selectivity relationships in asymmetric conjugate additions.