Abstract

The development of greener and more efficient synthetic methodologies is essential for organic chemistry to reach its full potential in its application to many applied and fundamental scientific problems. Over the last two decades C-H activation has emerged as a powerful tool to streamline syntheses, functionalize complex scaffolds, while massively improving atom and step economy. However, several challenges are still to be addressed before C-H functionalization can be widely applied: 1) the development of mild reaction conditions with a broad scope, including late-stage functionalization, 2) the control of the regioselectivity of C–H activation, 3) the control of the selectivity of homo- versus cross-coupling, and 4) the development of conditions that can be safely used in industry. Mechanistic understanding is a cornerstone for progress in organic chemistry. In this talk I will present some of our group’s approaches in applying the knowledge derived from mechanistic studies into the design of more efficient processes and of novel catalysts and catalytic systems, such as the use of bimetallic Pd/Ag,1 Pd/Cr2 and Au/Ag3 synergistic systems, and Ru-catalysts for late stage functionalization.4,5 Additionally, recent developments in the application of machine learning to mechanism elucidation will be discussed.6 Keywords: Catalysis; ruthenium catalysis; C-H activation; machine learning; mechanistic studies

References 1. Chiara Colletto, Adyasha Panigrahi, Jaime Fernandez-Casado and Igor Larrosa J. Am. Chem. Soc. 2018, 140, 9638-9643. 2. Maria Batuecas, Junfei Luo, Ivana Gergelitsová, Katrina Krämer, Daniel Whitaker, Iñigo J. Vitorica-Yrezabal and Igor Larrosa ACS Catal. 2019, 9, 5268. 3. Xacobe C. Cambeiro, Nanna Ahlsten and Igor Larrosa J. Am. Chem. Soc. 2015, 137, 15636. 4. Marco Simonetti, Diego M. Cannas, Xavier Just-Baringo, Iñigo J. Vitorica-Yrezabal and Igor Larrosa Nature Chem. 2018, 10, 724. 5. Gillian McArthur, Jamie H. Docherty, Mishra Deepak Hareram, Marco Simonetti, Inigo J. Vitorica-Yrezabal, James J. Douglas and Igor Larrosa Nature Chem. 2024, 16, 1141-1150. 6. Jordi Bures and Igor Larrosa Nature 2023, 613, 689-695.