Fonctionnalisation de groupements alkyles par activation C-H catalytique: méthodes, mécanismes et applications – ALCaCHA

The functionalization of unreactive groups in organic molecules by transition metal-catalyzed C-H activation constitutes an atom- and step-economical alternative to more traditional synthetic methods. This research field has grown very rapidly in the past few years. In this context, the coordinator group of Olivier Baudoin (University of Lyon) attempts to develop new efficient and selective methodological tools to functionalize alkyl groups, and to demonstrate their applicability in multi-step synthesis of complex organic molecules. Preliminary studies in this group focused on the palladium-catalyzed C-H activation of benzylic alkyl groups of bromobenzenes, that gives rise to a diverse array of attractive organic intermediates such as olefins, benzocyclobutenes or polycyclic compounds. In this research proposal, the coordinator group proposes to extend the synthetic possibilities offered by this new method, with the support of two complementary collaboration partners. First, the group of Eric Clot (University of Montpellier), that constitutes the second partner of the project, will focus on the intensification of mechanistic studies that were already initiated on C-H activation reactions developed by the Baudoin group. These studies will aim at modeling the catalytic cycles in the most accurate manner, by performing computational calculations on molecular species truly involved in the experimental conditions. These data will improve the understanding of the catalytic processes and thus the design of original substrates and catalysts by the other project partners. In addition, the third partner group of Steven P. Nolan (ICIQ, Spain) will share its know-how on the design of efficient transition metal catalysts based on N-heterocyclic carbene ligands. Based on evidence furnished by the Baudoin group that their C(sp3)-H activation reactions necessitate specific catalysts, the Nolan group will focus on the development of original and well-defined catalysts that allow these reactions to be performed in a milder, more efficient and selective fashion. In particular the design of catalytic enantioselective reactions will constitute a prime objective. Finally, with the mechanistic and methodological support of its two partners, the Baudoin group will focus on the development of new C(sp3)-H activation reaction variants. The reactivity of new substrates will be studied, in order to access a large array of functionalized organic molecules. In particular, the synthesis of polycyclic and heterocyclic compounds with original structures and of medicinal interest is proposed. Finally, the search for more atom-economical C(sp3)-H activation processes, that is envisaged by modification of the type of catalysis, will constitute one of the most challenging features in this project.