Description du projet
Un catalyseur plus durable pour certaines fonctionnalisations en phase finale exigeantes
Les complexes de tenailles sont des catalyseurs éprouvés, constitués d’un centre métallique et d’un ligand de type «tenaille». Ils ont fait grandement progresser le domaine de la synthèse organique grâce à leur stabilité et leur polyvalence. Les complexes de cobalt à ligands pris en tenailles sont des substituts prometteurs aux catalyseurs utilisant l’iridium, un métal précieux, mais ils n’ont pas été capables jusqu’à présent d’accomplir des fonctionnalisations en phase finale plus exigeantes. Avec le soutien du programme Actions Marie Skłodowska-Curie, le projet CobaltLSF ouvre la voie à l’utilisation du cobalt pour catalyser une fonctionnalisation de ce genre, à savoir celle d’un type d’hydrocarbure cyclique (arènes), à l’aide d’un ligand tenaille innovant.
Objectif
The depleting reserves of precious metals within the Earth’s crust has made their replacement with more abundant first-row transition metals of paramount importance. Pincer-ligated cobalt complexes have shown a unique ability to recapitulate the reactivity of commonly employed iridium catalysts for arene C–H borylation but, notably, with complementary ortho-to-fluorine site selectivity. However, the lower activity and functional group tolerance of cobalt catalysts has precluded their use in more demanding late-stage applications, depriving chemists of the possibility to selectively functionalize fluoroarenes within complex molecules. “CobaltLSF” aims to unlock the full potential of Co-catalyzed arene C–H functionalization with the use of a novel carbene-containing NCN-pincer ligand that is designed to promote metal-ligand cooperation to address three main challenges: (1) chemoselectivity, by facilitating key steps such as C–H bond cleavage and bond-forming reductive elimination, improving the efficiency of desired catalytic processes over competing side-reactions; (2) site selectivity, through ligand-assisted C–H activation which is predicted to result in a rapidly reversible process that would reinforce ortho-to-fluorine selectivity; (3) direct C–H alkylation using olefin coupling partners, with the aim of expanding the bond-forming capabilities of cobalt catalysis beyond C–H borylation in the context of a green, waste-free method for installing alkyl chains. Alongside the development of (NCN)Co catalysts, their application to the late-stage functionalization (LSF) of fluoroarene-containing drugs will be examined and their chemo- and site selectivity benchmarked against known LSF methods, providing useful comparative data for end-users, such as medicinal chemists. Overall, the successful realization of the proposal is expected to have far-reaching implications for the use of carbene-containing pincer ligands in C–H functionalization with earth-abundant metals.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
45470 Muelheim An Der Ruhr
Allemagne