Objective
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.
Fields of science
Programme(s)
Call for proposal
H2020-MSCA-IF-2020
See other projects for this call
Funding Scheme
MSCA-IF-GF - Global FellowshipsCoordinator
45470 Muelheim An Der Ruhr
Germany
Partners (1)
08544-2001 Princeton, Nj
