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Cobalt-catalyzed late-stage functionalization of arenes through metal-ligand cooperation

Project description

A more sustainable catalyst for certain demanding late-stage functionalisations

Pincer complexes are well-established catalysts consisting of a metallic centre and a so-called pincer-type ligand. They have significantly advanced the field of organic synthesis thanks to their stability and versatility. Pincer-ligated cobalt complexes are promising alternatives to catalysts using the precious metal iridium, but they have not been able to accomplish more demanding late-stage functionalisations until now. With the support of the Marie Skłodowska-Curie Actions programme, the CobaltLSF project is paving the way for the use of cobalt to catalyse one such functionalisation, that of a type of cyclic hydrocarbon (arenes), with the help of a novel pincer ligand.

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

MAX PLANCK INSTITUT FUER KOHLENFORSCHUNG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 246 669,12
Address
KAISER WILHELM PLATZ 1
45470 Muelheim An Der Ruhr
Germany

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Region
Nordrhein-Westfalen Düsseldorf Mülheim an der Ruhr
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 246 669,12

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