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Development of new sp3 C–H carboxylation strategies via interrupted Ni-catalyzed chain-walking catalysis

Project description

Improving chain-walking reactions

Many chemical reactions employ a catalytic chain-walking approach where the catalyst transfers the atom or group of atoms in a walking motion along a chain of molecules, thereby modifying the chain one step at a time. This approach offers the potential to generate complex molecules with precise control over their structure and function with application in the production of polymers. Funded by the Marie Skłodowska-Curie Actions programme, the CARBO-CHAIN project will focus on nickel catalysis, a popular method for these reactions. Researchers aim to isolate and study different nickel intermediates to better understand the mechanism and improve the efficiency and selectivity of these catalytic chain-walking reactions.

Objective

While originally designed to control the topology of polymers, catalytic chain-walking reactions have recently offered new vistas for forging carbon-carbon bonds at previously unfunctionalized C(sp3)–H sites by formally translocating the metal catalyst throughout the alkyl side-chain of a substrate. In particular, nickel catalysis has positioned at the forefront of this emerging field due to its modular reactivity through one- or two-electron pathways. Nevertheless, the chain-walking process is poorly understood in mechanistic terms, being the nature of the active intermediates still subject of considerable speculation, and with Ni(I) or Ni(II) species arbitrarily proposed with no supporting experimental evidence.
This project will tackle the challenge of isolating and characterizing discrete Ni(I) and Ni(II) intermediates to test their reactivity in chain-walking scenarios. Control at Ni disproportionation-comproportionation events, and the use of alkyl carbon fragments with appendant carbonyl chelating-motifs will materialize this goal by intramolecularly stabilizing the nickel complexes. The knowledge acquired will be utilized for a regiodivergent chelation-controlled carboxylation of Weinreb amides with CO2, delivering 1,4-dicarbonyl motifs with two orthogonal molecular handles. Lastly, the asymmetric variant of this transformation will strengthen future applications of this novel reactivity in de novo drug synthesis, late-stage functionalization approaches, and radiolabelling assays.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

FUNDACIO PRIVADA INSTITUT CATALA D'INVESTIGACIO QUIMICA
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.

€ 181 152,96
Address
AVENIDA PAISSOS CATALANS 16
43007 TARRAGONA
Spain

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Region
Este Cataluña Tarragona
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Research Organisations
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