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Design of unprecedented electrophilic SF5 reagents: applications in the synthesis of heteroatom-SF5/carbon-SF5 bonds and late-stage functionalization

Project description

The potential of next-generation fluorinated molecules

Fluorinated molecules play a crucial role in life sciences, with up to 50 % of agrochemicals and 20 % of pharmaceuticals featuring fluorinated motifs. The trifluoromethyl group is particularly prevalent. However, its stability issues limit its applications. In this context, the ERC-funded Give-Me-Five project aims to develop the pentafluorosulfanyl motif, a ‘super trifluoromethyl’ alternative that offers enhanced stability. The project will tackle two main challenges: the toxicity and limited reactivity of current pentafluorosulfanyl radical precursors. By creating shelf-stable pentafluorosulfanyl electrophiles and advancing new synthetic methods, Give-Me-Five seeks to unlock the potential of pentafluorosulfanyl-containing compounds, revolutionising agrochemicals, pharmaceuticals, and materials science.

Objective

The Give-Me-Five project will provide the next generation of fluorinated molecules that found plethora of applications in life science. Currently up to 50% of agrochemicals as well as 20% of pharmaceuticals contain a fluorinated motif. As an example, the trifluoromethyl (CF3) group is one of the most used fluorinated motifs in research and development. Although several research programs have been dedicated to the synthesis of CF3-molecules with numerous CF3-reagents being developed, recent reports pointed out a major stability drawback of the CF3 moiety impacting its usefulness. Thus, developing more stable fluorinated motifs that could replace the CF3 group is urgent. In this context, pentafluorosulfanyl (SF5) motif is considered as a “super trifluoromethyl motif” since it is more stable than the CF3 motif. However, two major drawbacks should be overcome to unlock the potential of SF5 molecules: (i) current direct methodologies to introduce the SF5 motif rely on scarcely commercially available and highly toxic SF5Cl – a SF5 radical precursor, and (ii) this precursor features a very limited reactivity. Although the availability and toxicity concerns have been recently addressed in my lab by developing an in situ protocol to generate and use SF5Cl, the problem of poor reactivity remains. Here, I propose to tackle this challenge by designing new, more sustainable and stable electrophilic SF5 sources
To provide the first general direct synthesis of SF5-molecules we will:
1. Synthesize the first shelf-stable family of reagents prone to be SF5 electrophile donor
2. Apply the new shelf-stable reagents to forge heteroatom-SF5 bonds
3. Develop a copper catalyzed approach to forge C-SF5 bonds using our shelf-stable reagents
This endeavour could provide the first direct general synthesis of SF5-molecules, paving the way to the next generation of fluorinated molecules. Hence, it will foster developments of agrochemical, pharmaceutical as well as material containing SF5 motif

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 1 999 984,00
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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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.

€ 1 999 984,00

Beneficiaries (1)

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