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Photochemical Skeletal Editing for Pyridine-to-Pyrrole, -Furan, and -Thiophene Conversion

Objective

Heteroaromatic like pyridines, pyrroles, furans, and thiophenes are privileged scaffolds in pharmaceuticals & agrochemicals. While functional group modifications are routine, direct interconversion between heteroaromatic rings typically requiring de novo synthesis . “Ring replacement” strategies could transform drug discovery by enabling late-stage modulations, yet no general methods exist for converting abundant pyridines into other heterocycles.

This project will pioneer a photochemical platform to directly convert pyridines into pyrroles, furans, and thiophenes. The approach exploits pyridine N-oxidation followed by visible-light-mediated deconstruction to nitrile-containing dienes. These intermediates will undergo divergent [4+1] cycloadditions with nitrenes, singlet oxygen, or sulfur to yield pyrroles, furans, and thiophenes, respectively.

The methodology will progress through: (1) development of pyridine-to-pyrrole transformation via Cu-catalysed nitrene insertion and rearrangement, (2) mechanistic elucidation, (3) extension to pyridine-to-furan and pyridine-to-thiophene conversions using singlet oxygen and elemental sulfur, and (4) demonstration of synthetic utility in late-stage ring replacement of drug molecules.

This disruptive strategy introduces the first general method for heteroaromatic-to-heteroaromatic replacement, a conceptually novel retrosynthetic paradigm. It transforms pyridines from static scaffolds into versatile precursors, enabling access to new heterocyclic space of high biological and industrial value.

Completion of this ambitious project at RWTH Aachen University will be supported by advanced mechanistic expertise, knowledge transfer, and dissemination, equipping the Researcher with unique skills at the interface of photochemistry, catalysis, and heteroaromatic synthesis and strongly enhancing her career trajectory toward independence.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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-2025-PF

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Coordinator

RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
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.

€ 202 125,12
Address
TEMPLERGRABEN 55
52062 Aachen
Germany

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Region
Nordrhein-Westfalen Köln Städteregion Aachen
Activity type
Higher or Secondary Education Establishments
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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.

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