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Direct Functionalization of Unprotected Aziridines via Boryl Radical-Induced β-Scission

Project description

Novel approach could yield single-step aziridine ring-opening and functionalisation

Beta-functionalised amines are essential building blocks in pharmaceuticals and agrochemicals, yet synthesising them efficiently remains challenging. Aziridines – highly reactive nitrogen-containing rings – are promising starting materials but current methods for opening them are limited to pre-activation of aziridines and there are no methods for their direct functionalisation into beta-amines. With the support of the Marie Skłodowska-Curie Actions programme, the AZIRIDINE project aims to change this with a new approach based on boryl radical chemistry, enabling direct, single-step ring-opening and functionalisation without pre-activation. This strategy could establish a powerful new synthetic platform for rapidly accessing medicinally relevant molecules and late-stage diversification of bioactive drug scaffolds.

Objective

β-Functionalized amines are privileged motifs in pharmaceuticals, and agrochemicals, yet their synthesis typically requires lengthy & challenging routes. Aziridines represent attractive starting points, but current ring-opening strategies are restricted to pre-activated substrates bearing strong electron-withdrawing groups, which limits their synthetic utility. No general methods exist for the direct functionalization of unprotected or N-alkyl aziridines into β-amines.

This project introduces a new approach that harnesses boryl radical chemistry to directly deconstruct aziridines. Coordination of BH₃ to the aziridine will enable generation of aziridine-bound boryl radicals, which undergo selective β-scission to produce β-aminoalkyl radicals. These intermediates will then be intercepted by radical acceptors to deliver a broad range of β-functionalized amines in a single step.

The methodology will progress in two stages: (1) development of photocatalytic ring-opening processes and divergent radical functionalizations using many SOMOphiles, and (2) integration with nickel catalysis to achieve cross-couplings with aryl, alkyl, and acyl partners. Mechanistic elucidation by spectroscopy, actinometry, and photolysis will underpin the design and guide reaction development.

This strategy establishes the first general platform for aziridine ring-opening and functionalization without pre-activation, opening a new retrosynthetic paradigm for the synthesis of β-amines. Beyond methodological innovation, it provides a blueprint for the late-stage diversification of bioactive scaffolds and creates powerful shortcuts to molecules of direct medicinal relevance.

Completion of this innovative and ambitious project at RWTH Aachen University will be supported by comprehensive training, knowledge transfer, and dissemination, enhancing the Researcher’s career trajectory and equipping him with unique expertise at the interface of synthesis, radical chemistry, and photochemistry.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Net EU contribution
€ 202 125,12
Address
TEMPLERGRABEN 55
52062 Aachen
Germany
Region
Nordrhein-Westfalen Köln Städteregion Aachen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data