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Asymmetric Cycloboration of Homoallylic Amine–Boranes for Stereodefined Amino Scaffolds

Objective

Organoborons are cornerstone intermediates in synthesis, enabling key transformations like the Suzuki-Miyaura coupling. While enantioenriched alkyl boronates are accessible through hydroboration and other methods, stereodefined amine-boranes are entirely absent from the synthetic toolbox. This is striking given their low-cost precursors and stability. Current strategies produce only linear and non-chiral amine-boranes.

This project will establish the first asymmetric cycloboration of homoallylic amine-boranes, unlocking a new class of chiral cyclic amine-boranes as stereodefined, modular building blocks. The transformation relies on [Rh(I)]-catalyzed B–H activation and intramolecular olefin insertion, delivering cyclic organoborons with precise stereocontrol. Crucially, the resulting products are chemically versatile and should undergo stereospecific oxidation and Suzuki-Miyaura cross-coupling, enabling direct conversion into γ-functionalized amines.

The methodology will be advanced through: (1) development and optimisation of enantioselective cycloboration with a diverse library of homoallylic amine-boranes, (2) mechanistic elucidation of B–H activation, migratory insertion, and reductive elimination steps through isotope labelling, ESI-MS, and DFT modelling, (3) exploration of scope across diverse amine and olefin substitution patterns, and (4) demonstration of synthetic utility in the preparation of pharmaceutically relevant scaffolds.

This approach introduces a new retrosynthetic paradigm, positioning amine-boranes as stereodefined chiral synthons. It opens avenues for asymmetric synthesis and expands the role of boron chemistry in high-value molecular synthesis.

Completion of this ambitious project at RWTH Aachen University will be supported by extensive mechanistic expertise, knowledge transfer, and dissemination activities, strongly enhancing the Researcher’s career trajectory toward independence in asymmetric catalysis and organoboron chemistry.

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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-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.

€ 217 965,12
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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