B-STRAIN · Boryl radicals-based strain-release startegies for the divergent assembly of polyfunctionalised 3D building blocks
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2024-01-01 → 2025-12-31
- EU contribution
- €173,847
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
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Results in brief
Boryl radicals-based strain-release startegies for the divergent assembly of polyfunctionalised 3D building blocks
The main objective of this Marie Skłodowska-Curie Postdoctoral Fellowship was the development of a radical borylation methodology, allowing the construction of complex organic structures using a boryl radical approach. The overarching goal was to develop a novel catalytic platform, powered by visible light, to enable the functionalisation forming organoboron species competent as reaction partners in traditional cross-coupling methods. As a result of the project we have discovered new processes for the preparation of sp3-rich borylated scaffolds. This involved mild photoredox reactivity facilitated by a catalyst enabling the formation of a key boryl radical. Starting materials for the substrate scope were commercial compounds, allowing us to demonstrate rapid functionalisation of these scaffolds. Our extensive mechanistic studies identified the nuances of the reactivity, employing fluorescence quenching and cyclic voltammetry. Additionally we have expanded this methodology to alpha-trifluoromethyl styrenes, motifs interesting for medicinal chemists. Here we showed the borylation of various styryl motifs that bear various aromatics including important heteroaromatic groups. Further we include the derivatization of these products allowing us to access a range of different compounds. Finally, we have also developed direct photochemistry that leverages the permutation of indazoles to benzimidazoles. This work demonstrates the simplicity of permutation chemistry allowing the access from a structurally distinct class of indazole compounds to benzimidazoles solely through irradiation by UV light. We have elucidated the mechanism through computational studies, highlighting the important role of the solvent for this process. This methodology allows practitioners of chemistry to utilize a very simple protocol to switch between different heteroaromatic backbones without the requirements for building these anew.
Data: CORDIS, © European Union
Project objective
Borylated molecules are some of the most used tools to aid molecular construction in both academia and industry, generally via the Nobel Prize winning Suzuki-Miyaura cross-coupling. The invention of methods to form CB bonds is of strategic importance to discover and evolve molecules with direct implications on our lives. Central to this quest is designing synthetic strategies able to explore novel areas of chemical space. As the pharmaceutical sector is now aware of the greater clinical success of molecules with 3D architectures, developing methods able to assemble 3D-shaped and saturated building blocks is a topic of continuous scientific endeavour. The bicyclo[1.1.1]pentyl motif has been identified as a valuable bioisotere to replace flat (2D) aromatics and improve the potency of lead molecules. However, difficulties in preparing and modifying this structural element have severely limited its use in synthesis. There is an urgent need to develop novel methods that can effectively manipulate and introduce this motif into organic compounds.This project seeks to substantially expand the fields of photocatalysis and boryl-radicals by introducing the concept of borylation by strain-release: a novel reactivity that explores the unprecedented ability of boryl-radicals to react with [1.1.1]propellane and enable a unique preparation of polyfunctionalized bicyclo[1.1.1]pentanes. This reactivity will allow the modular and divergent 1-step construction of many important borylated 3D-building blocks that cannot be prepared by any other method.This research capitalizes on recent developments of the Host group that has disclosed a novel way to generate and utilise boryl radicals and has also experience in radical strain-release.The completion of such an innovative and ambitious project at RWTH Aachen University will be facilitated by generating, transferring, sharing and disseminating knowledge, and will enhance my future career following the training plan envisioned
Original text from CORDIS.
Participants
- RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN · AachenCoordinatorGermany
Links
- View on CORDIS
- DOI: 10.3030/101102819
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e50fd9d21f&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e529d0322a&appId=PPGMS
Data: CORDIS, © European Union