Periodic Reporting for period 1 - B-STRAIN (Boryl radicals-based strain-release startegies for the divergent assembly of polyfunctionalised 3D building blocks)
Période du rapport: 2024-01-01 au 2025-12-31
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.
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.
We have made good process, demonstrating the propensity of the formed borylated molecules to undergo powerful cross-coupling methods. Further, our work has enabled cross-coupling methodologies reaching beyond C–C bond formation (Suzuki-Miyaura cross-coupling) but also expanding this to C–N and C–O (Chan-Lam cross-coupling) methodologies.
The project has delivered substantial scientific impact and made a clear contribution to advancing the state of the art in synthetic organic chemistry. It addressed long-standing limitations in boryl radical C–B bond formation and established a new retrosynthetic logic for the synthesis of key organic structures. Key scientific and technological achievements include the validation of this catalytic concept, the elucidation of its mechanistic basis, and the demonstration of its applicability to structurally diverse and medicinally relevant substrates.