Development of a boryl radical-mediated H-atom transfer umpolung blueprint to make nucleophilic radicals behave as electrophilic species

Project Information

BRAT

Grant agreement ID: 101150159

DOI

10.3030/101150159

Project closed

EC signature date 11 April 2024

Start date 3 June 2024

End date 2 June 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 189 687,36

Coordinated by

RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Germany

Periodic Reporting for period 1 - BRAT (Development of a boryl radical-mediated H-atom transfer umpolung blueprint to make nucleophilic radicals behave as electrophilic species)

Reporting period: 2024-06-03 to 2026-06-02

Summary of the context and overall objectives of the project

The main objective of this project was the development of a novel platform for radical polarity inversion ("umpolung"), enabling the efficient functionalisation of electron-rich aromatics and olefins. The overarching goal was to combine photoredox catalysis with boryl radical-mediated hydrogen atom transfer catalysis to generate electrophilic α,α-diborylated radicals from readily available α,α-diborylated alkanes.

This approach addresses a fundamental limitation in radical chemistry, namely the inability of conventional nucleophilic alkyl radicals to react with electron-rich π-systems. By generating highly electrophilic carbon-centred radicals, the methodology enables efficient bond formation with electron-rich aromatics and olefins, followed by diverse downstream functionalisation.

The project builds upon the Leonori group's expertise in photoredox catalysis, hydrogen atom transfer processes, and boryl radical chemistry. The successful implementation of this strategy is expected to provide streamlined access to valuable aliphatic molecular architectures, facilitate late-stage functionalisation, and significantly expand the synthetic utility of radical chemistry. Furthermore, the project contributes to knowledge generation and dissemination while supporting advanced scientific training and career development at RWTH Aachen University.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have made good process, demonstrating the propensity of amine-ligated boryl radicals to undergo a large number of chemical reactions including the fragmentation of cyclic systems. This has significantly expanded the toolbox of reactions that can be used for the synthesis of small molecules building blocks.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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 the functionalization of nitrogen heterocycles such as aziridines and it has provided a new retrosynthetic logic for the synthesis of key organic structures. Key scientific and technological achievements include the validation of this boryl radical reactivity concepts, the elucidation of its mechanistic basis, and the demonstration of its applicability to structurally diverse and medicinally relevant substrates.