Nitrogen-Radical-Based Radical Strain-Release Strategies for the Divergent Assembly of Polyfunctionalized 3D-Building Blocks

Project Information

N-STRAINED

Grant agreement ID: 842422

DOI

10.3030/842422

Project closed

EC signature date 22 March 2019

Start date 1 April 2019

End date 31 March 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 212 933,76

EU contribution

€ 212 933,76

Coordinated by

THE UNIVERSITY OF MANCHESTER
United Kingdom

Periodic Reporting for period 1 - N-STRAINED (Nitrogen-Radical-Based Radical Strain-Release Strategies for the Divergent Assembly of Polyfunctionalized 3D-Building Blocks)

Reporting period: 2019-04-01 to 2021-03-31

Summary of the context and overall objectives of the project

• What is the problem/issue being addressed?
This Fellowship aimed at delivering transformative advances towards the assembly of nitrogenate molecules of interest to the pharmaceutical and agrochemical sectors. The project was based on the use of visible-light as the source of energy for the generation and use of nitrogen radicals in catalysis. A relevant part of the project was based on achieving strai-release amination using [1.1.1]propellane and obtain in one single chemical step bicyclo[1.1.1]pentylamines.

• Why is it important for society?
This project aims at delivering fundamental advances for the preparation of nitrogenated molecules, which are fundamental to the discovery and evolution of drugs, agrochemicals and food additives. Improving the way we make these molecules underpins the manufacture of high-value materials that impact positively our lives.

• What are the overall objectives?
1) Develop novel starin-release startegies of nitrogen radicals to achieva aminochlorination.
2) Develop novel divergent and multicomponent processes for the single step assembly of bicyclo[1.1.1]pentylamines
3) Apply the starin-release experimentation in transition metal catalysis with nickel to expand the pool of divergent functionalizations.

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 started our work identifying conditions for the succesful preparation of [1.1.1]propellane in different organic solvents compatible for integration with photoredox catalysis.
• We then prepared a broad range of nitrogen radical precursors for the generation of amidyl radicals under photoredox conditions.
• We have spent considerable time optimising the key strain-release functionalization which meant solving problems of reactivity.
• Once the key reactions were optimised we evaluated the scope of the process trying to identify full applicability and also limiting factors
• Once the key substrates were prepared and purified we conducted detailed X-ray crystallography studies to determine the structural features of these building blocks. This information proved to be pivotal for understanding their ability of acting as aromatic bioisosteres.
• This work has been published in the peer-reviewed journal Angew. Chem. Int. Ed. 2020,59, 8225 and was highlighted in Synfact 2020, 16, 423.

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 results obtained in this Fellowship have demonstrated, for the first time, that nitrogen radicals can be used in radical strain-release amination reactions.
• the transformation that we have developed are a unique class of multicomponent processes that enable the divergent preparation of many high-value building block in one singlke chemical step.
• the mechanistic work that we have performed has shed light on many of the fundamental parameters that control both strain release chemistry but also the chemical nature of bicyclo[1.1.1]pentylamines

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