Visible Light-Mediated Synthesis of Nitrogen-Centered Radicals: New Reactivity via Photoredox Catalysis and Electron-Transfer Complexes

Project Information

NCR

Grant agreement ID: 703238

DOI

10.3030/703238

Project closed

EC signature date 24 February 2016

Start date 1 February 2017

End date 31 January 2019

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 183 454,80

EU contribution

€ 183 454,80

Coordinated by

THE UNIVERSITY OF MANCHESTER
United Kingdom

Periodic Reporting for period 1 - NCR (Visible Light-Mediated Synthesis of Nitrogen-Centered Radicals: New Reactivity via Photoredox Catalysis and Electron-Transfer Complexes)

Reporting period: 2017-02-01 to 2019-01-31

Summary of the context and overall objectives of the project

• What is the problem/issue being addressed?

This project aims at addressing two key questions:
1. Development of novel sustainable catalysis for the selective formation of C–N bonds.
2. Identification of novel reactivity modes for the photochemical generation and use of nitrogen radicals in synthesis.


• Why is it important for society?

Organic chemistry is fundamental to the weel-being of our society. It is thorugh the invention and the development of novel chemical processesthat we can identify new molecules and materials for industrial application.
Nitrogen-containing compounds underpin every aspect associated to our life. They consitute the core of almost all pharmaceuticals, agrochemicals and materials. As such the development of novel reactions able to assemble chemical bonds between atoms of carbon and nitrogen has the potential to facilitate the identification, the evolution and the large-scale production of molecules fundamental to our society.


• What are the overall objectives?

1 Develop novel approaches for the preparation of nitrogen-containing molecules using radical approaches
2 Develop novel multicomponent reactions via radical species.
3 Develop a novel approach for the assembly of anilines.

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

Scientific work and main results achieved so far:

1 We initially started the project by trying to develop reactions of nitrogen radical with very electron rich olefins like vinyl and allyl trifluoroborates – an important class of building blocks used for examples in the Nobel Prize winning Suzuki cross-coupling reaction.
This project was based on the idea that as nitrogen radicals are very electrophilic species, they should undergo very facile reaction with electron rich pi-systems. After a detailed reaction optimisation we were able to develop such a process and therefore provide a platform for the assembly of allyl and vinyl-substituted amides. However, the yield for this transformation were very low so we realised that even more electrophilic radicals were required to harness the full potential od this reactivity. We therefore screened highly electrophilic malonyl-type radicals. These species were efficiently generated by photoredox catalysis using the organic dye eosin Y and underwent a very efficient and selective reaction with the trifluoro-borates building blocks. This reactivity has provided a photo-organocatalytic Suzuki-type cross-coupling reaction and we applied it to the modification of veterinary products and sunscreen products.
Publication: ACS Catal. 2017, 7, 4126 and Org. Biomol. Chem. 2019, 17, 1839.

2 We tackled the fundamental question of introducting an amino-functionality onto an aromatic ring in place of a C–H bond. This is a fundamental challenge in synthetic chemistry as all methodologies able to aminate aromatics require functionalised arenes like aryl halides or aryl-boronic acids. We have tackled this project in two steps. Initially we have studies the reactivity of hihgly electron rich hydroxylamine derivatives (prepared in four steps) as nitrogen-radical precursors and we demonstrated that these species can react with several un-functionalised aromatics.
Publications: Angew. Chem. Int. Ed. 2017, 56, 14948.

3 We decided to tackle the ultimate challenge of forming C–N bonds between an aromatic and an amine without any functionalisation at both sides. This was possible by generating in situ N-chloroamines, which proved very powerful intermediates for achieving this goal. This work has received signficant publicity, including a press release from AstraZeneca (https://www.astrazeneca.com/content/astraz/media-centre/articles/2019/lighting-the-path-to-simplified-chemical-reactions16042019.html).
Publications: Nat. Chem. 2019, 11, 426.


Career development work and main results achieved so far:

1 The awardee has been involved in the superivison of several PhD and MChem students in the Host group. The ability to effectively supervise, coordinate and support young scientists is a fundamental skill required both in academia and industry. The awardee has excelled here and was able to efficiently manage and assist the students and also provide constructive feedbacks during formal weekly meetings with the Host supervisor.

2 IThe awardee has run 1st, 2nd and 3rd year tutorial at the University of Manchester. This activity involved marking MChem students assignements and then running a 1h tutorial to revise general concepts and promote scientific discussion. Before starting this activity, the awardee attended several training workshops offered by the University on the most effective approaches to facilitate students learning.

3 In the final months of the Fellowship, the Awardee has helped the Host group to run an outreach acitity at the Manchester Grammar School where he thought photochemistry to a class of 16 pupils.

4 Towards the end of the Fellowship the awardee has been able to propose a novel research project and he completely developed and executed it with the help of one visiting PhD student and one MChem student. This proejct was succesfully published in the RSC journal Organic and Biomolecular Chemistry and the awardee was the corresponding author.


Impact related work and main results achieved so far:

Academic impact. The results of this Fellowship have been pubblished in high-impact chemistry journals that have increased the visibility of both the awardee and the Host supervisor. As an example, a group of PhD students in the US have created a YouTube channel called the CycloEdition and created a video to discuss and explain the relevance of the chemistry developed by the awardee during the Fellowship (https://www.youtube.com/watch?v=ujjt-PlrUvg&app=desktop).

Industrial impact. Some of the results of this project have been developed in collaboration with AstraZeneca. Our work has provided an effective and industrially feasible way of forming carbon-nitrogen bonds. The host group is currently developing other projects in collaboration with AstraZeneca.

Societal impact. The Host supervisor has initiated an outreach activity at the Manchester Grammar School in Manchester where 16 students are run a photochemical experiments every Wednesday. This activity has provided the students exposure to chemistry research. This project has sparked significant interest into these pupils about science and more specifically the use of light in chemistry.

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)

There have been several impacts associate to this project:

• Through our work we have provided new advances in synthetic organic chemistry. In particular, we have developed several methodologies for the assembly of C–N and C–C bonds using photocatalysis. These methods enable the fast modification of high value materials in a simple, efficient and sustainable manner. As these materials are fundamental to our society (almost every drug contains a C–N bond), our work is streamlining access to endusers in an efficient, selective and simple manner.

• Our work on the synthesis of aniline using photocatalysis has been done in collaboration with AstraZeneca. Our work has provided a very powerful methodology for the preparation of these high-value material. The process that we developed has the potential to be applied in industrial settings and therefore facilitate the preparation of molecules fundamental to our society.

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