Nickel Catalysis: New Insights from Mechanistic Studies
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
Nickel catalysed cross-coupling chemistry is an attractive method for the synthesis of a range of molecules of societal need, including agrochemicals, pharmaceuticals, and materials. While it might replace some palladium-catalysed processes its real strengths are in the wider substrate scope that it offers, as well as its ability to couple sp3 centres more effectively. The area has been a focus for many research groups recently, but our mechanistic understanding regarding selectivity and reactivity lags somewhat behind. This project will combine approaches from organic and organometallic chemistry, as well as physical organic chemistry, to elucidate key mechanistic details and structure/relationship activities. This will be used to optimise, design, and develop cross-coupling reactions of utility.
PROJECT OBJECTVES:
The objectives of the project include:
* To understand how electrophile structure influences oxidative addition rate.
* To understand when and why Ni(I) complexes arise in catalysis.
* To understand the effect of ligand structure on reactivity and selectivity.
* To explore the reactivity of nickel with alkyl electrophiles and organometallic cross-coupling partners, and explore any observed differences between heteroaryl and aryl substrates.
* To understand the behaviour of heteroaryl substrates in nickel-catalysed reactions, and explore any observed differences between heteroaryl and aryl substrates.
* To use this information to allow the cross-coupling of electrophiles - especially alcohol-derived substrates - under mild and industrially-acceptable conditions (e.g. < 100 degreesC, < 1 mol% Ni, no large excesses of cross-coupling partners) so that molecules of relevance to Syngenta's business needs can be prepared.
* To train a PhD student in the study of catalysis using a broad range of techniques, contributing to the UK knowledge economy.
* To transfer learning from this project to researchers at Syngenta through regular meetings and discussions, and though a three-month placement for the PhD student.
PROJECT OBJECTVES:
The objectives of the project include:
* To understand how electrophile structure influences oxidative addition rate.
* To understand when and why Ni(I) complexes arise in catalysis.
* To understand the effect of ligand structure on reactivity and selectivity.
* To explore the reactivity of nickel with alkyl electrophiles and organometallic cross-coupling partners, and explore any observed differences between heteroaryl and aryl substrates.
* To understand the behaviour of heteroaryl substrates in nickel-catalysed reactions, and explore any observed differences between heteroaryl and aryl substrates.
* To use this information to allow the cross-coupling of electrophiles - especially alcohol-derived substrates - under mild and industrially-acceptable conditions (e.g. < 100 degreesC, < 1 mol% Ni, no large excesses of cross-coupling partners) so that molecules of relevance to Syngenta's business needs can be prepared.
* To train a PhD student in the study of catalysis using a broad range of techniques, contributing to the UK knowledge economy.
* To transfer learning from this project to researchers at Syngenta through regular meetings and discussions, and though a three-month placement for the PhD student.
People |
ORCID iD |
| David Nelson (Primary Supervisor) | |
| Alasdair Cooper (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/P51066X/1 | 01/10/2016 | 30/09/2021 | |||
| 1792766 | Studentship | EP/P51066X/1 | 01/10/2016 | 31/12/2020 | Alasdair Cooper |
| Description | So far, we have shown that nickel -based catalysts are much more susceptible to various structural (functional) groups present when carrying out carbon-carbon bond formation reactions. This effect can be used to achieve considerably high selectivity for such reactions when using these catalysts (an effect which is still present when using the much more industry-favoured palladium catalysts, but not as pronounced) which could impact the way in which various agrochemicals (herbicides, fungicides etc.) and pharmaceuticals (prescription drugs etc.) are synthesised. Some data on the rate of these kinds of reactions has been gathered which gives useful insight into how to make these kinds of reactions more efficient and (therefore) more environmentally friendly. |
| Exploitation Route | We plan to investigate the observed effects more thoroughly, with a view to expanding the applicability in order to make these catalysts more attractive to industry-based processes, as nickel is more abundant than palladium. |
| Sectors | Agriculture, Food and Drink,Chemicals,Education,Pharmaceuticals and Medical Biotechnology |
| Description | EPSRC NPIF Innovation Placement |
| Amount | £1,550 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2019 |
| End | 09/2019 |