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Details of Grant 

EPSRC Reference: EP/W012626/1
Title: Synthesis of enolates by nucleophilic substitution
Principal Investigator: Pattison, Dr G
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: School of Chemistry
Organisation: University of Lincoln
Scheme: New Investigator Award
Starts: 11 October 2022 Ends: 10 October 2025 Value (£): 405,713
EPSRC Research Topic Classifications:
Catalysis & Applied Catalysis Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
19 Oct 2021 EPSRC Physical Sciences October 2021 Announced
Summary on Grant Application Form
We need to be able to make new molecules to continue to advance technology that is available to society. The synthesis of new compounds underpins the discovery of new drugs, plastics, materials for displays and solar cells amongst a huge range of exciting applications. We need to be able to make these molecules in a way that is efficient as possible and minimises our impact on the environment. One factor that is extremely important for the efficiency of a synthesis is selectivity. A reaction must be as selective as possible so that it only generates our desired compound. A non-selective reaction will generate unwanted side-products that must be removed. This generates waste that must be removed, often using time-consuming procedures, and also must be disposed of in a way that minimises impact on the environment.

One class of chemical compound that are especially useful in synthesis are ketones. These compounds show very versatile reactivity and are able to form a diverse range of new bonds. One key way that ketones react is as a type of intermediate known as an enolate. Enolates are one of our key intermediates for forming new carbon-carbon bonds, which make up the framework of all organic molecules. Enolates are normally made by removing a hydrogen ion attached to a carbon directly adjacent to a carbonyl group using a base. This leaves behind a negatively-charged intermediate which can react with an electrophile (positively charged species)

This classical method for making an enolate can present several challenges with selectivity. The main one is that a ketone may have hydrogen atoms on either side of its carbonyl group, and either of these may be removed by a base. This leads to a mixture of enolates being formed and the final product will have a reduced yield as a result.

Our strategy for making enolates circumvents this challenge by making enolates in a new way. Instead of making enolates by removing a hydrogen ion, we generate our enolate intermediate by substitution of an ester. To do this we react the ester with a nucleophile containing an atom (boron) that will make it act as if it is negatively charged. This then controls the site of partial negative charge in the enolate selectively, as only the side of the carbonyl group where the boron-containing group was introduced can react further. This prevents issues with selectivity and means that we can make a range of highly valuable ketones more efficiently and higher yielding than we could previously. This project aims to explore this new selective ketone synthesis fully to understand the types of systems that we can make using this method.

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Organisation Website: http://www.lincoln.ac.uk