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Details of Grant 

EPSRC Reference: EP/T009292/1
Title: Cu-Catalysed Amination of Alkylboronic Esters
Principal Investigator: Partridge, Dr BM
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Redbrick Molecular Ltd
Department: Chemistry
Organisation: University of Sheffield
Scheme: New Investigator Award
Starts: 01 February 2020 Ends: 14 November 2022 Value (£): 312,477
EPSRC Research Topic Classifications:
Catalysis & Applied Catalysis Chemical Synthetic Methodology
Co-ordination Chemistry
EPSRC Industrial Sector Classifications:
Aerospace, Defence and Marine Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
24 Jul 2019 EPSRC Physical Sciences - July 2019 Announced
Summary on Grant Application Form
The more planar a drug candidate is, the more likely it is to show unwanted side effects and be rejected in clinical trials. It is therefore desirable to build more "3-dimensional" molecules where there are fewer aromatic rings and more alkyl groups. This concept is challenging as there are few general chemical coupling methods to build complex "3D" molecules in a predictable and reliable manner. An opportunity to achieve this is through the formation of amines, one of the most common functional groups found in medicinal drugs and agrochemicals. Traditional methods to make (chiral) alkyl amines, such as nucleophilic substitution and reductive amination, are often non-trivial. They suffer from poor control (e.g. over alkylation), require protecting groups to overcome issues of chemoselectivity, and are challenging reactions to control stereoselectively.

We aim to solve these difficulties by developing a Cu-catalysed amination of alkyl boronic esters, enabling access to complex "3D" amines. These organoboron reagents have several favourable properties which benefit this approach. They are air- and moisture-stable chemicals which tolerate a broad range of functional groups. They also show orthogonal reactivity to other common functionality, reducing the need for protecting groups. They can also be prepared stereoselectively, and typically do not racemise under conditions required for catalysis. These properties mean that formation of the key amine motif can be carried out at a late-stage in a synthetic sequence. This will enable the efficient preparation of diverse libraries of complex molecules from common boronic ester building blocks. Such technology will enable scientists in medicinal chemistry and agrochemical discovery to explore new chemical space, expediting the discovery of new medicines and crop protections.

In addition, we will apply our Cu-catalysed amination method to the intramolecular coupling of amine-containing diboronic esters. In this reaction, one boronic ester will react to form a saturated N-heterocycle, with the second boronic ester remaining as a handle for further functionalisation. This will allow access to complex saturated heterocyclic boronic ester building blocks, which currently have limited availability. These heterocyclic boronic esters are attractive scaffolds for medicinal chemistry and agrochemical discovery. By working with our industrial partner, Redbrick Molecular Ltd., these boron reagents will be made commercially available, providing direct impact for this grant.

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