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Details of Grant 

EPSRC Reference: EP/X026566/1
Title: New Photocatalytic C-C Bond-Forming Reactivity of Unprotected Primary Amines
Principal Investigator: Cresswell, Dr AJ
Other Investigators:
Researcher Co-Investigators:
Project Partners:
AstraZeneca BioTools Enamine Ltd
Department: Chemistry
Organisation: University of Bath
Scheme: Standard Research
Starts: 01 May 2023 Ends: 31 October 2026 Value (£): 481,106
EPSRC Research Topic Classifications:
Catalysis & Applied Catalysis Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
Manufacturing Chemicals
Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
07 Dec 2022 EPSRC Physical Sciences Prioritisation Panel - December 2022 Announced
Summary on Grant Application Form
Primary alkylamines are among the most ubiquitous of all aliphatic chemical building blocks, surpassing even the availability of alkyl carboxylic acids (e.g., >27,000 primary alkylamines commercially available from Enamine Ltd, versus >25,000 alkyl carboxylic acids). Seven of the top 20 reactions in medicinal chemistry either use or generate primary amines, and over 80% of marketed drugs feature alkylamine motifs. The archetypal chemical reactivity of primary alkylamines involves electrophilic attack at nitrogen, forming carbon-nitrogen bonds, and this process alone underpins much of drug discovery (e.g., amide formation, SNAr). Development of new and unconventional catalytic processes that form carbon-carbon bonds from primary amine feedstocks would be transformative, enabling highly simplifying disconnections and protecting group-free synthesis of complex amines used in pharmaceutical and agrochemical science. In this vein, we recently reported the first example of a catalytic alpha-C-H alkylation of unprotected primary amines with styrenes, using visible-light photocatalysis, and showcased this strategy in the shortest ever synthesis of a blockbuster MS drug called Fingolimod.

This project will capitalise on this world-leading breakthrough, developing new catalytic transformations of unprotected primary alkylamines that greatly expand the versatility of this critical functional group. Specifically, we will invent modular and scalable strategies for the synthesis of gamma-boryl amines, azetidines, cyclic sulfoximines, heterobenzylic amines, and alpha-amino ketones that use primary amines as feedstocks. Emphasis will lie on expedient access to areas of 3-dimensional, 'lead-like' chemical space that is currently underexplored due to a lack of synthetic chemistry enablement. The racemic amine products will be resolved into single enantiomers by AstraZeneca, and these processes will be scaled up to hundreds of grams by Enamine Ltd, such that novel, enantiopure building blocks for drug discovery can be made immediately available to the global community.

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