Wootton, Jack M, Roper, Natalie J, Morris, Catrin E et al. (9 more authors) (2025) Stereoselective synthesis of atropisomeric amides enabled by intramolecular acyl transfer. Chemical Science. ISSN 2041-6539
Abstract
C-N atropisomeric amides are important compounds in medicinal chemistry and agrochemistry. Atropselective methods for their synthesis are therefore important. In this study, a novel strategy to make C-N atropisomeric amides based on intramolecular acyl transfer via a tethered Lewis basic pyridine or tertiary amine group is reported. The reactions operate under kinetic control and in most cases are highly atropselective, with the products isolable as pure, single diastereoisomers following chromatography. The kinetically favored atropisomer can also be isomerised into the alternative thermodynamically favored atropisomer upon heating. The kinetic and thermodynamic outcomes are supported by computational studies, while additional mechanistic studies support operation via initial fast acylation of the Lewis basic group, followed by rate-determining acyl transfer, which also enables control over the atropisomer formed.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 07 Feb 2025 09:20 |
Last Modified: | 21 Feb 2025 00:10 |
Published Version: | https://doi.org/10.1039/d4sc05760k |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1039/d4sc05760k |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223008 |
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Description: Stereoselective synthesis of atropisomeric amides enabled by intramolecular acyl transfer
Licence: CC-BY 2.5