Yeo, S.-H., Choi, A., Greaves, S. et al. (3 more authors) (2023) Kinetic resolution of 2‐aryldihydroquinolines using lithiation – synthesis of chiral 1,2‐ and 1,4‐dihydroquinolines. Chemistry - A European Journal, 29 (36). e202300815. ISSN 0947-6539
Abstract
Highly enantiomerically enriched dihydrohydroquinolines were prepared in two steps from quinoline. Addition of aryllithiums to quinoline with tert-butoxycarbonyl (Boc) protection gave N-Boc-2-aryl-1,2-dihydroquinolines. These were treated with n-butyllithium and electrophilic trapping occurred exclusively at C-4 of the dihydroquinoline, a result supported by DFT studies. Variable temperature NMR spectroscopy gave kinetic data for the barrier to rotation of the carbonyl group (ΔG‡ ~ 49 kJ mol-1, 195 K). Lithiation using the diamine sparteine allowed kinetic resolutions with high enantioselectivities (enantiomer ratio up to 99:1). The enantioenriched 1,2-dihydroquinolines could be converted to 1,4-dihydroquinolines with retention of stereochemistry. Further functionalisation led to trisubstituted products. Reduction provided enantioenriched tetrahydroquinolines, whereas acid-promoted removal of Boc led to quinolines, and this was applied to a synthesis of the antimalarial compound M5717.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | Enantioselectivity; dihydroquinolines; kinetic resolution; lithiation; nitrogen heterocycles |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 May 2023 13:45 |
Last Modified: | 02 Oct 2024 11:05 |
Status: | Published |
Publisher: | John Wiley & Sons |
Refereed: | Yes |
Identification Number: | 10.1002/chem.202300815 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:199044 |