Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

Murie, Valter E.; Nicolino, Paula V.; dos Santos, Thiago; Gambacorta, Guido; Nishimura, Rodolfo H.V.; Perovani, Icaro S.; Furtado, Luciana C.; Costa-Lotufo, Leticia V.; Moraes de Oliveira, Anderson; Vessecchi, Ricardo; Baxendale, Ian R.; Clososki, Giuliano C.

Abstract

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives.

Citation

Murie, V. E., Nicolino, P. V., dos Santos, T., Gambacorta, G., Nishimura, R. H., Perovani, I. S., …Clososki, G. C. (2021). Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents. Journal of Organic Chemistry, 86(19), 13402-13419. https://doi.org/10.1021/acs.joc.1c01521

• Journal Article Type: Article
• Online Publication Date: Sep 23, 2021
• Publication Date: Oct 1, 2021
• Deposit Date: Jan 6, 2022
• Publicly Available Date: Sep 23, 2022
• Journal: The Journal of Organic Chemistry
• Print ISSN: 0022-3263
• Electronic ISSN: 1520-6904
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 86
• Issue: 19
• Pages: 13402-13419
• DOI: https://doi.org/10.1021/acs.joc.1c01521
• Public URL: https://durham-repository.worktribe.com/output/1219398