Synthesis of fluorinated isoxazoles using SelectfluorTM: preparation and characterization of 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline systems from one-pot and multi-step processes

Sato, K.; Sandford, G.; Shimizu, K.; Akiyama, S.; Lancashire, M.J.; Yufit, D.S.; Tarui, A.; Omote, M.; Kumadaki, I.; Harusawa, S.; Ando, A.

doi:10.1016/j.tet.2016.02.026

Synthesis of fluorinated isoxazoles using SelectfluorTM: preparation and characterization of 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline systems from one-pot and multi-step processes

Sato, K.; Sandford, G.; Shimizu, K.; Akiyama, S.; Lancashire, M.J.; Yufit, D.S.; Tarui, A.; Omote, M.; Kumadaki, I.; Harusawa, S.; Ando, A.

Authors

K. Sato

G. Sandford

K. Shimizu

S. Akiyama

M.J. Lancashire

D.S. Yufit

A. Tarui

M. Omote

I. Kumadaki

S. Harusawa

A. Ando

Abstract

3,5-Disubstituted 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline products were obtained from reaction of the corresponding isoxazoles with SelectfluorTM depending upon the reaction conditions. Although the fluorinations proceeded using conventional heating, microwave (μW) irradiation considerably shortened reaction times and enabled a high yielding one-pot cascade fluorination-cyclization from simple diketone substrates. In addition, a related 4-fluoroisoxazole-3-carboxyamide derivative was synthesized.

Citation

Sato, K., Sandford, G., Shimizu, K., Akiyama, S., Lancashire, M., Yufit, D., …Ando, A. (2016). Synthesis of fluorinated isoxazoles using SelectfluorTM: preparation and characterization of 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline systems from one-pot and multi-step processes. Tetrahedron, 72(13), 1690-1698. https://doi.org/10.1016/j.tet.2016.02.026

Journal Article Type	Article
Acceptance Date	Feb 8, 2016
Online Publication Date	Feb 10, 2016
Publication Date	Mar 31, 2016
Deposit Date	Feb 16, 2016
Publicly Available Date	Feb 10, 2017
Journal	Tetrahedron
Print ISSN	0040-4020
Publisher	Elsevier
Peer Reviewed	Peer Reviewed
Volume	72
Issue	13
Pages	1690-1698
DOI	https://doi.org/10.1016/j.tet.2016.02.026
Keywords	Fluoroheteroaromatic, Selective fluorination, 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline TRPV1 antagonist.

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© 2016 This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/