Direct nucleophilic difluoromethylation of aromatic isoxazoles activated by electron-withdrawing groups using (difluoromethyl)trimethylsilane

Abstract

The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups, such as the nitro, triflyl, and the phenylsulfonyl groups, at the 4-position has enabled the first regio- and diastereoselective difluoromethylation at the 5-position of isoxazoles by nucleophilic addition using (difluoromethyl) trimethylsilane, Me ₃SiCF ₂H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles were also nicely converted into the corresponding CF ₂H adducts with high regio- and excellent diastereoselectivities. Since the trifluoromethylated analogs of the corresponding diaryl-isoxazolines are effective ectoparasiticides, represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained, they would be of great importance as promising drug candidates in this field.

Contributors

Norio Shibata: (View ORCID Profile)

Journal

Journal ID (publisher-id): SOR-CHEM

Title: ScienceOpen Research

Publisher: ScienceOpen

ISSN (Electronic): 2199-1006

Publication date: 18 December 2014

Volume: 0 (ID: aeab23b4-61ff-4936-a252-0cd98d9fddcf )

Issue: 0

Pages: 1-7

Affiliations

[1 ]Department of Frontier Materials, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, Japan

[2 ]Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, Japan

Author notes

[* ]Corresponding author's e-mail address: nozshiba@ 123456nitech.ac.jp

Dedication: To Professor Iwao Ojima for his 70th birthday.

Article

Publisher ID: 2276:XE

DOI: 10.14293/S2199-1006.1.SOR-CHEM.AD1QVW.v1

Copyright statement: © 2014 Xin Wang et al.

License:

This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

Page count

Figures: 6, Tables: 3, References: 67, Pages: 7

Product

Categories

Subject: Original article