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. 2021 Jan 11:17:89-96.
doi: 10.3762/bjoc.17.9. eCollection 2021.

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

Yukiko Karuo  1 , Ayaka Kametani  1 , Atsushi Tarui  1 , Kazuyuki Sato  1 , Kentaro Kawai  1 , Masaaki Omote  1
Affiliations

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

Yukiko Karuo et al. Beilstein J Org Chem. .

Abstract

An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.

Keywords: 1,1-difluoroethene; aryl 1,1-difluoroethyl ether; fluorine compound; halothane; phenol.

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Figures

Figure 1
Figure 1
Medical compounds having a difluoromethyl group.
Scheme 1
Scheme 1
Methods for the synthesis of ethers containing fluorine substituents.
Scheme 2
Scheme 2
The previous work reported by Yagupol’skii et al.
Scheme 3
Scheme 3
Intramolecular 1,4-addition of 2o.
Scheme 4
Scheme 4
Proposed reaction mechanism.
See this image and copyright information in PMC

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