Issue 1, 2016

Access to a new class of synthetic building blocks via trifluoromethoxylation of pyridines and pyrimidines

Abstract

Since the first synthesis of trifluoromethyl ethers in 1935, the trifluoromethoxy (OCF3) group has made a remarkable impact in medicinal, agrochemical, and materials science research. However, our inability to facilely incorporate the OCF3 group into molecules, especially heteroaromatics, has limited its potential across a broad spectrum of technological applications. Herein, we report a scalable and operationally simple protocol for regioselective trifluoromethoxylation of a wide range of functionalized pyridines and pyrimidines under mild reaction conditions. The trifluoromethoxylated products are useful scaffolds that can be further elaborated by amidation and palladium-catalysed cross coupling reactions. Mechanistic studies suggest that a radical O-trifluoromethylation followed by the OCF3-migration reaction pathway is operable. Given the unique properties of the OCF3 group and the ubiquity of pyridine and pyrimidine in biologically active molecules and functional materials, trifluoromethoxylated pyridines and pyrimidines could serve as valuable building blocks for the discovery and development of new drugs, agrochemicals, and materials.

Graphical abstract: Access to a new class of synthetic building blocks via trifluoromethoxylation of pyridines and pyrimidines

Supplementary files

Article information

Article type
Edge Article
Submitted
12 Aug 2015
Accepted
05 Oct 2015
First published
07 Oct 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 424-429

Access to a new class of synthetic building blocks via trifluoromethoxylation of pyridines and pyrimidines

P. Feng, K. N. Lee, J. W. Lee, C. Zhan and M. Ngai, Chem. Sci., 2016, 7, 424 DOI: 10.1039/C5SC02983J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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