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Direct and Regioselective C-H Oxidative Difluoromethylation of Heteroarenes
Sheng-Qing Zhu1, Yin-Li Liu1, Huan Li2
1Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry, Chinese Academy of Science , 345 LinglingLu , Shanghai 200032 , China.
Abstract:
The difluoromethyl group (CF2H) is of great interest in the area of medicinal chemistry. However, the investigation of molecular scaffolds containing this group has been hampered by the limitation of synthetic methods for the introduction of CF2H into heteroarenes. Herein we disclose a new strategy for the direct introduction of a difluoromethyl group into heteroarenes via the copper-mediated C-H oxidative difluoromethylation of heteroarenes with TMSCF2H. This mild and regioselective method enables the convenient synthesis of a range of difluoromethylated heteroarenes in high yields. The usage of 9,10-phenanthrenequinone (PQ) as an oxidant is critical to the success of this new difluoromethylation reaction.
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