Easier Difluoromethylation | Chemical & Engineering News
Volume 90 Issue 3 | p. 30 | Concentrates
Issue Date: January 16, 2012

Easier Difluoromethylation

New reagent adds CF2H moiety to nitrogen-containing heteroarenes, as well as to thiols and enones
Department: Science & Technology
News Channels: JACS In C&EN
Keywords: difluoromethyl, heteroarene, thiol, enone, radical, fluorination

A reagent that directly difluoromethylates nitrogen-containing heteroarenes, as well as certain thiols and enones, has been reported by Phil S. Baran of Scripps Research Institute and colleagues (J. Am. Chem. Soc., DOI: 10.1021/ja211422g). The compound, Zn(SO2CF2H)2, is air-stable and works at room temperature. It’s amenable to gram-scale procedures, according to the inventors, and it could be used to make novel pharmaceuticals or materials with alkylfluorine substituents. To difluoromethylate heteroarenes, chemists previously had to prefunctionalize the substrates. But the reagent developed by Baran’s team adds CF2H groups to heteroarenes directly via a radical process. The researchers observed some regioselectivity in heteroarenes with multiple reaction sites, with the CF2H group tending to add to the most electron-deficient position. They note, however, that this regio­selectivity can be tuned by using organic cosolvents. In addition, the radical process transforms aromatic thiols into difluoromethyl thioethers and adds a CF2H group to α,β-unsaturated enones. Baran notes that, although the new reagent is easy to prepare, it’s also commercially available from Sigma-Aldrich (product number L510084).

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