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. 2012 Jan 25;134(3):1494-7.
doi: 10.1021/ja211422g. Epub 2012 Jan 13.

A new reagent for direct difluoromethylation

Yuta Fujiwara  1 , Janice A Dixon, Rodrigo A Rodriguez, Ryan D Baxter, Darryl D Dixon, Michael R Collins, Donna G Blackmond, Phil S Baran
Affiliations

A new reagent for direct difluoromethylation

Yuta Fujiwara et al. J Am Chem Soc. .

Abstract

Molecular scaffolds containing alkylfluorine substituents are desired in many areas of chemical research from materials to pharmaceuticals. Herein, we report the invention of a new reagent (Zn(SO(2)CF(2)H)(2), DFMS) for the innate difluoromethylation of organic substrates via a radical process. This mild, operationally simple, chemoselective, and scalable difluoromethylation method is compatible with a range of nitrogen-containing heteroarene substrates of varying complexity as well as select classes of conjugated π-systems and thiols. Regiochemical comparisons suggest that the CF(2)H radical generated from the new reagent possesses nucleophilic character.

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Figures

Figure 1
Figure 1
Invention of a new difluoromethylation reagent.
Figure 2
Figure 2
Regiochemical comparison of innate difluoro- and trifluoromethylations. Isolated yields after preparative HPLC purification.
Figure 3
Figure 3
Solvent effects on regioselectivity. aStandard conditions were followed. bSecond addition of DFMS (2.0 equiv) and tert-butyl hydroperoxide (3.0 equiv) was added.
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