Chemoselective Difluorination of Tetramic Acids in Water.

3,3-Difluorotetramic acids are key building blocks for the construction of medicinally relevant compounds. However, general methods for their synthesis via the direct electrophilic fluorination of tetramic acids are lacking. Herein we report such a method for the direct 3,3-difluorination of tetramic acids in water without any organic cosolvents utilizing Selectfluor as the electrophilic fluorine source. This reaction shows high chemoselectivity across a range of functional groups, including alkenes, alkynes, ketones, and aromatic rings, and tolerates a range of common nitrogen protecting groups. Finally, the reaction was successfully run at the multimillimole scale and was shown to tolerate an air atmosphere.