Chemoselective Difluorination of Tetramic Acids in Water
M M Swatscheno1, R Mahawongnan1, Itamar Blau1
1Department of Chemistry, University of West Florida, Pensacola, Florida 32514, United States.
Abstract:
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.
Related Concept Videos
Acid Halides to Carboxylic Acids: Hydrolysis
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields...
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
Preparation and Reactions of Sulfides
Acid Halides to Esters: Alcoholysis


