[124170-23-6] · C9H10FNO2S · 2-Fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole 1,1-Dioxide · (MW 215.24)
(electrophilic fluorinating agent)
Alternate Name: N-fluoro-2,a-cumenesultam.
Physical Data: mp 115-117 °C.
Solubility: sol various organic solvents including THF, diethyl ether, CH2Cl2, acetonitrile.
Form Supplied in: white or slightly yellow solid, &egt;98% purity; commercially available.
Analysis of Reagent Purity: 1H and 19F NMR.
Purification: flash chromatography (SiO2, CH2Cl2) and/or crystallization from Et2O/pentane.
Handling, Storage, and Precautions: handle and store at rt or below; protected from light, preferably under nitrogen or argon. Thermally stable up to 200 °C; decomposes exothermally above 200 °C. Reacts with easily oxidized compounds such as iodide or tetramethylphenylenediamine. This reagent should be handled in a fume hood.
Nitrogen-fluorine bond-containing compounds are among the most useful electrophilic fluorinating agents due to their easy access, their inherent stability, and the ease with which they can be handled. 2-Fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (1) is one of the most thoroughly studied reagents, both from a preparative and a mechanistic point of view.1 -8 There is evidence, both preparative and mechanistic, that direct nucleophilic attack at fluorine occurs. Electron transfer is a competing reaction, which leads to nonfluorinated products.5,6,8
N-Fluorosultam (1) has been successfully used to prepare a-fluorocarbonyl compounds by electrophilic fluorination starting, for example, from disubstituted enolates derived from ketones, esters, and b-dicarbonyl compounds (eqs 1-3).1 The related N-fluorosulfonamide reagents9 give considerably lower yields due to the elimination of HF by proton abstraction from the carbon a to the nitrogen atom.1
Monosubstituted enolates can be selectively monofluorinated using slightly more than 1 equiv of base and N-fluorosultam. The influence of the counterion is crucial and the selectivity decreases in the order Li > Na > K, although Potassium Hexamethyldisilazide often gives higher yields, especially with esters (eqs 4-6).4
See also the related chiral N-fluorosultam reagents derived from camphor which allow for enantioselective fluorination with modest enantiomeric excesses (up to 75%).10,11
Double fluorination of monosubstituted enolates is achieved selectively in a one-pot procedure by adding the starting carbonyl compound to 2.4-3.6 equiv of base in THF at -78 °C followed by the addition of 2.6-3.6 equiv of the N-fluorosultam, and warming up to room temperatures. For this process, KHMDS and Potassium Diisopropylamide are the bases of choice (eqs 7-9).4
Aryl fluorides can be prepared by reacting the corresponding aryllithium compound with (1) (eq 10). Grignard reagents give significantly lower yields, probably due to competing electron transfer reactions since radical-derived side products have been isolated and characterized (eq 11).6
For a more reactive nitrogen-fluorine bond containing reagent, see N-Fluoro-N-(phenylsulfonyl)benzenesulfonamide.12
UCB, Braine l'Alleud, Belgium
Robert W. Lang
Ciba-Geigy, Basel, Switzerland