[133745-75-2]  · C12H10FNO4S2  · N-Fluoro-N-(phenylsulfonyl)benzenesulfonamide  · (MW 315.33)

(electrophilic fluorinating agent)

Alternate Names: N-fluorobenzenesulfonimide; N-fluorobis(phenylsulfonyl)amine; N-fluorodibenzenesulfonimide.

Physical Data: mp 114-116 °C.

Solubility: sol various organic solvents, including THF (0.24 g ml-1), CH2Cl2 (0.40 g ml-1), acetonitrile (0.25 g ml-1), and toluene (0.09 g ml-1).

Form Supplied in: white or slightly yellow solid, &egt;98% purity; commercially available.

Analysis of Reagent Purity: 1H and 19F NMR.

Preparative Method: pressureless fluorination on a 0.2 mol scale with F2 in N2 (F2/N2 10% v/v) in the presence of powdered NaF in acetonitrile at -40 °C.1

Purification: flash chromatography (SiO2, CH2Cl2) and/or crystallization from Et2O.

Handling, Storage, and Precautions: handle and store at rt or below; protected from light, preferably under nitrogen or argon. Thermally stable up to 180 °C; decomposes exothermally at higher temperatures. Reacts with easily oxidized compounds such as iodide. This reagent should be handled in a fume hood.

Fluorination of Enolates and Silyl Enol Ethers.

N-Fluoro-N-(phenylsulfonyl)benzenesulfonamide (1) can be used successfully to prepare a-fluorocarbonyl compounds starting from esters, ketones, or b-dicarbonyl precursors by electrophilic fluorination of the corresponding enolates (eqs 1-3) or silyl enol ethers (eq 4).1 Diastereoselective fluorination of enolates with (1) has recently been reported.7

Fluorination of Organometallic Reagents.

Aryl and vinyl fluorides are conveniently prepared by reacting the corresponding lithium derivatives with (1).1 For example, anthracenyllithium, generated from bromoanthracene with n-Butyllithium, is fluorinated in THF at -78 °C (eq 5). 1-Phenyl-2-lithiopropene, obtained by reacting the corresponding iodoalkene with t-Butyllithium, requires a lower reaction temperature (-105 °C, THF/Et2O/pentane). This reaction affords the fluoroalkene with complete retention of configuration at the double bond (eq 6).

Fluorination of Alkyl Phosphonate Carbanions.

a-Fluoro- and a,a-difluoroalkyl phosphonates are prepared in good yields by electrophilic fluorination of phosphonate-derived carbanions (eqs 7 and 8).2 The yields in the reaction strongly depend on the nature of the base, Potassium Diisopropylamide being the base of choice. a,a-Difluoroalkyl phosphonates are obtained in 54-70% yield from the corresponding monofluorinated precursors after deprotonation at low temperature (-90 °C). In situ double fluorination starting from alkyl phosphonates by using an excess of both base and (1) give only low yields (10-20%) of a,a-difluorinated products.

Electrophilic Addition to Aromatics.

Aromatic compounds are fluorinated with (1) by heating without a solvent to about 100-150 °C, or, for low-boiling compounds, up to reflux temperature.1 Activated aromatics, such as anisole or N-acetylaniline, react smoothly, whereas toluene requires considerably longer reaction times and gives low yields (eqs 9-11). In all cases the regioselectivities are consistent with an electrophilic addition mechanism: ortho and para substituted products predominate over the meta isomers. (1) has recently been used in orthometalation-directed fluorination of aromatics.8

Related Reagents.

These include N-fluorobenzenedisulfonimide,3 N-fluoroperfluoroalkane sulfonimides,4 and 2-Fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole 1,1-Dioxide.5 For a review on electrophilic fluorinating agents, see German and Zemskov.6

1. Differding, E.; Ofner, H. SL 1991, 187.
2. Differding, E.; Duthaler, R. O.; Krieger, A.; Rüegg, G. M.; Schmit, C. SL 1991, 395.
3. Davis, F. A.; Han, W. TL 1991, 32, 1631.
4. Singh, S.; DesMarteau, D. D.; Zuberi, S. S.; Witz, M.; Huang, H.-N. JACS 1987, 109, 7194.
5. Differding, E.; Rüegg, G. M.; Lang, R. W. TL 1991, 32, 1779 and refs. cited therein.
6. New Fluorinating Agents in Organic Synthesis; German, L.; Zemskov, S. Eds.; Springer: Berlin, 1989.
7. Davis, F. A.; Reddy, R. E. TA 1994, 5, 955.
8. Snieckus, V.; Beaulieu, F.; Mohri, K.; Han, W.; Murphy, C. K.; Davis, F. A. TL 1994, 35, 3465.

Edmond Differding

UCB, Braine-l'Alleud, Belgium

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.