Trifluoromethanesulfonyl Chloride1

[421-83-0]  · CClF3O2S  · Trifluoromethanesulfonyl Chloride  · (MW 168.53)

(trifluoromethylsulfonation agent;1 chlorinating agent;2 metal-catalyzed chlorotrifluoromethylation of alkenes3)

Alternate Name: triflyl chloride.

Physical Data: bp 29-32 °C, d 1.583 g cm-3.

Solubility: sol CH2Cl2, THF, dioxane.

Form Supplied in: colorless liquid, 99 +%.

Analysis of Reagent Purity: IR: 1424, 1306, 1237, 1115, 771, 611, 565, 532, 404 cm-1.4

Preparative Methods: dried Zinc Trifluoromethanesulfonate is heated with PCl5.2ZnCl at 260 °C. Fractional distillation of the volatile products gives TfCl (94% yield).5

Handling, Storage, and Precautions: moisture sensitive; store under N2 in the cold. This toxic reagent is corrosive and is a lachrymator. It should only be handled in a fume hood.

Triflate and Triflamide Formation.

Triflyl chloride (TfCl) reacts as an electrophile with oxygen and nitrogen nucleophiles to produce triflate or triflamide derivatives. The trifluoromethanesulfonate group is a highly electron-withdrawing moiety and is a useful leaving group in organic synthesis for nucleophilic displacement, solvolysis, and metal-catalyzed coupling reactions.1 The sulfonation reaction works well with amines6 and alcohols, and is especially suitable for phenols.7 An amine base such as Triethylamine or Diisopropylethylamine is usually added as an acid scavenger and to activate the substrates; however, the reactivity of the starting materials can be increased with prior anion formation by a stronger base.8 Less reactive substrates may be sulfonated using Trifluoromethanesulfonic Anhydride or other derivatives of triflic acid such as those formulated from imidazole9 or amides.10 These are the reagents of choice for the formation of enol triflates from carbonyl compounds having a-hydrogens.1 Mixed sulfonic anhydrides can be formed by reaction of the silver salt of an alkylsulfonic acid with triflyl chloride.11

An enol has been activated toward intramolecular nucleophilic addition with TfCl (eq 1).12 A pyridine heterocycle reacts in a similar way.13 In these reactions the triflinate anion (CF3SO2-) functions as the leaving group. This sulfinate anion has also been studied as a nucleophile and potassium trifluoromethanesulfinate may be prepared by the reduction of TfCl with Potassium Iodide.14

Chlorination of Activated Methylenes.

Triflyl chloride acts as a mild chlorinating reagent with certain carbon acids and nucleophiles.15 Carbon acids in the pKa range between diethyl malonate and methyl dichloroacetate react with TfCl in the presence of an amine base such as Et3N or 1,8-Diazabicyclo[5.4.0]undec-7-ene to replace one or two acidic hydrogens with chlorine. The reaction is highly selective with the rate of chlorination being at least 105 greater than the rate of sulfonation. Yields are generally excellent and the reagent is often much more efficient than other chlorinating agents such as N-Chlorosuccinimide. This transformation has been utilized for the synthesis of 2,2-disubstituted tetrahydrofurans, pyrans, and pyrrolidines (eq 2).16

When triflyl chloride and Sodium Azide are added to carbon acids, a similar reaction is observed and the corresponding azides are obtained in 50-60% yields.17 The reactive species in this transformation is thought to be F3CSO2N2. Similar reactivity has been seen with TfCl and Silver(I) Nitrate. The intermediate F3CSO2NO2 reacts with activated methylenes and Potassium t-Butoxide to give nitro derivatives in fair yields.18

Metal-Catalyzed Chlorotrifluoromethylation of Alkenes.

Dichlorotris(triphenylphosphine)ruthenium(II) catalyzes the reaction between triflyl chloride and alkenes to give vicinally chloro/trifluoromethyl-substituted alkanes with the extrusion of sulfur dioxide.19 The reaction works well for alkenes bearing either electron-withdrawing or electron-donating substituents (eq 3). Terminal alkenes give the best yields but the reaction works with internal double bonds as well. Temperatures &egt;120 °C are required for complete extrusion of sulfur dioxide. Treatment of the products with aqueous Potassium Hydroxide causes the elimination of HCl to give vinyltrifluoromethane derivatives. The same ruthenium catalyst promotes the reaction between triflyl chloride and arenes to give trifluoromethylated aromatic compounds.20 Trifluoromethyl iodide, an alternative reagent for the introduction of the trifluoromethane group, is less convenient to work with since it is a gas at rt.3


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2. Hakimelahi, G. H.; Just, G. TL 1979, 3645.
3. Kamigata, N.; Fukushima, T.; Terakawa, Y.; Yoshida, M.; Sawada, H. JCS(P1) 1991, 627.
4. (a) Pouchert, C. J. Aldrich Library of FT-IR Spectra; Aldrich: Milwaukee, 1989; Vol. 1, p 901B. (b) Robinson, E. A. CJC 1961, 39, 247.
5. (a) Tiers, G. V. D. JOC 1963, 28, 1244. (b) Haszeldine, R. N.; Kidd, J. M. JCS 1955, 2901.
6. Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi, S. T 1992, 48, 5691.
7. (a) Keumi, T.; Saga, H.; Taniguchi, R.; Kitajima, H. CL 1977, 1099. (b) Showalter, H. D. H.; Berman, E. M.; Johnson, J. L. TL 1985, 26, 157. (c) Lau, C. K.; Bélanger, P. C.; Dufresne, C.; Scheigetz, J. JOC 1987, 52, 1670. (d) Reference 1.
8. Williams, H. W. R.; Rooney, C. S.; Bicking, J. B.; Robb, C. M.; de Solms, S. J.; Woltersdorf, O. W., Jr.; Cragoe, E. J., Jr. JOC 1979, 44, 4060.
9. Effenberger, F.; Mack, K. E. TL 1970, 3947.
10. Hendrickson, J. B.; Bergeron, R. TL 1973, 4607.
11. Moe, G. R.; Sayre, L. M.; Portoghese, P. S. TL 1981, 537.
12. Norris, C. P.; Berke, H.; Lombardino, J. G.; Bordner, J. JHC 1985, 22, 837.
13. Pasutto, F. M.; Knaus, E. E. CJC 1979, 57, 2371.
14. (a) Hendrickson, J. B.; Giga, A.; Wareing, J. JACS 1974, 96, 2275. (b) Bordwell, F. G.; Bares, J. E.; Bartmess, J. E.; Drucker, G. E.; Gerhold, J.; McCollum, G. J.; Van Der Puy, M.; Vanier, N. R.; Matthews, W. S. JOC 1977, 42, 326.
15. (a) Hakimelahi, G. H.; Just, G. TL 1979, 3643. (b) Hafner, K.; Stowasser, B.; Sturm, V. TL 1985, 26, 189. (c) Sato, K.; Kinoto, T.; Sugai, S. CPB 1986, 34, 1553.
16. Hakimelahi, G. H.; Just, G. TL 1979, 3645.
17. Hakimelahi, G. H.; Just, G. SC 1980, 10, 429.
18. Hakimelahi, G. H.; Sharghi, H.; Zarrinmayeh, H.; Khalafi-Nezhad, A. HCA 1984, 67, 906.
19. (a) Kamigata, N.; Sawada, H.; Suzuki, N.; Kobayashi, M. PS 1984, 19, 199. (b) Kamigata, N.; Fukushima, T.; Yoshida, M. CC 1989, 1559. (c) Ref. 3.
20. Kamigata, N.; Fukushima, T.; Yoshida, M. CL 1990, 649.

Paul A. Wender & Thomas E. Smith

Stanford University, CA, USA



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