Zinc Trifluoromethanesulfonate

(CF3SO3)2Zn

[54010-75-2]  · C2F6O6S2Zn  · Zinc Trifluoromethanesulfonate  · (MW 363.55)

(mild Lewis acid; catalyst for a variety of reactions)

Alternate Name: zinc triflate.

Physical Data: mp >300 °C.

Solubility: insol CH2Cl2; slightly sol MeOH; sol MeCN, H2O.

Form Supplied in: white powder; commercially available.

Preparative Method: may be prepared from addition1 of Trifluoromethanesulfonic Acid to Zinc Carbonate in MeOH, filtration, and drying in vacuo.

Handling, Storage, and Precautions: moderately hygroscopic; store well sealed.

Introduction.

The mild Lewis acidic properties of this metal trifluoromethanesulfonate, similar in many ways to magnesium triflate1 but with some distinct differences from other metal triflates2 (notably Copper(II) Trifluoromethanesulfonate2c), have been exploited in several delicate synthetic operations. It will undoubtedly find more uses in the future. Some specific examples follow.

Thioacetalization.1

The thioacetalization of (1) with ethane-1,2-dithiol proved to be impossible by a variety of more traditional methods,3 but could be effected by zinc triflate without b-elimination of the lactone oxygen (eq 1).

Magnesium triflate can similarly be used to effect the reaction, but on occasion may require a more extended reaction time. In the case of D4-cholesten-3-one, however, magnesium triflate (but not the zinc reagent) causes some double bond isomerization. a,b-Unsaturated ketones may also react by conjugate addition of the thiol in addition to acetalization.

Glycosylation.4

Zinc triflate is one of a number of Lewis acids which can catalyze glycosylation reactions (eq 2). The choice of catalyst is highly dependent upon substrate and leaving group OX, and on occasion zinc triflate can be more suitable than, for example, Boron Trifluoride Etherate or Trimethylsilyl Trifluoromethanesulfonate. Stereochemical control at the anomeric center, however, is also variable, and far from complete.

A catalytic amount (0.1 mol %) of Zn(OTf)2 gives low stereoselectivity in reaction of cholesterol with 2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl chloride.4b Other zinc salts, notably zinc p-(t-butyl)benzoate,4b give a much more selective b-glycosylation product.

Onium Ion Formation.5

Zn(OTf)2 permits replacement of the MeO group of (2) with a carbon substituent (eq 3), presumably via onium ion intermediates.5a Reaction with Titanium(IV) Chloride in CH2Cl2, however, resulted in cleavage of the alternative (endocyclic) acetal bond, possibly owing to coordination5a to both O and N atoms. O-Addition to such onium ions may also be effected with zinc triflate.5b

Alkylation of Electron-Rich Aromatics.

Aziridines (3) react with indoles (X = electron-releasing group) to give tryptophan derivatives only in the presence of Zn(OTf)2 (eq 4).6a Although yields are fairly poor (19-60%), optical purity is excellent (>95%). Addition of other carbon nucleophiles (organocuprates7) to (3) can also lead to mixtures of products, in which a-amino acid derivatives may predominate.

Intramolecular alkylation of electron-rich aromatics (eq 5)6b can be an effective procedure, giving rise to benzofurans, benzothiophenes, indoles, or naphthalene derivatives. TMS triflate is also effective.


1. (a) Corey, E. J.; Shimoji, K. TL 1983, 24, 169. (b) Corey, E. J.; Shimoji, K. JACS 1983, 105, 1662.
2. (a) Kobayashi, S.; Hachiya, I.; Araki, M.; Ishitani, H. TL 1993, 34, 3755 and refs. therein. (b) Stang, P. J. Aldrichim. Acta 1983, 16, 15. (c) Laali, K.; Gerzina, R. J.; Flajnik, C. M.; Geric, C. M.; Dombroski, A. M. HCA 1987, 70, 607.
3. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd Ed.; Wiley: New York, 1991; p 201. (b) Perni, R. B. SC 1989, 19, 2383 and refs. therein.
4. (a) Rathore, H.; Hashimoto, T.; Igarashi, K.; Nukaya, H.; Fullerton, D. S. T 1985, 41, 5427 and refs. therein. (b) Nishizawa, M.; Garcia, D. M.; Shin, T.; Yamada, H. CPB 1993, 41, 784.
5. (a) Kozikowski, A. P.; Stein, P. D. JACS 1985, 107, 2569. (b) Kozikowski, A. P.; Li, C.-S. JOC 1985, 50, 778.
6. (a) Sato, K.; Kozikowski, A. P. TL 1989, 30, 4073. (b) Kozikowski, A. P.; Cheng, X.-M. CC 1987, 680.
7. Baldwin, J. E.; Spivey, A. C.; Schofield, C. J.; Sweeney, J. B. T 1993, 49, 6309.

Peter Ham

SmithKline Beecham Pharmaceuticals, Harlow, UK



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