Triisopropylsilyl Trifluoromethanesulfonate1

(i-Pr)3SiOSO2CF3

[80522-42-5]  · C10H21F3O3SSi  · Triisopropylsilyl Trifluoromethanesulfonate  · (MW 306.46)

(highly reactive silylating agent and Lewis acid capable of converting primary and secondary alcohols1 to the corresponding triisopropylsilyl ethers and converting ketones1 and lactones2 into their enol silyl ethers; protection of terminal alkynes;3 promoting conjugate addition of alkynylzinc compounds to a,b-enones;4 preparation of (triisopropylsilyl)diazomethane5)

Alternate Name: TIPS triflate.

Physical Data: colorless oil; bp 83-87 °C/1.7 mmHg; d 1.173 g cm-3.

Solubility: sol most organic solvents, such as pentane, CH2Cl2, etc.

Form Supplied in: liquid; widely available.

Analysis of Reagent Purity: 1H NMR (CDCl3) d 1.6-1.05 (m).

Preparative Methods: to 38.2 g (0.242 mol) of triisopropylsilane at 0 °C under argon is added 23.8 mL (0.266 mol) of Trifluoromethanesulfonic Acid dropwise. The solution is stirred at 22 °C for 16 h, at which time no further hydrogen gas evolves (removed through a bubbler). The resulting product is distilled through a 30-cm vacuum jacketed Vigreux column under reduced pressure: 71.7 g (97% yield) of TIPS triflate; bp 83-87 °C/1.7 mmHg.1a

Handling, Storage, and Precautions: store under argon at 0 °C; unpleasant odor; reacts rapidly with water and other protic solvents.

Silylation of Alcohols.1

Primary and secondary alcohols are silylated by TIPS triflate in excellent yields. Treatment of 1-phenylethanol with 1.3 equiv of TIPS triflate and 2.5 equiv of 2,6-Lutidine in CH2Cl2 at 0 °C for 2 h provides a 98% yield of a-(triisopropylsilyloxy)ethylbenzene (eq 1).1a

Formations of Enol Silyl Ethers.1,2

Aldehydes, ketones, and lactones are readily converted into the corresponding enol TIPS ethers. Reactions of cycloalkanones with 1.1 equiv of TIPS triflate and 1.5 equiv of Triethylamine in benzene at 23 °C for 1 h gives >98% yields of the corresponding enol silyl ethers (eq 2).1a

Silylation of 2-morpholinones with 1.2 equiv of TIPS triflate and 1.5 equiv of triethylamine in CDCl3 for 2 min provides silyl ketene acetals, which upon standing at rt undergo Claisen rearrangement to afford pipecolic esters (eq 3).2

Alkynyltriisopropylsilanes.3

The acidic alkynic H can be protected with TIPS triflate. Silylation of 1-lithiopropyne with 1 equiv of TIPS triflate in ether at -40 to 0 °C gives an 87% yield of 1-TIPS-propyne (eq 4).3a 1,3-Bis(triisopropylsilyl)propyne, derived from treatment of 1-TIPS-propyne with n-Butyllithium in THF at -20 °C for 15 min followed by TIPS triflate at -78 to -40 °C (eq 5), is lithiated with n-BuLi in THF at -20 °C for 15 min and then allowed to react with aldehydes (eq 6). The cis-enynes are isolated in high yields.3a TIPS-propargylmagnesium bromide together with Copper(I) Iodide has been used in the displacement of the mesylate derivative of farnesol.3b

Conjugate Addition of Alkynylzinc Bromides.4

Alkynylzinc bromides undergo conjugate addition with a,b-unsaturated ketones in the presence of t-Butyldimethylsilyl Trifluoromethanesulfonate or TIPS triflate (Trimethylsilyl Trifluoromethanesulfonate is also effective) in ether-THF at -40 °C to give the corresponding 1,4-adducts (54-96% yields). A representative example is illustrated in eq 7.

(Triisopropylsilyl)diazomethane.5

Silylation of Diazomethane with TIPS triflate and Diisopropylethylamine in ether at -20 °C to 25 °C gives a 45% yield of (triisopropylsilyl)diazomethane (eq 8).5 This silylated diazomethane is used to prepare stable silyl-substituted nitrilimines.5

Related Reagents.

Triisopropylsilyl Chloride.


1. (a) Corey, E. J.; Cho, H.; Rucker, C.; Hua, D. H. TL 1981, 22, 3455. (b) For a review of trialkylsilyltriflates: Emde, H.; Domsch, D.; Feger, H.; Frick, U.; Gotz, A.; Hergott, H. H.; Hofmann, K.; Kober, W.; Krageloh, K.; Oesterle, T.; Steppan, W.; West, W.; Simchen, G. S 1982, 1.
2. Angle, S. R.; Breitenbucker, J. G.; Arnaiz, D. O. JOC 1992, 57, 5947.
3. (a) Corey, E. J.; Rucker, C. TL 1982, 23, 719. (b) Marshall, J. A.; Andersen, M. W. JOC 1992, 57, 2766.
4. Kim, S.; Lee, J. M. TL 1990, 31, 7627.
5. Castan, F.; Baceiredo, A.; Bigg, D.; Bertrand, G. JOC 1991, 56, 1801.

Duy H. Hua & Jinshan Chen

Kansas State University, Manhattan, KS, USA



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