Di-t-butylsilyl Bis(trifluoromethanesulfonate)


[85272-31-7]  · C10H18F6O6S2Si  · Di-t-butylsilyl Bis(trifluoromethanesulfonate)  · (MW 440.44)

(reagent for the protection of diols)

Physical Data: bp 73-75 °C/0.35 mmHg; d 1.208 g cm-3.

Solubility: sol most common organic solvents.

Form Supplied in: liquid.

Preparative Method: by the treatment of di-t-butylchlorosilane with Trifluoromethanesulfonic Acid, followed by distillation (71% yield).1

Purification: distillation.

Handling, Storage, and Precautions: moisture sensitive; reacts with hydroxylic solvents; corrosive.

Protection of Alcohols.

Di-t-butylsilyl bis(trifluoromethanesulfonate) is a reagent for the selective protection of polyhydroxy compounds. This reagent reacts with 1,2-, 1,3-, and 1,4-diols under mild conditions to give the corresponding dialkylsilylene derivatives in high yield (0-50 °C, 79-96%). Deprotection is conveniently achieved by using aqueous Hydrofluoric Acid in acetonitrile (eq 1).

Unlike Di-t-butyldichlorosilane, this reagent reacts with hindered alcohols. Even pinacol reacts to give the silylene derivative (100 °C, 24 h, 70%). Di-t-butylsilylene derivatives of 1,2-diols are more reactive than those of 1,3- and 1,4-diols and undergo rapid hydrolysis (5 min) in THF/H2O at pH 10, while the 1,3- and 1,4-derivatives are unaffected at pH 4-10 (22 °C) for several hours. This protecting group is stable under the conditions of PDC oxidation of alcohols (CH2Cl2, 25 °C, 27 h) and tosylation of alcohols (pyridine, 25 °C, 27 h).

The reagent has seen limited use for the protection of alcohols but has been used to protect nucleosides (eq 2).2-5 The procedure consists of sequential addition of the ditriflate and Triethylamine to the nucleoside in DMF. The choice of solvent is critical.

The ribonucleosides of uracil, adenine, and guanine give the protected derivative in 94-95% yield.2 Cytidine gives a low yield of the desired product under these conditions. Subsequent studies suggested that O2 of cytosine participates in the reaction. Addition of Trifluoromethanesulfonic Acid or Silver(I) Trifluoromethanesulfonate at 0 °C prior to addition of the silylating agent results in a 99% yield of the desired derivative.3 The derivatives are acid sensitive, presumably due to the proximity of the 2-hydroxy group. Acetylation, tetrahydropyranylation, methoxytetrahydropyranylation, and silylation of the 2-hydroxy group are accomplished without affecting the dialkylsilylene protecting group. The 2-deoxyribonucleosides, including 2-deoxycytidine, can also be prepared by the aforementioned procedure (yields 90-99%). These cyclic silylene derivatives of nucleosides can be deprotected conveniently using tributylamine hydrofluoride in THF (5 min, 1 M, rt, 20 equiv).4 A one-pot procedure has been reported for simultaneously protecting the 2-, 3-, and 5-hydroxys of a ribonucleoside, which utilizes the acid generated upon silylating the 3- and 5-hydroxys for catalyzing the formation of a THP acetal at the 2-position (eq 3).5

Derivatization of Alcohols.

Di-t-butylsilyl bis(trifluoromethanesulfonate) has been used to derivatize hindered diols, to give derivatives such as (1), for analysis by gas chromatography-electron impact mass spectrometry.6 The major fragmentation is that of the Si-C bonds.

Reagent in Enantioselective Additions.

In a study of enantioselective conjugate addition to cyclohexanone it was found that the presence of HMPA and various silyl reagents markedly increases the enantioselectivity (eq 4).7 Di-t-butylsilyl bis(trifluoromethanesulfonate) gives a 67% yield and 40% ee but t-Butyldiphenylchlorosilane gives a 97% yield and 78% ee.

Other Substitution Reactions.

An extremely hindered silyl reagent, tri-t-butylsilyl trifluoromethanesulfonate, was prepared from di-t-butylsilyl bis(trifluoromethanesulfonate) and t-Butyllithium (eq 5).8 This reagent might find use in the protection of alcohols.

In conjunction with the study of alkyl-substituted silyl triflates, (2) and (3) have been prepared from the corresponding alkynyllithium reagents and di-t-butylsilyl bis(trifluoromethanesulfonate).9

The preparation of other derivatives of di-t-butylsilyl bis(trifluoromethanesulfonate) using germanium10 and phosphorus11 nucleophiles has been reported and provides bifunctional silanes such as (4) and (5).

A compound closely related to di-t-butylsilyl bis(trifluoromethanesulfonate) is di-t-butylchlorosilyl trifluoromethanesulfonate, which has been used to tether two structurally different alcohol derivatives in order to effect an intramolecular Diels-Alder reaction (eq 6).12

1. Corey, E. J.; Hopkins, P. B. TL 1982, 23, 4871.
2. Furusawa, K.; Ueno, K.; Katsura, T. CL 1990, 97.
3. Furusawa, K. Chem. Express 1991, 6, 763.
4. Furusawa, K. CL 1989, 509.
5. Furusawa, K.; Sakai, T. Jpn. Kokai Tokkyo Koho 1989, 629.
6. Brooks, C. J. W.; Cole, W. J. Analyst (London) 1985, 110, 587.
7. Ahn, K-H.; Klassen, R. B.; Lippard, S. J. OM 1990, 9, 3178.
8. Uhlig, W. CB 1992, 125, 47.
9. Uhlig, W. Z. Anorg. Allg. Chem. 1991, 603, 109.
10. Uhlig, W. JOM 1991, 421, 189.
11. Uhlig, W. Z. Anorg. Allg. Chem. 1991, 601, 125.
12. Gillard, J. W.; Fortin, R.; Grimm, E. L.; Maillard, M.; Tjepkema, M.; Bernstein, M. A.; Glaser, R. TL 1991, 32, 1145.

Snorri T. Sigurdsson & Paul B. Hopkins

University of Washington, Seattle, WA, USA

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