t-Butyldimethylsilyl Trifluoromethanesulfonate1

t-BuMe2SiOSO2CF3

[69739-34-0]  · C7H15F3O3SSi  · t-Butyldimethylsilyl Trifluoromethanesulfonate  · (MW 264.33)

(highly reactive silylating agent and Lewis acid capable of converting primary, secondary, and tertiary alcohols1b to the corresponding TBDMS ethers, and converting ketones2 and lactones2a,3 into their enol silyl ethers; promoting conjugate addition of alkynylzinc compounds4 and triphenylphosphine5 to a,b-enones; activation of chromones in [4 + 2] cycloaddition reactions;6 rearrangement of allylic tributylstannyl silyl ethers;7 activation of pyridine rings toward Grignard reagents8 and transalkylation of tertiary amine N-oxides;9 and transformation of N-t-butoxycarbonyl groups into N-alkoxycarbonyl groups10)

Alternate Name: TBDMS triflate.

Physical Data: bp 60 °C/7 mmHg; colorless oil, d 1.151 g cm-3.

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

Analysis of Reagent Purity: 1H NMR (CDCl3) d 1.00 (s, 9H, t-Bu), 0.45 (s, 6H, Me).

Form Supplied in: liquid; widely available.

Preparative Method: 1b to 24 g (0.16 mol) of t-Butyldimethylchlorosilane at 23 °C under argon is added 14 mL (0.16 mol) of Trifluoromethanesulfonic Acid dropwise. The solution is heated at 60 °C for 10 h, at which time no further hydrogen chloride evolves (removed through a bubbler). The resulting product is distilled under reduced pressure: 34 g (80% yield) of TBDMS triflate; bp 60 °C/7 mmHg.

Handling, Storage, and Precautions: the material should be stored under argon at 0 °C. The compound has an unpleasant odor and reacts rapidly with water and other protic solvents.

Silylation of Alcohols.1

Primary, secondary, and tertiary alcohols are silylated by reaction with TBDMS triflate in excellent yields. For instance, treatment of t-butanol with 1.5 equiv of TBDMS triflate and 2 equiv of 2,6-Lutidine in CH2Cl2 at 25 °C for 10 min gives a 90% yield of (t-butoxy)-t-butyldimethylsilane.1b The following alcohols are similarly silylated in excellent yields (70-90%): 2-phenyl-2-propanol, endo-norborneol, cis-2,2,4,4-tetramethylcyclobutane-1,3-diol, and 9-O-methylmaytansinol (converted to the 3-TBDMS derivative) (eq 1).1b

Formation of Enol Silyl Ethers.2,3

Various sterically hindered ketones have been converted into enol silyl ethers by treatment with 1-2 equiv of TBDMS triflate and 1.5 equiv of Triethylamine in CH2Cl2 or 1,2-dichloroethane at rt. A representative example is depicted in eq 2.2a

Reactions of chiral b-keto sulfoxides with 1.1 equiv of Lithium Diisopropylamide in THF at -78 °C followed by 1.2 equiv of TBDMS triflate at -78 °C produce the corresponding (Z)-enol silyl ethers (eq 3).2b

Lactones have also been transformed into silyl ketene acetals upon treatment with TBDMS triflate and triethylamine in CH2Cl2 (eqs 4 and 5).2a,3 In the case of 8a-vinyl-2-oxooctahydro-2H-1,4-benzoxazine, the resulting silyl ketene acetal undergoes Claisen rearrangement to provide the octahydroquinoline (eq 6).3

Conjugate Addition of Alkynylzinc Bromides.4

Alkynylzinc bromides undergo conjugate addition with a,b-unsaturated ketones in the presence of TBDMS triflate in ether-THF at -40 °C to give the corresponding 1,4-adducts (54-96% yields). A representative example is illustrated in eq 7.4 Other trialkylsilyl triflates such as Triisopropylsilyl Trifluoromethanesulfonate or Trimethylsilyl Trifluoromethanesulfonate can effectively replace TBDMS triflate.

Phosphoniosilylation.5

Cyclic enones treated with TBDMS triflate and Triphenylphosphine in THF at rt provide the corresponding 1-(3-t-butyldimethylsilyloxy-2-cycloalkenyl)triphenylphosphonium triflates (eq 8) which, upon lithiation with n-Butyllithium followed by Wittig reaction with aldehydes, afford various conjuated dienes.5

Silylation of Chromones.6

The preparation of 4-t-butyldimethylsilyloxy-1-benzopyrylium triflate is carried out by heating chromone and TBDMS triflate at 80 °C for 1 h (without solvent) under nitrogen (eq 9).6b The silylated chromones undergo addition reaction with enol silyl ethers and 2,6-lutidine,6b and [4 + 2]-type cycloaddition reactions with a,b-unsaturated ketones in the presence of TBDMS triflate and 2,6-lutidine. An example of the cycloaddition reaction is shown in eq 10.6a

Rearrangement of Allylic Tributylstannyl Silyl Ethers.7

a-Silyloxy allylic stannanes are isomerized with TBDMS triflate to (Z)-g-silyloxy allylic stannanes (eq 11).7 The resulting allylic stannanes undergo addition reactions with aldehydes in the presence of Boron Trifluoride Etherate to provide the 3-(t-butyldimethylsilyloxy)-4-hydroxyalkenes.7a

Activation of Pyridine.8

N-(t-Butyldimethylsilyl)pyridinium triflate, prepared from pyridine and TBDMS triflate in CH2Cl2 at rt, undergoes addition reactions with alkyl and aryl Grignard reagents to give 4-substituted pyridines after oxidation with oxygen (eq 12).8 Only about 1% of the 2-substituted pyridines were formed in the cases studied.

Transalkylation of Tertiary Amine N-Oxides.9

N-(t-Butyldimethylsilyloxy)-N-methylpiperidinium triflate is quantitatively formed from the reaction of N-methylpiperidine N-oxide (eq 13).9b The resulting amine salts derived from various trialkylamine N-oxides undergo transalkylation by treatment with Methyllithium in THF at 0 °C followed by alkyl halides and Tetra-n-butylammonium Fluoride in a sealed tube at 110 °C for 10 h, to afford trisubstituted amines (eq 14).9a

Interconversion of N-Boc Group into N-Alkoxycarbonyl Group.10

Treatment of t-butyl alkylcarbamates with 1.5 equiv of TBDMS triflate and 2 equiv of 2,6-lutidine in CH2Cl2 at rt for about 15 min furnishes the corresponding TBDMS carbamates (eq 15).10 Desilylation of these silyl carbamates with aqueous fluoride ion gives excellent yields of the corresponding primary amines. The silyl carbamates are also converted into other N-alkoxycarbonyl derivatives by treatment with TBAF and alkyl halides in THF at 0 °C (82-88% yields).10


1. (a) Stewart, R. F.; Miller, L. L. JACS 1980, 102, 4999. (b) Corey, E. J.; Cho, H.; Rucker, C.; Hua, D. H. TL 1981, 22, 3455. (c) For a review of trialkylsilyl triflates: 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. (a) Mander, L. N.; Sethi, S. P. TL 1984, 25, 5953. (b) Solladie, G.; Mangein, N.; Morreno, I.; Almario, A.; Carreno, M. C.; Garcia-Ruano, J. L. TL 1992, 33, 4561.
3. Angle, S. R.; Breitenbucker, J. G.; Arnaiz, D. O. JOC 1992, 57, 5947.
4. Kim, S.; Lee, J. M. TL 1990, 31, 7627.
5. Kozikowski, A. P.; Jung, S. H. JOC 1986, 51, 3400.
6. (a) Lee, Y.; Iwasaki, H.; Yamamoto, Y.; Ohkata, K.; Akiba, K. H 1989, 29, 35. (b) Iwasaki, H.; Kume, T.; Yamamoto, Y.; Akiba, K. TL 1987, 28, 6355.
7. (a) Marshall, J. A.; Welmaker, G. S. JOC 1992, 57, 7158. (b) Marshall, J. A.; Welmaker, G. S. TL 1991, 32, 2101. (c) Marshall, J. A.; Welmaker, G. S. SL 1992, 537.
8. Akiba, K.; Iseki, Y.; Wata, M. TL 1982, 23, 3935.
9. (a) Tokitoh, N.; Okazaki, R. CL 1984, 1937. (b) Okazaki, R.; Tokitoh, N. CC 1984, 192.
10. Sakaitani, M.; Ohfune, Y. TL 1985, 26, 5543.

Duy H. Hua & Jinshan Chen

Kansas State University, Manhattan, KS, USA



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