Trimethylsilyl trifluoromethanesulfonate explained

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) is an organosilicon compound with the formula . It is a colorless moisture-sensitive liquid. It is the trifluoromethanesulfonate derivative of trimethylsilyl.^[1] It is mainly used to activate ketones and aldehydes in organic synthesis.

Reactions

TMSOTf is quite sensitive toward hydrolysis:

It is far more electrophilic than trimethylsilyl chloride.

Related to its tendency to hydrolyze, TMSOTf is effective for silylation of alcohols:^[2]

A common use of is for the preparation of silyl enol ethers.^{[3] [4]} One example involves the synthesis of the silyl enol ether of camphor:

It was also used in Takahashi Taxol total synthesis and in chemical glycosylation reactions.^[5]

Trimethylsilyl trifluoromethanesulfonate has a variety of other specialized uses. It has been used to install tert-alkyl groups on phosphine (R = alkyl):^[6]

PH₃ + R₃C–OAc + Me₃SiOTf → [(R₃C)₂PH₂]OTf

Deprotection of Boc-protected amines can be achieved using trimethylsilyl trifluoromethanesulfonate and triethylamine or 2,6-lutidine.^{[7] [8]}

TMSOTf is also a useful reagent to replace metal-halogen bonds with a covalent M-O(SO2CF3) bond, the by-product being the highly volatile TMSCl which is easily removed.

Notes and References

1. Trimethylsilyl Trifluoromethanesulfonate. Joseph Sweeney . Gemma Perkins . Enrique Aguilar . Manuel A. Fernández-Rodríguez . Rodolfo Marquez . Eric Amigues . Ricardo Lopez-Gonzalez . Encyclopedia of Reagents for Organic Synthesis. 2018. 10.1002/047084289X.rt338. 978-0-471-93623-7 .
2. 10.15227/orgsyn.092.0309 . (S)-1,1-Diphenylprolinol Trimethylsilyl Ether . 2015 . Boeckman . Robert . Douglas J.. Tusch. Kyle F.. Biegasiewicz. Organic Syntheses . 92 . 309–319 . free .
3. 10.15227/orgsyn.069.0129. N-Fluoropyridinium Triflate: An Electrophilic Fluorinating Agent. Organic Syntheses. 69. 129. 1990. Teruo. Umemoto. Kyoichi . Tomita. Kosuke. Kawada.
4. Efficient Stereoselective Synthesis of Proanthocyanidin Trimers with TMSOTf-Catalyzed Intermolecular Condensation. Akiko Saito, Akira Tanaka, Makoto Ubukata and Noriyuki Nakajima, Synlett, 2004, volume 6, pages 1069-1073,
5. 10.15227/orgsyn.081.0225. Synthesis and Use of Glycosyl Phosphates as Glycosyl Donors. Organic Syntheses. 81. 225. 2005. Kerry R. . Love. Peter H. . Seeberger. free.
6. Barber. Thomas. Argent. Stephen P.. Ball. Liam T.. 2020-05-15. Expanding Ligand Space: Preparation, Characterization, and Synthetic Applications of Air-Stable, Odorless Di- tert -alkylphosphine Surrogates. ACS Catalysis. en. 10. 10. 5454–5461. 10.1021/acscatal.0c01414. 219017552. 2155-5435.
7. Kuehne . Martin E. . Xu . Feng . Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 10. An Enantioselective Synthesis of (−)-Strychnine through the Wieland−Gumlich Aldehyde . The Journal of Organic Chemistry . 1 December 1998 . 63 . 25 . 9427–9433 . 10.1021/jo9813989.
8. Doi . Takayuki . Numajiri . Yoshitaka . Munakata . Asami . Takahashi . Takashi . Total Synthesis of Apratoxin A . Organic Letters . 1 February 2006 . 8 . 3 . 531–534 . 10.1021/ol052907d. 16435877 .