Trimethylsilyl trifluoromethanesulfonate

Trimethylsilyl trifluoromethanesulfonate

Names
Preferred IUPAC name Trimethylsilyl trifluoromethanesulfonate
Other names TMSOTf Trimethylsilyl triflate TMS triflate Trifluoromethanesulfonic acid trimethylsilyl ester
Identifiers
CAS Number	27607-77-8  Y
3D model (JSmol)	Interactive image
ChemSpider	58839
ECHA InfoCard	100.044.136
EC Number	248-565-4
PubChem CID	65367
UNII	Z84V0CBH9J  Y
CompTox Dashboard (EPA)	DTXSID2067325
InChI InChI=1S/C4H9F3O3SSi/c1-12(2,3)10-11(8,9)4(5,6)7/h1-3H3 Key: FTVLMFQEYACZNP-UHFFFAOYSA-N
SMILES C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Properties
Chemical formula	C4H9F3O3SSi
Molar mass	222.25 g·mol−1
Appearance	Colorless liquid
Density	1.225 g/mL
Boiling point	140 °C (284 °F; 413 K)
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H226, H314
Precautionary statements	P210, P233, P240, P241, P242, P243, P260, P264, P280, P301+P330+P331, P302+P361+P354, P303+P361+P353, P304+P340, P305+P354+P338, P316, P321, P363, P370+P378, P403+P235, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) is an organosilicon compound with the formula (CH₃)₃SiO₃SCF₃. 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:

(CH₃)₃SiO₃SCF₃ + H₂O → (CH₃)₃SiOH + HO₃SCF₃

It is far more electrophilic than trimethylsilyl chloride.

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

(CH₃)₃SiO₃SCF₃ + ROH + Et₃N → ROSi(CH₃)₃Si + [Et₃NH]O₃SCF₃

A common use of (CH₃)₃SiO₃SCF₃ 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.

References

1. Joseph Sweeney; Gemma Perkins; Enrique Aguilar; Manuel A. Fernández-Rodríguez; Rodolfo Marquez; Eric Amigues; Ricardo Lopez-Gonzalez (2018). "Trimethylsilyl Trifluoromethanesulfonate". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rt338. ISBN   978-0-471-93623-7.
2. Boeckman, Robert; Tusch, Douglas J.; Biegasiewicz, Kyle F. (2015). "(S)-1,1-Diphenylprolinol Trimethylsilyl Ether". Organic Syntheses. 92: 309–319. doi: 10.15227/orgsyn.092.0309 .
3. Umemoto, Teruo; Tomita, Kyoichi; Kawada, Kosuke (1990). "N-Fluoropyridinium Triflate: An Electrophilic Fluorinating Agent". Organic Syntheses. 69: 129. doi:10.15227/orgsyn.069.0129.
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, doi : 10.1055/s-2004-822905
5. Love, Kerry R.; Seeberger, Peter H. (2005). "Synthesis and Use of Glycosyl Phosphates as Glycosyl Donors". Organic Syntheses. 81: 225. doi: 10.15227/orgsyn.081.0225 .
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. 10 (10): 5454–5461. doi:10.1021/acscatal.0c01414. ISSN   2155-5435. S2CID   219017552.
7. Kuehne, Martin E.; Xu, Feng (1 December 1998). "Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 10. An Enantioselective Synthesis of (−)-Strychnine through the Wieland−Gumlich Aldehyde". The Journal of Organic Chemistry. 63 (25): 9427–9433. doi:10.1021/jo9813989.
8. Doi, Takayuki; Numajiri, Yoshitaka; Munakata, Asami; Takahashi, Takashi (1 February 2006). "Total Synthesis of Apratoxin A". Organic Letters. 8 (3): 531–534. doi:10.1021/ol052907d. PMID   16435877.