Trifluoromethyltrimethylsilane

Trifluoromethyltrimethylsilane
Names
Preferred IUPAC name
Trimethyl(trifluoromethyl)silane
Other names
Ruppert's reagent; TFMTMS; CF3SiMe3
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.106.346
UNII
  • InChI=1S/C4H9F3Si/c1-8(2,3)4(5,6)7/h1-3H3
    Key: MWKJTNBSKNUMFN-UHFFFAOYSA-N
  • C[Si](C)(C)C(F)(F)F
Properties
C4H9F3Si
Molar mass 142.196 g·mol−1
Appearance Colorless liquid
Density 0.9626 g/cm3 at 20 °C
Boiling point 54 to 55 °C (129 to 131 °F; 327 to 328 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Trifluoromethyltrimethylsilane (known as Ruppert-Prakash reagent, TMSCF3) is an organosilicon compound with the formula CF3Si(CH3)3. It is a colorless liquid. The compound is a reagent used in organic chemistry for the introduction of the trifluoromethyl group.

History

The compound was first prepared in 1984 by Ingo Ruppert[1] It was further developed as a reagent by G. K. Surya Prakash, who reported activation of TMSCF3 by fluoride to perform nucleophilic trifluoromethylation of carbonyl compounds.[2][3][4] In the same year, Stahly described similar reactions for the synthesis of trifluoromethylated phenols and anilines.[5] Since then TMSCF3 has been widely used as a nucleophilic trifluoromethylating agent.[6][7][8] Potassium (trifluoromethyl)trimethoxyborate for this purpose has been synthesised from B(OMe)3, CF3SiMe3 and KF.[9] Aryl functionalization by C-H activation has also been reported.[10][11]

Preparation

The reagent is prepared from trimethylsilyl chloride and bromotrifluoromethane in the presence of a phosphorus(III) reagent that serves as a halogen acceptor.[12]

Mechanism of action

In the presence of a metal salt (M+ X−), the reagent reacts with aldehydes and ketones to give a trimethylsilyl ether, the net product of insertion of the carbonyl into the Si-CF3 bond. Hydrolysis gives trifluoromethyl methanols. The reagent also converts esters to trifluoromethyl ketones. A typical initiator is a soluble fluoride-containing species such as tetrabutylammonium fluoride; however, simple alkoxides such as KOtBu are also effective.[13] The mechanism begins by generation of Si(CH3)3X and a highly reactive [CF3]− (trifluoromethide) intermediate. The [CF3]− attacks the carbonyl to generate an alkoxide anion. The alkoxide is silylated by the reagent to give the overall addition product, plus [CF3]−, thus propagating an anionic chain reaction. The reagent competes with the carbonyl for the reactive intermediate, rapidly sequestering [CF3]− in a reversibly-generated -ate complex [(CF3)2Si(CH3)3]−. This -ate complex is unable to react directly with the carbonyl, resulting in powerful inhibition of the chain reaction by the reagent. This inhibitory process is common to all anion-initiated reactions of the reagent, with the identity of the counter-cation (M+) playing a major role in controlling the overall rate.[14]

Applications

One of the known uses of TMSCF3 is in the synthesis of Alpelisib.[15]

References

  1. ^ Ruppert, Ingo; Schlich, Klaus; Volbach, Wolfgang (1984). "Fluorinated organometallic compounds. 18. First trifluoromethyl-substituted organyl(chloro)silanes". Tetrahedron Letters. 25 (21): 2195–2198. doi:10.1016/S0040-4039(01)80208-2.
  2. ^ Prakash, G. K. Surya; Yudin, Andrei K. (1997-05-01). "Perfluoroalkylation with Organosilicon Reagents". Chemical Reviews. 97 (3): 757–786. doi:10.1021/cr9408991. ISSN 0009-2665. PMID 11848888.
  3. ^ Liu, Xiao; Xu, Cong; Wang, Mang; Liu, Qun (2015-01-28). "Trifluoromethyltrimethylsilane: Nucleophilic Trifluoromethylation and Beyond". Chemical Reviews. 115 (2): 683–730. doi:10.1021/cr400473a. ISSN 0009-2665. PMID 24754488.
  4. ^ Prakash, G. K. Surya; Krishnamurti, Ramesh; Olah, George A. (January 1989). "Synthetic methods and reactions. 141. Fluoride-induced trifluoromethylation of carbonyl compounds with trifluoromethyltrimethylsilane (TMS-CF3). A trifluoromethide equivalent". Journal of the American Chemical Society. 111 (1): 393–395. Bibcode:1989JAChS.111..393P. doi:10.1021/ja00183a073.
  5. ^ Stahly, G. Patrick; Bell, Donald R. (June 1989). "A new method for synthesis of trifluoromethyl-substituted phenols and anilines". The Journal of Organic Chemistry. 54 (12): 2873–2877. doi:10.1021/jo00273a020.
  6. ^ G. K. Surya Prakash; Andrei K. Yudin (1997). "Perfluoroalkylation with Organosilicon Reagents". Chemical Reviews. 97 (3): 757–786. doi:10.1021/cr9408991. PMID 11848888.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Xiao Liu, Cong Xu, Mang Wang, and Qun Liu (2015). "Trifluoromethyltrimethylsilane: Nucleophilic Trifluoromethylation and Beyond". Chemical Reviews. 115 (2): 683–730. doi:10.1021/cr400473a. PMID 24754488.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Oishi, Masahiro; Kondo, Hideaki; Amii, Hideki (2009). "Aromatic trifluoromethylation catalytic in copper". Chemical Communications. 2009 (14): 1909–1911. doi:10.1039/B823249K. PMID 19319442.
  9. ^ Knauber, T.; Arikan, F.; Röschenthaler, G.-V.; Gooßen, L. J. (2011). "Copper-Catalyzed Trifluoromethylation of Aryl Iodides with Potassium (Trifluoromethyl)trimethoxyborate". Chemistry: A European Journal. 17 (9): 2689–2697. Bibcode:2011ChEuJ..17.2689K. doi:10.1002/chem.201002749. PMID 21274956.
  10. ^ Ye, Yingda; Lee, Shin Hee; Sanford, Melanie S. (2011). "Silver-Mediated Trifluoromethylation of Arenes Using TMSCF3". Organic Letters. 13 (20): 5464–5467. doi:10.1021/ol202174a. PMC 3229100. PMID 21932827.
  11. ^ Hafner, A.; Bräse, S. (2012). "Ortho-Trifluoromethylation of Functionalized Aromatic Triazenes". Angewandte Chemie International Edition. 51 (15): 3713–3715. Bibcode:2012ACIE...51.3713H. doi:10.1002/anie.201107414. PMID 22318969.
  12. ^ Pichika Ramaiah; Ramesh Krishnamurti; G. K. Surya Prakash (1995). "1-Trifluoromethyl-1-cyclohexanol". Org. Synth. 72: 232. doi:10.15227/orgsyn.072.0232.
  13. ^ George. A. Olah; G. K. Surya Prakash; Qi Wang; Xing-Ya Li; María Sánchez-Roselló; Carlos del Pozo Losada; José Luis Aceña (2009). Trifluoromethyltrimethylsilane. doi:10.1002/047084289X.rt253.pub2. ISBN 978-0471936237. {{cite book}}: |journal= ignored (help)
  14. ^ Craig P. Johnston; Thomas H. West; Ruth E. Dooley; Marc Reid; Ariana B. Jones; Edward J. King; Andrew G. Leach; Guy C. Lloyd-Jones (2018). "Anion-Initiated Trifluoromethylation by TMSCF3: Deconvolution of the Siliconate–Carbanion Dichotomy by Stopped-Flow NMR/IR". Journal of the American Chemical Society. 140 (35): 11112–11124. Bibcode:2018JAChS.14011112J. doi:10.1021/jacs.8b06777. hdl:10023/16552. PMC 6133236. PMID 30080973.
  15. ^ Flick, A. C., Leverett, C. A., Ding, H. X., McInturff, E., Fink, S. J., Mahapatra, S., Carney, D. W., Lindsey, E. A., DeForest, J. C., France, S. P., Berritt, S., Bigi-Botterill, S. V., Gibson, T. S., Liu, Y., O’Donnell, C. J. (8 April 2021). "Synthetic Approaches to the New Drugs Approved during 2019". Journal of Medicinal Chemistry. 64 (7): 3604–3657. doi:10.1021/acs.jmedchem.1c00208.
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