Trifluoromethyltrimethylsilane

History

The compound was first prepared in 1984 by Ingo Ruppert 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. In the same year, Stahly described similar reactions for the synthesis of trifluoromethylated phenols and anilines. Since then TMSCF3 has been widely used as a nucleophilic trifluoromethylating agent. Potassium (trifluoromethyl)trimethoxyborate for this purpose has been synthesised from B(OMe)3, CF3SiMe3 and KF. Aryl functionalization by C-H activation has also been reported.

Preparation

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

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. 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.

References

References

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5. (June 1989). "A new method for synthesis of trifluoromethyl-substituted phenols and anilines". The Journal of Organic Chemistry.
6. G. K. Surya Prakash; Andrei K. Yudin. (1997). "Perfluoroalkylation with Organosilicon Reagents". Chemical Reviews.
7. Xiao Liu, Cong Xu, Mang Wang, and Qun Liu. (2015). "Trifluoromethyltrimethylsilane: Nucleophilic Trifluoromethylation and Beyond". Chemical Reviews.
8. (2009). "Aromatic trifluoromethylation catalytic in copper". Chemical Communications.
9. (2011). "Copper-Catalyzed Trifluoromethylation of Aryl Iodides with Potassium (Trifluoromethyl)trimethoxyborate". Chemistry: A European Journal.
10. (2011). "Silver-Mediated Trifluoromethylation of Arenes Using TMSCF3". Organic Letters.
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13. (2009). "Trifluoromethyltrimethylsilane". Encyclopedia of Reagents for Organic Synthesis.
14. (2018). "Anion-Initiated Trifluoromethylation by TMSCF₃: Deconvolution of the Siliconate–Carbanion Dichotomy by Stopped-Flow NMR/IR". Journal of the American Chemical Society.