Trifluoromethyl trimethylsilane

Trimethylsilyl trifluoromethane (trifluoromethyl trimethylsilane) [81290-20-2] M 142.2, b 54-55°, 55-55.5°, d 0.962, n 1.332. Purified by distilling from trap to trap in a vacuum of 20mm using a bath at 45° and Dry ice-Me2CO bath for the trap. The liquid in the trap is then washed with ice cold H2O (3x), the top layer is collected, dried (Na2S04), the liquid was decanted and fractionated through a helices packed column at atmospheric pressure. H, C, F, and Si NMR can be used for assessing the purity of fractions. [Tetrahedron Lett 25 2195 1984 J Org Chem 56 984 1991.]... 

Nucleophilic Perfluoroalkylation of Nitrones The reaction of a,N-diaryl nitrones with (trifluoromethyl)trimethylsilane (TMSCF3) gives O-trimethylsilyl ethers of a-(trifluoromethyl)-hydroxylamines. This reaction is initiated by potassium ten -butoxide. Removal of the trimethylsilyl group on acid treatment leads to a-(trifluoromethyl)hydroxylamines, whereas catalytic hydrogenation gives a-(trifluoromethyl)amines (Scheme 2.194). 

The enantioselective addition of a nucleophile to a carbonyl group is one of the most versatile methods for C C bond formation, and this reaction is discussed in Chapter 2. Trifluoromethylation of aldehyde or achiral ketone via addition of fluorinated reagents is another means of access to fluorinated compounds. Trifluoromethyl trimethylsilane [(CF SiCFs] has been used by Pra-kash et al.87 as an efficient reagent for the trifluoromethylation of carbonyl compounds. Reaction of aldehydes or ketones with trifluoromethyltrime-thylsilane can be facilitated by tetrabutyl ammonium fluoride (TBAF). In 1994, Iseki et al.88 found that chiral quaternary ammonium fluoride 117a or 117b facilitated the above reaction in an asymmetric manner (Scheme 8-42). 

The proton NMR of the distillate shows the two methyl group absorptions of (trifluoromethyl)trimethylsilane and chlorotrimethylsilane in a ratio of about 85 15. The material solidifies in a dry ice-acetone cooled trap. 

Trifluoromethyl)trimethylsilane has been prepared by a modification5 of the procedure originally published by Ruppert.4 The optimized yield is 75%. Other less convenient methods are also available for its preparation. (Trifluoromethyl)trimethylsilane acts as an in situ trifluoromethide equivalent under nucleophilic initiation and reacts with a variety of electrophilic functional groups. Carbonyl compounds such as aldehydes, ketones and lactones react rather readily5 7 with (trifluoromethyl)trimethylsilane under fluoride initiation. The reagent also reacts with oxalic esters,8 sulfonyl fluorides,9 a-keto esters,10 fluorinated ketones,11 and... 

Trifluoromethyl)trimethylsilane Silane, trimethyl(trifluoromethyl)- (11) (81290-20-2) Chlorotrimethylsilane Silane, chlorotrimethyl- (8,9) (75-77-4)... 

The boiling point for (trifluoromethyl)trimethylsilane is reported as 45°C.4 The submitters report a boiling point of 55.5°C. 

The nucleophilic addition of a trifluoromethyl anion or its equivalent to an activated carboxylic acid derivative is another potential method for the synthesis of trifluoromethyl ketones (Scheme 8). Due to the well-known instability of the trifluoromethyl anion, the organometallic approach (Section 15.1.4.3.3) is often difficult to utilize. However, a trifluoromethyl anion equivalent, (trifluoromethyl)trimethylsilane (CF3TMS), was developed in 1984 by Ruppert and co-workers.[30] This reagent, known as Ruppert s reagent, is stable and does not undergo fluoride elimination like other equivalent trifluoromethyl anions. An obvious limitation to this method is that it is only useful for the synthesis of a-amino trifluoromethyl ketones unless other fluoroalkyl analogues of Ruppert s reagent are developed. 

Scheme 8 Synthesis of Trifluoromethyl Ketones by Reaction of (Trifluoromethyl)trimethylsilane with Amino Acid Oxazolidin-5-ones[301...

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Trifluoromethyl)trimethylsilane is a highly useful trifluoromethylating reagent. Efficient electrochemical trimethylsilylation of bromotrifluoromethane has been developed (equation 84)108. 

Trifluoromethyl)tributyl tin, prepared from (trifluoromethyl)trimethylsilane and bis(tributyltin) oxide, has been reported81 to react with disilyl sulphides to give the corresponding (trifluoromethyl)di- and (trifluoromethyl)trialkylsilanes. 

The interaction between (trifluoromethyl)trimethylsilane and TV-(phenyl)-benzimidoyl chloride (or fluoride) in the presence of a source of the fluoride ion gives 7V-(phenyl)iminotrifluoroacetophenone 23 along with 2,4-di(trifuoromethyl)-2,4-diphenyl-1,3-diazetidine 24 (94UP1). 

Portella, C., Brigaud, T., Lefebvre, O., Plantier-Royon, R. Convergent synthesis of fluoro and gem-difluoro compounds using (trifluoromethyl)trimethylsilane. J. Fluorine Chem. 2000,101, 193-198. 

The hemiketal 12 was easily prepared in high yield (80%) from artemisinin by treatment with trifluoromethyl trimethylsilane (TMSCF3) in the presence of tetrabutylammonium fluoride trihydrate (TBAF, 3H20). Complete desilylation occurred after addition of water (see Scheme 6.5). The reaction was stereoselective, and the a configuration of the CF3 group was unambiguously determined (P-12) [40,44], However, this configuration at C-10 is not the result of an a approach of the CF3 but of a thermodynamic equilibrium of the... 

Trifluoromethylation (perfluoroalkylation) by reaction of carbonyl compounds with (trifluoromethyl)trimethylsilane or (perfluoroalkyl)trimethylsilane. 

Organic fluorine compounds and methods for their preparation are the central topic of the next four procedures. Much of the synthetic versatility of methyl phenyl sulfone is embodied in FLUOROMETHYL PHENYL SULFONE and the fluoro Pummerer reaction of methyl phenyl sulfoxide with DAST is a key step in its preparation. The utility of this fluoromethyl sulfone in the preparation of fluoroalkenes Is demonstrated in a companion procedure for Z-[2-(FLUOROMETHYLENE) CYCLOHEXYL]BENZENE, a procedure with several prominent stereoselective features. Geminal difluoroalkenes are featured in the following procedure. (3,3 DIFLUOROALLYL)TRIMETHYLSILANE is prepared by a method in which the radical addition of dibromodifluoromethane to alkenes and the selective reduction of a-bromoalkylsilanes are key steps. A procedure for nucleophilic introduction of the trifluoromethyl group completes this set. The key reagent, (TRIFLUOROMETHYL)-TRIMETHYLSILANE is obtained by reductive coupling of TMS chloride and bromotrifluoromethane. Liberation of a CF3- equivalent with fluoride ion in the presence of cyclohexanone affords 1-TRIFLUOROMETHYL-1-CYCLOHEXANOL. 

Nucleophilic trifluoromethylation reactions of organic compounds (in particular, heterocycles) with (trifluoromethyl)trimethylsilane 00T7613. 

Perfluorocarbonyl compounds, obtained by the interaction of (trifluoromethyl)-trimethylsilane with diacetyl fluorides FC(0)(CF2) C(0)F (n = 2, 3) in the presence of KF, exhibit high reactivity with nucleophiles, for example, with water, giving cyclic diols 33 due to intramolecular cyclization (93IC5079) (Scheme 33). 

The synthesis of fluoroalkyl-substituted heterocycles is a subject of continuous interest this challenging issue has been presented in details in reviews [107,108]. It has been shown that trifluoromethyl carbanion, generated from (trifluoromethyl) trimethylsilane (the Ruppert reagent), adds easily to 2-chloro-3-nitropyridine. The produced o adducts can be oxidized with dimethyldioxirane (DMD) to form two isomeric 2-chloro-4-(and 6-)trifluoromethyl-3-hydroxypyridines (Scheme 30) [109]. 

---