Ruppert reagent

Example 51 Michalski and associates have found that P hp compounds react with Ruppert reagent (MesSiCFs) at 20 °C in THF in an almost quantitative yield [84]. This efficient reaction was applied to synthesize trifluo-romethylphosphonate analogues of dinucleosides. 

Figure 2.31 Nucleophilic trifluoromethylation with Ruppert reagent.

It has recently been shown that when the tetrahedral intermediate of the reaction is cyclic, it is a better donor of nucleophilic CF3. These cyclic intermediates can be generated intramolecularly from trifluoroacetamides or trifluorosulfmamides derived from (9-silylated ephedrine. These reagents are able to trifluoromethylate aldehydes and ketones, even in the case of enolizable substrates, as a strong base is not required (Figure 2.34). However, while the source of CF3 is chiral, there is no chirality transfer to the addition product, and the replacement of ephedrine by other chiral amino alcohols did not show any improvement. " Similar to asymmetric trifluoromethylation with the Ruppert reagent, only the use of a fluoride salt of cinchonine can increase the enantioselectivity. " " ... 

Trifluoromethyl phenylsulfone is accessible from fluoroform and diphenyldisul-fide, and it has been proposed as a donor of CF3. However, the reaction must be performed in basic medium (f-BuOK) and is then limited to nonenolizable aldehydes and ketones. But it can also be used as a precursor of the Ruppert reagent. This latter... 

The oldest methods for synthesis involve the condensation-cyclization of trifluor-omethyl or fluoroalkyl pyrroles in the presence of a metal salt. These reactions afford tetrakis(fluoroalkyl) porphyrins. The electrophilic trifluoromethylation of porphyrins is selective and leads to /I-CF3 and meso-CVT, porphyrins. While condensation of meio-trifluoromethyl-dipyrromethane with an aldehyde in acidic medium is rather difficult, it proceeds with better yields and permits a selective introduction of trifluoromethyl groups in meso The Ruppert reagent (CF3TMS) has been used to... 

Ruppert reagent (CF3TMS), by radical trifluoromethylation, and finally by total synthesis starting from alicyclic precursors. 

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]. 

Ruppert reagent (CFsSiMes) Carbonyl compounds (nucleophilic) Aromatics Safe and easy to handle Silicon-containing waste generated Expensive... 

Convenient reagents for incorporation of perfluoroalkyl groups in a molecule of pyridine are 1,10-phenanthroline-ligated (perfluoroalkyl) copper (I) complexes 274 [166], which were obtained by reaction of copper 1,10-phenanthroline complex with Ruppert reagent and its CaFs-analog. The 1,10-phenanthroline complex (274a) has been used in reaction with 3-iodopyridine (273) for synthesis 3-trifluoromethylpyridine (275) [167, 168] (Scheme 81). 

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