Reactions trifluoromethyl

Oxazolidin-5-one, bis(trifluoromethyl)-reactions, 6, 213 Oxazolidinones polymers, 1, 281-282 reactions, 6, 213 Oxazolidinones, imino-rearrangement, 5, 775 Oxazolidinones, vinyl-polymers, 1, 281 Oxazolidin-2-ones circular dichroism, 6, 185 H NMR, 6, 181 IR spectroscopy, 6, 183 PE spectroscopy, 6, 183 reactions, 6, 213... 

In most of cases, the fluorine atom(s) or the CF3 group(s) is borne by aromatic rings. Synthesis of these compounds for the optimization of hits as well as for parallel synthesis is done using the numerous fluoro aromatic or heterocyclic compounds that are commercially available. These latter compounds generally come from aromatic fluorination or trifluoromethylation reactions (especially the Balz-Schiemann reaction) and from heterocyclization reactions. However, fluoroaliphatic chains and fluorofunctionalities are more and more present, because of their pharmacological properties. Some examples are given in this section. 

The main challenge in this approach lies in the synthesis of the electrophilic reagent, and indeed in understanding the mechanism, which shows some most unusual characteristics [47], and therefore the operating limits of the trifluoromethylation reaction. Chemistry in this area is developing rapidly and further significant progress may be anticipated. 

Table 7 Summary of the results obtained for the continuous flow trifluoromethylation reactions of carbonyl-containing compounds...

Diazetine, see Diazete, dihydro-Diazirines, calculations, 56, 373 Diazirine, 3-chloro-3-trifluoromethyl-, reaction with pyrrole, 59, 10 3//-Diazirine, 3-fluoro-3-methoxy-, 59, 3 Diazo coupling... 

In 1994, the first enantioselective trifluoromethylation reaction was achieved with the Ruppert-Prakash reagent, TMSCF3, in the presence of the cinchona-based quaternary ammonium fluoride 140 [65]. The chiral induction can arise from the dual activation mode of the catalyst, that is, the fluoride anion acts as the nucleophilic activator of (TMS)CF3 and the chiral ammonium cation activates the carbonyl group of 141. However, the observed ee values of the obtained carbinols 142 do not exceed 51 % and decrease considerably when nonaromatic carbonyl compounds (15% ee for R1 = n-C7H15 R2 = H) are used, which implies that 7t-7t stacking interactions between the carbonyl compound and cinchoninium occur (Scheme 8.54). 

Scheme 3.8 Examples of trifluoromethylation reactions with salt (35)...

Table 8 2 Comparative reactivity of the sulfur reagents (46), (48) and the selenium reagents (47), (49) in the trifluoromethylation reaction of various types of nucleophiles...

Similar trifluoromethylation reactions of anilines, phenols or pyrroles were performed in the presence of sodium dithionite (ref. 27). 

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

Trifluoromethylation. Reaction with enolate anions requires the presence of S-phenylcatecholborane. ... 

Trifluoromethylation reactions of heteroaromatic compounds represent a majority of reported nucleophihc perfluoroalkylations. For example, trifluoromethylation of halogenated quinolines, isoquinolines, or pyridines carried out under pressure using CF3X/CU powder system (X = 1 or Br) in DMF or (Me0)3P=0 solvent affords the corresponding trifluoromethylated heterocycles in 22-60% yield (Fig. 7.21). ... 

However, the selectivity for the trifluoromethylation reactions has been rather low in many cases. For example, anodic trifluoromethylation of olefins provides a mixture of several products in general as shown in Eq. 68 and control of the product selectivities has been... 

Trifluoromethylation reactions of imines, nitrones, hydrazones, iminium ions and azomethine ylides have been reviewed. Activating properties and recent synthetic applications of the arylsulfonyl group,as well as the development of the Ramberg-Backlund reaction over the last 70 years have been highlighted. 

An efficient copper-catalysed allylic trifluoromethylation reaction has been developed. This reaction provides a general and straightforward way to construct allylic trifluoromethylated compounds under mild conditions. The reaction employs cheap copper chloride as the catalyst and a hypervalent iodine(III) reagent as both the oxidant and the CF3 source. 

An efficient method to prepare l /f-spiro-[indoline-3,3 -quinoline]-2, 4 -diones and their trifluoromethylated products was developed hy Wang and co-workers in 2014. The reaction proceeds via a palladium-catalyzed Sono-gashira coupling-Wacker-type ojqqjalladation-cyclization cascade reaction sequence. The amount of water in the reaction system played an important role in the in situ trifluoromethylation reaction, and the trifluoromethylation exhibited excellent molecular self-induced stereoselectivity. 

On the other hand, oxygen- and nitrogen-based nucleophiles mostly need the addition of a Brpnsted or Lewis acid, often in stoichiometric amounts, even though some trifluoromethylation reactions allow the use of catalytic amounts of acid (Scheme 5) [17, 18]. The role of the acid is central and is discussed in more detail in Sect. 5.1. In several cases it has been observed that deprotonation or silylation of the substrate enhances reactivity, in parallel with the activation of the reagent by Brpnsted or Lewis acids. 

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