Trifluoromethyl anion

A trifluoromethyl anion is also difficult to generate because it easily lose a fluoride ion to form difluoro carbene. Shono and Kashimura et al have similarly achieved the generation of such a species from trifiuoromethane using the electrogenerated a-pyrrolidone anion. The efficient trifluoromethylation of aldehydes and ketones in the presence of hexamethyldisilazane (HMDS) can thus be obtained (Scheme 4.3) [32]. 

Trifluoromethyl thioethers are produced in a fluoride-catalysed one-pot reaction of alkyl or aryl thiocyanates with trifluoromethyl silanes [37]. The reaction is initiated by fluoride ion displacement of the trifluoromethyl anion from the silane the thioether is formed from the thiocyanate by displacement by the trifluoromethyl anion of the cyanide ion, which then perpetuates the reaction. Trifluoromethyl selenoethers are obtained by an analogous route. In a similar manner, disulphides can be converted into trifluoromethyl thio- or selenoethers [38],... 

Due to the poor efficiency of trifluoromethylated organometaUic derivatives as trifluoromethylating reagents, nucleophilic trifluoromethylation has remained unattractive for a long time. Indeed, in the absence of stabilization, the trifluoromethyl anion is very unstable and is quickly transformed into difluorocarbene (cf. Chapter 1). When the carbon-metal bond is relatively covalent, the organometaUic species becomes more stable but it is then less reactive toward an electrophile. On the synthetic level, only zinc and copper derivatives have found real applications in... 

The furo[3,4-ri]oxazoie 54, constracted by cyclisation of a rhodium carbenoid, is a useful compound for the production of unusual benzoxazoles for example, cycloaddition of Al-phenylmaleimide gave the benzoxazole 55 <98JOC7680>. Simpler benzoxazole syntheses include the base catalysed cyclizsation (with loss of the trifluoromethyl anion) of the imines 56 <99TL4119> and the acid catalysed cyclisation of diacylated aminophenols 57 <99H(51)979>. ... 

Recently, Olah and co-workers reported a new route to tributyl(trifluoro-methyl)tin via in situ formation and capture of the trifluoromethyl anion by trialkyltin oxide [106]. Reaction of trimethyl(trifluoromethyl)silane with tribu-tyltin oxide in the presence of catalytic TBAF in THF afforded the corresponding tributyl(trifluoromethyl)tin in good yield (Scheme 38). This reaction system was first reported by Warner and Buchwald [107]. 

All of the C = C bond migrations discussed above involve the shift of an atom, usually fluorine. In one case, a perfluoroalkyl group shift has been observed. Chambers and co-workers reported that perfluoro(4,4-dimethylpent-2-ene) (16) isomerizes almost quantitatively to alkcnc 17 when heated with cesium fluoride in sulfolane at 150— 160 C for 5 hours.36 Based on trapping experiments, the authors concluded that the reaction involves an intcrmolccular transfer of a trifluoromethyl anion. 

The reaction of peptide aldehydes with ICF Zn has the obvious advantage that it allows the stereoselective synthesis of trifluoromethyl ketones since it avoids the use of an achiral carbanion in the carbon bond forming step, a requirement for the previously discussed synthetic procedures. In this method, a trifluoromethyl anion equivalent is reacted with a peptide aldehyde, which already contains the chiral a-carbon (Scheme 7). Provided the... 

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. 

Fluoride ion-catalysed addition of trifluoromethyltrimethylsilane to acyl silanes occurs to give l,l-difluoro-2-trimethylsilyloxyalkenes (silyl enol ethers of difluoromethyl ketones), through nucleophilic addition of trifluoromethyl anion, Brook rearrangement and loss of fluoride. These compounds could be isolated when tetrabutylammonium difluorotriphenylstannate was used as a catalyst use of tetrabutylammonium fluoride gave the product corresponding to subsequent aldol reaction with the difluoromethyl ketone (Scheme 78)m. 

Intermolecular transfer of trifluoromethyl has been demonstrated in the fluoride ion induced rearrangement of the perfluorinated alkene (77) to the isomer (78). Again, the driving force in this process is to produce an isomer (78) with fewer vinylic fluorine sites than in the starting isomer (77). The intermediate trifluoromethyl anion has been trapped with perfluoropyrimidine (79)... 

The trifluoromethyl anion itself, which has no covalent character, has been shown to have the most deshielded fluorines of any group in the scheme. 

Trimethyl(trifluoromcthyl)siIanc is easily fluorodesilylated by tris(dimethyIamino)suIfonium difluorotrimethylsilicate [TASF(Me)], tetrabutylammonium fluoride, or tris(diethylamino) (methylamino)phosphonium hydrogen difluoride and, if arenesiilfonyl fluorides are used to trap the trifluoromethyl anion, trifluoromethyl sulfones are formed in high yield. Trisfdiethyl-amino)(methylamino)phosphonium phenolate is also an effective catalyst for this reaction, but TASF(Me) is favored as it can achieve the quantitative transformation of ArSOjF into aryl trifluoromethyl sulfones. ... 

Phosphane 9 is a useful intermediate which can be converted easily into trifluoromethyl anion equivalents, e. g. trimclhyl(trifluoromethyl)silane. Similarly, 1,2-bis(dichlorophosphi-iio)cthanc (10) and bromotrifluoromclhane react in the presence of 8 to form l,2-bis[bis(tri-fluoromethyl)phosphino]ethane (11). ... 

Among the simple transient species of carbon and fluorine are included trifluoromethyl cation, CF3+, which has a very transient existence trifluoromethyl anion, CF3, which is stable at low temperature and can be generated from CF3TMS (trimethylsilyltrifluoromethane) CF3-, a free radical available from irradiation of CF3I and difluorocarbene, CF2 , which exists as a ground-state singlet. 

In the presence of fluoride ion trimethyl(trifluoromethyl) silane works as an effective trifluoromethyl anion equivalent [570]. According to a recent report a catalytic amount of N-benzylcinchonium fluoride, a chiral source of fluoride ion, enables asymmetric trifluoroniethylation of aldehydes (up to 51% ee) [571]. 

Bu3Bi mediates the allylation of carbonyl compounds with allyl bromide to give a mixture of homoallyl alcohols and fheir allyl ethers (Scheme 14.133) [278], Tris(4-methoxyphenyl)bismuthane catalyzes the cyanation of carbonyl compounds with MesSiCN [175], In the presence of fluoride ions (CeFsjsBi undergoes nucleophilic substitution with an activated C-F bond of perfluorinated compounds to transfer three CgFj groups [279]. (CFsjsBi can also act as a trifluoromethyl anion equivalent [280]. 

The trifluoromethyl anion, generated in situ from (trimethylsilyl)trifluoromethane and catalytic quantities of dry KF, reacts with (toxic) dibutyl fluorophosphate to give dibutyl trifluoromethylphos-phonate in 93% yield.°°°... 

Scheme 2.109 Principal methods for generation of fluorinated carbanions and perfluoroalkyl metal compounds (Rp = (per)fluoroalkyl, Arp = (per)fluoroaryl, M = metal, X = halogen, B = base, S = solvent). The particularly unstable trifluoromethyl anion can be stabilized by formation of an adduct with a suitable solvent, for example DMF, which itself acts as a CFj"" source in a haloform-like reaction (bottom).

Probably the most efficient way to generate CFf from the view point of atom economy is deprotonation of inexpensive CHFj with a strong base [59]. Unfortunately, this route poses two problems. First, the low boiling point of fluoroform (—82.2 °C) creates - at least on the laboratory scale - the practical problem of handling a gas. The second problem is the need to trap and stabilize the trifluoromethyl anion immediately after its generation, to suppress fragmentation. This second complication, in particular, impeded the apparently straightforward preparative... 

Finally, the trifluoromethyl anion decomposes on warming to give fluoride ion and difluorocarbene if it is not captured by a suitable electrophile. 

Trifluoromethylation. Nascent trifluoromethyl anions are generated when CFjSiMej is in contact with a fluoride ion. Nucleophilic trifluoromethylation of oxazolidinones is for the synthesis of protected a-amino trifluoromethyl ketones. ... 

TBAF-assisted Trifluoromethylation, Perfluoroalkylation, and Polyfluoroalkoxylation. TBAF combines with TMSCF3 to form nucleophilic trifluoromethyl anion equivalents. The precise structure of this nucleophile is unknown, although it is likely that a pentacoordinate silicon intermediate is involved. The TBAF/TMSCF3 combination leads to smooth trifluoromethylation of aldehydes,ketones, esters, imines, nitroso compounds, a-ketoesters, Q -ketoamides (eq and... 

Trimethyl(trifluoromethyl)silane (Me3SiCF3), commonly referred to as the Ruppert-Prakash reagent, serves as a trifluoromethyl anion equivalent, which is remarkable because of the instability of the anion with respect to decomposition to difluorocar-bene and fluoride ... 

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