Trifluoromethyl lithium

Trifluoromethyl-lithium, prepared by metal/halogen exchange, is unstable its decomposition probably involves generation of difluorocarbene, which dimerises [54] (Figure 6.38). 

Higher homologues of perfluoroalkyl lithium compounds are usually generated at very low temperatures (—78 °C or below) in situ and directly reacted with a suitable electrophile, often a carbonyl compound, for example an aldehyde, ketone [45], or ester [46] (Scheme 2.117). If this carbonyl compound is chiral, reasonable diastereo-meric excesses can be obtained [47]. The corresponding trifluoromethyl lithium (CFjLi) is still unknown, because of its immediate a-elimination with difluorocar-... 

Trifluoromethyl thiirane is formed by the action of tris(diethylamino)-phosphineon l-chloromethyl-2,2,2-trifluoroethyldisulfide [S2] (equation 73) Difluoromethyl phenyl selenide is prepared by treatment of lithium phenyl-selemde with chlorodifluoroniethane via a carbene mechanism [Si] (equation 44) Bis(2,2,2-trifluoroethyl)diselenide is formed in the reaction of 2,2,2-trifluoroethyl mesylate with lithium diselenide [84] (equation 74). 

Lithium silylamides react smoothly with tiifluoronitrosomethane to give diazenes Traces ot water initiate the decomposition of the latter with liberation of a trifluoromethyl carbanion, which is trapped by carbonyl compounds [775] (equation 116) Desilylation of trialkyl(trifluoromethyl)silanes by fluoride ion produces also a trifluoromethyl carbanion, which adds to carbonyl carbon atoms [136, 137] (equations 117 and 118)... 

This complex is not the actual catalyst for the hydrovinylation, but needs to be activated in the presence of a suitable co-catalyst. The role of this additive is to abstract the chloride ion from the nickel centre to generate a cationic allyl complex that further converts to the catalytically active nickel hydride species. In conventional solvents this is typically achieved using strong Lewis acids such as Et2AlCl. Alternatively, sodium or lithium salts of non-coordinating anions such as tetrakis-[3,5-bis(trifluoromethyl)phenyl]borate (BARF) can be used to activate hydrovinylation... 

The procedure illustrates a fairly general method for the preparation of -substituted perfiuoroolefins. The method has been applied to the synthesis of 2-cyclohexyl- (70%), 2-benzyl- (61%), and 2-(/>-fluorophenyl)perfluoropropenes (67%), and it is probably applicable to any a-trifluoromethyl ketone. Olefins containing a perfluoroalkyl group other than trifluoromethyl can be prepared by the same procedure by the substitution of lithium chlorodifluoroacetate for sodium chlorodifluoroacetate.7 Other routes to / -substituted perfiuoroolefins are not general or convenient. Routes to perfiuoroolefins generally yield the a-substi-tuted olefin rather than the /3-substituted olefin. 

Silyl enol ethers have also been used as a trap for electrophilic radicals derived from a-haloesters [36] or perfluoroalkyl iodides [32]. They afford the a-alkylated ketones after acidic treatment of the intermediate silyl enol ethers (Scheme 19, Eq. 19a). Similarly, silyl ketene acetals are converted into o -pcriluoroalkyl esters upon treatment with per fluoro alkyl iodides [32, 47]. The Et3B/02-mediated diastereoselective trifluoromethylation [48,49] (Eq. 19b) and (ethoxycarbonyl)difluoromethylation [50,51] of lithium eno-lates derived from N-acyloxazolidinones have also been achieved. More recently, Mikami [52] succeeded in the trifluoromethylation of ketone enolates... 

It is interesting to note that asymmetric induction was also observed (308) during generation of ylide 288 from achiral sulfonium salt 287a by means of chiral lithium 2,2,2-trifluoromethyl-a-phenylethoxide. The [2,3]sigmatropic rearrangement of the chiral ylide 288 obtained in situ in this way leads to optically active sulfide 289 of 5% optical purity. 

Lithium phenylacetylide was trifluoromethylated with the less powerful Se-triflate 26 in high yield (Eq. 20). 

The carbonyl of trifluoroacetates is reactive enough to react with phosphoranes and to yield trifluoromethyl enol ethers (the reaction must be conducted without lithium salts i.e., the phosphorane must be generated without a nonlithiated base). In the same way, trifluoroacetamides and trifluorothioacetates afford, respectively, trifluoromethyl enamines and vinyl thioethers (Figure 2.44). " ... 

Chiral derivatives of hemiacetal from fluoral have been prepared by adding an alcohol to fluoral in the presence of (l )-BlNOL— Ti(0—iPr)2 or by HPLC resolution of the racemate. The displacement of the sulfonate moiety from the tosyl derivative, by an alkyl lithium aluminate, affords the trifluoromethyl ether with inversion of configuration and an excellent chirality transfer (Figure 2.49). ° ... 

Reaction of 3-trifluoromethyl-substituted 1,2-oxazine 5 with lithium diisopropylamide (LDA) resulted in smooth deprotonation at C-4 and allowed subsequent alkylation with various electrophiles. Reaction of 5 with Mel furnished the 4-methyl-l,2-oxazine 54 in good yield and with excellent r-diastereoselectivity, whereas carbonyl compounds could not be employed successfully as electrophiles <1996JFC( 80)21 1 reatment of 3,4,6-trisubstituted l,2"Oxazine... 

Metalation of only the bromine of 2-bromo-3,5-dichloro-6-(trifluoromethyl)-4-trimeth-ylsilylbenzoic acid proceeded smoothly with lithium tributylmagnesate (equation 34). ... 

Only a few reports have appeared of reactions of substituted 1,8-phenanthrolines. From spectroscopic evidence it has been established that 4-hydroxy-2-trifluoromethyl-l,8-phenanthroline exists as the 4-oxo tautomer.38 It is converted with phosphorus bromides into 4-bromo-2-trifluoromethyl-l,8-phenanthroline. The bromo group has been replaced by lithium with w-butyl lithium and the lithio derivative converted into 4-carboxy-2-trifluoromethyl-l,8-phenanthroline with carbon dioxide.215... 

The bromine group in 4-bromo-5-methoxy-2-trifluoromethyl-l,10-phenanthroline has been replaced by lithium with w-butyllithium and the lithio derivative reacted with pyridine 2-aldehyde.215... 

Schlosser and co-workers have reported the shift of lithium in lithiated l-bromo-3-(tri-fluoromethyl)benzene 2,fa Quenching at — 100 C gives exclusively the product derived from 2, whereas after 2 hours at — 75 C, arene 2 is completely converted into less basic 3. A lithium-iodine exchange takes place in lithiated 2-chloro-3-iodo-6-(trifluoromethyl)pyridine 4, which at —85 C is totally converted into the less basic isomer 5.7 These rearrangements have been discussed in terms of a base-catalyzed halogen dance or halogen-shuffling mechanism. 

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