Enolate carbanion trapping

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

The carbanion generated by ot-proton abstraction of a 2-alkyloxazoline is capable of typical enolate chemistry. Thus, the carbanion was found to react with nitriles to give an enamine, with formate esters to give an aldehyde that can be trapped,with chiral sulfinate esters to give chiral sulfoxides,and with alkylating agents. A carbamate-protected aminomethyl chiral oxazoline was deprotonated and alkylated with diastereoselectivities up to 92% de. ... 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

Simpkins and coworkers reported the use of chiral bases in the enantioselective generation of bridgehead enolates (Scheme 36)76. Initial studies revealed that external quench protocols were ineffective in trapping the carbanion. Addition of a mixture containing chiral base (R,R) 3 and LiCl to a solution of ketone 55 and TMSC1 at —105 °C gave mono (—)-a-silylated ketone 56 in 76% yield and >96% ee. 

The radical generated by the reduction of an N-acyliminium ion pool can be trapped with an electron-deficient olefin, such as acrylate ester, which is known to be a good radical acceptor (Scheme 5.29). In the presence of a large excess amount of proton, a 1 1 adduct is obtained in good yield. A mechanism involving radical addition to the electron-deficient olefin followed by one-electron reduction to give the carbanion or enolate anion that is trapped by a proton has been suggested. 

The intermediate carbanion or ketone enol can be trapped by carrying out the decarboxylation in the presence of bromine or iodine,28 which leads to the formation of the bromo or iodo ketone the rate of this reaction is unaffected by the concentration of oxo acid, whence it follows that the halogenation does not precede the decarboxylation also halogenation is not subsequent to formation of the ketone, since the ketone is not halogenated under the conditions used for the decarboxylation. If then halogenation follows decarboxylation and precedes ketone formation, the only possibility is reaction of the short-lived intermediate carbanion or enol. 

Scheldt and coworkers reported the addition of amide enolates to acylsilanes for generation of p-silylojq homoenolate equivalents 62, based on the fact that less electrophilic p-carbonyl groups disfavor the formation of cyclopropanolates 63 by internal carbanion attack (Scheme 6.30). Instead, the carbanion generated in situ can be trapped by allq l halides, aldehydes, ketones, and imines. The use of optically active amide enolates delivers p-hydroxy amides with high levels of diastereoselectivity. 

Following the VNS mechanism, the first step of the reaction is the nucleophilic addition of the enolate of ethyl 2-cloropropionate to the nitrobenzene ring (the ester forms the enolate in the reaction medium in the presence of NaH). As stated above, the ortho/para selectivity in VNS reactions is controlled by steric factors. Hence, a tertiary carbanion like 8 would attack exclusively in the para-position leading to o-adduct 9. The next step will be the base-induced elimination of HCl in 9 to yield anion intermediate 10, which is trapped by the electrophile (benzyl bromide) giving the reaction product 11 (Scheme 36.6). 

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