Alkyllithium compounds lithiation

Another possibility of transforming indirectly alcohols into alkyllithium compounds consists in nsing the corresponding sulfates. Alkyl sulfates 60 were lithiated using naphthalene (4%) as the electron carrier catalyst in THF at —78 °C yielding two equivalents of the corresponding alkyllithinm 61. Further addition of an electrophile at —78 to 0°C led to the formation, after hydrolysis, of the final prodncts 20 (Scheme 22) ... 

In contrast to the 5-endo-trig anionic cyclization reactions, rarely observed, there are several examples in which 5-endo-dig processes are involved. Hence 2,3-disubstituted benzofurans, benzothiophenes and indoles 374 have been synthesized starting from triflu-oroethyl ethers, thioethers and anilines 373, respectively, and alkyllithium compounds. A 5-endo-dig carbolithiation reaction on 375, generated by two successive eliminations, one substitution and one ortho-lithiation reactions, is proposed to account for the formation of the corresponding 2-lithiated heterocycles. Further reaction of these intermediates with electrophiles affords compounds 374 (Scheme 98)159. In the case of thioether 373 (X = S) a bromine substituent must be present at the ortho position. 

In the reaction of 1,3-pentadiyne with an alkyllithium reagent, lithiation occurs across only one of the triple bonds. However, when this reaction is conducted in the presence of TMEDA a tetralithiated species forms (d). The presence of the TMEDA acts to catalyze the C-Li bond formation. Organic compounds that ordinarily do not undergo polymetallation with n-BuLi may do so in the presence of TMEDA. This has been demonstrated, for example, with toluene . 

Simple, unfunctionalized organolithium compounds are usually prepared by reductive lithiation of alkyl halides with lithium metal at ambient temperature or above [26]. Reductive lithiation is fastest for alkyllithium compounds (the more substituted the better) and slowest for aryllithium compounds. The order of reactivity follows logically from the relative stabilities of the intermediate radicals, whose formation is the rate-determining step of the sequence. 

This test showed that a-amino- [7] and a-oxy- [8] alkyllithium compounds except for their benzyl- or allyllithium compounds are configurationally highly stable, and a-thio-[9], a-selenoalkyllithium compounds [10], and lithiated phosphine oxides [11] are labile. Thus, this test proves that lithium carbanions are either configurationally stable or labile and affords reliable evidence to de-... 

Lithiation ortho to functional groups of arenes followed by trapping with electrophiles is an appealing synthetic methodology. The directed ortho metalation (DoM) is the reaction of an alkyllithium compound with an arene bearing a direct metalation group (DMG) that leads to an ori/jo-lithiated intermediate. The abiHty of DMGs to effect the ortho metalation process... 

Bromo- and iodo-heterocycles react rapidly with alkyllithiums, even at temperatnres as low as -100 °C, to give the lithio-heterocycle. Exchange of flnorine is unknown and of chlorine, rare, but is known under special circnmstances, snch as in polychloro compounds. The apparent preparation of a number of lithio-heterocycles by direct reaction of a chloro heterocycle using lithium metal with naphthalene has been reported. Since snch lithiations have to be carried out in the presence of the electrophile, it may be that the process is more complex than it seems. ... 

In 1971 the second perlithio compound, C5Li4, was obtained by lithiation of 1,3-pentadiyne (7, 8). When the latter is treated with alkyl-lithium compounds in the absence of TMEDA, addition of alkyllithium reagents to one of the triple bonds is the main reaction, and no highly metalated products form. However with TMEDA, polylithiation takes... 

One of the earliest descriptions of an asymmetric lithiating reagent was reported by Nozaki and co-workers in 1968 (35). (—)-Sparteine was used to coordinate n-butyllithium, and this complex stereoselectively added to several carbonyl compounds (Reaction 32). Moreover, the Skattebol-Moore method (which consists of dehalogenating gem-dihalo-cyclopropanes with an alkyllithium complex) by Nozaki to synthesize allenes gave optically active products when the n-butyllithium/ ( —)-sparteine complex was used (36). 

Pyrazinyl ketones have been prepared by treatment of pyrazinecarboxylic esters with an organo-metallic (alkyllithium or Grignard) reagent <84MI 603-01 >. Homolytic acylation of pyrazines and quinoxalines with a-keto acids is an important method for preparation of the acyl compounds (Section 6.03.5.6.1), but the procedure for monosubstitution needs care because the electron-withdrawing effect of the first-formed monoacyl compounds facilitates further substitution. An additional synthesis of pyrazinyl ketones is the lithiation of halogenopyrazines followed by treatment with carboxylic esters or carboxamides (Equation (8) and Scheme 24). Reaction of 2-chloropyrazine... 

To obtain catalytically active compounds, a phosphine or a sulfide substituent has to be introduced in the position adjacent to the amine in the cyclopentadienyl ring. This is achieved by a metalation/substitution sequence. The metalation with alkyllithium reagents is a highly diastereoselective process which produces the diastereomers in a ratio of 96 421 22. Thus, from the (R)-amine, the (/ ,p/ )-lithioamine is obtained in high yield. As an alternative to the lithiation procedure, mercuration and cyclopalladation have been used for the preparation of phosphine derivatives32, however, this is a less convenient and less selective approach. 

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