Alkyllithium reagent

These conditions are so harsh that they are applicable only to indoles with the most inert substituents. Cyclization can be achieved at much lower temperatures by using alkyllithium reagents as the base. For example, treatment of o-methylpivalanilide with 3 eq. of n-butyllithium at 25 C gives 2-terr-butylindole in 87% yield[2]. These conditions can be used to make... 

The rates of the reactions of several aromatic ketones with alkyllithium reagents have been examined. The reaction of 2,4-dimethyl-4 -(methylthio)benzophenone with methyl-lithium in ether exhibits the rate expression ... 

In general terms, it appears likely that alkyllithium reagents have the possibility of reacting through any of several aggregated and dissociated forms. 

The kinetics of addition of alkyllithium reagents to esters have been studied using a series of ethyl benzoates. The rates show a rather complex dependence on both alkyllithium concentration and the nature of aiyl substituents in the ester. The rapid formation of an initial ester-alkyllithium complex can be demonstrated. It is believed that... 

The number of examples of reaction with alkyllithium reagents is very limited (14,48). The similarity of the reaetion to Grignard addition suggests that similar products will be obtained. This suggestion is supported by the examples shown in Table 6. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

The mechanism of organolithium addition to naphthyl oxazolines is believed to occur via initial complexation of the alkyllithium reagent to the oxazoline nitrogen atom and the methyl ether to form chelated intermediate 17. Addition of the alkyl group to the arena 7t-system affords azaenolate 18, which undergoes reaction with an electrophile on the opposite face of the alkyl group to provide the observed product 4. The chelating methyl... 

Many other kinds of organometallic compounds can be prepared in a manner similar to that of Grignard reagents. For instance, alkyllithium reagents, RLi, can be prepared by the reaction of an alkyl halide with lithium metal. Alkyllithiums are both nucleophiles and strong bases, and their chemistry is similar in many respects to that of alkylmagnesium halides. 

These reagents are not isolated but are used directly in reactions with aldehydes, after generation of ate complexes via the addition of an alkyllithium reagent or pyridine11. 2-(2-Propenyl)-1,3,2-dioxaborolane is also metalated upon treatment with lithium tetramethylpiperidide, but mixtures of a- and y-substitution products are obtained upon treatment of this anion with alkylating agents20. Consequently, this route to a-substituted allylboron compounds appears to be rather limited in scope. 

A Lewis acid is involved in the reaction media when RCu BF3 or R3Al is used to cleave an acetal or ketal framework, and the resulting enol ether contains a E double bond. This is quite reasonable, since the overall reaction proceeds in an anti-SN2 manner. When a v>- -SN2 process is involved, the formation of products containing a Z double bond is observed60 (Table 2). The reaction of alkyllithium reagents with a./J-ethylcnic acetals and ketals proceeds in a. H7i-SN2 manner without assistance of Lewis acids, giving mainly the Z-products61-63. 

The addition of various alkyllithium reagents to ( )-2-(l-alkenyl)-4,5-dihydrooxazoles in THF at —78 °C followed by acid hydrolysis gave nonracemic chiral / ,/>-disubstituted carboxylic acids in high enantiomeric purity (>91% ee). 

Likewise, addition of aryl-, vinyl-, and alkyllithium reagents to tetrahydro-2-[2-(phcnylsul-fonyl)-2-(trimethylsilyl)ethenyl]-2tf-pyran followed by desilylation gives the. syn-products12 13. 

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-31). For an indirect way to convert carboxylic esters to ketones, see 16-33. 

The alkylation of heterocyclic nitrogen compounds with alkyllithium reagents is called Ziegler alkylation. Aryllithium reagents give arylation. The reaction occurs... 

The reaction has been applied to nonheterocyclic aromatic compounds Benzene, naphthalene, and phenanthrene have been alkylated with alkyllithium reagents, though the usual reaction with these reagents is 12-20, and Grignard reagents have been used to alkylate naphthalene. The addition-elimination mechanism apparently applies in these cases too. A protected form of benzaldehyde (protected as the benzyl imine) has been similarly alkylated at the ortho position with butyl-lithium. ... 

Phosphinous amides of general structure R R PNHR are easily converted to their respective anions by metals or bases. For instance, they can be easily deprotonated by alkyllithium reagents to give the [R R PNR ] anions (8-A or 8-B, illustrated in Scheme 12). 

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