Alkyllithiums primary

Good yields of ketones can often be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent, followed by hydrolysis.The R group may be aryl or primary, secondary, or tertiary alkyl. Both MeLi and PhLi have been employed most often. The R group may be alkyl or aryl, though lithium acetate generally gives low yields. Tertiary alcohols are side products. 

The synthesis of alkali metal organophosphides and arsenides is usually most conveniently achieved by the direct metalation of a primary or secondary phosphine/arsine with a strong deprotonating agent such as an alkyllithium or an alkali metal hydride ... 

Iron-acyl enolates, such as 2, prepared by x-deprotonation of the corresponding acyl complexes with lithium amides or alkyllithiums, are nearly always generated as fs-enolates which suffer stereoselective alkylation while existing as the crmt-conformer which places the carbon monoxide oxygen anti to the enolate oxygen (see Section 1.1.1.3.4.1.). These enolates react readily with strong electrophiles, such as primary iodoalkanes, primary alkyl sulfonates, 3-bromopropenes, (bromomethyl)benzenes and 3-bromopropynes, a-halo ethers and a-halo carbonyl compounds (Houben-Weyl, Volume 13/9 a, p 413) (see Table 6 for examples). 

Addition of a primary alkyl group to enolizable ketones can be performed using magne-sium-ate complexes . The additional presence of 2,2 -bipyridyl (1 equiv.) in the reaction mixture improves the yields. The ate complexes are prepared in situ from the corresponding Grignard reagents and alkyllithium compounds (equations 140 and 141). 

For the preparation of primary alkyllithiums by this reaction, sec Bailey Punzalan J. Org. Chem. 1990, 55, 5404 Ncgishi Swanson Roussel 3. Org. Chem. 1990, 55, 5406. 

The great synthetic utility of the reaction of alkyllithium and Grignard reagents with ketonic functions has been well documented.105 These reactions take place via the intermediacy of alkoxy derivatives formed by addition of the M—C bond across the C=0 function. Hence ketones, aldehydes and formaldehyde will lead to tertiary, secondary and primary alkoxides, respectively. This type of reactivity is known for a number of other carbanionic metal alkyl derivatives, both main group and transition metals, although the synthetic utility of the reactivity has in most cases not been well documented. 

A second cognate preparation in Expt 5.94 describes a general procedure for the conversion of /V,/V-dimethylcarboxamides into ketones by reaction with primary alkyllithiums.127c As the reaction is not successful with secondary alkyllithiums, a branched chain ketone such as 4-methylheptan-3-one is prepared from ethyllithium and /V,/V,2-trimethylpentanamide, and not from 2-pentyllithium and N,N-dimethylpropanamide. 

Formylation of an alkyllithium (1, 280).1 Formylation of an alkyllithium or a Grignard reagent with DMF (Bouveault reaction) is generally unsatisfactory because of side reactions. However, sonication of the mixture of an alkyl or aryl halide, lithium, and DMF substantially improves the rate and the yield. The method is applicable to primary, secondary, and tertiary bromides or chlorides. Typical yields are in the range 65-85%. 

However, the decrease in rate was initially explained by the difference in reactivity of the alkyllithiums present, i.e., whether or not a primary or secondary anion was involved. Yet, the propagation reaction was quite different because the structure of the active species did not vary after the addition of the first ethylene unit. The fact that the constant rate (the rate after 1 mole of ethylene is consumed per mole of BuLi) varied linearly with initiator concentration at TMEDA /-BuLi = 1.0 indicated that a monomeric complex was responsible for the propagation reaction (PELi-TMEDA) [Eqs. (13), (14)]. 

Primary alkyllithiums.1 These alkyllithiums are usually prepared by reaction of alkyl chlorides or bromides with lithium metal, but can be obtained in 85-95%... 

Among unsolvated organolithium compounds only the alkyllithiums are soluble in noncoordinating solvents such as alkanes and arenes. Their states of aggregation depend on the structure close to lithium. Thus primary, tertiary and secondary alkyllithiums, all unsolvated, assemble into respectively hexamers, tetramers and equilibrium mixtures of hexamers and tetramers. Most organolithium compounds dissolve in and coordinate with donor compounds such as ethers and tertiary amines. The actual structures depend critically on the nature of the donor. Thus, diethyl ether solvates tend to be mainly cubic tetramers (with some dimers) while THF favors mixtures of monomers and dimers. Tertiary vicinal diamines such as TMEDA and 1,2-di-Af-piperidinoethane, DPE, favor bidentated coordinated dimers. Finally, in the presence of triamines such as pentamethyl-triethylenediamine PMDTA and l,4,7-trimethyl-l,4,7-triazacyclononane TMTAN, many organolithium compounds form tridentately complexed monomers. 

In 1950, Letsinger reported that carbonation of 2-lithiooctane, 15, prepared by exchange of (—)-2-iodooctane with s-butyllithium in petroleum ether at —70 °C, gave (—)-2-methyl-heptanoic acid21. However, after first warming the 2-lithiooctane solution to 0°C over 20 minutes the resulting carboxylic acid was racemic. This was the first observation that a secondary alkyllithium compound inverts much more slowly than does a primary RLi compound. 

Primary as well as secondary alkyllithiums lead to identical enantioselection. Whereas the asymmetric carbolithiation of 39E gives the (,Y)-alkylatcd product 46, the reaction of the 39Z leads to (/ )-51 or ( R)-52 (Scheme 20). When the allylic alcohol is unsubstituted a racemic product is formed, as is the case with 2-propen-l-ol, 52. 

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