Primary alkyllithium preparation

Table 1. Primary Alkyllithiums Prepared from Li Metal with Organic Halides...

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. 

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. 

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%... 

The choice of solvent for reaction (a) is important. Alkyllithiums (except CH3Li) react with ethers. Primary alkyllithiums may be prepared in ether if storage of the reagent is not necessary, or in the even more reactive tetrahydrofuran (THF) at low T (ca. — 50°C) when the reagent is to be used promptly. For more reactive secondary and tertiary alkyllithiums, hydrocarbon solvents are used. The less reactive methyl-, aryl- and vinyllithiums are prepared in ethers. 

The first total synthesis of the Stemona alkaloid (-)-tuberostemonine was accomplished by P. Wipf and co-workers. " The installation of the butyrolactone moiety commenced with the preparation of a Weinreb s amide from a methyl ester. The tricyclic methyl ester substrate was exposed to A/,0-dimethylhydroxylamine hydrochloride and Me2AICI and the tertiary amide was isolated in excellent yield. Next, the bromo ortho ester was treated with LDBB in THF to generate the corresponding primary alkyllithium species, which cleanly and efficiently added to the Weinreb s amide to afford the desired ketone. 

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). 

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. 

When 1,3,5-triphosphabenzenes 107 are treated with an alkyllithium, adducts 108 are formed which release phosphinidene when heated, thus producing 1,3-dipohospholide anions 109 which can be trapped by P-alkylation with primary alkyl halides, thus producing 1/7-1,3-diphospholes 110 (Scheme 20) <2003S2720>. When 2-pyridyl-lithium, prepared by reaction of 2-bromopyridine with -butyllithium, was used, the -BuBr produced in the... 

Mi) Secondary Alkyllithiums. These are more difficult to prepare via reaction (a) than are their primary counterparts. Yields are higher with chlorides because the bromide precursors react more readily in secondary reactions with the organolithiums. Because of the increased reactivity of secondary alkyllithiums, hydrocarbons are used in their preparation instead of ethers. 

The cleavage of alkyl phenyl sulfides by naphthalenelithium or a lithium dispersion in THF to afford alkyllithium reagents has been studied initially by Screttas and Micha-Screttas [309,310) as part of their hydrolithiation of a-olefins process. They prepared primary, secondary and tertiary alkyllithium reagents in fair to good yields, as shown by carbonation. 

Quantitative primary amine functionalization was obtained using these procedures (alkyllithium initiation, hydrocarbon solution, added lithium chloride) and 2,2,5,5-tetramethyl-1 - (3 -chloropropyl) -1 -aza-2,5 -disilacyclopentane (protected primary amine see Scheme 14). Terminal secondary amine-functionalized polymers have been prepared in high yield (99% for PBDLi) using N-methyl-N-benzylaminopropyl chloride as terminating agent in the presence of lithium chloride followed by hydrogenolysis of the benzyl group. ... 

Electrophilic Amination. r-Butyl )V-lithio-)V-(/)-toluenesulfonyloxy)carbamate (1) is prepared from Abutyl W(/)-toluenesulfonyloxy)carbamate, which is easily obtained on a large scale by tosylation of the commercially available f-butyl )V-hydroxycarbamate. (1) is an electrophilic aminating reagent and a synthetic equivalent of +NHBoc . It reacts with alkyllithium reagents (eq 1) or arylcopper reagents (eq 2) to provide primary amines in their (V-Boc protected form. 

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