Secondary alkyllithium preparation

Table 2. Secondary Alkyllithiums Prepared from Li Metal with Organic Halides...

The classical preparation of alkyllithium compounds by reductive cleavage of alkyl phenyl sulfides with lithium naphthalene (stoichiometric version) was also carried out with the same electron carrier but under catalytic conditions (1-8%). When secondary alkyl phenyl sulfides 73 were allowed to react with lithium and a catalytic amount of naphthalene (8%) in THF at —40°C, secondary alkyllithium intermediates 74 were formed, which finally reacted successively with carbon dioxide and water, giving the expected carboxylic acids 75 (Scheme 30) °. 

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. 

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. 

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. 

Cyclopropyllithiums are exceptions. These species are stabler than other secondary alkyllithium reagents and are prepared in ether from cyclopropyl bromides. 

Heteroconjugate addition (9. 311). The diastcrcoselcctive conjugate addition of methyllithium to a secondary allylic alcohol substituted with a SO,C,H, and a Si(CH,)< group to give the. yvn-adduct as the only or major product (equation I) has been extended to other alkyllithiums and used to prepare sytt and u/(//-diastercomcrs with different... 

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. 

Tertiary alkyllithiums are prepared in hydrocarbons from the appropriate alkyl chlorides with Li dispersions. Once the reaction is initiated, secondary reactions between the reagent and its precursor halide may cause low yields. Slow rates of addition of the alkyl chloride minimize these secondary reactions . Polycyclic and bridgehead reagents are less susceptable to such bimolecular reactions with their precursor chlorides. 

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. ... 

The preparation and immediate reaction of alkyllithium for deprotonation of various acidic compoimds precisely illustrate this aspect (Fig. 34).i 8 representative reaction is the quantitative formation in a few minutes of 2-lithio-1,3-dithiane by sonication of f-butyl chloride, lithium, and 1,3-dithiane in THF. In situ generated butyllithium was used for the deprotonation of alkynes and phosphonium salts. With secondary amines, the strongly basic lithium amides are produced (p. 368). This procedure avoids the use of organolithium auxiliaries with solvent and temperature adjustments. o The isotopically labeled Li hexamethyl disilazide was obtained by this method.i i... 

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