Deprotonation by Strongly Basic Reagents

The parent hydrocarbons benzene and naphthalene have a poor kinetic acidity and attempts at metallation using alkyllithium in THF or Et20 result only in attack on the solvent. Quantitative conversion into phenyllithium can be effected however, if a large excess of benzene is allowed to react with BuLi TMEDA in hexane at reflux temperature [9, 167]. In the case of naphthalene this metallation procedure has no practical importance, because 1- and 2-naphthyllithium are produced in comparable amounts, along with some dimetallated naphthalene ([9], compare also [160]). 

A convenient way to prepare phenylpotassium consists of reacting an equimolar mixture of BuLi f-BuOK and TMEDA with an excess of benzene in hexane. The metallation is complete within 1 hour at —20 °C [9]. 

This ternary mixture gives more satisfactory results than the binary mixture of /-BuOK and BuLi, which is insoluble in alkanes and therefore requires the use of a very large excess of benzene [235]. Naphthalene and the cocktail of the three bases produce a 85 15 mixture of 2-naphthylpotassium and the 1-isomer in a reasonable yield, together with some 1,8-dipotassionaphthalene [9]. As 2-naphthyl derivatives in general are not easily accessible by the other methods, the metallation with BuLi /-BuOK TMEDA has some practical importance. 

Metallation of naphthalene with BuLi in THF and Et20 has been reported to give comparable amounts of the two mono-lithium compounds in a modest yield [160]. 

The metallation of biphenyl with BuLi or BuLi TMEDA, as reported in an early paper [163], leads to mixtures of comparable amounts of o-, m- and p-lithio-biphenyl. A recent paper dealing with the 0,0-dilithiation of biphenyl [165] reports 

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Another notable difference between the Zr-catalyzed ethylmagnesations of allylic ethers and alcohols is the effect of solvent Lewis basicity on reaction selectivity. Thus, as iUustrated in Scheme 3.79, whereas reactions with allylic ethers are entirely insensitive to variations in solvent structure, those of allylic alcohols are strongly influenced. These observations led Hoveyda and coworkers to conclude that for allylic alcohols (allyhc alkoxides after rapid deprotonation by the Grignard reagent) there is chelation between the Lewis basic heteroatom and a metal center (Zr or Mg) this association, which gives rise to transition state organization and high diastereocon-trol, is altered in the presence of Lewis basic THF, with diminution in selectivity. 

Direct metallation. Direct C-H metallations are of several types, of which the most important is reaction ( deprotonation ) with a strongly basic reagent, usually a lithium compound, but is also possible for magnesium and zinc. Electrophilic metallation can be carried out with palladium(II) and mercury(II) salts, and neutral C-H insertion by other transition metals is becoming increasingly important, usually for catalytic reactions. 

Exp. 7 describes the metallation of the olefins with a 1 1 complex of BuLi and t-BuOK (prepared in situ) in a THF-hexane mixture. The deprotonations proceed with high efficiency, provided that a large excess of the olefins are used to suppress the competitive attack of THF by the strongly basic reagent. The system BuLi t-BuOK TMEDA is soluble in hexane and has a reasonable stability below —20 °C. The metallations can be carried out with excellent results in a relatively short time (up to 2 h), using a moderate excess of the olefins. 

From the practical piont of view however, due to other favorable possible pathways a- or -deprotonation) as depicted above, it is interesting to differentiate between simple organolithium reagents, which show a high basicity, and stabilized organolithium reagents, with a lower basicity, but also a moderate nucleophihcity. In many cases, activation of the reaction can be obtained by the addition of a strong Lewis acid. 

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