Preparation of Organolithium Compounds

Electrostatic potential maps of (a) methyl fluoride and ib) methyllithium. The electron distribution is reversed in the two compounds. Carbon is electron-poor (blue) in methyl fluoride, but electron-rich (red) in methyllithium. 

Conversely, when carbon is bonded to a less electronegative element, such as a metal, the electrons in the bond are more strongly attracted toward carbon. 

Before we describe the applications of organometallic reagents to organic synthesis, let us examine their preparation. Organolithium compounds and other Group 1 organometallic compounds are prepared by the reaction of an alkyl halide with the appropriate metal. 

The alkyl halide can be primary, secondary, or tertiary. Alkyl iodides are the most reactive, followed by bromides, then chlorides. Fluorides are relatively unreactive. 

Unlike elimination and nucleophilic substitution reactions, formation of organolithium compounds does not require that the halogen be bonded to 5p -hybridized carbon. Compounds such as vinyl halides and aryl halides, in which the halogen is bonded to sp -hybridized carbon, react in the same way as alkyl halides, but at somewhat slower rates. 

Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but normally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the aUcyl halide. Fnrthermore, organolithium reagents are strong bases and react rapidly with even weak proton sonrces to form hydrocarbons. We shall discuss this property of organolithium reagents in Section 14.5. 

PROBLEM 14.2 Write an equation showing the formation of each of the following from the appropriate bromide  

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As pointed out in Note 1 a nitrogen atmosphere is preferred for the preparation of organolithium compounds. In the present example exclusion of oxygen is attained fairly satisfactorily by keeping the solution at the reflux point throughout an atmosphere of ether vapour is thus maintained. 

The order of reactivity of halides is RI > RBr > RC1 (Alkyl and aryl fluorides are seldom used in the preparation of organolithium compounds). 

SAMPLE SOLUTION (a) In the preparation of organolithium compounds from organic halides, lithium becomes bonded to the carbon that bore the halogen. Therefore, isopropenyllithium must arise from isopropenyl bromide. 

The equilibrium in these reactions favors formation of the organometallic compound with the metal attached to the more electronegative R group. The method is mainly used in the preparation of organolithium compounds derived... 

There is no doubt that in these. reactions the nitrogen atom of the pyridine ring is complexed with either the lithium alkyl or aryl or with the lithium bromide which is usually present in many preparations of organolithium compounds. It has been established that, either in the presence of an excess of lithium bromide or in the total absence of this salt, phenyllithium still gives the same ortho .para ratio on reaction with 3-picoline.229 To account for the predominant formation of the 2,3-isomer in the reaction of CH3Li with 3-alkylpyridines, it was suggested261 that the transition states for these reactions were similar... 

The preparation of organolithium compounds and of Grignard reagents from halides is successful only when these reagents contain virtually no functional groups. Furthermore, these C nucleophiles can be added to the C=0 double bond of a carbonyl compound only when this carbonyl compound also contains practically no additional electrophilic group(s). 

The reductive metallation of aryl sulfides allows the preparation of organolithium compounds. Cohen showed that soluble Mg-anthracene complex can be used instead of Li-naphthalenide for the reductive metallation of allyl phenyl sulfides (Scheme 5).15... 

Transmetalation using tin-lithium exchange is an excellent method — even better than mercury-lithium exchange — for the preparation of organolithium compounds, but it works only for compounds being more stable than n-butyllithium. This is also true for the synthesis of polylithiumorganic compounds. Examples are ( , )-1,5-dilithio-1,4-pentadiene 99the (Z,Z)-l,5-dilithio-l,4-pentadiene derivative 101 —... 

Scheme 5.12 Preparation of organolithium compounds (a) halogen-lithium exchange reaction (b) hydrogen-lithium exchange reaction...

Tetrahydrofuran is used as a solvent, especially for Grignard reactions, and at low temperature also for the preparation of organolithium compounds. 

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