Organolithium Reagent - Uses

Uses

Organolithium compounds are strongly polarised by the electropositive character of lithium. They are therefore highly reactive nucleophiles and react with almost all types of electrophiles. They are comparable to Grignard reagents, but are much more reactive. Due to this reactivity they are incompatible with water, oxygen (O₂), and carbon dioxide, and must be handled under a protective atmosphere such as nitrogen or, preferably, argon.

A common use of simple commercially available organolithium compounds (like n-BuLi, sec-BuLi, t-BuLi, MeLi, PhLi) is as very strong bases. Organolithium compounds can deprotonate almost all hydrogen-containing compounds (the metalation or Li/H exchange reaction), with the exception of alkanes. In principle, a deprotonation can go to completion if the acidic compound is 2 pK_A units stronger than the lithium species, although in practice a larger pK_A difference is required for useful rates of deprotonation of weakly acidic C-H acids. As alkyl groups are weakly electron donating, the basicity of the organolithium compound increases with the number of alkyl substituents on the charge-bearing carbon atom. This makes tert-butyllithium the single strongest base that is commercially available, with a pKa greater than 53. The metalation reaction is an important synthetic method for the preparation of many organolithium compounds. Some examples are shown below:

Organolithium compounds are also commonly used for nucleophilic addition reactions to carbonyl compounds and other carbon electrophiles. Deprotonation can be a side reaction with enolizable carbonyl compounds, especially with hindered organolithium reagents such as t-butyllithium. Grignard reagents, although much less reactive, are an alternative in addition reactions, with less problems with deprotonation.

An important use of organolithium reagents is in the preparation or other organometallic compounds, usually by reaction with metal halides. Especially important in synthetic organic chemistry is the formation of organocopper reagents (including Gilman reagents) by reaction of RLi with CuI or CuBr, and the preparation of organozinc reagents by reaction with ZnCl₂. Even Grignard reagents are sometimes prepared by reaction of RLi with MgBr₂, in situations where the lithium reagent (but not the Grignard) can be easily prepared by a metalation reaction. Organotin, organosilicon, organoboron, organophosphorus, and organosulfur compounds are also frequently prepared by reaction of RLi with appropriate electrophiles.

A recent review of process chemistry indicates that the following are the most commonly used organolithium reagents: butyllithium, hexyllithium, sec-butyllithium, and phenyllithium. Methyllithium is also commonly used. Two very commonly used strong bases prepared using butyllithium are lithium diisopropylamide (LDA), and lithium hexamethyldisilazide (LiHMDS).

Aryllithium derivatives are intermediates in directed ortho metalation such as Me₂NCH₂C₆H₄-2-Li obtained from dimethylbenzylamine and butyllithium.