Alkyllithium-lithium halide exchange reactions

Reductive Metalation. The powerful reductive nature of this reagent makes it an important tool for lithium-heteroatom exchange reactions. Thus, it was established early on that (phenylthio)alkanes can be converted into their requisite alkyl-lithium species. This has become the method of choice over generation by lithium metal alone. The resultant alkyllithium species can either be quenched with a proton source (eq 1), or intercepted with an electrophile. This has subsequently evolved into a powerful technique, since the reaction is general for all chalcogens (eq 2f and halides (eq 3). ... 

Aryl halides readily undergo lithium-halogen exchange with alkyllithiums in ethereal solvents at temperatures at or below —78°C and the less expensive n-BuLi is often used for this purpose. However, the presence of the n-butyl halide product can cause complications when the aryllithium is warmed since a coupling reaction may ensue (for example, the reaction of phenyllithium with n-butyl iodide in THF at —78 °C has a half-life of 30 min). This potential problem is avoided when 2 equiv of r-BuLi are used for the generation of aryllithiums. 

Diethyl ether is the best solvent found for the reaction the reagent grade solvent was noticeably better after being refluxed with lithium for an hour prior to addition of the alkyl halide. After formation of the alkyllithium, the diethyl ether can be replaced by another solvent if the temperature is kept below 10° during the exchange. 

Although halogen-lithium exchange can occur at very low temperatures (< -100 °C), it is often necessary to employ two equivalents of alkyllithium for each equivalent of aryl halide so as to "neutralize" the alkyl halide, lest it destroy the aryllithium. This is illustrated below for the reaction between... 

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