Aryl halogen-lithium exchange reactions

The University of Kyoto, Japan, reports about a halogen-lithium exchange reaction of aryl bromides with butyl lithium (see Figure 5.20) [53,57]. The intermediate was trapped with an electrophile. The whole process was done under noncryogenic conditions at 0°C. 

The use of a microflow system is effective in solving this problem, and a pilot plant for the halogen-lithium exchange reaction of aryl bromides and heteroaryl bromides with butyllithium (Scheme 10.4) has already... 

Ortho lithiation of arenes directed by CONRj, OCONRj, OMOM, or NHCOR (Eq. 5), or the halogen-lithium exchange reaction (Eq. 6) provides various aryllithiums regioselectively. In situ treatment of these lithium intermediates with trimethyl- or tri(isopropyl) borate gives variously functionalized arylboronic acids. Trapping aryl-lithium or aryl-magnesium intermediates with trimethylchlorosilane, followed by transmetallation to BClj or is a convenient alterna-... 

The halogen-lithium exchange reaction of an aryl halide using a flow microreactor system has been discussed in the previous chapters. If the aryllithium species can be used in a coupling reaction catalyzed by a Pd complex in the flow microreactor system, this would provide an efficient and effective method of synthesis. However, the two reactions cannot simply be carried out sequentially. For... 

Coupling of certain lithiated reagents with aryl and vinyl halides is also possible.82 These reactions probably proceeds by a fast halogen-lithium exchange, generating the alkyl halide, which then undergoes substitution. This reaction has been applied to P-lithiobenzamides.83... 

In principle, each of the above protodelithiation reactions is in equilibrium. It is clear that, in practice, they are not. The protonating species, HBr, isopropanol and 2-butanol, are simply too acidic for the reaction to be reversible. Although the hydrogen/lithium exchange equilibria cannot be smdied in both directions, halogen/Uthium exchange reactions with aryl substituents evidently are true equilibrium processes. Winkler and Winkler studied reaction 11 (among others), in either diethyl ether or in THF at 25 °C. 

It is sometimes more convenient to prepare organolithium reagents by halogen-lithium exchange between an aryl halide and butyllithium (BuLi). The reaction takes place because the aryllithium is more stable than butyllithium an sp- carbon is better able to stabilize a negative charge than an sp carbon (Scheme 10.2). Butyllithium is available commercially in bulk quantities. 

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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