Lithium-halogen exchange aryl halide

The scope of the Negishi-coupling is not limited to aryl and vinyl halides and sometimes acyl chlorides might also be converted to ketones by this protocol. The 2,3-dihalopyrrole derivative shown in 6.22. was converted into its 2-lithio derivative by selective lithium-halogen exchange at -78 °C. Addition of zinc chloride effected the formation of the appropriate pyrrolylzinc chloride, which was coupled with a functionalised butyroyl chloride in the presence of tetrakis(triphenylphosphino)palladium and furnished the expected 2-acylpyrrole in 61% yield.27... 

Ham and coworkers85 have developed a one-pot synthetic method for the formation of aryl-alkyl sulfides, 94, from various alkyl halides and lithium aryl thiolates 93, which are prepared in situ from 92 formed by lithium—halogen exchange of 91, employing n-butyllithium (Scheme 31). The method avoids the use of unstable arylthiols and a catalyst is not required. Several aryl bromides were successfully employed in the reaction, and the corresponding sulfides were obtained in 71 to 96% yields. 

Lithium-Halogen Exchange of Aryl Halides and Vinyl Halides.206... 

LITHIUM-HALOGEN EXCHANGE OF ARYL HALIDES AND VINYL HALIDES... 

Lithium-halogen exchange. The reagent is useful for preparation of organo-lithiums from acetal-containing substrates, dihaloarenes (monofunctionalization), and halopyridines. Dechlorination of /V-(/3-chloroalkyl)amides apparently cannot be achieved with BuLi alone (stops at (V-deprotonation ), and the use of LN is required." Of course the N,C-dithio derivatives may be employed in C-C bond formation (remarkably the coupling with aryl and vinyl halides). Barbier-type reactions have been achieved."... 

The next series of fully-conjugated indeno[l,2-b]fluorenes synthesized by Haley et al. was 6,12-diarylindeno[l,2-b]fluorenes (Scheme 26) [77]. Similar to 96a-i, lithium-halogen exchange with the appropriate aryl halide and reaction with 22 afforded mixtures of stereoisomers 97a-i. Reduction using anhydrous SnCl2 at elevated temperatures provided 87a-j in 36-59% yield. The electron-withdrawing... 

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. 

Figure 5.4 Selective lithium-halogen exchange on multisubstituted aryl halides...

Successful lithiation of aryl halides—carbocyclic or heterocyclic—with alkyUithiums is, however, the exception rather than the rule. The instability of ortholithiated carbocyclic aryl halides towards benzyne formation is always a limiting feature of their use, and aryl bromides and iodides undergo halogen-metal exchange in preference to deprotonation. Lithium amide bases avoid the second of these problems, but work well only with aryl halides benefitting from some additional acidifying feature. Chlorobenzene and bromobenzene can be lithiated with moderate yield and selectivity by LDA or LiTMP at -75 or -100 °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. 

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