Li/Br exchange

The same ketene acetal, as well as telluro(thio)ketene acetals has been obtained with retention of configuration by subsequent treatment of ( )-l-bromo-l-seleno(or thio) alkenes with n-BuLi and diphenyl ditelluride, resulting from the preferential Br/Li exchange over chalcogeno exchange. ... 

After the optimization of the conditions for the production of o-bromophenyl-lithium to —78°C with a 0.8 s residence time, the scope was extended to sequential Br-Li exchange of both bromine substituents on the benzene ring and the reaction with electrophiles to form o-disubstituted benzene rings. This was done in a four-step reaction in one flow using four-linked microreactors (MRi ). For the second lithiation, the temperature of 0°C was sufficient, which was expected since the aryllithium intermediate is more stable than o-bromophenyllithium. 

Nagaki A, Tomida Y, Usutani H et al (2007) Integrated micro flow synthesis based on sequential Br-Li exchange reactions of p-, m-, and o-dibromobenzenes. Chem Asian J 2(12) 1513-1523... 

Method A, H-Li exchange method B, Br-Li exchange method C, I-Li exchange. 

Aryl bromides can be converted to aryl Grignard or aryllithium compounds in three ways (Figure 5.41). In the first two methods, the aryl bromide is reacted with Mg shavings or with Li wire, respectively (see Section 17.4.1 for the mechanism). In the third method—which is especially convenient for small-scale preparations—aryl bromides are converted into aryllithium compounds either with 1 equivalent of butyllithium (w-BuLi) or with 2 equivalents of fert-butyllithium (terf-BuLi) by the so-called Br/Li exchange reaction. 

I f n-BuLi is used for the Br/Li exchange in Figure 5.41, the reaction is completed when the lithio-aromatic compound and n-butyl bromide have formed. It is different when this Br/Li exchange is carried out with ierf-BuLi, where tert-BuLi and /erf-butyl bromide necessarily would have to coexist during the reaction. However, tert-BuLi reacts very fast as a base with tert-butyl bromide via an E2 elimination. Therefore, Br/Li exchange reactions with ferf-BuLi can go to completion only when 2 equivalents of the reagent are used. 

Fig. 16.16. Stereoselective preparations of cis-alkenyl-boronic acids and the corresponding diisopropyl ester starting with cis-bromoalkenes. The first step involves a Br/Li exchange to form the alkenyl-lithium compound B. This organolithium compound is subsequently transmetalated to give complex C by using B(0/Pr)3.

When one is working on a very small scale, one can prepare aryllithium compounds through a Br/Li exchange reaction (path 3 in Figure 5.34) in a much simpler way than aryl Grignard reagents. 

The rather unstable 1,1-difluoroallyllithium has been prepared by transmetallation from the corresponding tin derivative, according to Seyferth et al. 65). These authors 66) have also reported a more efficient access to this carbenoid, and a possible appli-tability is achieved by Br/Li exchange reaction with 3,3-difluoroallyl bromide, as outlined by Eq. (60). 

Method A Br-Li exchange, n-BuLi/Et20 followed by CO2 quench. Method B NaNH2 promoted Haller-Bauer cleavage of phenyl ketone. Method C LDA/THF, — 72°C, quench with Mel or MeOD. Method D H-D exchange vs. racemization using NaOMe. Method E LDA/Et20 at 25°C. Method F DNMR. 

Reactions of n-BuLi with halopyridines can lead also to Li-halogen exchange (see 5.5.2.3.3). The reaction between n-BuLi and 3-Br-2-Cl-pyridine gives products of Br-Li exchange and metallation of the ring at the 4-position . 5-Methyl- and 5-bromopyrimidines " also are ring metallated ... 

Normal Br-Li exchange occurs with the bromide, but Si—O cleavage results with the chloride. 

The choice of reaction of vinylic bromides with n-BuLi can be governed by donor groups e.g., Br-Li exchange occurs with (Z)CHBr=CHOEt at —80°C in Et20 ... 

Bromocyclooctatetraene also reacts by Br-Li exchange with n-BuLi to give lithio-cyclooctatetraene ... 

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