Butyllithium permutational halogen/metal

Bromo- and iodoarenes are the oldest and most typical substrates for permutational halogen/metal interconversions. Butyllithium is routinely used for this purpose (Table 16). Hetero-substituents such as dialkylamino or bis(trialkylsilyl)amino, cyano or nitro (Table 17), alkoxy and 2-tetrahydropyranyloxy (Table 18), lithiooxy or lithiooxycarbonyl (Table 19) and fluoro or trifluoromethyl (Table 20) and chloro, bromo or iodo (Table 21) are well tolerated. 

AUcoxy groups or halogen atoms at the a- or -position of open-chain or cyclic alkyl-lithiums diminish the basicity of such species and hence facilitate the halogen/metal permutation. Other than fert-butyllithium, also iec-butyUithium or butyllithium, even methyllithium, or phenyllithium, can now be employed (Tables 10 and 11). 

TABLE 16. Heteroatom-free aryllithiums Li—R by halogen/metal permutation between bromo- or iodoarenes and butyllithium... 

TABLE 21. Chloro-, bromo- and iodo-substituted aryUithiums Li—R by halogen/metal permutation between bromoarenes and butyllithium in diethyl ether... 

TABLE 23. Pyrryl-, indolyl-, pyrazolyl- and imidazolyllithiums Li—R by halogen/metal permutation between a five-membered bromoheterocycle and butyllithium in an ethereal solvent... 

Halogen/metal permutation and hydrogen/metal permutation (usually apostrophed as "metalation") dominate the interconversion methods. They employ organoalkali reagents such as phenyllithium, methyllithium, -butyllithium, iec-butyllithium, or the superbasic LIC-KOR mixture. However, even if commercial, these reagents have to be made beforehand. The reaction of a chloro- or bromo-substituted hydrocarbon with lithium, sodium, or magnesium offers a standard entry to them. Thus, ultimately one always has to revert to the metal. 

Finally, even phosphine-derived ate complexes have been brought into being. Lithium bis(2,2 -biphenylene)phosphinate (65) is readily produced from (2 -bromo-biphenyl-2-yl)-2,2 -biphenylenephosphine by halogen/metal permutation and the ensuing spontaneous cyclization of the lithiated intermediate (Scheme 1-46, lower part). Alternatively, it may be obtained by converting bis(2,2 -biphenylene)phosphonium iodide first into hydridobis(2,2 -biphenylene)phosphorane and treating the latter with tert-butyllithium (Scheme 1-46, upper part). ... 

It is very simple to trade in a bromine atom against an iodine atom by the consecutive treatment of the bromo compound with -butyllithium and molecular iodine. Such an exchange may offer practical advantages as only the derivatives of the heaviest halogen undergo halogen/metal permutations very rapidly even at -100 °C and in poorly polar solvents such as toluene. Bromo analogs react several powers of ten more slowly. 

When treated with butyllithium in diethyl ether at —50°C, bromobenzene undergoes the permutational exchange of the halogen against the metal only slowly, but rapidly at 0 °C. The transformation is complete after a few seconds if conducted in tetrahydrofuran at —75 °C. lodobenzene reacts instantaneously in any case. 

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