Halogen/metal permutations

TABLE 8. Primary aliphatic organoUthiums Li—R by halogen/metal permutation between haloalkanes X—R and tert-butylUthium in diethyl ether at —75°C... 

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 10. a-Fluoro-, a-chloro-, a-bromo- and a-iodoalkyllithiums Li—R by halogen/metal permutation using organometalUc reagents Li—R ... 

TABLE 11. O - or /S-Alkoxy- and a-halocyclopropyllithiums Li—R by halogen/metal permutation... 

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

TABLE 17. Amino-, cyano- and nitro-substituted aryUithiums Li—R by halogen/metal permutation using butylUthium or phenyUithium... 

TABLE 19. Lithiooxy-substituted aryUithiums Li—R by halogen/metal permutation between butyl-Uthium and O-lithiated bromophenols, bromobenzyl alcohols, bromo-2-phenethyl alcohols and bro-... 

OLi by deprotonation of OH prior to the halogen/metal permutation. Solvent (Sv) DEE = diethyl ether, THF = tetrahydrofuran. 

TABLE 20. Fluoro- and trifluoromethyl-substituted aryUthium Li—R by halogen/metal permutation between bromoarenes and butyUithium... 

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

TABLE 24. Furyl-, thienyl-, benzothienyl- and selenophenyllithiums Li—R by halogen/metal permutation between haloheterocycles and butyllithium in diethyl ether... 

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. 

Scheme 1-4. Stereocontrolled debromination of gem-dibromoalkenes and ge/w-dibromocyclopropanes by halogen/metal permutation.

In the aromatic and heterocyclic series, no hydroboration is possible. In general, an organoalkali intermediate is prepared by metalation or halogen/metal permutation before being treated with a boric acid derivative such as trimethyl borate or, because of its cleaner reaction, triisopropyl borate. The resulting ate complex sets free the oxidizable boronate upon addition of water or a stoichiometric amount of diluted hydrochloric acid. The boronate can be accessed directly when fluorodimethoxyborane is used instead of a boric acid ester as the adduct eliminates lithium fluoride spontaneously. The oxidation relies on the same procedures and principles as outlined above. 

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. 

Scheme 1-99. Two halogen/metal permutation equilibria coupled to the 5-hexenyllithium/cyclopentylmethyllithium rearrangement.

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