REGIOINTEGRITY OF CARBANIONS DERIVED BY SELECTIVE METALATIONS OF DIMETHYLPYRIDINES AND -QUINOLINES

Article abstract of DOI:10.1016/S0022-328X(00)82948-4

Metalation of 2,4-dimethylpyridine and -quinolines by strong basic reagents in ethyl ether in the absence of HMPA affords 2-lithiomethyl derivatives regardless of the reaction length.The use of THF in such metalations promotes the formation of the 2-lithiomethyl reagents which isomerize to the more thermodynamically stable 4-lithiomethyl derivatives after relatively long reaction periods or in the presence of amines or an excess of the parent heterocycle.The latter derivatives appear to be formed directly from the heterocycles in ammonia or in the presence of HMPA.The results are discussed in terms of "coordination-only" versus "acid-base" limiting mechanisms for metalations as a function of ion pairing.NMR spectra for certain of the carbanions in ethyl ether and THF are described which support the above concepts.Related metalations of 2,4-dimethylquinoline-N-oxide give only the 2-lithiomethyl derivative.Similar reactions of 7-hydroxy-2,4-dimethyl-1,8-naphthyridine lead in synthetically useful yields to derivatization of the 2- and 4-methyl groups via dianions by using n-butyllithium in ethyl ether and sodium amide in liquid ammonia, respectively, followed by the addition of appropriate electrophiles.