Lithiation of pyridine

Scheme 3.23 Lithiation of pyridine derivatives (172) on a polymeric support [279].

Lithiation of pyridine itself (and quinoline) is best carried out using a combination of BuLi and the lithiated amino alcohol LiDMAE 176 (Scheme 88). ... 

The pffa of 3-methylpyridine, whose anion cannot be delocalized onto N, is closer to that of toluene, and deprotonation gives only low yields with most bases. However, with a combination of BuLi and lithiodimethylaminoethanol (LiDMAE) deprotonation is quantitative but yields products 561 arising from apparent lithiation a to N (Scheme 224) Trying to force lateral lithiation of pyridines is generally doomed to failure, as ring lithiation or nucleophilic addition nsnally takes place first . 

Direct lithiation of pyridine is a common method of generating the precursors required for the organopalladium cross-coupling reactions. However, if one is not carefiil, the pyridine ring is susceptible to direct addition of the alkyllithium reagent (Chichibabin reaction) as opposed to deprotonation of the ring. 

Tandem Double Lithiation The asymmetric synthesis of camptothecin Tandem Lithiation of Pyridine A-Oxides and Nucleophilic Substitution... 

Lithiation of pyridines. 3-Methylpyridine is regioselectively lithiated at C-6 with this base system, which is markedly different from its behavior toward LDA (benzylic lithiation). 2-Chloropyridine behaves similarly. ... 

Direct regioselective a lithiation of pyridine, 2-methoxypyridine, or 2-methylthio-pyridine, can be carried out using a complex base consisting of a mixture of butyllithium and the lithium salt of 2-dimethylaminoethanol. The process may be more complex than simple deprotonation, possibly involving a radical anion intermediate. ... 

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