Side-chain lithiation of 2- and 4-substituted pyridines: Synthesis of more complex substituted pyridines

Lithiation of pyridines substituted in the 2- and 4-positions by acylaminomethyl groups, namely of the corresponding N-(pyridinylmethyl) pivalamides, N'-(pyridinylmethyl)-N,N-dimethylureas and tert-butyl N-pyridinylmethylcarbamates, with two mole equivalents of t-BuLi in anhydrous THF at -78 °C takes place on the nitrogen and on the methylene group of the side-chain. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding side-chain substituted derivatives in high yields.