Improved synthesis of 2,3-disubstituted pyridines by metallation of 2-chloropyridine: a convenient route to fused polyheterocycles

Chemoselective directed metallation of 2-chloropyridine allows the synthesis of 2-substituted 3-carbonylated pyridines, advantage being taken of the metallation ortho-directing effect of the halogen, as well as its reactivity towards nucleophiles. Thus (2-chloro-, 2-methoxy-, and 2-amino-3-pyridyl)-ethanones and -arylmethanones as well as carbaldehydes have been prepared. Some of these ortho-disubstituted intermediates have been readily cyclized to fused polyheterocycles such as naphthyridines and aza-analogues of coumarins, xanthones, and acridones.