P. Rocca et al., 1ST METALATION OF ARYL IODIDES - DIRECTED ORTHO-LITHIATION OF IODOPYRIDINES, HALOGEN-DANCE, AND APPLICATION TO SYNTHESIS, Journal of organic chemistry, 58(27), 1993, pp. 7832-7838
Metalation of iodopyridines was successfully achieved by LDA at low te
mperature. In many cases, lithiation is ortho directed by the iodo gro
up which subsequently ortho-migrates very fast to give stabilized iodo
lithiopyridines. This procedure was applied to 2-fluoro-and 2-chloro-3
-iodopyridines, 3-fluoro-4-iodopyridine, and 2-chloro-3-fluoro-4-iodop
yridine. The resulting lithio intermediates were obtained in high yiel
ds before being reacted with electrophiles leading to various polysubs
tituted pyridines. Some of these iodopyridines were used as key molecu
les for the synthesis of fused polyaromatic alkaloids. Thus, perlolidi
ne, delta-carbolines, and 2,10-diazaphenanthrenes were readily prepare
d in few steps taking advantage of the iodo reactivity for heteroring
cross-coupling.