1ST METALATION OF ARYL IODIDES - DIRECTED ORTHO-LITHIATION OF IODOPYRIDINES, HALOGEN-DANCE, AND APPLICATION TO SYNTHESIS

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.