First Metalation of Aryl Iodides: Directed Ortho-Lithiation of Iodopyridines, Halogen-Dance, and Application to Synthesis

Abstract

Metalation of iodopyridines was successfully achieved by LDA at low temperature. In many cases, lithiation is ortho directed by the iodo group which subsequently ortho-migrates very fast to give stabilized iodolithiopyridines. This procedure was applied to 2-fluoro- and 2-chloro-3-iodopyridines, 3-fluoro-4-iodopyridine, and 2-chloro-3-fluoro-4-iodopyridine. The resulting lithio intermediates were obtained in high yields before being reacted with electrophiles leading to various polysubstituted pyridines. Some of these iodopyridines were used as key molecules for the synthesis of fused polyaromatic alkaloids. Thus, perlolidine, δ-carbolines, and 2,10-diazaphenanthrenes were readily prepared in few steps taking advantage of the iodo reactivity for heteroring cross-coupling. © 1993, American Chemical Society. All rights reserved.