Metalation/SRN1 Coupling in Heterocyclic Synthesis. A Convenient Methodology for Ring Functionalization

Article abstract of DOI:10.1021/jo00247a016

Lithiation, iodination, and fluorine substitution on 2-fluoropyridine gave 2-substituted 3-iodopyridines, which were further subjected to iodine S_RN1 substitution by carbon, sulfur, and phosphorus nucleophiles.Iodine substitution by enolates on 2-amino-3-iodopyridines afforded ketones, which were further cyclized to various 1,2-disubstituted pyrrolo<2,3-b>pyridines. 2-Amino-3-iodo-, 3-amino-4-iodo, and 4-amino-3-iodopyridines were prepared by directed metalation of 2-, 3-, and 4-(pivaloylamino)pyridines.Substitution of iodine by enolates under S_RN1 conditions and acidic cyclization led to various 2-substituted pyrrolo<2,3-b>, -<2,3-c>-, and -<3,2-c>pyridines in high yields.