Regiocontrolled Microwave Assisted Bifunctionalization of 7,8-Dihalogenated Imidazo[1,2-<em>a</em>]pyridines: A One Pot Double-Coupling Approach

Abstract

The reactivity of the 7-chloro-8-iodo- and 8-chloro-7-iodoimidazo[1,2-<em>a</em>]pyridines <strong>1a</strong>–<strong>e</strong> diversely substituted on the 2 position, towards Suzuki-Miyaura, Sonogashira, and Buchwald-Hartwig cross-coupling reactions as well as cyanation was evaluated. Various methodologies are proposed to introduce aryl, heteroaryl, alkyne, amine or cyano groups in the two positions depending on the nature of the substituent present in position 2. In both series, the substitution of the iodine atom was totally regioselective and the difficulty was to substitute the chlorine atom in a second step. Until now, only hetero(aryl) groups could be introduced though Suzuki-Miyaura cross-coupling. We overcame this problem evaluating both regioisomers in parallel. The double coupling approach was also studied allowing the one pot Suzuki/Suzuki, cyanation/Sonogashira and cyanation/Buchwald reactions leading to polyfunctionnalized imidazo[1,2-<em>a</em>]pyridines.

Keywords

• imidazo[1,2-&lt;em&gt;a&lt;/em&gt;]pyridine
• metallo-catalyzed cross-coupling reaction
• microwave irradiation
• Suzuki-Miyaura cross-coupling
• Sonogashira cross-coupling
• cyanation
• Buchwald-Hartwig cross-coupling