One-Pot Tandem Amidation, Knoevenagel Condensation, and Palladium-Catalyzed Wacker Type Oxidation/C–O Coupling: Synthesis of Chromeno-Annulated Imidazopyridines

Abstract

A direct one-pot synthesis of chromeno-annulated imidazo[1,2-a]pyridines is achieved by the reaction of 2-amino-1-(2-ethoxy-2-oxoethyl)pyridinium salts with 2-bromoarylaldehydes using Pd(TFA)2 as a catalyst and Cu(OAc)2 as an oxidant. The overall strategy involves tandem base-mediated amidation and Knoevenagel condensation, followed by palladium-catalyzed Wacker type oxidation and intramolecular C–O coupling reaction. The method is simple, tolerates different functional groups, and gives moderate to good yields of chromeno[2′,3′:4,5]imidazo[1,2-a]pyridin-12-one derivatives. The developed tandem reaction was also successfully applied for the synthesis of pyrano-fused imidazo[1,2-a]pyridines by using 3-bromo-3-arylacrylaldehydes.