Palladium-catalyzed microwave-assisted direct arylation of imidazo[2,1-b]thiazoles with aryl bromides: synthesis and mechanistic study

Abstract

A palladium-catalyzed direct C–H arylation of various imidazo[2,1-b]thiazoles with a range of aryl bromides under microwave irradiation is described. 6-Phenyl substituted imidazo[2,1-b]thiazoles could be regioselectively C-5 arylated using the developed protocol. The utility of this method enables the representative coupling product to be achieved by a sequential one-pot reaction. Density functional theory (DFT) calculations show that this arylation proceeds via a concerted metalation–deprotonation (CMD) pathway, which is in agreement with our experimental results. This work provides a convenient access to a variety of biologically active imidazo[2,1-b]thiazole derivatives. Also, it enriches the mechanism study of site-selective C–H arylation in fused heterocycles, and offers a valuable guide to design highly efficient catalytic systems for the preparation of similar compounds.