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

• Published in: Organic & biomolecular chemistry Vol. 12; no. 30; pp. 5773 - 5780
• Main Authors: Zhu, Yi-Shuo, Shi, Benyi, Fang, Ran, Wang, Xiaoxuan, Jing, Huanwang
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 14.08.2014
• Subjects: Bromides - chemical synthesis; Bromides - chemistry; Catalysis; Chemistry; Chemistry, Organic; Microwaves; Palladium - chemistry; Physical Sciences; Proton Magnetic Resonance Spectroscopy; Protons; Science & Technology; Thermodynamics; Thiazoles - chemical synthesis; Thiazoles - chemistry; H BOND ACTIVATION; HALIDES; FUNCTIONALIZATION; INTRAMOLECULAR ARYLATION; METALATION-DEPROTONATION MECHANISM; THIAZOLE DERIVATIVES; C-2 ARYLATION; PROTON-ABSTRACTION MECHANISM; C-H; PIFITHRIN-ALPHA
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c4ob00600c

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.