Regiocontrolled Synthesis of 1,2-Diaryl-1H-imidazoles by Palladium- and Copper-Mediated Direct Coupling of 1-Aryl-1H-imidazoles with Aryl Halides under Ligandless Conditions

✍ Scribed by Fabio Bellina; Silvia Cauteruccio; Luisa Mannina; Renzo Rossi; Stéphane Viel

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 221 KB
• Volume: 2006
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200500636

✦ Synopsis

Abstract

A large variety of 1,2‐diaryl‐1__H__‐imidazoles, including a selective COX‐2 inhibitor, have been regioselectively synthesised in moderate to high yields by direct coupling of 1‐aryl‐1__H__‐imidazoles with aryl iodides or bromides in DMF in the presence of CsF and catalytic amounts of Pd(OAc)~2~ under ligandless conditions. A possible mechanism for this new highly regioselective C‐2 arylation reaction, involving the formation of an organocopper(I) derivatives followed by a transmetallation reaction with an arylpalladium(II) halide species and a reductive elimination, is proposed. New one‐step procedures for the synthesis of 1,2,5‐triaryl‐1__H__‐imidazoles, based on palladium‐ and copper‐mediated arylation of 1‐aryl‐1__H__‐imidazoles, have also been developed. Interestingly, some imidazole derivatives prepared in this study have been found to exhibit significant cytotoxic activity against some human tumour cell lines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)