Copper-catalyzed oxidative arylation of heteroarenes under mild conditions using dioxygen as the sole oxidant.

Arylation of heteroarene has been intensively studied over the past few years because aryl-substituted aromatic heterocycles are known to exhibit interesting biological activities and are also useful as electronic materials. Numerous methods have been reported to successfully construct this motif by transition-metal-catalyzed cross-coupling and most of them required expensive transition-metal catalysts such as Rh and Pd. It is ideal to replace these catalysts by cheap metals. In 2007, Daugulis and co-workers first reported a copper-catalyzed cross-coupling of heteroarenes and aryl iodide under high temperature. You and co-workers modified a prior reported method by using aryl bromide as the electrophile; however, the reaction needed to be kept at high temperature for at least for one day. Very recently, Miura and Itami reported the Ni-catalyzed cross-coupling between heteroarenes and aryl halide, respectively. Their protocols also suffered from harsh conditions; for example, high temperatures and long reaction times. Therefore, finding a more practical and efficient method to achieve this aim remains a challenge. Like the traditional transition-metal-catalyzed cross-coupling reactions, previously reported catalytic methods for arylation of heteroarenes normally worked between heteroarene nucleophiles and aryl halide electrophiles (Scheme 1, A). Recently, remarkable progress has been made in oxidative cross-coupling. Unlike the traditional cross-coupling reactions, the oxidative cross-coupling needs two nucleophilic partners in the reaction and the transformation includes three steps: a two-stage transmetalation to high-valent metal catalyst, reductive elimination, then reoxidation of the catalyst to high valency by the external oxidant. The terminal oxidant that serves in oxidative cross-coupling always involves metal salts, organohalide, or benzoquinone, and so on. Replacement of these oxidants by dioxygen is more practical and more economical since this oxidant is very cheap and produces no environmentally hazardous byproduct. The C-2 position of azole or thiazole is easily deprotonated under basic conditions. It may serve as a nucleophile and cross-couple with another nucleophile under oxidative coupling conditions (Scheme 1, B). Recently, Su and coworkers reported the Cu-catalyzed oxidative amination of azoles and thiazoles by using O2 as the oxidant. [6] Only a few examples have been reported on oxidative arylation of azoles and thiazoles. Miura and co-workers developed an oxidative arylation and alkenylation of heteroarenes including azole and thiazole with organosilicon reagents by a nickel catalyst. You reported a Pd-catalyzed oxidative cross-coupling reaction between heteroarenes and aryl boronic acid. Both of them require metal salts and/or benzoquinone as oxidant. Very recently, Pdand Ni-catalyzed oxidative arylation of azoles and thiazoles with aryl boronic acid by using dioxygen as oxidant have been achieved. The reactions also proceeded under high temperature and/or for a long reaction time. All above mentioned drawbacks have made the prior methods less attractive. In our study, we found that CuCl could very efficiently catalyze the oxidative cross-coupling between heteroarenes and arylboronic esters with good yields and selectivities. This reaction was complete in only minutes under mild conditions by using dioxygen as the sole oxidant. We initiated our investigation by using Pd as the catalyst and dioxygen as the oxidant (Table 1, entry 1). Under variant conditions, only low yields were obtained (details are shown in the Supporting Information). We then switched [a] F. Yang, Prof. Z. Xu, Z. Wang, Prof. Z. K. Yu Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 (P.R. China) Fax: (+86)411-84379227 E-mail : [email protected] [email protected] [b] F. Yang, Z. Wang, Prof. R. Wang Key Laboratory of Preclinical Study for New Drugs of Gansu Province Department Institute of Biochemistry and Molecular Biology Lanzhou University, Lanzhou 730000 (P.R. China) Fax: (+86)931-8911255 E-mail : [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201100136. Scheme 1. Two pathways for the arylation of heteroarene.