Direct arylation of benzothiazoles and benzoxazoles with aryl boronic acids.

Aryl-substituted benzothiazoles and benzoxazoles are an important class of heterocyclic compound and have shown a wide range of biological activities, such as antitumor, antiviral, and antimicrobial activities. In addition, these compounds have become essential building blocks for the synthesis of conjugated functional materials, such as industrial dyes and plant growth regulators. The conventional methods for the synthesis of these compounds typically involve either the metal-catalyzed intramolecular cyclization of thioformanilides or the cross-coupling of carboxylic acids with 2-aminophenol (or 2-aminothiophenol) in the presence of the Lawesson reagent. Alternatively, aryl-substituted benzothiazoles and benzoxazoles can be prepared by direct arylation of heterocycles through metal-catalyzed C H bond activation with aryl halides. We have recently demonstrated that benzothiazole compounds can be obtained by a decarboxylative C S cross-coupling of 2-nitrobenzoic acid with benzyl thiol, under relatively harsh conditions. More recently, we have shown that the cross-coupling of nitro-substituted aryl halides with benzyl thiol can also afford aryl-substituted benzothiazole derivatives in moderate yield. As part of our ongoing effort to synthesize aryl-substituted benzothiazoles and benzoxazoles, we describe herein a novel synthetic pathway that involves direct C H bond functionalization of benzothiazole and benzoxazole precursors by using arylboronic acids and transition-metal catalysts under aerobic conditions. It should be noted that You et al. have recently reported the direct arylation of azoles through metal-catalyzed C H bond functionalization with aryl boronic acids. The reaction of benzothiazole (1a) with phenylboronic acid (2a) was selected as a prototype reaction. Selected results from our experiments are summarized in Table 1. We observed that the reactions involving monometallic systems, such as Pd ACHTUNGTRENNUNG(OAc)2 (10 mol%) or CuACHTUNGTRENNUNG(OAc)2 (50 mol%), re-