Copper-Catalyzed Domino Annulation Approaches to the Synthesis of Benzoxazoles under Microwave-Accelerated and Conventional Thermal Conditions
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- 作者：Russell D. Viirre ; Ghotas Evindar ; Robert A. Batey
- 刊名：Journal of Organic Chemistry
- 出版年：2008
- 出版时间：May 2, 2008
- 年：2008
- 卷：73
- 期：9
- 页码：3452 - 3459
- 全文大小：266K
- 年卷期：v.73,no.9(May 2, 2008)
- ISSN：1520-6904
文摘
Two domino annulation approaches for benzoxazole synthesis have been developed. In the first approach, copper-catalyzed intermolecular cross-coupling of 1,2-dihaloarenes with primary amides initially forms the Ar−N bond of the benzoxazole ring, followed by copper-catalyzed intramolecular cyclization to form the Ar−O bond. Benzoxazoles were formed in good yields for the reaction of 1,2-dibromobenzene, but the reaction was not regioselective for the reaction of 3,4-dibromotoluene. Furthermore, the method is limited by the availability of 1,2-dihaloarenes. As a result of these limitations, an alternative more versatile one-pot domino annulation strategy was developed involving reaction of 2-bromoanilines with acyl chlorides in the presence of Cs2CO3, catalytic CuI, and the non-acylatable ligand 1,10-phenanthroline. Under these conditions initial acylation of the aniline is followed by copper-catalyzed intramolecular cyclization of the resultant 2-haloanilide to form the Ar−O bond of the benzoxazole ring. Optimized conditions using microwave irradiation achieved much shorter reaction times than conventional heating (i.e., 210 °C for 15 min versus 95 °C for 24 h) and were applied to the synthesis of a small library of benzoxazoles. These copper-catalyzed approaches complement existing strategies for benzoxazole synthesis, which typically utilize 2-aminopheonls as precursors.