School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University , Xinxiang, Henan 453007, China.
J Org Chem. 2017 Jul 21;82(14):7363-7372. doi: 10.1021/acs.joc.7b01013. Epub 2017 Jun 29.
In this paper, an efficient and convenient one-pot synthesis of diversely substituted 4-acylpyrazole derivatives via copper-catalyzed one-pot cascade reactions of saturated ketones with hydrazones is reported. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through the dehydrogenation of a saturated ketone and the [2 + 3] cyclization of the enone with hydrazone followed by an aromatization-driven C-C bond cleavage and reorganization. To our knowledge, this is the first example in which the biologically and pharmaceutically important yet otherwise difficult-to-obtain 4-acylpyrazole derivatives are directly prepared from saturated ketones and hydrazones featured with multiple aliphatic C-H bond functionalization and C-C bond cleavage and reorganization. Compared with literature methods, this novel process has advantages such as simple and economical starting materials, a sustainable oxidant, excellent regioselectivity, and good efficiency.
本文报道了一种高效、便捷的通过铜催化饱和酮与腙的一锅多步级联反应合成多取代 4-酰基吡唑衍生物的方法。在机理上，标题化合物的形成涉及通过饱和酮的脱氢形成烯酮中间体，以及烯酮与腙的[2+3]环化，然后是芳构化驱动的 C-C 键断裂和重排。据我们所知，这是首次直接从具有多个脂肪族 C-H 键官能化和 C-C 键断裂和重排的饱和酮和腙中制备生物和药物上重要但难以获得的 4-酰基吡唑衍生物。与文献方法相比，这种新方法具有简单经济的起始原料、可持续的氧化剂、优异的区域选择性和良好的效率等优点。
