Synthesis of 4-Acylpyrazoles from Saturated Ketones and Hydrazones Featured with Multiple C(sp3)-H Bond Functionalization and C-C Bond Cleavage and Reorganization.
Synthesis of 4-Acylpyrazoles from Saturated Ketones and Hydrazones Featured with Multiple C(sp3)-H Bond Functionalization and C-C Bond Cleavage and Reorganization.
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DOI：
10.1021/acs.joc.7b01013
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
M. Tian;Xiaonan Shi;Xinying Zhang;Xuesen Fan
中科院分区：
文献类型：
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作者：
M. Tian;Xiaonan Shi;Xinying Zhang;Xuesen Fan
报道了一种铜催化的饱和酮和腙的一锅级联反应，合成了双取代的4-酰基吡唑衍生物。从机理上讲，标题化合物的形成涉及通过饱和酮的脱氢和烯酮与腙的[2 + 3]环化，然后由芳构化驱动的C-C键断裂和重组原位形成烯酮中间体。据我们所知，这是第一个从具有多个脂肪族C-H键官能化和C-C键断裂和重组特征的饱和酮和腙直接制备生物学和药学上重要但难以获得的4-酰基吡唑衍生物的实例。与文献方法相比，该新工艺具有原料简单经济、氧化剂可持续、区域选择性好、效率高等优点。
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.