Regioselective Synthesis of Acylated N‑Heterocycles via the Cascade Reactions of Saturated Cyclic Amines with 2‑Oxo-2-arylacetic Acids

A highly regioselective and versatile synthesis of acylated N-heterocycles from the cascade reactions of saturated cyclic amines with 2-oxo-2-arylacetic acids is presented. Mechanistically, the formation of the title compounds involves first a C­(sp3)–H bond dehydrogenation of cyclic amine to give an enamine intermediate followed by its cross coupling with the acyl species in situ generated through the decarboxylation of 2-oxo-2-arylacetic acid. Interestingly, in this cascade process, the copper catalyst is believed to play a crucial role not only in dehydrogenation but also in the decarboxylation and cross coupling reaction. To the best of our knowledge, this is the first example in which different classes of acylated N-heterocycles were directly prepared from the readily available saturated cyclic amines by using 2-oxo-2-arylacetic acids as the noncorrosive and easy to handle acylating reagents. Compared with literature methods, this new protocol has the advantages such as readily obtainable substrates, broad substrate scope, high efficiency, and good selectivity.本文报道了一种高区域选择性且通用的合成方法，可由饱和环胺与2-氧代-2-芳基乙酸（2-oxo-2-arylacetic acids）的级联反应制备酰化氮杂环化合物。从反应机理来看，目标化合物的生成首先经历环胺的C(sp³)-H键脱氢步骤，得到烯胺中间体；随后该中间体与由2-氧代-2-芳基乙酸脱羧原位生成的酰基物种发生交叉偶联反应。值得注意的是，在该级联过程中，铜催化剂不仅在脱氢步骤中发挥关键作用，同时参与了脱羧与交叉偶联反应。据我们所知，这是首例以无腐蚀性、易操作的2-氧代-2-芳基乙酸作为酰化试剂，由易得的饱和环胺直接制备不同种类酰化氮杂环化合物的案例。与已有文献报道的方法相比，该新型合成策略具有底物易得、底物适用范围广、效率高以及选择性良好等优势。