On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition.
On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition.
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DOI：
10.1002/tcr.201600002
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发表时间：
2016-06
期刊：
影响因子：
6.6
通讯作者：
Lei Zhu;C. Brassard;Xiaoguang Zhang;Pampa M. Guha;R. Clark
中科院分区：
文献类型：
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作者：
Lei Zhu;C. Brassard;Xiaoguang Zhang;Pampa M. Guha;R. Clark
铜（I）催化的叠氮化物-炔环加成（CuAAC）反应区域特异性地产生1，4-二取代-1，2，3-三唑分子。该杂环形成化学对反应条件和底物结构具有高耐受性。因此，它不仅在杂环化学领域内，而且远远超出了杂环化学领域。在此，CuAAC的机制的理解进行了总结，特别强调铜/叠氮化物相互作用的意义。我们的分析得出结论，在反应的早期阶段形成的叠氮化物/铜（I）乙炔化物复合物决定了反应速率。随后的三唑环形成步骤是快速的，因此可能在动力学上不可见。因此，底物和铜催化剂的结构以及有助于形成易于环加成的铜/炔/叠氮化物三元络合物的其它反应变量将导致高效的CuAAC反应。具体而言，具有相对低的pKa值和与铜（I）进行π-背键的倾向的末端炔、具有辅助铜结合配体的叠氮化物（又称螯合叠氮化物）和抗聚集、平衡氧化还原活性与刘易斯酸度并允许双核协同催化的铜催化剂在CuAAC反应中是有利的。简要讨论的机制方面的内部炔参与CuAAC反应，也包括在这一点上，相对有限的数据的基础上。
The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction regiospecifically produces 1,4-disubstituted-1,2,3-triazole molecules. This heterocycle formation chemistry has high tolerance to reaction conditions and substrate structures. Therefore, it has been practiced not only within, but also far beyond the area of heterocyclic chemistry. Herein, the mechanistic understanding of CuAAC is summarized, with a particular emphasis on the significance of copper/azide interactions. Our analysis concludes that the formation of the azide/copper(I) acetylide complex in the early stage of the reaction dictates the reaction rate. The subsequent triazole ring-formation step is fast and consequently possibly kinetically invisible. Therefore, structures of substrates and copper catalysts, as well as other reaction variables that are conducive to the formation of the copper/alkyne/azide ternary complex predisposed for cycloaddition would result in highly efficient CuAAC reactions. Specifically, terminal alkynes with relatively low pKa values and an inclination to engage in π-backbonding with copper(I), azides with ancillary copper-binding ligands (aka chelating azides), and copper catalysts that resist aggregation, balance redox activity with Lewis acidity, and allow for dinuclear cooperative catalysis are favored in CuAAC reactions. Brief discussions on the mechanistic aspects of internal alkyne-involved CuAAC reactions are also included, based on the relatively limited data that are available at this point.