Base dependence in copper-catalyzed Huisgen reactions: Efficient formation of bistriazoles
Base dependence in copper-catalyzed Huisgen reactions: Efficient formation of bistriazoles
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DOI：
10.1002/anie.200700399
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Burgess, Kevin
中科院分区：
文献类型：
--
作者：
Angell, Yu;Burgess, Kevin
叠氮化物与炔烃的铜加速 [1, 2] Huisgen 加成 [3, 4] 是“点击化学”的典型例子。 [5]这些最初由 Meldal 和同事报告。[1]从那时起，Sharpless 和同事认识到了他们的特权地位：反应在温和条件下以高产率发生，并且使用对大多数其他官能团没有影响的铜源。 [2]这些反应在当代有机化学中无疑是有用的。[6]在我们的研究小组中，当我们通过这些铜介导的反应制备三唑文库时，我们经常通过分析型 HPLC 观察到少量杂质。 LC-MS 分析表明这些是所需产物的氧化二聚体（即[2M+±2H]）。 Sharpless 和同事之前注意到了如此少量的副产物，并且在没有报告其特征的情况下，他们将这些副产物归因于 CuI 物种的直接使用。 [2]然而，当我们尝试对粗底物进行叠氮化物-炔烃偶联反应时，即使使用 CuSO4/Cu 粉末系统，我们也观察到了大量的这些产物。在这里，我们报告这些氧化二聚体具有结构 1，并且它们可以是碱性条件下的主要产物 [Eq.(1)]。我们改变反应条件，试图优化此 Cu 介导过程中化合物 1a 的产率，但大多数尝试均不成功（参见支持信息）。例如，当在氮气下与 Cu/CuSO4 进行反应时，三唑 2（表 1）是主要产物，但当
Copper-accelerated [1, 2] Huisgen additions [3, 4] of azides to alkynes are archetypical examples of “click chemistry”.[5] These were originally reported by Meldal and co-workers.[1] Since then Sharpless and co-workers recognized their privileged status: the reactions take place with high yields, under mild conditions, and use copper sources that have no impact on most other functional groups.[2] These reactions are undeniably useful in contemporary organic chemistry.[6] In our research group, we often observed a minor impurity by analytical HPLC when we prepared libraries of triazoles through these copper-mediated reactions. LC-MS analyses indicated these were oxidative dimers of the desired product (that is,[2M+À2H]). Sharpless and co-workers previously noticed such minor amounts of by-products and, without reporting their characterization, they attributed these byproducts to the direct use of CuI species.[2] However, we observed significant amounts of these products when we attempted azide–alkyne coupling reactions of crude substrates, even with a CuSO4/Cu powder system. Here we report that these oxidative dimers have the structure 1 and that they can be the major products under basic conditions [Eq.(1)].We varied the reaction conditions in an attempt to optimize the yield of compound 1a in this Cu-mediated process, but most attempts were unsuccessful (see the Supporting Information). For example, triazole 2 (Table 1) was the main product when the reaction was performed under nitrogen with Cu/CuSO4, but the catalyst was rapidly deactivated and the starting materials remained when the