Copper-free azide-alkyne cycloadditions: New insights and perspectives
Copper-free azide-alkyne cycloadditions: New insights and perspectives
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DOI：
10.1002/anie.200705365
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Lutz, Jean-Francois
中科院分区：
文献类型：
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作者：
Lutz, Jean-Francois
由Sharpless、Kolb和Finn于2001年提出的“点击”概念无疑是新世纪最引人注目的合成趋势之一。[1]“点击”这个吸引人的术语指的是能量上有利的、特定的和多功能的化学转化，它导致单一的反应产物。换句话说，“点击”化学的本质是简单和高效。[2，3]这个诱人的概念似乎完美地回答了现代科学家在分子生物学，药物设计，生物技术，大分子化学或材料科学等不同研究领域工作的需求。[3，4]确实值得注意的是，近年来，需要复杂仪器、苛刻实验条件或高纯化技术的复杂反应的研究频率低于上个世纪，并逐渐被更简单的工具所取代。在这种背景下，直接的“点击”反应在学术和工业研究中都变得非常流行。“点击”类型的反应相当罕见。然而，在过去的几年里，出现了一个基本的“点击”工具箱，其中包括，例如狄尔斯-阿尔德环加成，硫醇-烯加成，肟形成，和铜催化的Huisgen叠氮化物-炔环加成（CuAAC）。[5]然而，在最近的文献中，术语“点击化学”几乎专门用于表示后一种反应。叠氮化物和炔的1，3-偶极环加成反应合成1，2，3-三唑是由亚瑟Michael在19世纪末发现的，并由Rolf Huisgen在20世纪60年代显着发展。在不存在过渡金属催化剂的情况下，这些反应不是区域选择性的，相对缓慢，并且需要高温以达到可接受的产率（方案1A）。在2002年初，Meldal和同事报道了使用催化量的铜（I），其可以结合到末端炔，导致在室温下在有机介质中快速、高效和区域选择性的叠氮化物-炔环加成（方案1B）。[8]不久之后，Sharpless和Fokin证明了CuAAC可以在极性介质中成功地进行，例如叔丁醇，乙醇或纯水。[9]这两个重要的突破导致了Huisgen环加成在合成化学中的显着复兴。因此，在过去几年中，在有机合成、无机化学、高分子化学和生物化学中对CuAAC的研究呈指数级增长。许多作者共同证明了CuAAC是有效和多功能的“点击”化学的真正例子。[10个国家]
The “click” concept, proposed by Sharpless, Kolb, and Finn in 2001, is undeniably one of the most noticeable synthetic trends in this new century.[1] The catchy term “click” refers to energetically favored, specific, and versatile chemical transformations, which lead to a single reaction product. In other words, the essence of “click” chemistry is simplicity and efficiency.[2, 3] This tantalizing concept seems to answer perfectly the needs of modern scientists working in areas of research as diverse as molecular biology, drug-design, biotechnology, macromolecular chemistry, or materials science.[3, 4] It is indeed noteworthy that over recent years, complicated reactions requiring either complex apparatus, harsh experimental conditions, or high-purification techniques, have been less frequently studied than in the last century and gradually replaced by simpler tools. In this context, the straightforward “click” reactions have become tremendously popular in both academic and industrial research. Reactions of the “click” type are rather rare. Yet, the last few years saw the emergence of a rudimentary “click” toolbox, which includes, for example Diels–Alder cycloadditions, thiol–ene additions, oxime formation, and coppercatalyzed Huisgen azide–alkyne cycloadditions (CuAAC).[5] However, in recent literature, the term “click chemistry” has been used almost exclusively to denote the latter reactions. The synthesis of 1, 2, 3-triazoles by 1, 3-dipolar cycloaddition of azides and alkynes was discovered by Arthur Michael at the end of the 19th century and significantly developed by Rolf Huisgen in the 1960s.[6, 7] In the absence of a transition-metal catalyst, these reactions are not regioselective, relatively slow, and require high temperatures to reach acceptable yields (Scheme 1 A). In early 2002, Meldal and co-workers reported that the use of catalytic amounts of copper (I), which can bind to terminal alkynes, leads to fast, highly efficient, and regioselective azide–alkyne cycloadditions at room temperature in organic medium (Scheme1B).[8] Shortly after, Sharpless and Fokin demonstrated that CuAAC can be successfully performed in polar media, such as tert-butyl alcohol, ethanol or pure water.[9] These two important breakthroughs led to a remarkable renaissance of Huisgen cycloadditions in synthetic chemistry. Hence, research on CuAAC has increased exponentially in the last few years in organic synthesis, inorganic chemistry, polymer chemistry, and biochemistry. Numerous authors collectively demonstrated that CuAAC is a true example of efficient and versatile “click” chemistry.[10]