Active-Metal Template Synthesis of a Molecular Trefoil Knot
Active-Metal Template Synthesis of a Molecular Trefoil Knot
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DOI：
10.1002/anie.201105012
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Zengerle, Michael
中科院分区：
文献类型：
--
作者：
Barran, Perdita E.;Cole, Harriet L.;Zengerle, Michael
虽然已经引入了许多不同的方法来合成索烃和轮烷，[1]但很少有成功开发用于合成分子结的策略。[2]三叶结，除了拓扑上平凡的解结（即任何环或简单的大环）之外最简单的素结，[3]已经在DNA，[4]蛋白质，[5]和合成聚合物中发现。[6]Sauvage及其同事通过使用围绕两个四面体CuI中心的两条配体链的预组织作为关键模板相互作用来制备第一个合成分子结，以产生三叶结所需的三个交叉点。[7]随后，供体-受体相互作用，[8]沃森-克里克碱基配对，[9]酰胺氢键，[10]和八面体金属离子周围的配体折叠[11]都被用来模板形成分子三叶结。[12]几年前，一种合成轮烷和索烃的策略被引入，其中金属离子扮演双重角色，作为模板来包裹或缠绕结构单元，同时还积极催化共价捕获互锁结构的键形成反应。[13]这种“活性模板”方法已被证明是获得各种类型的机械互锁分子的有效途径，并且可以通过使用越来越多的不同过渡金属催化反应来应用。[13j]在这里，我们报告的活性模板反应，发生通过经典的“被动模板”协调，合成迄今为止报道的最小三叶结生成的环。通过1H和13 C NMR光谱、质谱和漂移管离子迁移质谱（DT IM-MS）实验表征三叶结，所述实验表明分子结具有比相应的开链和非结大环异构体显著更小的横截面积（具有更窄的分布）。为了将活性模板合成应用于三叶结结构，我们设想了一种系统（图1），其中每个末端（X和Y）具有反应性官能团的单个分子链可以通过与金属离子（M）的多次相互作用进行几何操作和打结。首先，通过链中的两个双齿结合位点与四面体金属离子配位，在链中形成环（图1，步骤1）。第二金属离子通过单齿连接位点在环内内局部结合，然后将执行以下双重任务：1）以由金属的优选配位几何形状决定的特定取向聚集两个官能端基，并将它们置于环的相对侧（图1，步骤2），和2）催化端基之间的共价键形成反应以产生分子三叶结（图1，步骤3）。配体1（方案1）由市售起始材料（用于实验）以九个步骤合成。
Although many different approaches to catenanes and rotaxanes have been introduced,[1] few strategies have been successfully developed for the synthesis of molecular knots.[2] Trefoil knots, the simplest prime knot other than the topologically trivial unknot (ie, any ring or simple macrocycle),[3] have been found in DNA,[4] proteins,[5] and in synthetic polymers.[6] Sauvage and co-workers prepared the first synthetic molecular knot by using the preorganization of two ligand strands around two tetrahedral CuI centers as the key template interaction to generate the three crossing points required for a trefoil knot.[7] Subsequently, donor–acceptor interactions,[8] Watson–Crick base pairing,[9] amide hydrogen bonding,[10] and ligand folding around an octahedral metal ion [11] have all been used to template the formation of molecular trefoil knots.[12] A few years ago a strategy for the synthesis of rotaxanes and catenanes was introduced in which metal ions play a dual role, acting as a template to entwine or thread the building blocks while also actively catalyzing the bond-forming reaction that covalently traps the interlocked structure.[13] This “active-template” approach has proven to be an effective route to various types of mechanically interlocked molecules and can be applied by using an increasing number of different transition-metal-catalyzed reactions.[13j] Herein we report an active-template reaction that occurs through a loop generated through classical “passive-template” coordination to synthesize the smallest trefoil knot reported to date. The trefoil knot was characterized by 1H and 13C NMR spectroscopy, mass spectrometry, and by drift tube ion mobility mass spectrometry (DT IM-MS) experiments that show that the molecular knot has a significantly smaller cross-sectional area (with a narrower distribution) than the corresponding open-chain and unknot-macrocycle isomers. To apply active-template synthesis to a trefoil knot architecture, we envisaged a system (Figure 1) in which a single molecular strand with reactive functional groups at each terminus (X and Y) could be geometrically manipulated and knotted through multiple interactions with metal ions(M). First, a loop in the strand would be formed by coordination of two bidentate binding sites in the strand to a tetrahedral metal ion (Figure 1, step 1). A second metal ion, bound endotopically within the loop by a monodentate ligating site, would then perform the twofold tasks of 1) gathering both functional end groups in a specific orientation that is dictated by the metal s preferred coordination geometry and places them on opposite sides of the loop (Figure 1, step 2), and 2) catalyzing a covalent-bond-forming reaction between the end groups to generate the molecular trefoil knot (Figure 1, step 3). Ligand 1 (Scheme 1) was synthesized in nine steps from commercially available starting materials (for experimental