Cationic Multidentate Halogen-Bond Donors in Halide Abstraction Organocatalysis: Catalyst Optimization by Preorganization
Cationic Multidentate Halogen-Bond Donors in Halide Abstraction Organocatalysis: Catalyst Optimization by Preorganization
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DOI：
10.1021/jacs.5b07863
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发表时间：
2015-09-23
影响因子：
15
通讯作者：
Huber, Stefan M.
中科院分区：
文献类型：
--
作者：
Jungbauer, Stefan H.;Huber, Stefan M.
与氢键相比，氢键在有机催化中已经牢固地建立起来，而卤素键在这一领域的应用仍然很少。在此，我们提出了阳离子卤素键给体在卤化物萃取反应中的首次催化应用。首先，系统地测试了卤代吡啶、卤代咪唑和卤代1,2,3-三唑基催化剂。与吡啶类化合物相比，咪唑和三唑盐均表现出良好的效力。对于以卤咪唑为基础的有机催化剂，我们可以证明其催化活性是基于卤素键的，例如，氯化衍生物作为参考化合物。在这些研究的基础上，对卤苯并咪唑类有机催化剂进行了研究。单齿化合物具有与相应的咪唑类似物相同的趋势，但表现出更强的催化活性。为了制备阴离子结合预组织的双齿化合物，合成了一类新的刚性双卤苯并咪唑化合物并对其结构进行了表征。相应的同分异构体表现出前所未有的催化效能，可用于低至0.5 mol %的1-氯异色胺与硅烯醇醚的基准反应。计算证实，syn同分异构体可能以双齿方式与氯化物结合。相应的反异构体活性较低，以单齿方式结合卤化物。动力学研究证实，与中性三齿卤素键供体相比，syn异构体导致了20倍的速率加速。在反应条件下，预组织卤素键供体的强度似乎接近极限，因为在较高温度下，在同一溶剂中存在氯化物时观察到分解。与溴化物同分异构体的量热滴定证实了前者的强卤素键给体强度（K约为4 × 10(6) M-1， δ G约为38 kJ/mol）。
In contrast to hydrogen bonding, which is firmly established in organocatalysis, there are still very few applications of halogen bonding in this field. Herein, we present the first catalytic application of cationic halogen-bond donors in a halide abstraction reaction. First, halopyridinium-, haloimidazolium-, and halo-1,2,3-triazolium-based catalysts were systematically tested. In contrast to the pyridinium compounds, both the imidazolium and the triazolium salts showed promising potency. For the haloimidazolium-based organocatalysts, we could show that the catalytic activity is based on halogen bonding using, e.g., the chlorinated derivatives as reference compounds. On the basis of these studies, halobenzimidazolium organocatalysts were then investigated. Monodentate compounds featured the same trends as the corresponding imidazolium analogues but showed a stronger catalytic activity. In order to prepare bidentate versions which are preorganized for anion binding, a new class of rigid bis(halobenzimidazolium) compounds was synthesized and structurally characterized. The corresponding syn isomer showed unprecedented catalytic potency and could be used in as low as 0.5 mol % in the benchmark reaction of 1-chloroisochroman with a silyl enol ether. Calculations confirmed that the syn isomer may bind in a bidentate fashion to chloride. The respective anti isomer is less active and binds halides in a monodentate fashion. Kinetic investigations confirmed that the syn isomer led to a 20-fold rate acceleration compared to a neutral tridentate halogen-bond donor. The strength of the preorganized halogen-bond donor seems to approach the limit under the reaction conditions, as decomposition is observed in the presence of chloride in the same solvent at higher temperatures. Calorimetric titrations of the syn isomer with bromide confirmed the strong halogen-bond donor strength of the former (K approximate to 4 X 10(6) M-1, Delta G approximate to 38 kJ/mol).