Fakultät für Chemie und Biochemie, Organische Chemie I, Ruhr-Universität Bochum , Universitätsstrasse 150, 44801 Bochum, Germany.
J Am Chem Soc. 2015 Sep 23;137(37):12110-20. doi: 10.1021/jacs.5b07863. Epub 2015 Sep 10.
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 ≈ 4 × 10(6) M(-1), ΔG ≈ 38 kJ/mol).
与在有机催化中牢固确立的氢键不同，卤素键在该领域的应用仍然非常有限。在此，我们首次展示了阳离子卤素键供体在卤化物消除反应中的催化应用。首先，系统地测试了基于卤代吡啶鎓、卤代咪唑鎓和卤代-1,2,3-三唑鎓的催化剂。与吡啶鎓化合物相比，咪唑鎓和三唑鎓盐都显示出了有希望的潜力。对于基于卤代咪唑鎓的有机催化剂，我们可以证明使用氯化衍生物等作为参考化合物，催化活性基于卤素键。在此基础上，进一步研究了卤代苯并咪唑鎓有机催化剂。单核化合物表现出与相应的咪唑鎓类似物相同的趋势，但具有更强的催化活性。为了制备预组织用于阴离子结合的双齿化合物，合成并结构表征了一类新型刚性双（卤代苯并咪唑鎓）化合物。相应的顺式异构体表现出前所未有的催化效力，在 1-氯异吲哚与硅烯醇醚的基准反应中，只需使用低至 0.5 mol%的催化剂即可进行。计算确认顺式异构体可能以双齿方式结合氯离子。相应的反式异构体活性较低，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，顺式异构体导致 20 倍的速率加速。在相同溶剂中较高温度下存在氯离子时，观察到分解，表明预组织卤素键供体的强度接近反应条件下的极限。顺式异构体与溴化物的量热滴定证实了前者的强卤素键供体强度（K≈4×10(6)M(-1)，ΔG≈38kJ/mol）。
