Cationic Iodine(I)-based halogen bond donors in enantioselective organocatalysis

卤素键合（XB）在非共价有机催化中的应用现在可以被认为是已经建立的，然而到目前为止，只有两个实例已经发表，其中对映选择性转化主要基于XB。以成功的XB催化的不对称向山羟醛缩合反应为起点，该研究领域将在本项目中得到决定性的进一步发展。在第一个子项目中，将通过DFT计算和实验研究详细阐明不对称诱导的机制，以便能够系统地进一步优化催化剂。在第二个子项目中，将实现使双齿双（碘咪唑）基催化剂结构多样化的各种选择：a）除了目前使用的1，3-苯骨架外，还将利用已经在非手性体系中研究过的1，4取代模式。因此，扩展的咬合角应允许接近新的基材。B）通过使用不同的结构单元（氨基醇）和合成路线，刚性手性侧臂的环尺寸将系统地变化。然后可以预期结合口袋的根本不同的几何形状。c）通过这些方法产生的所有核心结构将配备有另外的取代基。除了使用相应的更复杂的氨基醇作为起始原料之外，更重要的是，将根据我们小组已经进行的初步工作开发催化剂结构后期官能化的方法。除了纯粹的空间修饰，这也将允许获得强大的双官能卤素键供体。在第三个子项目中，新的底物和反应将通过更大的催化剂选择来实现不对称XB催化。特别是在这个项目中开发的双功能催化剂应该能够显着扩展可以催化的反应的剧目。此外，将特别研究“软”底物的活化（根据HSAB原理），因为具有类似“软”卤素原子的XB供体应该理想地适合于这些化合物。因此，对这种不对称诱导的更深入理解和催化剂结构基础的显着拓宽应该为建立对映选择性XB催化作为HB催化的互补对应物提供基础-并且从长远来看，系统地利用这种相互作用的特殊功能。

The use of halogen bonding (XB) in noncovalent organocatalysis can be considered as established by now, however only two examples have so far been published in which enantioselective transformations are based primarily on XB. With a successfully XB-catalyzed asymmetric Mukaiyama aldol reaction as starting point, this field of research will be decisively developed further in this project. In the first subproject, the mechanism of the asymmetric induction will be elucidated in detail via DFT calculations and experimental studies, in order to be able to systematically further optimize the catalysts.In the second subproject, various options to diversify the structure of a bidentate bis(iodoimidazolium)-based catalyst will be realized:a) next to the currently employed 1,3-benzene backbone, a 1,4 substitution pattern will also be utilized which has already been investigated for achiral systems. The thus-extended bite angle should allow access to novel substrates. b) The ring sizes of the rigid chiral sidearms will be systematically varied by using different building blocks (amino alcohols) and synthesis routes. A fundamentally different geometry of the binding pocket can then be expected.c) All core structures generated by these means will be equipped with further substituents. Next to the use of corresponding more complex amino alcohols as starting materials, more importantly a method for late-stage functionalization of the catalyst structure will be developed based on preliminary work already performed in our group. In addition to purely steric modifications, this will also allow access to powerful bifunctional halogen bond donors. In the third subproject, new substrates and reactions will be made accessible to asymmetric XB catalysis via the larger selection of catalysts. Especially the bifunctional catalysts developed in this project should be able to significantly extend the repertoire of reactions that can be catalyzed. Furthermore, the activation of „soft“ substrates (according to the HSAB principle) will be investigated in particular, as XB donors with their similarly „soft“ halogen atoms should be ideally suited for these compounds. A deeper understanding of this asymmetric induction and a significant broadening of the structural basis of the catalysts should thus provide the foundations to establish enantioselective XB catalysis as complementary counterpart to HB catalysis – and, in the long term, to systematically utilize the special features of this interaction.