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

卤素键（XB）在非共价有机催化中的应用现在可以被认为是建立起来的，但是迄今为止只发表了两个主要基于XB的对映选择性转化的例子。以xb催化的不对称Mukaiyama醛醇反应的成功进行为起点，本项目将在该领域的研究领域进行决定性的进一步发展。在第一个子项目中，将通过DFT计算和实验研究来详细阐明不对称诱导的机理，以便能够系统地进一步优化催化剂。在第二个子项目中，将实现双齿双（碘咪唑）基催化剂结构多样化的各种选择：a)在目前使用的1,3-苯主链旁边，还将使用已经研究过的非手性体系的1,4取代模式。由此延长的咬角应该允许接触新的基材。b)刚性手性侧臂的环尺寸将通过使用不同的构建单元（氨基醇）和合成路线而系统地改变。然后可以预期，结合袋的几何形状将会完全不同。)通过这些方法生成的所有核心结构都将配备进一步的取代基。除了使用相应的更复杂的氨基醇作为起始材料外，更重要的是，我们将在前期工作的基础上，开发一种后期功能化催化剂结构的方法。除了纯粹的立体修饰外，这也将允许获得强大的双功能卤素键供体。在第三个子项目中，新的底物和反应将通过更多的催化剂选择来实现不对称XB催化。特别是本项目开发的双功能催化剂应该能够显著地扩展可催化的反应范围。此外，“软”底物的活化（根据HSAB原理）将被特别研究，因为具有类似“软”卤素原子的XB供体应该非常适合这些化合物。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著拓宽，将为建立对映选择性XB催化剂作为HB催化剂的互补对应物提供基础，并从长远来看，系统地利用这种相互作用的特殊特征。

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.