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

对映选择性有机催化中基于碘 (I) 的阳离子卤素键供体

• 批准号: 469036898
• 负责人: Professor Dr. Stefan Huber
• 金额: --
• 依托单位: Lehrstuhl für Organische Chemie I - Organokatalyse und supramolekulare Chemie (AG Huber)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/469036898?language=en
• 关键词: Cationic; Iodine; based; halogen; bond

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.

到目前为止，在非共价有机催化中使用卤素键合（XB）可以认为是确定的，但是到目前为止，只有两个示例已发表，其中对映选择性转换主要基于XB。随着XB催化的不对称的Mukaiyama aldol反应作为起点，该项目将在该项目中坚定发展。 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 birdate bis(iodoimidazolium)-based catalyst will be realized:a) next to the currently employed 1,3-benzene backbone, a还将利用1,4个替代模式，该模式已经针对ACHIRAL系统进行了研究。如此扩展的咬合角应允许进入新的底物。 b）通过使用不同的构件（氨基醇）和合成路线，将系统地改变刚性手性侧侧的环尺寸。然后可以预期结合口袋的根本不同的几何形状。除了使用相应的更复杂的氨基醇作为起始材料之外，更重要的是，将根据我们组中已经进行的初步工作开发催化剂结构的晚期功能化的方法。除了纯粹的空间修改外，这还将允许使用强大的双功能卤素键供体。在第三个底物项目中，将通过较大的催化剂选择使新的底物和反应可用于非对称XB催化。特别是该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曲目。 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 complete counterpart to HB catalysis - 从长远来看，要系统地利用这种交互的特殊功能。