Organocatalysis with cationic chalcogen bond donors

阳离子硫属键供体的有机催化

• 批准号: 457341038
• 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/457341038?language=en
• 关键词: Organocatalysis; cationic; chalcogen; bond; donors

Even though chalcogen-bonding-based non-covalent organocatalysis is a comparably novel field of research, several studies have by now demonstrated proof-of-principle cases of this concept. The respective catalysts were structurally quite different and were based on neutral polyfluorinated compounds, chalkogen-containing heteroaromatics or (poly)cationic backbones. Next to SN1 substrates, imines as well as carbonyl and nitro derivatives could be successfully activated as well. However, all previously reported catalysts were achiral. In this project, chalcogen-bonding-based organocatalysis will be further developed. In the first subproject, known achiral catalysts will be employed to:a) conduct mechanistic studies of known catalyses via the analyses of reaction kinetics.b) determine the effect of various parameters on the Lewis acidity of catalysts via systematic ITC- or NMR-titrations.c) extend this catalysis concept continuously toward further substrate classes and reactions.d) study the regioselectivity in the activation of bifunctional substrates.In the second subproject, chiral chalogen bond donors will be developed for the first time and will be used in enantioselective transformations. All catalysts will be based on achiral dicationic backbones established by our group, but now chiral substituents will be introduced at the chalcogen centers. In this context, annelated ring systems will in particular be utilized to provide rigid chiral structures. Suitable bidentate catalysts will then be employed in potentially enantioselective reactions which have already been activated by achiral chalcogen bond donors. In the third subproject, novel mixed Lewis acids with a halogen- and chalcogen-bonding donor motif each will be synthesized. The primary focus will be on studies toward the cooperativity of both Lewis acidic centers, especially in comparison with the respective „pure“ bidentate variants. In the mid-term, both donor centers will be fixed in space via hindered rotation in a fashion which will generate atropisomers with intrinsic chirality. These unprecedented chiral Lewis acids will then also be used for asymmetric induction. By the further advancements in this projects, chalcogen-bonding-based non-covalent organocatalysts shall be established as „soft“ alternatives to hydrogen bond donors in the long term. First studies indicate already that the Lewis acidity of chalcogen-based catalysts is apparently superior to the one of comparable hydrogen- or halogen-bond-donors. In addition, the existence of a second substituent on the chalcogen center makes this interaction seem particularly predestined for chiral structures.

尽管基于硫键的非共价有机催化是一个相对较新的研究领域，但目前已有几项研究证明了这一概念的原理。这两种催化剂在结构上有很大的不同，它们都是基于中性多氟化合物、含硫杂芳烃或（聚）阳离子骨架。在SN1底物旁边，亚胺以及羰基和硝基衍生物也可以被成功激活。然而，所有先前报道的催化剂都是非手性的。在本项目中，将进一步发展基于硫键的有机催化。在第一个子项目中，已知的非手性催化剂将被用于：a)通过反应动力学分析对已知催化剂进行机理研究。b)通过系统的ITC-或核磁共振滴定来确定各种参数对催化剂路易斯酸度的影响。c)将这一催化概念不断扩展到进一步的底物类别和反应中。D)研究双功能底物活化的区域选择性。在第二个子项目中，将首次开发手性氯基键供体，并将其用于对映选择性转化。所有的催化剂都将基于我们小组建立的非手性骨架，但现在将在硫中心引入手性取代基。在这种情况下，环形系统将特别用于提供刚性手性结构。然后，合适的双齿催化剂将用于潜在的对映选择性反应，这些反应已经被非手性碳键供体激活。在第三个子项目中，将合成具有卤素键和硫键给体基序的新型混合路易斯酸。主要的重点将是研究两个刘易斯酸性中心的协同性，特别是与各自的“纯”双齿变体进行比较。在中期，两个供体中心将通过阻碍旋转在空间中固定，从而产生具有固有手性的旋回体。这些前所未有的手性路易斯酸也将用于不对称诱导。随着该项目的进一步进展，从长远来看，基于硫键的非共价有机催化剂将成为氢键供体的“软”替代品。最初的研究已经表明，基于硫的催化剂的刘易斯酸度明显优于类似的氢或卤素键供体催化剂。此外，在硫原中心的第二个取代基的存在使得这种相互作用似乎特别注定了手性结构。