Organocatalysis with cationic chalcogen bond donors

尽管基于硫族元素键合的非共价有机催化是一个非常新颖的研究领域，但到目前为止，已有几项研究证明了这一概念的原理。各自的催化剂在结构上完全不同，并且基于中性多氟化化合物、含白垩基的杂芳族化合物或（聚）阳离子主链。除了SN 1底物，亚胺以及羰基和硝基衍生物也可以成功地活化。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族化合物键合的有机催化。在第一个子项目中，已知的非手性催化剂将用于：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NMR-滴定确定各种参数对催化剂的刘易斯酸性的影响。c）将这种催化概念不断扩展到更多的底物类别和反应。d）研究双官能底物活化中的区域选择性。在第二子项目中，将首次开发手性卤素键供体，并将其用于对映选择性转化。所有的催化剂将基于我们小组建立的非手性双阳离子骨架，但现在手性取代基将被引入硫族中心。在本文中，稠环体系将特别用于提供刚性手性结构。合适的双齿催化剂然后将用于已经被非手性硫属元素键供体活化的潜在的对映选择性反应。在第三个子项目中，将合成具有卤素和硫属元素键合供体基序的新型混合刘易斯酸。主要重点将是对两个刘易斯酸性中心的协同性的研究，特别是与各自的“纯”双齿变体的比较。在中期，两个供体中心将通过受阻旋转以产生具有固有手性的阻转异构体的方式固定在空间中。这些前所未有的手性刘易斯酸也将用于不对称诱导。通过该项目的进一步发展，硫族化合物键合基非共价有机催化剂将被确立为氢键供体的长期“软”替代品。最初的研究已经表明，硫属元素基催化剂的刘易斯酸性明显上级可比的氢键或卤素键供体。此外，硫族元素中心上第二个取代基的存在使得这种相互作用似乎特别适合手性结构。

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.