超分子锚定的有机催化剂的设计合成及其在合成SuFEx点击反应合成子中的应用

Important trends in organic conversions combine keywords like: ‘water-based’, ‘continuous rather than batch-wise’, ‘(organo)catalytic’, and ‘regeneration’. Yet the currently predominating situation for reactions in which a catalyst is immobilized onto a surface is that the reaction functions for a while, after which the catalyst becomes deactivated. As a result, the reaction vessel need to be reloaded with new catalyst-functionalized material. This is a time-consuming, material-wasting effort. In the current proposal we aim for a way out that hinges on a very strong, yet reversible supramolecular binding of various catalysts to the surface...We aim to construct in a stepwise fashion a multi-step reactor that is locally functionalized with macrocyclic host molecules –cucurbituril[7] (CB[7]) and pillar[5]arene (P5) dimers– that are covalently bound to the surface of e.g. plastic or glass microspheres (see Figure 1). These hosts can bind, in water and in a specific and mutually orthogonal manner, adamantane and pyridinium-based derivatives, respectively. These adamantyl/pyridinium guests can thus function as an anchor for the organocatalyst. This catalyst immobilization has many advantages, including highly improved purification of reaction product; easy removal/replacement of the anchor upon deactivation of the catalyst; compatibility with continuous flow and thus strongly reducing handling; mimicking of homogenous reactions by choice of an appropriate linker; if desired: catalyst regeneration, leading to reduced waste and costs. We will use this reaction sequence to develop novel routes to wide-classes of SuFEx-ready materials, as SuFEx is one of the upcoming click reactions1-3 for which novel entries are of significant interest...This project hinges on strong binding of the anchor. While a plethora of anchors is available, up to now there is actually only one that is stable enough to function in this manner in aqueous flow (i.e. is not eventually washed out), namely the adamantyl-CB[7 or 8] system, for which binding constants of 1011-1014 M–1 have been reported.4 For example, the P5-pyridinium system typically yields K ~ 105 M–1 and lower, and this is not enough. Therefore we will also develop a novel P5-based anchor that should bind anchor molecules much more strongly, via a fully novel route to so-called ‘extended barrel’ P5-dimers. In fact, to the best of our knowledge we introduce here an altogether novel type of multivalency, in-line multivalency, in which the positioning of the first ligand induces the position of the second. ..Using surface-bound CB[7] and P5-dimer hosts we will selectively immobilize two organocatalysts –for Michael additions and 1,2-additions, respectively–, thus creating a cascade of catalysts. While tightly bound, for regeneration the catalysts can simply be removed by application of the appropriate external trigger (e.g. solvent, temperature).

针对固相催化的催化剂失活和再生的问题，我们提出使用可逆的超分子相互作用连接的催化剂，即超分子锚定的催化体系来解决这个问题。除了现有的葫芦脲[7]-金刚烷体系可用作这种超分子锚，还设计了一种新型的柱[5]芳烃二聚体作为超分子锚，这类分子不仅可以高效地结合吡啶类客体，而且可以实现概念上全新的“线性多价相互作用”。由于葫芦脲[7]-金刚烷和柱[5]芳烃二聚体-吡啶盐的正交性，我们将构建一个串联反应器，该反应器的不同模块分别用葫芦脲 [7]和柱[5]芳烃（P5）二聚体功能化，这些主体可以在水中以特定且相互正交的方式分别与带有不同催化剂的金刚烷和吡啶盐衍生物结合。这些金刚烷基/吡啶盐客体因此可以用作有机催化剂的锚，这样带有锚定分子的催化剂的局部定位以及特定时间后的流动去除成为可能。通过这种方式，可以显著延长催化剂本身的寿命，并且催化剂本身可以通过注入新鲜催化剂而被重新激活。

针对固相催化的催化剂失活和再生的问题，我们提出使用可逆的超分子相互作用连接的催化剂，即超分子锚定的催化体系来解决这个问题。除了现有的葫芦脲[7]-金刚烷体系可用作这种超分子锚，还设计了一种新型的柱[5]芳烃二聚体作为超分子锚，这类分子不仅可以高效地结合吡啶类客体，而且可以实现概念上全新的“线性多价相互作用”。由于葫芦脲[7]-金刚烷和柱[5]芳烃二聚体-吡啶盐的正交性，我们将构建一个串联反应器，该反应器的不同模块分别用葫芦脲 [7]和柱[5]芳烃（P5）二聚体功能化，这些主体可以在水中以特定且相互正交的方式分别与带有不同催化剂的金刚烷和吡啶盐衍生物结合。这些金刚烷基/吡啶盐客体因此可以用作有机催化剂的锚，这样带有锚定分子的催化剂的局部定位以及特定时间后的流动去除成为可能。通过这种方式，可以显著延长催化剂本身的寿命，并且催化剂本身可以通过注入新鲜催化剂而被重新激活。我们聚焦于新型柱芳烃作为主体分子通过主客体“线性多价相互作用”的构建来解决催化剂固载问题，成功地合成了一系列单边缘修饰柱[5]、柱[6]芳烃，并对柱芳烃单体和二聚体的主客体性质进行了研究，取得了一系列重要研究成果。这些研究成果均已发表，为后续的应用研究奠定了基础。