A New Class of Hybrid Polyoxometalate Catalysts for C-H Functionalisation

几十年的化学合成研究提供了许多新的反应来制备社会所需的分子，如药物、农用化学品和材料。现代合成的前沿是后期催化C-H官能化(LSF)，与传统的合成方法相比，它可以更快、更有效地生产各种化合物的库，因为传统的合成方法在早期阶段就发生了多样化，需要更高官能化的底物。然而，尽管取得了许多进展，但仍然存在重大挑战。大多数LSF反应发生在由底物的内在反应性决定的位置，根据空间和/或电子因素定义。在这一领域取得进展的关键是开发一种根本性的新型催化剂，它以独特的设计原则工作，以覆盖固有的底物反应性并控制位点选择性。特别是，需要利用广泛的非共价和动态共价相互作用来结合和定向底物，以暴露一个特定的位置朝向催化剂的反应部分。在这个项目中，我们建议开发一类新的催化剂，利用光化学活化来实现高位置选择性的C-H官能化。多金属氧酸盐簇合物将被有机基团修饰，得到含有底物结合单元的有机-无机杂化材料，以配位和定向底物，以取代固有的反应性。这些新型混合催化剂将用于多种化合物的不同C-H官能化反应，如类固醇和多肽。手性催化剂的制备也将被用来合成富含一种特定对映体(非重叠镜像)的手性产物。我们希望这一研究将有助于开发越来越多的通用和高效的化学合成催化剂。

Many decades of research in chemical synthesis have provided numerous new reactions to prepare molecules required by society, such as pharmaceuticals, agrochemicals, and materials. At the forefront of modern synthesis is late-stage catalytic C-H functionalisation (LSF), which can be faster and more efficient for producing libraries of diverse compounds compared with conventional synthetic approaches, where diversification occurs at an early stage and more highly functionalised substrates are required. However, despite numerous advances, significant challenges remain. The majority of LSF reactions occur at positions dictated by the intrinsic reactivity of the substrates, defined on the basis of steric and/or electronic factors. The ability to override intrinsic substrate reactivity to functionalise at "unexpected" sites in a controllable and switchable manner, is an ongoing challenge.Key to making advances in this area is the development of fundamentally new types of catalysts operating on unique design principles to override intrinsic substrate reactivity and control site-selectivity. In particular, harnessing a wide range of non-covalent and dynamic covalent interactions to bind and orient substrates to expose one particular site towards the reactive part of the catalyst will be required. In this project, we propose to develop a new class of catalysts for highly site-selective C-H functionalisation, using photochemical activation. Polyoxometalate clusters will be modified with organic groups to give organic-inorganic hybrids containing substrate binding units to coordinate and orient substrates to override intrinsic reactivity. These new hybrid catalysts will be used for diverse C-H functionalisation reactions of a wide range of compounds, such as steroids and peptides. The preparation of chiral catalysts to enable the synthesis of chiral products enriched in one particular enantiomer (non-superimposable mirror image) will also be investigated.We hope this research will enable the development of increasingly more versatile and efficient catalysts for chemical synthesis.