New photocatalytic methods for the synthesis of complex heterocyclic scaffolds and base metal-catalysed cross-coupling

本项目福尔斯属于EPSRC合成有机化学研究领域。自大约十年前兴起以来，光氧化还原催化已迅速发展成为合成有机化学的有力工具，应用于放射性标记，聚合物制造和天然产物的全合成等领域。除了为传统的光化学方法提供更温和的替代方案外，可见光光催化剂提供的独特反应模式从根本上改变了有机化学家设计新反应和断开目标分子的方式。在这方面，可见光催化剂在有机合成中的巨大未开发潜力是一个重要的研究途径，特别是考虑到对“绿色”化学的需求日益增长，以确保大规模化学品制造的长期可持续性。在这个项目中，我们的目标是利用几个在可见光下的未开发的反应平台，使新的，广泛适用的合成方法的利益，制药，农业化学和精细化工industries.In第一个实例中，我们的目标是开发新的光催化级联过程能够提供访问以前未知的3-D化学空间。以这种方式快速生成分子复杂性与小分子药物设计特别相关，其中含有高比例的sp3杂化原子的临床候选物比目前占主导地位的商业片段库的“平坦”、富含sp2的支架更有可能成功。我们设想，在这种转化中使用的柠檬酸盐底物，如芳基碘，将促进最近出现的强还原有机染料光催化剂，其显着的成本优势，其贵金属为基础的同行。此外，我们的战略从事未活化的有机卤化物在氧化还原中性光催化循环将克服目前的限制，国家的最先进的转换，涉及这些现成的化合物，这是典型的净reduction.We还试图确定新的可见光诱导的C-C和C-杂原子键形成反应的铜和其他容易获得的过渡金属催化。过渡金属催化是广泛的交叉偶联反应的成熟策略;然而，这种活化模式通常依赖于昂贵且不可持续的催化剂。因此，迫切需要避免高温和贵金属如钯的用于工业相关偶联反应的温和和立体选择性方法，以提高大规模化学过程的成本和能量效率。我们寻求解决这个问题，通过开发新的光化学方法催化的廉价的贱金属催化剂，如铜，用于耦合不同的反应伙伴;原则上，这些反应可以在金属光氧化还原催化（光氧化还原和过渡金属催化的融合）或通过直接激发的光响应过渡金属络合物，这是相对未开发的。

This project falls within the EPSRC Synthetic Organic Chemistry research area.Since its rise to prominence roughly a decade ago, photoredox catalysis has rapidly evolved into a powerful tool in synthetic organic chemistry, with applications in fields as diverse as radiolabelling, polymer manufacture, and the total synthesis of natural products. In addition to providing a milder alternative to traditional photochemical methods, the unique modes of reactivity offered by visible light photocatalysts are fundamentally changing the ways in which organic chemists approach the design of new reactions and the disconnection of target molecules. In this respect, the vast untapped potential of visible light photocatalysis in organic synthesis represents an important avenue of research, especially considering the growing need for 'greener' chemistry to ensure the long-term sustainability of large-scale chemical manufacture. In this project, we aim to exploit several underexplored reactivity platforms in visible light photocatalysis to enable the development of new, broadly applicable synthetic methods of interest to the pharmaceutical, agrochemical and fine chemical industries.In the first instance, we aim to develop novel photocatalytic cascade processes capable of providing access to previously uncharted 3-D chemical space. The rapid generation of molecular complexity in this manner is particularly relevant to small-molecule drug design, where clinical candidates containing a high fraction of sp3-hybridized atoms are more likely to succeed than the 'flat', sp2-rich scaffolds that presently dominate commercial fragment libraries. We envisage that the use of recalcitrant substrates such as aryl iodides in such transformations will be facilitated by the recent advent of strongly reducing organic dye photocatalysts, which present significant cost advantages over their precious metal-based counterparts. Moreover, our strategy for engaging unactivated organyl halides in a redox-neutral photocatalytic cycle will overcome the current limitations of state-of-the-art transformations involving these readily available compounds, which are typically net-reductive.We also seek to identify new visible light-induced C-C and C-heteroatom bond-forming reactions catalysed by copper and other readily available transition metals. Transition metal catalysis is a well-established strategy for a wide range of cross-coupling reactions; however, this mode of activation typically relies on costly and unsustainable catalysts. Mild and stereoselective methods for industrially relevant coupling reactions that avoid high temperatures and precious metals such as palladium are therefore urgently needed to improve the cost and energy efficiency of large-scale chemical processes. We seek to address this problem by developing new photochemical methods catalysed by inexpensive base metal catalysts, such as copper, for the coupling of diverse reaction partners; in principle, these reactions could operate under metallaphotoredox catalysis (the fusion of photoredox and transition metal catalysis) or via the direct excitation of a photoresponsive transition metal complex, which is relatively unexplored.