Harnessing continuous flow for the synthesis of complex functional molecules. The project will deliver a new approach to the synthesis of medinally im

现有的合成复杂功能分子的“基准”方法通常是逐步的，涉及分离中间体。这可能会降低效率和总体化学产量；同时增加了费用并产生了大量的化学废物。相比之下，连续流技术可以适应多种化学反应，而无需分离任何中间体。现成的、负担得起的、连续流动的技术有可能彻底改变化学合成。传统的、循序渐进的复杂化学合成方法现在可以使用该技术进行顺序合成，从而降低成本、浪费和重要的时间。该项目将利用这种方法，通过检查具有重要医学意义的化合物（如杂环、构象受限的环丁烷）的顺序形成，以及使用这种连续流动方法探索具有挑战性的化学键（如C-CF3）的形成。最初的工作将研究使用一种新的光氧化还原有机催化烯胺和烯胺二聚化的构象限制环丁烷的形成。这将是过程，然后将被转移到连续流。随着有效条件的发现，这种方法将扩展到具有挑战性的杂环支架的合成（例如氮杂啶）和具有挑战性的化学键的形成。大部分化学将使用我们最近获得的连续流设备进行，并将为成功的申请人提供21世纪制药行业所需的必要技能。此外，考虑到目标分子的性质，该项目将使申请人接触到现有的并发项目，例如我们最近的EPSRC AMR计划。这个项目符合EPSRC Dial-a-Molecule的大挑战。

The existing 'benchmarked' methodology for the synthesis of complex functional molecules is typically step-wise in nature and involving isolation of intermediates. This can compromise efficiency and overall chemical yields; while increasing expense and generating significant chemical waste. In contrast, Continous Flow Technology can potentially be adapted to undertake multiple chemical reactions, without isolation of any intermediates. Off-the-shelf, affordable, continuous flow technology has the potential to revolutionise chemical synthesis. The traditional, step-wise approaches to complex chemical synthesis can now potentially be undertaken sequentially using this technology, therefore reducing cost, waste and importantly time. This project will exploit this approach by examining the sequential formation of medicinally important compounds such as heterocycles, conformationally restricted cyclobutanes, as well as exploring the formation of challenging chemical bonds (such as C-CF3) using this continuous flow approach. Initial work will investigate the formation of conformationally restricted cyclobutanes using a novel photoredox organcatalytic dimerisation of enamines and allenamines. This will be process will then be transferred into continuous-flow. With effective conditions found, this approach this will be expanded to the synthesis of challenging heterocyclic scaffolds (e.g. azetidines) and the formation of challenging chemical bonds. Much of this chemistry will be undertaken using our recently acquired continuous flow apparatus, and will equip the successful applicant with the requisite skill-set required in the 21st century pharmaceutical industry. Additionally, given the nature of the target molecules, the project will expose the applicant to existing concurrent projects such as our recent EPSRC AMR initiative. This project fits within the EPSRC Dial-a-Molecule grand challenge.