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

现有的用于合成复杂功能分子的“基准”方法在本质上通常是逐步的，并且涉及中间体的分离。这可能会损害效率和总化学产率;同时增加费用并产生大量化学废物。相比之下，连续流技术可以潜在地适用于进行多个化学反应，而无需分离任何中间体。现成的，负担得起的，连续流技术有可能彻底改变化学合成。传统的、逐步的复杂化学合成方法现在可以使用这种技术依次进行，从而减少成本、浪费和重要的时间。该项目将利用这种方法，检查杂环、构象限制的环丁烷等医学重要化合物的顺序形成，以及使用这种连续流方法探索具有挑战性的化学键（例如C-CF 3）的形成。初步工作将调查构象限制环丁烷的形成使用一种新的光氧化还原有机催化二聚的烯胺和丙二烯胺。这将是一个过程，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（例如氮杂环丁烷）的合成和具有挑战性的化学键的形成。大部分的化学将使用我们最近获得的连续流动装置进行，并将装备成功的申请人在21世纪世纪制药行业所需的必要技能。此外，鉴于目标分子的性质，该项目将使申请人接触现有的并行项目，如我们最近的EPSRC AMR计划。该项目符合EPSRC Dial-a-Molecule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.