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”方法通常是分步进行的，涉及中间体的分离。这可能会影响效率和总的化学品产量，同时增加费用并产生大量的化学品废物。相比之下，连续流动技术可能适用于进行多个化学反应，而不需要隔离任何中间体。现成、经济实惠的连续流动技术有可能给化学合成带来革命性的变化。传统的、循序渐进的复杂化学合成方法现在可以使用这种技术按顺序进行，因此减少了成本、浪费，重要的是减少了时间。该项目将通过检查杂环、构象受限的环丁烷等医学上重要化合物的顺序形成，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)的形成来利用这一方法。最初的工作将使用一种新的光氧化还原组织催化烯胺和联烯胺二聚反应来研究构象受限环丁烷的形成。这将是一个流程，然后将转化为连续流程。随着有效条件的发现，这种方法将扩展到合成具有挑战性的杂环支架(例如氮杂环类)和形成具有挑战性的化学键。大部分化学实验将使用我们最近购买的连续流动仪器进行，并将为成功的申请者配备21世纪制药业所需的必要技能。此外，鉴于目标分子的性质，该项目将使申请者接触到现有的同时进行的项目，如我们最近的EPSRC AMR倡议。这个项目符合EPSRC拨打分子的重大挑战。

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.