Development of Novel Synthetic Methods Using Flow Chemistry Techniques

需要新的合成方法来克服目前化学转化的局限性，使合成更短、更环保、更节省原子。流动化学领域有望对有机合成学科产生革命性的影响，使化学能够提高合成效率，并提供获得新反应和新反应的途径。流动化学技术与传统的间歇式方法相比具有许多实用的优势，例如提高了光化学效率，易于放大，将多个合成步骤结合到一个流程序列中，增强了对活性中间体和放热反应的控制，同时允许快速反应优化和避免昂贵的纯化过程。我计划利用流动化学的许多优点来创建一个创新合成方法的工具箱，为化学家提供合成杂环和天然产物(聚酮)的下一代策略，克服目前的限制。我的研究计划的中心主题是发现和开发新的C-C键形成反应，并将包括两个长期目标：(OBJ。1)流动化学方法的发现和发展，用于合成有问题的杂环；2)天然产物合成的流动光氧化还原催化方法的发展和新的反应发现。我还为每个目标提出了2个短期目标，作为初步结果的延续(5篇同行评审稿)，并将重点放在流动合成方法的发现和开发上，这些方法包括：a)杂环的α官能化；b)用于合成有问题的杂环的流动光环化方法的开发；c)通过利用流动光氧化还原催化合成α-羰基化合物来增强聚酮的组装；以及d)利用流动光氧化还原催化发现新的反应。通过我们的研究计划，我和我的HQP将开发新的方法，利用现有的方法提供获取杂环和目前构成合成挑战的天然产品的途径，开发合成高价值复杂分子的新方法。其影响和好处将是开发新的合成转化，利用流动化学的许多优势来大幅降低合成成本，允许更绿色的加工，并实现快速合成，同时还提供了优于传统间歇方法的新转化。此外，行业对具备有机化学和合成技术方面高水平能力的学员的需求也很大，我的培训计划(13+HQP)直接解决了这一差距，培养出了拥有这种高需求的跨学科技能的学生。

New synthetic methods are required to overcome the limitations of current chemical transformations, making syntheses shorter, greener and more atom economical. The field of flow chemistry is poised to have a transformative effect on the discipline of organic synthesis by enabling chemistries that enhance synthetic efficiency and by providing access to novel reactions and new reactivities. Flow chemistry techniques offer numerous practical advantages over conventional batch methods, such as increased photochemical efficiency, ease of scale-up, combining multiple synthetic steps into a single flow sequence, and enhanced control over reactive intermediates and exothermic reactions, while simultaneously allowing for rapid reaction optimizations and avoiding costly purification procedures. I plan to use the many benefits of flow chemistry to create a toolbox of innovative synthetic methods that will provide chemists with the next generation of strategies for the synthesis of heterocycles and natural products (polyketides), overcoming current limitations. The central theme of my research program is to discover and develop novel C-C bond forming reactions and will be comprised of 2 long-term objectives: (Obj. 1) the discovery and development of flow chemistry methods for the generation of synthetically problematic heterocycles; (Obj. 2) the development of flow photoredox catalysis methods for natural product synthesis and novel reaction discovery. I have further proposed 2 shorter-term goals per objective as a continuation of preliminary results, (5 peer-reviewed manuscripts) and will focus on the discovery and development of flow synthesis methods for: a) The α-functionalization of heterocycles; b) Development of flow photocyclization methods for the synthesis of problematic heterocycles; c) The enhanced assembly of polyketides via the synthesis of α-carbonyl compounds using flow photoredox catalysis; and d) The discovery of novel reactions using flow photoredox catalysis. Through our research program, my HQP and I will develop new methods that provide access to heterocycles and natural products that currently pose synthetic challenges using existing methods, developing new approaches to the synthesis of high-value, complex molecules. The impact and benefit will be to develop new synthetic transformations that will utilize the many advantages of flow chemistry to drastically reduce synthesis costs, allow for greener processing, and enable rapid synthesis, while also providing access to new transformations that are superior to conventional batch methods. Additionally, a strong need exists in industry for trainees that possess high-level competencies in both organic chemistry and enabling synthetic technologies, with my training plan (13+ HQP) directly addressing this gap and producing students that possess this cross-disciplinary skill set that is in high demand.