Development of Novel Synthetic Methods Using Flow Chemistry Techniques

需要新的合成方法来克服当前化学转化的局限性，使合成更短，更环保，更原子经济。流动化学领域将对有机合成学科产生变革性的影响，使化学能够提高合成效率，并提供新的反应和新的反应性。与传统的批量方法相比，流动化学技术具有许多实际优势，例如提高光化学效率，易于放大，将多个合成步骤合并到单个流动序列中，增强对反应中间体和放热反应的控制，同时允许快速反应优化并避免昂贵的纯化程序。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工具箱，为化学家提供下一代合成杂环和天然产物（聚酮）的策略，克服目前的限制。我的研究计划的中心主题是发现和发展新的C-C键形成反应，并将由2个长期目标组成：（目标1）发现和发展流动化学方法，用于合成有问题的杂环；（目的2）天然产物合成的流动光氧化还原催化方法的发展和新反应的发现。作为初步结果的延续，我进一步提出了每个目标的2个短期目标（5份同行评审的手稿），并将重点关注流动合成方法的发现和发展：a)杂环的-官能化；b)针对问题杂环的流动光环合成方法的发展；c)通过流动光氧化还原催化合成-羰基化合物，增强了聚酮的组装；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，提供目前使用现有方法合成挑战的杂环和天然产物，开发合成高价值复杂分子的新方法。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点，大大降低合成成本，允许更环保的加工，实现快速合成，同时也提供了优于传统批处理方法的新转化。此外，行业对具有有机化学和合成技术高水平能力的学员有强烈的需求，我的培训计划（13+ HQP）直接解决了这一差距，并培养了具有高需求的跨学科技能组合的学生。

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 -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 -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.