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。流动化学领域有望对有机合成学科产生变革性的影响，通过使化学提高合成效率，并提供新的反应和新的反应性。流动化学技术提供了许多优于传统分批方法的实际优点，例如增加的光化学效率、易于放大、将多个合成步骤组合成单个流动序列、以及增强对活性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好处来创建一个创新合成方法的工具箱，为化学家提供下一代杂环化合物和天然产物（聚酮化合物）的合成策略，克服当前的限制。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2个长期目标：（目标1）发现和开发用于合成有问题的杂环的流动化学方法;（目标2）开发用于天然产物合成和新反应发现的流动光氧化还原催化方法。我进一步提出了每个目标2个短期目标，作为初步成果的延续，（5篇同行评议的手稿），并将重点放在发现和发展流动合成方法：a）杂环的-官能化; B）发展流动光环化方法合成有问题的杂环; c）通过使用流式光氧化还原催化合成-羰基化合物来增强聚酮化合物的组装;以及d）使用流式光氧化还原催化发现新的反应。通过我们的研究计划，我和HQP将开发新的方法，提供使用现有方法合成目前构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。其影响和益处将是开发新的合成转化，这些转化将利用流动化学的许多优点来大幅降低合成成本，允许更绿色的加工，并实现快速合成，同时还提供上级传统分批方法的新转化。此外，行业中存在对在有机化学和合成技术方面拥有高水平能力的学员的强烈需求，我的培训计划（13+ HQP）直接解决了这一差距，并培养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 -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.