Pyridine Synthesis via Directed Aziridination of Phenols in Continuous Flow

项目摘要/摘要 吡啶杂环是一种特殊的基序，存在于无数天然产品、药物和 材料。作为化学治疗中最常见的杂环芳环，吡啶的基序是 出现在大量重磅炸弹药物中，如Xalkori、Prilosec和Zytiga。由于巨大的 吡啶在人类生活中的普遍存在，获取这一主题的新的和创新的方法仍然很高 很受追捧。许多制备方法需要专门的起始材料，也需要严格的 已定义的替代模式，限制了结构多样性。相反，转变现成的和 廉价的前体，所有的取代都完好无损，直接到吡啶支架上将构成一个 访问这些框架的简单、灵活和强大的方法。拟议的研究旨在开发一种 连续流动反应器中的定向氮杂环化方法，允许从 易得的苯酚起始原料。这种转变在历史上一直具有挑战性，因为 芳环与氮源的非区域选择性氮杂环化，这导致了复杂的 产品。这一强大的新策略将依赖于定向氮杂环化反应，以在活动中提供区域选择性。 连续流动技术将被证明是这一关键转变的关键，以避免各种不必要的 反应途径在标准间歇合成中是无与伦比的。最后，环状收缩 然后，Process将以多步骤、一流的方法提供高价值的吡啶的库。

Project Summary/Abstract The pyridine heterocycle is a privileged motif that appears in countless natural products, drugs, and materials. As the most prevalent heterocyclic aromatic ring in chemical therapeutics, the pyridine motif is featured in a plethora of blockbuster drugs such as Xalkori, Prilosec, and Zytiga. Due to the enormous prevalence of pyridines in human life, new and innovative methodologies to access this motif remain highly sought after. Numerous preparative methods require specialized starting materials and also necessitate strictly defined substitution patterns, which limit structural diversity. Conversely, transforming readily available and inexpensive precursors, that have all substitution intact, directly to the pyridine scaffold would constitute a simple, flexible, and powerful means to access these frameworks. The proposed research aims to develop a directed aziridination methodology in a continuous flow reactor that would allow access to pyridines from readily available phenol starting materials. This transformation has been historically challenging because of the nonregioselective aziridination of the arene ring with nitrene sources, which leads to complex mixtures of products. This powerful new strategy will rely on a directed aziridination to provide regioselectivity in the event. Continuous flow techniques will prove critical to this key transformation in order to avoid various undesired reaction pathways by means that are unparalleled in standard batch synthesis. Finally, a ring contraction process would then furnish libraries of highly valued pyridines in a multi-step, one-flow approach.