Novel syntheses of functionalized indoles, quinolines, and isoquinolines

项目摘要 该提案的目标是开发创新的新合成方法 用于合成吲哚、喹啉和异喹啉支架。预计该 提出的方法将提供简单，温和，灵活的合成路线， 官能化吲哚、N-羟基、N-烷氧基吲哚、喹啉、喹啉N- 氧化物、异喹啉和异喹啉N-氧化物。这项研究与以下方面有关： 合成，医药和药物化学家和相关领域的科学家， 工业界和学术界。 拟议的工作分为四个部分，每个部分描述一种新的方法 用于方便地合成官能化的杂环化合物。在第一部分中， 钯催化、碱和CO介导的吲哚/喹啉/异喹啉合成 将与吡咯并喹啉生物碱的简短合成一起提出。的 第二部分在第一部分的基础上扩展到4-芳基喹啉的合成， 在吡啶并吖啶类生物碱合成中的应用。光化学诱导，钯 催化，反应将在第三部分进行审查，与预期的 开发互补的温和方法。最后，碱介导的反应 在没有催化剂的情况下，将在第四部分中研究N-含氧环系统 科. 参与者，其他PI，对该项目将是一个本科生（3 三年中每个夏天三个月）和两名研究生（三年全日制） 年）。学生将接受最先进的有机和有机金属的培训 合成，包括实验设计和执行、产物纯化和产物纯化。 通过光谱方法（NMR，IR，HRMS，UV-VIS， 等）。

Project Summary The objective of this proposal is to develop innovative new synthetic methodologies for the synthesis of indole, quinoline, and isoquinoline scaffolds. It is anticipated that the methodologies proposed would furnish simple, mild, and flexible synthetic routes to an array of functionalized indoles, N-hydroxy, N-alkoxyindoles, quinolines, quinoline N- oxides, isoquinolines, and isoquinoline N-oxides. The research is of relevance to synthetic, medicinal, and pharmaceutical chemists and scientists in related fields both in industry and academia. The proposed work is divided into four sections each describing a novel methodology for expedient synthesis of functionalized heterocyclic compounds. In the first section, palladium catalyzed, base and CO mediated, indole/quinoline/isoquinoline syntheses will be presented together with a short synthesis of pyrroloquinolines alkaloids. The second section expands on the first section into the synthesis of 4-arylquinolines and applications in pyridoacridine alkaloid synthesis. Photochemically induced, palladium catalyzed, reactions will be examined in the third section, with the expectation of the development of complementary, mild, methodologies. Finally, base-mediated reactions to N-oxygenated ring systems in the absence of a catalyst will be studied in the fourth section. The participants, other that the PI, on the project will be one undergraduate student (3 months during each summer for three years) and two graduate students (full time for 3 years). The students will be trained in state of the art organic and organometallic synthesis including experimental design and execution, product purification, and product identification and characterization by spectroscopical means (NMR, IR, HRMS, UV-VIS, etc.).