New Heterocyclic Architectures from Cascade Processes

应用有机化学的所有方面都依赖于产生具有有趣性质的各种新型分子结构的能力。这对合成有机化学家提出了持续的要求，以开发和微调各种程序，从而能够合成所需的结构框架。在NSERC的支持下，我的研究实验室和研究计划积极参与了新的合成方法的开发，以从萘/四氢萘核心合成新颖和复杂的分子框架。扩展这方面的专业知识，我计划发明和应用战略使用独特的键形成反应的某些反应性中间体和他们随后使用级联的方式来构建一系列重要的新型分子框架体育各种分子拓扑结构和官能团。本工作采用一锅级联法制备了双极性邻醌甲基化物、邻氮醌甲基化物、N-酰基异喹啉离子及其相关物种，并研究了它们与外/内捕获基团的协同/非协同反应。虽然已知相对较长的时间，这些中间体仍然提供了多种方法来创造性地利用它们来追求新颖和复杂的杂环实体。还将探索在组装框架上进一步创新化学转化的可能性，以制备天然产物和生物活性分子的类似物。在开发这些化学的同时，将通过催化或手性底物采用手性诱导进行不对称合成。为本次调查选择的特定目标骨架预计将拥有各种各样的拓扑结构和属性。在可能的情况下，将进行研究，以揭示合成分子的任何有趣的光谱和电子特性。还将尝试使库的化合物合成提供给同行科学家与互补的专业知识，以研究其作为催化剂，荧光团，分子电子学，药物等的潜力，这项工作需要多步合成，广泛的反应优化和结构测定。因此，我的实验室为高素质的人才提供了一个良好的培训环境。在此资助的任期内，约8名研究生和约15名高级本科生将接受有机合成艺术和科学写作等研究相关技能的高质量培训。这一奋进的研究成果将有利于a）合成化学社区与新方法的发展，B）材料科学社区与新的荧光团和分子电子学的发展，和c）药物开发社区与生物相关分子的几个库的合成。

All aspects of applied organic chemistry rely on the ability to generate a vast variety of novel molecular architectures with interesting properties. This places a persistent demand on the synthetic organic chemists to develop and fine-tune various procedures that enable the synthesis of the desired structural frameworks. With the support from NSERC, my research laboratory and research program has actively been involved in the development of new synthetic methodologies towards the synthesis of novel and complex molecular frameworks from naphthalene/tetralin core. Expanding on this expertise, I plan to invent and apply strategic use of unique bond-forming reactivity of certain reactive intermediates and their subsequent use in a cascade fashion to construct an array of important novel molecular frameworks sporting a variety of molecular topology and functional groups. The proposed work employs generating bipolar o-quinone methides, o-azaquinone methides, N-acyliminium ions and related species and their concerted/non-concerted reactions with external/internal trapping groups in a one-pot cascade process. Although known for a relatively long time, these intermediates still offer a multitude of ways to creatively exploit them in pursuit of novel and complex heterocyclic entities. The possibility of further innovative chemical transformations on the assembled framework will also be explored to prepare analogs of natural products and bioactive molecules. While developing these chemistries, asymmetric synthesis will be undertaken employing chiral induction through catalysis or chiral substrates. The specific target skeletons selected for this investigation are expected to possess a wide variety of topologies and properties. Wherever possible, studies will be undertaken to unravel any interesting spectroscopic and electronic properties of the molecules synthesized. Attempts will also be made to make the library of compounds synthesized available to fellow scientists with complementary expertise to study their potential as catalysts, fluorophores, molecular electronics, pharmaceuticals, etc. This work entails multistep synthesis, extensive reaction optimization, and structure determination. As a result, my lab offers an excellent training environment for highly qualified personnel. During the tenure of this grant, ~8 graduate students and ~15 advanced undergraduate students will receive high quality training in the art of organic synthesis and scientific writing among other research related skills. The research outcome of this endeavor will benefit a) synthetic chemistry community with the development of new methodologies, b) material science community with the development of new fluorophores and molecular electronics, and c) drug development community with the synthesis of several libraries of biologically relevant molecules.