New Heterocyclic Architectures from Cascade Processes

应用有机化学的所有方面都依赖于产生各种具有有趣性质的新颖分子结构的能力。这对合成有机化学家提出了持久的要求，要求他们开发和微调各种程序，使之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项目一直积极参与开发新的合成方法，以合成新颖和复杂的分子骨架。在此专业知识的基础上，我计划发明和应用某些活性中间体独特的成键反应能力的战略应用，并随后以级联方式使用它们来构建一系列具有各种分子拓扑和官能团的重要的新型分子框架。建议的工作是在一锅级联过程中产生双极性邻苯二酚甲基、邻氮喹酮甲基、N-酰亚胺离子和相关物种，以及它们与外部/内部捕获基团的协同/非协同反应。虽然人们知道这些中间体的时间相对较长，但它们仍然提供了多种创造性地利用它们来追求新的和复杂的杂环实体的方法。还将探索在组装的框架上进行进一步创新的化学转化的可能性，以制备天然产品和生物活性分子的类似物。在发展这些化学的同时，不对称合成将通过催化或手性底物进行手性诱导。为这项研究选择的特定目标骨架预计具有广泛的拓扑和性质。只要有可能，就会进行研究，以揭示所合成分子的任何有趣的光谱和电子性质。还将努力使合成的化合物库可供具有互补专业知识的同事使用，以研究它们作为催化剂、荧光团、分子电子学、制药等的潜力。这项工作需要多步骤合成、广泛的反应优化和结构确定。因此，我的实验室为高素质的人员提供了良好的培训环境。在这项资助的任期内，约8名研究生和约15名高级本科生将在有机合成艺术和科学写作以及其他研究相关技能方面接受高质量的培训。这一努力的研究成果将使a)合成化学界开发新的方法学，b)材料科学界开发新的荧光团和分子电子学，以及c)药物开发界合成几个生物相关分子的文库。

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.