Strategies and Methods for the Synthesis of Aromatic Molecules

芳香族分子的合成策略和方法

• 批准号: RGPIN-2020-06251
• 负责人: Snieckus, Victor
• 金额: $ 2.32万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741118
• 关键词: Strategies; Methods; Synthesis; Aromatic; Molecules

Aromatic molecules constitute 80% of marketed drugs and increasingly are components of new materials, eg sensors and smartphone batteries. Invention and development of new methodology for construction of aromatic compounds based on directed ortho metalation (DoM) reaction has been a central theme of our research. DoM has overtaken traditional electrophilic substitution as the principal means for making substituted aromatic rings and the technology, alone or aligned with transition metal-catalyzed chemistry, has been transferred to the synthesis of commercial drugs. Our research will focus on 1. Metalation Routes to Polysubstituted a-Naphthols and Dihydrobenzofurans. These protocols aim to supercede traditional routes and establish new general methods for the construction of a-naphthols, bioactive natural products, and a class of ligands. 2. DoM-DMG Dance in the Synthesis of Heteroaromatics. This project develops new functional group migration (`dance') reactions for the construction of valuable classes of pharmaceutically relevant heterocycles, overcoming lengthy routes. 3. Photoredox Reactions of DMG-bearing Aromatics. The project aims to discover and develop photoredox-catalyzed reactions to complement or supercede our DoM chemistry. 4. DoM-Kulinkovich Reaction link. The project aims to develop a new general route to optically-active cyclopropanols and to discover a Kulinkovich reaction on DoM-derived aromatic molecules of pharmaceutical value. 5. DoM for Azaborinine Synthesis. Molecules of Project 2 will provide precursors for the synthesis of a new class of B-N heterocycles that have distinct properties of future value for organic electronic and sensing materials. 6. Total Synthesis of Natural Products. The project concerns the total synthesis of several bioactive natural products, e.g. alkaloids, aromatic polyketides). The syntheses will showcase our DoM and DreM strategies of broad applicability. 7. Biaryl Atropisomerism. Biaryl atropisomers are molecules that are optically active by virtue of restricted rotation about the central aryl-aryl bond. We aim to synthesize and correlate experimental-computational rotational barriers of simple and macrocyclic biaryls, molecules that are of current interest in drug discovery programs. 8. Amide DMG-directed Ir-catalyzed C-H Bond Activation/Borylative Coupling. In this project, the scope/limitations of the reaction and the orthogonal C-H activation-Suzuki-Miyaura process will be studied. The requested funding will support research activity of 7 MSc, 3 PhD, 10 undergrads, and several visiting grad students (Australia, France, Germany, and Spain).

芳香分子占上市药物的80%，并且越来越多地成为传感器和智能手机电池等新材料的组成部分。基于定向邻位金属化（DoM）反应的芳香族化合物新方法的发明和发展一直是我们研究的中心主题。DoM已经取代传统的亲电取代作为制备取代的芳环的主要手段，并且该技术，单独或与过渡金属催化化学结合，已经转移到商业药物的合成中。我们的研究将集中在1。多取代α-萘酚和二氢苯并呋喃的金属化路线。这些方案的目的是取代传统的路线，并建立新的通用方法，为建设a-萘酚，生物活性的天然产物，一类配体。 2. DoM-DMG在杂环化合物合成中的应用该项目开发了新的官能团迁移（“舞蹈”）反应，用于构建有价值的药物相关杂环类，克服冗长的路线。3.含DMG芳烃的光氧化还原反应该项目旨在发现和开发光氧化还原催化反应，以补充或取代我们的DoM化学。4. DoM-Kulinkovich反应链接。该项目旨在开发一种新的光学活性环丙醇的通用路线，并发现具有药用价值的DoM衍生芳香分子的Kulinkovich反应。5.用于氮杂硼烷合成的DoM。项目2的分子将为合成一类新的B-N杂环化合物提供前体，这些化合物具有未来有机电子和传感材料的独特价值。6.天然产物的全合成。该项目涉及几种生物活性天然产物的全合成，例如生物碱、芳香聚酮化合物。综合将展示我们的DoM和DreM战略的广泛适用性。7.联芳基阻转异构。联芳基阻转异构体是由于围绕中心芳基-芳基键的受限旋转而具有光学活性的分子。我们的目标是合成和相关的实验计算旋转障碍的简单和大环联芳基，分子是目前的兴趣，在药物发现计划。8.酰胺DMG定向Ir催化的C-H键活化/硼化偶联。在本项目中，将研究反应的范围/限制和正交C-H活化-Suzuki-Miyaura过程。所要求的资金将支持7个硕士，3个博士，10个本科生和几个访问格拉德生（澳大利亚，法国，德国和西班牙）的研究活动。