New Catalysis and Continuous Flow Strategies Toward the Synthesis of Compounds of Interest in Medicinal Chemistry and Materials Science

药物化学和材料科学中感兴趣的化合物合成的新催化和连续流动策略

• 批准号: RGPIN-2015-04062
• 负责人: Collins, Shawn
• 金额: $ 3.28万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689047
• 关键词: New; Catalysis; Continuous; Flow; Strategies

Chemical synthesis plays a critical role in the development of fields such as the medicinal and the materials sciences. The present proposal describes new synthetic strategies to access molecules that can significantly impact medicinal chemistry (macrocycles) and materials science (helically chiral aromatics), but suffer from a lack of efficient synthetic methods for their preparation. The proposal addresses the longstanding synthetic challenges associated with each of the classes of compounds. In particular, new forms of catalysis and continuous flow technology will be developed. For the synthesis of macrocycles, the development of new catalytic methods to generate diversely functionalized skeletons is a limiting factor in the exploration of new properties of macrocycles. Our proposal describes the development of novel annulations reactions of diynes, an underexplored functional group in organic chemistry, in macrocyclization chemistry. The annulations allow for the rapid introduction of heterocycles into macrocyclic frameworks. Through exploiting macrocyclization technology in continuous flow, large quantities of macrocyclic frameworks can be formed early in a synthetic route at high concentrations. The new macrocycles with embedded heterocycles can be further functionalized using established protocols to afford diverse unique macrocyclic structures. The second aspect of the proposal concerns the synthesis of helically chiral carbon based materials, or helicenes, which have found numerous applications in chemical sciences. Unfortunately, the exploration of higher derivatives is limited by the traditional UV light mediated methods developed over 40 years ago. The proposal describes a combination of visible light-mediated photoredox strategies and continuous flow techniques to improve the synthesis of smaller helicenes while allowing access to higher carbo- and heterohelicenes. The synthesis of new sensitizer structures based on earth-abundant metals, or organic chiral sensitizers for enantioselective catalysis is motivated by the need to develop "greener" synthetic processes. The application of flow technologies significantly accelerates photochemical processes and will allow gram-scale syntheses of the target compounds for the first time. Altogether, the fundamental research in molecular synthesis described in the present proposal aims to provide methods which are ever more energy efficient, environmentally friendly, safe and produce less waste. While the methods proposed would allow access to interesting and important molecular structures, the catalysis and continuous flow techniques would also have application for a wide variety of compound classes. Consequently, the proposed research should have a significant impact and form HQP that are trained in state-of-the-art synthetic techniques.

化学合成在医药和材料科学等领域的发展中起着至关重要的作用。本提案描述了新的合成策略，以获得可以显著影响药物化学（大环化合物）和材料科学（螺旋手性芳族化合物）的分子，但缺乏有效的合成方法用于其制备。该提案解决了与每类化合物相关的长期合成挑战。 特别是，将开发新形式的催化和连续流动技术。 对于大环化合物的合成，开发新的催化方法来生成双取代基官能化骨架是探索大环化合物新性质的限制因素。我们的建议描述了在大环化化学中，二炔，一个在有机化学中研究较少的官能团的新型成环反应的发展。 环化允许将杂环快速引入大环框架中。通过开发连续流中的大环化技术，可以在合成路线的早期以高浓度形成大量的大环骨架。具有嵌入的杂环的新大环可以使用已建立的方案进一步官能化以提供不同的独特大环结构。 该提议的第二个方面涉及螺旋手性碳基材料或螺旋烯的合成，其在化学科学中有许多应用。不幸的是，高级衍生物的探索受到40多年前开发的传统紫外光介导方法的限制。该提案描述了可见光介导的光氧化还原策略和连续流技术的组合，以改善较小的螺旋烯的合成，同时允许获得更高的碳和杂螺旋烯。基于地球上丰富的金属的新敏化剂结构的合成，或用于对映选择性催化的有机手性敏化剂的合成是由开发“绿色”合成方法的需要所激发的。流动技术的应用大大加速了光化学过程，并将首次实现目标化合物的克级合成。总之，本提案中所述的分子合成基础研究旨在提供更节能、更环保、更安全和产生更少废物的方法。虽然提出的方法将允许访问有趣的和重要的分子结构，催化和连续流动技术也将有各种各样的化合物类的应用。 因此，拟议的研究应该有重大的影响，并形成HQP，在国家的最先进的合成技术的培训。