New Directions in Photoredox Gold Catalysis and Total Synthesis

光氧化还原金催化和全合成的新方向

• 批准号: RGPIN-2020-06187
• 负责人: Barriault, Louis
• 金额: $ 6.85万
• 依托单位: University of Ottawa
• 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=741081
• 关键词: New; Directions; Photoredox; Gold; Catalysis

The development of new methods and strategies for the effective synthesis of molecules with important applications in medicine and materials science is of paramount importance. Since most traditional chemical reactions to build carbon-carbon bonds have a poor atomic economy, i.e. the quantity of reagents is not equal to the quantity of all products manufactured, catalysis by transition metals has become one of the essential fields in organic chemistry. In the recent years, homogenous catalysis by coinage metals has received considerable attention by the scientific community, notably catalysis by gold (Au). The goal of this research program is to address fundamental challenges associated with the formation of carbon-carbon and carbon-nitrogen by developing new Au(I)-catalyzed cyclization and photoredox transformations of general applicability for the synthesis of complex natural products. The high affinity of Au(I/III) salts for alkynes and allenes in the presence of many other functional groups, combined with its ability to stabilize cationic charge provide tremendous opportunities for the discovery novel and useful reactions. In addition, phosphino dimeric gold complexes can be used as photocatalyst given their high-energy and long-lived excited states and strong reduction potentials. The unique properties of the photoexcited dimeric gold complex offer new chemical reactivities that are complementary but also different from the popular catalysts such as Ir (III) and Ru (II)-based polypyridyl complexes. Specifically, we will develop new photoredox transformations via Au(I)/Au(III) redox cycle for the formation carbocycles and heterocycles through radical cascade and cross-coupling reactions. We will also explore the synergistic merger of photoredox and transition metal catalysis using earth-abundant lanthanides for the formation of carbon-carbon bonds. Taking advantage of the inherent mechanistic divergence of the Au(I)-catalyzed cyclization, we will develop a general strategy to construct triterpene scaffolds in a single operation through an exo-Diels-Alder/Au(I)-catalyzed polycyclization. This creates a unique platform for the efficient synthesis of complex triterpenes, notably quassines which are particularly difficult to synthesize. To complement this research program, we will propose an efficient total synthesis ginkgolides B & C through a careful orchestration of transformations minimizing the use of protecting groups and redox flow. This project provides a fertile ground for innovation, discovery and strategic planning. Overall, this research program provides a new platform for the development efficient synthetic methods and strategies for the synthesis of important molecules. Also, this program offers an inclusive collaborative training environment that fosters critical scientific thinking, creation of innovative solutions and provide broad synthetic expertise and strategic planning experiences to HQP.

在医学和材料科学中有效应用有效合成分子的新方法和策略至关重要。由于大多数建立碳碳键的传统化学反应的原子经济性较差，即，试剂量不等于所有生产的产品的数量，因此通过过渡金属催化已成为有机化学的重要领域之一。近年来，造币金属的同质催化受到了科学界的极大关注，特别是黄金催化（AU）。该研究计划的目的是通过开发新的AU（I）催化的环化和光电毒素转化，以解决与复杂天然产物合成的一般适用性，以解决与形成碳碳和碳氮相关的基本挑战。在许多其他功能组的情况下，AU（I/III）盐对炔烃和艾伦斯的高亲和力，结合其稳定阳离子电荷的能力为发现新颖的新颖和有用的反应提供了巨大的机会。此外，鉴于它们的高能量和长寿的激发态和强大的还原电位，磷酸二聚体二聚体复合物可以用作光催化剂。光激发二聚体金配合物的独特特性提供了互补的新化学反应性，但与流行的催化剂（例如IR（III）和RU（II）基于基于的polypyridylyyl络合物）不同。具体而言，我们将通过Au（i）/AU（III）氧化还原循环开发新的Photoredox变换，以通过自由基级联反应和交叉偶联反应来形成碳循环和异环体。我们还将探索使用含量丰富的灯笼形成碳碳键的光毒素和过渡金属催化的协同合并。利用AU（i）催化环化的固有机械差异，我们将通过exo-Diels-alder/au（i）催化的多环化在单个操作中制定一般策略，以在单个操作中构建三萜支架。这为有效合成复杂的三萜，尤其是难以合成的明星，为有效合成而创建了一个独特的平台。为了补充该研究计划，我们将通过仔细的转换编排最小化保护组和氧化还原流的使用，提出有效的总合成Ginkgolides B＆C。该项目为创新，发现和战略规划提供了肥沃的基础。总体而言，该研究计划为开发有效的合成方法和策略提供了一个新的平台，以合成重要分子。此外，该计划还提供了包容性的协作培训环境，该环境促进了批判性的科学思维，创建创新解决方案，并为HQP提供广泛的综合专业知识和战略计划经验。