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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718065
• 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.

有效合成在医学和材料科学中具有重要应用的分子的新方法和策略的开发至关重要。 由于大多数建立碳-碳键的传统化学反应具有较差的原子经济性，即试剂的量不等于所制造的所有产品的量，过渡金属催化已成为有机化学中的重要领域之一。 近年来，钴金属的均相催化作用受到了科学界的广泛关注，尤其是金（Au）的催化作用。该研究计划的目标是通过开发新的Au（I）催化的环化反应和光氧化还原转化，解决与碳-碳和碳-氮形成相关的基本挑战，该反应具有合成复杂天然产物的普遍适用性。 Au（I/III）盐在许多其它官能团存在下对炔和联烯的高亲和性，结合其稳定阳离子电荷的能力，为发现新颖和有用的反应提供了巨大的机会。此外，膦基二聚金配合物可以用作光催化剂，因为它们具有高能量和长寿命的激发态和强还原电位。光激发的二聚金络合物的独特性质提供了新的化学反应性，这些化学反应性是互补的，但也不同于流行的催化剂，如基于Ir（III）和Ru（II）的多吡啶络合物。具体而言，我们将开发新的光氧化还原转换通过Au（I）/Au（III）氧化还原循环的形成碳环和杂环通过自由基级联和交叉偶联反应。我们还将探索光氧化还原和过渡金属催化的协同合并，使用地球丰富的镧系元素形成碳-碳键。 利用Au（I）催化的环化反应的内在机理差异，我们将开发一种通用策略，通过exo-Diels-桤木/Au（I）催化的多环化反应在单一操作中构建三萜支架。 这为复杂三萜类化合物的有效合成创造了独特的平台，特别是特别难以合成的苦木碱。 为了补充这项研究计划，我们将提出一个有效的全合成银杏内酯B & C通过精心编排的转换，最大限度地减少使用保护基团和氧化还原流。该项目为创新、发现和战略规划提供了肥沃的土壤。 总的来说，该研究计划为开发有效的合成方法和合成重要分子的策略提供了新的平台。 此外，该计划提供了一个包容性的合作培训环境，培养批判性科学思维，创造创新解决方案，并为HQP提供广泛的综合专业知识和战略规划经验。