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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748182
• 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.

开发有效合成在医学和材料科学中有重要应用的分子的新方法和新策略是至关重要的。由于大多数传统的建立碳-碳键的化学反应具有较差的原子经济性，即试剂的数量并不等于所有产物的数量，因此过渡金属的催化作用已成为有机化学的重要领域之一。近年来，铸币金属的均相催化受到了科学界的极大关注，尤其是金(Au)催化。该研究计划的目标是通过开发新的Au(I)催化的环化和光氧化还原转化来解决与碳-碳和碳-氮的形成相关的基本挑战，这些转化普遍适用于合成复杂的天然产物。Au(I/III)盐在存在许多其他官能团的情况下对炔烃和烯烃具有很高的亲和力，再加上其稳定阳离子电荷的能力，为发现新的有用的反应提供了巨大的机会。此外，由于亚膦二聚体金络合物具有高能、长寿命的激发态和较强的还原电势，因此可以作为光催化剂。光激发二聚体金络合物的独特性质提供了新的化学反应活性，这些化学反应与常用的催化剂如Ir(III)和Ru(II)基多吡啶配合物是互补的，但也不同。具体地说，我们将通过Au(I)/Au(III)氧化还原循环开发新的光氧化还原转化，通过自由基级联反应和交叉偶联反应生成碳环和杂环。我们还将探索利用富含稀土的稀土元素来形成碳-碳键的光氧化还原和过渡金属催化的协同融合。利用Au(I)催化的环化反应的内在机理的发散性，我们将开发一种通用的策略，通过外Diels-Alder/Au(I)催化的多环化反应在一次操作中构建三萜支架。这为高效合成复杂的三萜创造了一个独特的平台，特别是特别难合成的喹啉。为了补充这一研究计划，我们将提出一种有效的全合成银杏内酯B和C，通过仔细编排转化，最大限度地减少保护基团的使用和氧化还原流动。该项目为创新、发现和战略规划提供了肥沃的土壤。总体而言，本研究项目为发展高效的合成方法和重要分子的合成策略提供了新的平台。此外，该计划还提供了一个包容的协作培训环境，培养批判性的科学思维，创造创新的解决方案，并为总部提供广泛的综合专业知识和战略规划经验。