Developing Asymmetric Gold Redox Catalysis for Challenging Chemical Transformations

开发不对称金氧化还原催化来应对具有挑战性的化学转化

• 批准号: 10686074
• 负责人: Xiaodong Shi
• 金额: $ 1.13万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-08-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686074
• 关键词: 3-hydroxybutanal; Acids; Alkenes; Alkynes; Azoles; Biochemistry; Biological; Carbon; Catalysis; Chemicals; Chemistry; Collection; Coupling; Development; Employment; Funding; Goals; Gold; Health; Human; Hydrogen Bonding; Investigation; Iron; Lead; Ligands; Macrocyclic Compounds; Medicine; Methodology; Methods; Molecular Probes; Organic Synthesis; Outcome; Oxidants; Oxidation-Reduction; Pathway interactions; Periodicity; Phosphines; Physical condensation; Preparation; Process; Production; Reaction; Reporting; Research; Research Project Grants; Rest; Science; Skeleton; Structure; System; Therapeutic; Transition Elements; United States National Institutes of Health; Work; biological research; carbene; catalyst; chemical synthesis; cost; insight; novel; novel strategies; novel therapeutics; nucleophilic addition; oxidation; photoactivation; prevent; process optimization; programs; small molecule; small molecule libraries; stereochemistry

Project Summary/Abstract The proposed project’s goal is to develop organic synthesis methodologies for potential applications in biochemistry and medicinal science to solve important problems (optimizing API production process and providing new methods for lead compound preparation etc.), which could ultimately benefit human health. Previous work by this project’s research team has focused on developing new transition metal catalysts with applications for challenging chemical transformation to reach an efficient synthesis of diverse chemicals for medicinal and biological research. Recently, with the employment of strong oxidants or photoactivation conditions, gold(I) oxidation to gold(III) were realized, despite the intrinsic high oxidation potential. These discoveries further advanced the field of gold catalysis, adding redox chemistry as an alternative path into the catalytic cycle. However, major hurdles in the current gold catalytic system exist that limit its full utility to promote some typical chemical synthesis such as asymmetric transformations in redox chemistry, accessing vinyl-gold intermediate without rapid protodeauration, and integration of gold p- acid reactivity with redox chemistry, etc. The proposed project will address these hurdles by developing new strategies and catalysts and by providing new medicinally important avenues toward structures which are often difficult to access. The project aim will address two fundamental questions in the gold catalysis: 1) Can asymmetric gold redox catalysis be achieved through chiral ligand control with gold(I) as the resting state? and 2) Will the integration of multiple gold catalysis reaction modes (p-acid, vinyl-gold and redox chemistry) be integrated in one cycle to achieve highly efficient transformations with good stereoselectivity. Our research program will focus on the following four specific directions: 1) developing new oxidation conditions to achieve gold oxidation for a broader scope of substrates for gold redox catalysis; 2) applying gold/iron dual catalytic system to access vinyl-gold reactivity for direct C-C and C-X bond construction and macrocyclic compound synthesis; 3) applying chiral N,P ligand to achieve enantioselective alkene di- functionalization to provide the key factors that might influence asymmetric gold redox catalysis; and 4) developing new triazole-based chiral ligands systems to achieve gold(III) asymmetric catalysis for rapid and stereoselective C-C and C-X bond constructions. The research’s expected outcomes will result in new strategies and methods for alternative approaches toward biomedically important molecules and new building blocks as molecular probes or potential therapeutic solution.

项目总结/摘要 拟议的项目的目标是开发有机合成方法， 生物化学和医药科学，以解决重要问题（优化API生产工艺， 为先导化合物的制备提供新的方法等），这最终将有益于人类健康。 该项目的研究小组以前的工作主要集中在开发新的过渡金属催化剂上 具有挑战性的化学转化的应用，以实现多种化合物的有效合成， 用于医学和生物学研究的化学品。最近，随着强氧化剂或 在光活化条件下，尽管存在固有的高氧化，但仍实现了金（I）氧化为金（III） 潜力这些发现进一步推进了金催化领域，增加了氧化还原化学作为一种新的催化剂。 进入催化循环的替代路径。然而，目前的金催化体系存在主要障碍 这限制了它在促进某些典型化学合成，如在 氧化还原化学，获得乙烯基-金中间体而无需快速脱质子，以及金p- 酸反应性与氧化还原化学等。拟议的项目将解决这些障碍， 新的策略和催化剂，并提供新的医学重要途径， 往往很难接近。该项目的目标是解决金催化中的两个基本问题： 1)不对称金氧化还原催化能否通过手性配体控制以金（I）作为静止的 州？2）将多种金催化反应模式（p-酸、乙烯基金和氧化还原）的集成 化学）被整合在一个循环中以实现具有良好立体选择性的高效转化。 我们的研究计划将集中在以下四个具体方向：1）开发新的氧化 条件，以实现金氧化，用于金氧化还原催化的更广泛的基底; 2）应用 金/铁双催化体系，以获得用于直接C-C和C-X键构建的乙烯基-金反应性， 大环化合物的合成; 3）应用手性N，P配体实现对映选择性的烯烃双- 官能化以提供可能影响不对称金氧化还原催化的关键因素;以及4） 开发新的基于三唑的手性配体体系，以实现金（III）的不对称催化， 立体选择性C-C和C-X键结构。该研究的预期结果将导致新的 战略和方法的替代方法对生物医学上重要的分子和新的 作为分子探针或潜在的治疗溶液的构建块。