Catalytic Asymmetric Oxidation of Alkenes and Alkanes

烯烃和烷烃的催化不对称氧化

• 批准号: 9889145
• 负责人: DUY H HUA
• 金额: $ 29.99万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9889145
• 关键词: Acetamides; Acetates; Acids; Alkanes; Alkenes; Alzheimer' s Disease; Amines; Amino Acids; Aptitude; Atmosphere; Biological; Carbon; Chemicals; Chemistry; Circular Dichroism; Complement; Complex; Copper; Cyclization; Cyclohexanes; Cycloparaffins; Data; Diamide; Distal; Economics; Erythro; Esters; Estrone; Generations; Goals; Gold; Hydrogen; Hydrogen Bonding; Hydrogen Peroxide; Hydroxyl Radical; Image; Imines; Imprisonment; Investigation; Ketones; Knowledge; Lactams; Lactones; Light; Malignant Neoplasms; Metals; Methodology; Methods; Molecular Conformation; Natural Product Drug; Nitrogen; Optics; Oxidants; Oxides; Oxygen; Palladium; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Polymers; Property; Pyrrolidinones; Reaction; Reporting; Research Project Grants; Ribose; Site; Vertebral column; Water; base; bioactive natural products; carbene; catalyst; chiral molecule; design; diene; dimer; functional group; hydrophilicity; improved; interest; metal oxide; nanoGold; nanocluster; nanoparticle; nanoscale; oxidation; particle; stereochemistry

Project Summary The discovery of new methodologies to advance the fields of synthetic organic, medicinal, and material chemistry is critical in the synthesis of pharmaceuticals. Particularly, catalytic asymmetric oxidation reactions are economic, since only a small amount of the catalyst is needed. The oxidation reactions provide chiral molecules and additional functionalities onto the molecules for functional group manipulation. Recently, we discovered a new class of polymers, namely chiral-substituted poly-N-vinylpyrrolidinones (CSPVPs), for stabilization of bimetallic nanoclusters such as palladium/gold or copper/gold nanoparticles in the induction of chirality. These chiral polymers wrap around (or incarcerate) the nanometer-sized (~3 nm) bimetallic nanoparticles and catalyze a number of enantioselective oxidation reactions using oxygen or hydrogen peroxide as the oxidant. For example, alkenes were oxidized by 0.5 mol% of Pd/Au (3:1)-chiral polymer 2R under 2 atmospheric of oxygen in water to give the syn-dihydroxylated products in 73 – 86% chemical and 97 - 99% ee optical yields. Various cycloalkanes underwent regio- and enantio-selective C-H oxidation with 5 mol% Cu/Au (3:1)-2R and 30% hydrogen peroxide to produce the corresponding chiral oxo-molecules in very good chemical and excellent optical yields. We further discovered enantioselective desymmetrization of -dialkenyl-alkanols and -dialkenyl–amino acid ethyl esters with 4 mol% Cu/Au-2R and hydrogen peroxide to give chiral disubstituted lactones and lactams, respectively, in 91 – 96% ee. A number of medium-sized natural products and drugs including N- acetylamantadine, oxymetrine, ambroxide, and 3-pivaloyl estrone were also oxidized regioselectively to give the corresponding mono-oxygenated products in good yields. These exciting results prompted us to propose studies of the scope and mechanisms of the catalytic asymmetric oxidation reactions and late-stage aliphatic C-H oxidation of bioactive complex molecules. Our goal is to discover useful synthetic methodologies in catalytic asymmetric synthesis. Three specific aims are designed to achieve our goal: (1) optimization of the CSPVPs and studies of the scope, mechanisms, and regio- and enantio-selectivity in the oxidation of alkenes and alkanes; (2) investigation of the catalytic asymmetric ring closing reactions by forming C-O and C-N bond from dienols and diene amines, respectively, and the asymmetric imine-Heck C-C bond forming reaction; and (3) investigation of the predictive regioselectivity of C-H oxidation of bioactive complex molecules, which may alter or improve the pharmacological and biological properties of the molecules.

项目摘要 发现新的方法来推进合成有机，医药和材料化学领域 在药物合成中至关重要。特别地，催化不对称氧化反应是经济的， 因为只需要少量的催化剂。氧化反应提供手性分子， 在分子上添加额外的官能团以进行官能团操作。最近，我们发现了一种新的 一类聚合物，即手性取代的聚-N-乙烯基吡咯烷酮（CSPVP），用于稳定聚乙烯 纳米团簇如钯/金或铜/金纳米颗粒诱导手性。这些手性 聚合物包裹（或嵌顿）纳米尺寸（~3 nm）的纳米颗粒，并催化 使用氧或过氧化氢作为氧化剂的对映选择性氧化反应的数目。比如说， 在2个大气压的氧气下，在水中用0.5摩尔%的Pd/Au（3：1）-手性聚合物2 R氧化烯烃， 以73 - 86%的化学产率和97 - 99%ee的光学产率得到顺式-二羟基化产物。各种环烷烃 用5 mol% Cu/Au（3：1）-2R和30% H2 O2进行区域和对映选择性C-H氧化 以非常好的化学产率和优异的光学产率制备相应的手性氧代分子。我们进一步 发现了顺式-二烯基-烷醇和顺式-二烯基-氨基酸乙基的对映选择性去对称化 与4摩尔% Cu/Au-2 R和过氧化氢的酯，得到手性二取代的内酯和内酰胺， 一些中等规模的天然产物和药物，包括N- 乙酰金刚烷胺、羟甲四环素、氨溴素和3-新戊酰基雌酮也被区域选择性氧化，得到 以良好的产率得到相应的单氧化产物。这些令人兴奋的结果促使我们提出研究 催化不对称氧化反应的范围和机理以及后期脂肪族C-H 生物活性复合物分子的氧化。我们的目标是发现催化领域有用的合成方法 不对称合成为实现这一目标，本文设计了三个具体目标：（1）优化CSPVP 以及烯烃和烷烃氧化反应的范围、机理、区域选择性和对映选择性的研究; (2)双烯醇形成C-O和C-N键的催化不对称闭环反应的研究 和二烯胺的不对称亚胺-Heck C-C键形成反应;（3）研究 生物活性复合物分子的C-H氧化的预测区域选择性，这可能会改变或改善生物活性复合物分子的生物活性。 分子的药理学和生物学性质。