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 发展合成有机、药物和材料化学领域的新方法的发现 在药物合成中起着至关重要的作用。特别是，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和 分子上的附加官能团用于官能团操纵。最近，我们发现了一种新的 用于稳定双金属的一类聚合物，即手性取代的聚N-乙烯基吡咯烷酮(CSPVPs) 纳米团簇，如钯/金或铜/金纳米粒子在手性诱导中的作用。这些手性 聚合物包裹(或包埋)纳米尺寸(~3 nm)的双金属纳米颗粒，并催化 以氧或过氧化氢为氧化剂的对映选择性氧化反应的数目。例如, 用0.5mol%的Pd/Au(3：1)-手性聚合物2R在2个大气压的氧气中氧化烯烃. 以73-86%的化学产率和97%-99%的ee光学收率得到合成的二羟基化产物。各种环烷烃 用5mol%Cu/Au(3：1)-2R和30%过氧化氢进行了区域和对映体选择性的C-H氧化 以非常好的化学和光学产率制备相应的手性氧代分子。我们进一步 -二烯基-烷醇和-二烯基-氨基乙酸乙酯的对映体选择性去对称化 含有4摩尔%铜/金-2R和过氧化氢的酯，以得到手性二取代内酯和内酰胺， 分别为91-96%的ee。一些中型天然产品和药物，包括N- 乙酰金刚烷胺、羟甲氧胺、氨溴氧化物和3-甲氧基雌酮也被区域选择性地氧化，以得到 相应的单含氧产物的产率很高。这些令人兴奋的结果促使我们提出了研究 催化不对称氧化反应和晚期脂肪族C-H的范围和机理 生物活性复杂分子的氧化。我们的目标是在催化领域发现有用的合成方法 不对称合成。为了实现我们的目标，我们设计了三个具体目标：(1)CSPVP的优化 以及对烯烃和烷烃氧化的范围、机理、区域选择性和对映体选择性的研究； (2)二烯醇生成C-O键和C-N键催化不对称环合反应的研究 和二烯胺以及不对称亚胺-Heck C-C键形成反应；以及(3)研究 活性复杂分子C-H氧化的预测区域选择性，这可能改变或改善 分子的药理和生物学特性。