Catalytic Asymmetric Oxidation of Alkenes and Alkanes

烯烃和烷烃的催化不对称氧化

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目概要发现新方法来推进合成有机、药物和材料化学领域的发展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并且最近，我们发现了一种新的功能。一类聚合物，即手性取代的聚-N-乙烯基吡咯烷酮 (CSPVP)，用于稳定双金属纳米团簇，例如钯/金或铜/金纳米粒子，可诱导手性。聚合物包裹（或嵌入）纳米尺寸（~3 nm）双金属纳米粒子并催化使用氧气或过氧化氢作为氧化剂的对映选择性氧化反应的数量。在水中2个大气压的氧气下，0.5 mol%的Pd/Au (3:1)-手性聚合物2R将烯烃氧化为得到各种环烷烃的化学产率 73 – 86% 和 ee 光学产率 97 – 99% 的顺式二羟基化产物。使用 5 mol% Cu/Au (3:1)-2R 和 30% 过氧化氢进行区域选择性和对映选择性 C-H 氧化我们进一步以非常好的化学产率和优异的光学产率生产相应的手性含氧分子。发现 α-二烯基-烷醇和 -二烯基-氨基酸乙基的对映选择性去对称化与 4 mol% Cu/Au-2R 和过氧化氢形成酯，得到手性二取代内酯和内酰胺，一些中等规模的天然产物和药物，包括 N-，分别为 91 – 96% ee。乙酰金刚烷胺、氧米曲林、氨溴索和 3-新戊酰雌酮也被区域选择性氧化，得到相应的单氧化产物具有良好的产率。这些令人兴奋的结果促使我们提出研究建议。催化不对称氧化反应和后期脂肪族C-H的范围和机制我们的目标是发现催化中有用的合成方法。不对称合成设计了三个具体目标来实现我们的目标：（1）CSPVP 的优化。以及烯烃和烷烃氧化的范围、机制以及区域和对映选择性的研究； (2)二烯醇形成C-O和C-N键催化不对称闭环反应的研究和二烯胺，以及不对称亚胺-Heck C-C键形成反应和（3）研究；生物活性复合物分子 C-H 氧化的预测区域选择性，这可能会改变或改善分子的药理学和生物学特性。