Nitrile Anions: Unmasking Fundamental Reactivity

腈阴离子：揭示基本反应性

• 批准号: 0210955
• 负责人: Fraser Fleming
• 金额: $ 26.5万
• 依托单位: Duquesne University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0210955&HistoricalAwards=false
• 关键词: Nitrile; Anions; Unmasking; Fundamental; Reactivity

Professor Fleming and his coworkers have discovered that cyclic nitrile anions generated in tetrahydrofuran or toluene can be selectively alkylated intramolecularly to generate trans- and cis-decalins, respectively. They will apply this discovery to the syntheses of two decalin containing clerodane natural products. With the help of his collaborator, Professor Madura, computational modelling of the structures of the metallated nitriles which participate in these reactions will be investigated. Lastly, the PI will generate chiral metallated nitriles and investigate their enantioselective intramolecular alkylation.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Fraser F. Fleming of the Department of Chemistry at Duquesne University. Professor Fleming along with his collaborator, Professor Jeffrey D. Madura, and their students will study the structures and reaction chemistry of a class of molecules known as nitrile anions. Intramolecular carbon-carbon bond forming reactions of these nitrile anions will be used to construct two naturally occurring diterpenes, strigillanoic acid and epi-strigillanoic acid. Nitriles which can be metallated on the carbon next to the nitrile functional group will then be used in enantioselective carbon-carbon bond forming reactions called intramolecular alkylation reactions. These alkylation reactions produce cyclic molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer). Development of this family of reactions is one of the most important problems facing the pharmaceutical industry today. Students trained during the course of this work will gain skills in computational chemistry and organic synthesis. These skills are needed by the pharmaceutical and speciality chemicals industries.

弗莱明教授和他的同事发现，在四氢呋喃或甲苯中产生的环腈阴离子可以在分子内选择性地烷基化，分别生成反式和顺式十卡林。他们将把这一发现应用于合成两种含十烷烷的天然产物。在他的合作者Madura教授的帮助下，参与这些反应的金属化腈结构的计算模型将被研究。最后，PI将生成手性金属腈并研究其分子内对映选择性烷基化。通过这个奖项，有机和大分子化学项目支持了杜肯大学化学系弗雷泽·f·弗莱明博士的研究。弗莱明教授和他的合作者杰弗里·d·马杜拉教授以及他们的学生将研究一类被称为腈阴离子的分子的结构和反应化学。这些腈阴离子的分子内碳-碳成键反应将被用来构造两种天然存在的二萜：三癸烷酸和外三癸烷酸。可以在腈官能团旁边的碳上金属化的腈，然后用于被称为分子内烷基化反应的对映选择性碳-碳键形成反应。这些烷基化反应产生手性环状分子（有两个不重叠的镜像），并且只产生两种可能形式中的一种（单一对映体）。这类反应的发展是当今制药工业面临的最重要问题之一。在这项工作的过程中训练的学生将获得计算化学和有机合成的技能。这些技能是制药和特种化学品行业所需要的。