Nitrile Anions: Unmasking Fundamental Reactivity

Fleming教授和他的同事们发现，在四氢呋喃或甲苯中产生的环腈阴离子可以选择性地在分子内烷基化，分别生成反式和顺式十肽。他们将把这一发现应用于合成两种含十氢化氢的天然产物。在他的合作者马杜拉教授的帮助下，将对参与这些反应的金属氰化物的结构进行计算建模。最后，PI将生成手性金属氰化物，并研究它们的对映选择性分子内烷基化反应。有了这个奖项，有机和高分子化学计划将支持杜肯大学化学系的弗雷泽·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氰基阴离子的分子的结构和反应化学。这些丁腈阴离子的分子内碳-碳键形成反应将被用来构建两个天然存在的二萜类化合物--三叉草酸和环三叉酸。可以在氰基旁边的碳上金属化的氰化物随后将用于不对称的碳-碳键形成反应，称为分子内烷基化反应。这些烷基化反应产生的环状分子是手性的(有两个不可重叠的镜像)，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行业面临的最重要的问题之一。在这项工作的过程中培训的学生将获得计算化学和有机合成方面的技能。这些技能是制药和特种化学品行业所需要的。

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.