Nitrile Anions: Unmasking Fundamental Reactivity

这一更新项目旨在挖掘碳金属氰化物在执行以前困难或不可能的转化方面的潜力。五个具体目标解决了几个长期存在的合成挑战：1)通过1，2-和1，3-内部不对称诱导，开发了第一个构象控制的C-金属腈的不对称烷基化反应；2)开发了C-金属腈的内部1，3-和1，4-不对称烷基化的螯合反应；开发了第一个手性格氏试剂的通用合成；4)进行了第一个一般的分子内和分子间的共轭加成-烷基化反应；以及5)计算确定了含镁、锌和铜反离子的碳和氮金属腈的结构和13C核磁共振位移。该项目的一部分将通过与德国慕尼黑路德维希-马克西米连大学的保罗·诺切尔教授的国际合作实现。通过这一奖项，有机化学和高分子化学项目以及国际科学和工程办公室将支持杜奎恩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。这一系列反应的发展有望为发现和开发新药物所需的复杂有机分子的受控合成提供新的工具。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。通过与Paul Knochel博士的合作，研究生交换预计将使Duqune大学的一批研究生受益，因为在Knochel小组中学到的想法和技术将被带回并在PI的研究小组中实施。

This renewal project seeks to exploit the potential of C-metallated nitriles in performing previously difficult or impossible transformations. Five specific objectives address several long-standing synthetic challenges: 1) development of the first conformationally controlled asymmetric alkylation of C-metallated nitriles through 1,2- and 1,3-internal asymmetric induction; 2) exploitation of chelation for internal 1,3- and 1,4-asymmetric alkylations of C-metallated nitriles; development of the first general synthesis of chiral Grignard reagents; 4) execution of the first general intra- and intermolecular conjugate addition-alkylation to alkenenitriles; and 5) computational determination of the structure, and 13C NMR shifts, of C- and N-metallated nitriles with Mg, Zn, and Cu counter ions. Portions of the project will be achieved through an international collaboration with Professor Paul Knochel, at Ludwig-Maximilian's University in Munich, Germany.With this award, the Organic and Macromolecular Chemistry Program and the Office of International Science and Engineering are 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. Development of this family of reactions promises to provide new tools for the controlled synthesis of the complex organic molecules required in the discovery and development of new pharmaceuticals. Students trained during the course of this work will gain skills in computational chemistry and organic synthesis. Graduate student exchange, through collaboration with Dr. Paul Knochel, is anticipated to benefit the a cadre of graduate students at Duquesne University as ideas and techniques learned in the Knochel group are brought back and implemented in the PI's research group.