A New Paradigm for Ether Synthesis

在这项由化学系化学合成计划资助的项目中，内布拉斯加州-林肯大学的Pat Dussault教授和Macalester学院的Keith Kuwata教授正在开发合成醚的新方法。含碳-氧-碳键的醚是存在于药物、天然产品、溶剂和有机材料中的一种重要功能。根据这一奖项进行的研究预计将在化学和相关领域产生影响，如药物发现和材料科学。Dussault和同事们还在创建一个实用的、可广泛访问的与有机过氧化物合成应用有关的知识交流中心，这将鼓励更广泛地开发和更安全地应用丰富的过氧化物化学。这项工作的其他更广泛的影响包括对本科生和研究生进行实验和计算研究方法的培训，以及研究型大学和主要本科生机构之间的相互促进合作。现有的引入醚基的方法主要是基于亲核氧和亲电碳的反应。该奖项的研究采用了实验和理论两种方法来探索一种新的合成模式，这种模式是基于碳亲核试剂对有机过氧化物中的亲电氧原子的攻击。本研究围绕两个主要研究目标展开。目的1采用实验和理论相结合的方法，改进了过氧化氢与碳负离子反应合成乙醚的方法。重点是了解影响过氧化氢反应活性的因素，成键步骤的机理，通过该策略可接近的C-O键的范围，以及对不对称过氧化氢攻击的选择性的控制。目的2研究分子间C-O键形成反应作为特定类型官能化醚类的方法，以及分子内反应作为环醚和螺环醚的方法。

AbstractIn this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Pat Dussault of the University of Nebraska-Lincoln and Prof. Keith Kuwata of Macalester College are developing new approaches to the synthesis of ethers. Ethers, which contain a Carbon-Oxygen-Carbon linkage, are an important functionality present in medicines, natural products, solvents, and organic materials. The research pursued under this award is anticipated to have impact both in chemistry and in associated fields such as drug discovery and materials science. Dussault and coworkers are also creating a practical and widely accessible knowledge clearinghouse related to the synthetic application of organic peroxides, that is encouraging wider exploitation and safer application of the rich chemistry of peroxides. Other broader impacts of this work include the training of both undergraduate and graduate students in experimental and computational research methods and the mutual enrichment of collaboration between a research university and a primarily undergraduate institution.Existing methods for the introduction of the ether group are predominantly based upon reaction of nucleophilic oxygen with electrophilic carbon. The research under this award employs both experimental and theoretical approaches to explore a new mode of synthesis based upon attack of carbon nucleophiles on the electrophilic oxygen atoms within organic peroxides. The research is organized around two major research aims. Aim 1 combines experimental and theoretical approaches to develop improved methods for ether synthesis by the reaction of peroxides with carbanions. Emphasis is placed on understanding the factors that influence peroxide reactivity, the mechanism of the bond-forming step, the scope of C-O bonds that are approachable via this strategy, and control of selectivity in attack on unsymmetrical peroxides. Aim 2 investigates intermolecular C-O bond forming reactions as an approach to specific classes of functionalized ethers and intramolecular reactions as an approach to cyclic and spirocyclic ethers.