A New Paradigm for Ether Synthesis

内布拉斯加大学林肯分校的Pat Dussault教授和Macalester学院的Keith Kuwata教授正在研究合成醚的新方法，该项目由化学学部化学合成项目资助。醚含有碳-氧-碳键，是存在于药物、天然产物、溶剂和有机材料中的重要功能物质。在该奖项下进行的研究预计将对化学和相关领域产生影响，如药物发现和材料科学。Dussault和他的同事们还在创建一个实用的、可广泛获取的与有机过氧化物合成应用相关的知识交流中心，这鼓励了对过氧化物丰富化学性质的更广泛开发和更安全的应用。这项工作的其他更广泛的影响包括在实验和计算研究方法方面对本科生和研究生的培训，以及研究型大学和主要本科院校之间相互丰富的合作。现有的引入乙基的方法主要是基于亲核氧与亲电碳的反应。该奖项的研究采用实验和理论两种方法，探索了一种新的合成模式，该模式基于有机过氧化物中亲核碳试剂对亲电氧原子的攻击。这项研究是围绕两个主要的研究目标组织的。目的1结合实验和理论方法，通过过氧化物与碳离子的反应来开发改进的醚合成方法。重点是了解影响过氧化物反应性的因素，成键步骤的机制，通过该策略可接近的C-O键的范围，以及攻击不对称过氧化物的选择性控制。目的2研究分子间C-O键形成反应作为特定类别的功能化醚的方法和分子内反应作为环和螺环醚的方法。

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.