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Development of carbon-carbon bond forming reaction under environmentally benign conditions and its application to combinatorial synthesis

环境友好条件下碳-碳键形成反应的进展及其在组合合成中的应用

基本信息

批准号：
13557197
负责人：
NAITO Takeaki
金额：
$ 7.62万
依托单位：
Kobe Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

1. Carbon-carbon bond formation by radical reactionThe use of water as a solvent has generated considerable interest from both economical and environmental points of view. Employment of a moisture-resistant radical species would eliminate the cumbersome operations involved in conventional ionic reactions. We have developed novel carbon-carbon forming reactions employing radical as a crucial reaction species and aqueous media as solvent. Newly-found radical reactions are proved to be synthetically useful by completing synthesis of several biologically active compounds.Triethylborane, zinc metal, and indium are selected as a radical initiator. The first ionization potential of indium is as low as that of lithium and sodium but indium is stable in water. Triethylborane-, zinc-, and indium-mediated carbon-carbon bond forming reactions proceeded smoothly even in aqueous media to afford alkyl radical addition products. We also investigated diastereoselective radical addition reaction of chir … More al substrates carrying the Oppolzer's camphorsultam and found that these stereoselective radical reactions are very efficient and highly promising approach to biologically active compounds such as α-amino acids and heterocycles. The radical reactions using three initiators were successfully extended to intramolecular radical addition cyclization reactions. Particularly, indium-mediated intramolecular reaction with alkyl iodide in water provides efficient tandem addition-cyclization-trap reaction.The solid-phase tandem radical reactions of oxime ethers proceeded effectively under iodine atom-transfer reaction conditions to give the azacydes or chiral oxacycles after cleavage of the resin.2. Rearrangement reaction under mild conditionsRearrangement reaction is one of atom-economy reactions. We investigated 1,2-Wittig rearrangement of hydroximates under the basic conditions and found that chiral hydroximate containing phenethyl alcohol moiety on nitrogen of the oxime ether group undertook effective rearrangement to afford hydroxy oxime ether which was successfully converted into (+)-cytoxazone. Based upon our previous work on [3,3]-sigmatropic rearrangement of hydrazones under the acylating conditions, we succeeded in the synthesis of natural indole compounds. Additionally, novel and efficient synthetic method for benzofurans is developed via the route involving sigmatropic rearrangement followed by cyclization under the mild reaction conditions. Less

1.通过自由基反应形成碳-碳键从经济和环境的角度来看，使用水作为溶剂已经引起了相当大的兴趣。采用耐湿自由基物质将消除常规离子反应中涉及的繁琐操作。我们已经开发了新的碳-碳形成反应，采用自由基作为一个关键的反应物种和水介质作为溶剂。通过完成几种生物活性化合物的合成，证明了新发现的自由基反应在合成中的应用。铟的第一电离电位与锂和钠一样低，但铟在水中稳定。三乙基硼烷，锌，和铟介导的碳-碳键形成反应进行顺利，即使在水介质中，以提供烷基自由基加成产物。我们还研究了手性的非对映选择性自由基加成反应 ...更多信息通过对带有Oppolzer’s β-氨基磺内酰胺的底物的研究，发现这些立体选择性自由基反应是制备具有生物活性的化合物如α-氨基酸和杂环化合物的非常有效和非常有前途的方法。将三种引发剂引发的自由基反应成功地推广到分子内自由基加成环化反应。特别是在水中，铟与碘代烷的分子内反应提供了高效的串联加成-环化-捕获反应;肟醚的固相串联自由基反应在碘原子转移反应条件下有效地进行，裂解树脂后得到氮杂环或手性氧杂环.温和条件下的重排反应重排反应是一种原子经济性反应。研究了肟酸酯在碱性条件下的1，2-Wittig重排反应，发现肟醚基氮上含有苯乙醇的手性肟酸酯发生了有效的重排反应，得到了羟基肟醚，并成功地转化为（+）-环恶酮。在前人工作的基础上，我们成功地合成了天然吲哚类化合物。此外，通过σ-转移重排，在温和的反应条件下环合，发展了一种新型高效的苯并呋喃类化合物的合成方法。少