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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。使用防潮自由基物质将消除传统离子反应中涉及的繁琐操作。我们开发了新型碳-碳形成反应，采用自由基作为关键反应物种，水介质作为溶剂。新发现的自由基反应通过完成几种生物活性化合物的合成被证明具有合成用途。选择三乙基硼烷、金属锌和铟作为自由基引发剂。铟的第一电离势与锂和钠一样低，但在水中很稳定。三乙基硼烷、锌和铟介导的碳-碳键形成反应即使在水介质中也能顺利进行，产生烷基自由基加成产物。我们还研究了携带 Oppolzer 樟脑磺内酰胺的 chir ... More al 底物的非对映选择性自由基加成反应，发现这些立体选择性自由基反应对于生物活性化合物（如 α-氨基酸和杂环）是非常有效且非常有前景的方法。使用三种引发剂的自由基反应成功地扩展到分子内自由基加成环化反应。特别是，在水中，铟介导的与烷基碘的分子内反应提供了有效的串联加成-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进行，在树脂裂解后得到氮杂环化合物或手性氧杂环化合物。 2．温和条件下的重排反应重排反应是原子经济反应之一。我们在碱性条件下研究了异羟肟酸酯的1,2-Wittig重排，发现肟醚基团氮上含有苯乙醇部分的手性异羟肟酸酯进行了有效的重排，得到羟基肟醚，并成功转化为(+)-cytoxazone。基于我们之前在酰化条件下腙的[3,3]-σ重排的工作，我们成功合成了天然吲哚化合物。此外，通过在温和的反应条件下进行σ重排和环化，开发了新型、高效的苯并呋喃合成方法。较少的