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。通过根本反应形成碳 - 碳键，将水作为溶剂的使用从经济和环境的角度引起了人们的考虑。使用耐水性的自由基物种将消除常规离子反应所涉及的繁琐操作。我们已经开发了新型的碳碳形成反应，利用自由基作为至关重要的反应物种和水性培养基作为溶剂。通过完成几种生物活性化合物的合成，新发现的自由基反应在综合上是有用的。三乙基硼烷，锌金属和鉴赏剂被选为自由基引发剂。依赖的第一个电离潜力与锂和钠的电离潜力低，但依赖依赖性在水中稳定。即使在水性培养基中，三乙基硼烷 - ，锌和辅助介导的碳 - 碳键形成反应也顺利进行，以提供烷基自由基添加产物。我们还研究了CHIR的非对映选择性的根本性添加反应……更多的载有Oppolzer露营的α底物，发现这些立体选择性自由基反应是针对生物活性化合物（如α-氨基酸和杂物）的非常有效且高度有前途的方法。使用三个启动器的自由基反应成功地扩展到分子内根部添加环化反应。尤其是，在水中与烷基碘化烷基分子反应的分子内反应可有效地串联添加环化陷阱反应。在碘原子 - 转移反应条件下有效地进行了氧气或chiral氧化的固体相串联氧气反应，从而在碘或chir氧化反应下有效地进行了。在轻度条件下，重排反应是定性反应是原子经济反应之一。我们在基本条件下研究了1,2-wittig的重排，发现手性氢氧含有苯乙基醇部分在氧气组的氮中进行有效的重排以实现有效的重排，从而获得了羟基氧气，从而成功地转化为（+） - 胞毒素。基于我们先前在[3,3] - 含氢气中的 - 含量重排的工作，我们成功地合成了天然吲哚化合物。此外，苯并呋喃的新型合成方法是通过涉及乙状结波重排的途径开发的，然后在轻度反应条件下进行了环化。较少的