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

1.自由基反应生成碳-碳键从经济和环境的角度来看，水作为溶剂的使用引起了人们的极大兴趣。采用一种防潮的自由基物种将消除传统离子反应中涉及的繁琐操作。我们开发了以自由基为关键反应物种，以水介质为溶剂的新型碳-碳形成反应。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被证明是有用的。三乙基硼烷、金属锌和铟被选为自由基引发剂。铟的第一电离电势与锂和钠一样低，但在水中很稳定。即使在水介质中，三乙基硼烷、锌和铟介导的碳-碳键的形成反应也能顺利进行，得到烷基自由基加成产物。我们还研究了CHIR…的非对映选择性自由基加成反应。更多的铝底物携带了Oppolzer‘s樟脑舒坦，并发现这些立体选择性自由基反应是非常有效和非常有前途的生物活性化合物的方法，如α-氨基酸和杂环。将三种引发剂引发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，铟与烷基碘在水中的分子内反应提供了高效的串联加成-环化-陷阱反应；在碘原子转移反应条件下，肟醚的固相串联自由基反应在树脂裂解后有效地进行，得到氮杂环类或手性氧环类化合物。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羟肟酸酯的1，2-Wittig重排反应，发现含苯乙醇基团的手性羟肟酸酯在酮醚基团的氮上进行了有效的重排，得到了羟基肟醚，并成功地转化为(+)-环恶酮。在已有工作的基础上，我们成功地合成了天然吲哚类化合物。此外，在温和的反应条件下，通过S型重排和环合反应开发了一种新的高效的苯并呋喃的合成方法。较少

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