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

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。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。新发现的自由基反应被证明是有用的合成通过完成几个生物活性化合物的合成。我们首先研究了选择性和有效的烷基自由基加成到各种类型的亚胺衍生物。通过碳、氢和硼NMR分析，牢固地建立了由烷基自由基加成到肟醚产生的中间体的结构。首次通过自由基加成反应完成了异常氨基酸--青霉酸的全合成。多米诺型自由基加成-环化-（捕获）反应也被开发并用于有效构建官能化环状化合物。首次发现吡咯并喹啉类生物碱Martinellic acid，开发了新的合成路线，新发现的自由基加成-羟醛缩合反应有望成为一种高效、环境友好的反应.温和条件下的重排反应重排反应是一种原子经济性反应。在对肟酸酯的1，2-Wittig重排反应进行系统研究的过程中，我们完成了（+）-环磷酰胺的全合成。在酰化条件下酰化腙的[3，3]-σ-转移重排反应的研究中，我们发展了一种在非常温和的反应条件下，甚至在自由羟基存在下，通过O-芳基肟醚的酰化反应合成苯并呋喃的短步骤和有效的方法，并发展了一种环境友好的由肟醚一锅法合成N-烷基芳胺的方法。

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. 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.We firstly investigated selective and efficient alkyl radical addition to various types of imine derivatives. Structure of an intermediate generated by alkyl radical addition to oxime ethers was firmly established by carbon, hydrogen, and boron NMR analyses. Total synthesis of an abnormal amino acid, penmacric acid was completed for the first time via our radical addition reaction. Domino type of radical addition-cydization-(trapping) reaction was also developed and used for efficient construction of functionalized cyclic compounds. Novel synthetic route for Martinellic acid, isolated as a first pyrroloquinoline alkaloid was developed.Newly-found radical addition-aldol type of reaction is expected to be an efficient and environmentally benign reaction.2. Rearrangement reaction under mild conditionsRearrangement reaction is one of atom-economy reactions. During our systematic investigation on 1,2-Wittig rearrangement of hydroximates, we completed the total synthesis of (+)-cytoxazone. In our continuing study on [3, 3]-sigmatropic rearrangement of hydrazones under the acylating conditions, we developed a short step and efficient method for the synthesis of benzofurans via acylation of O-aryl oxime ethers under very mild reaction conditions, even in the presence of free hydroxyl group.As an environmentally benign synthetic method, one-pot synthesis of N-alkyl arylamines from oxime ethers was also developed.