Development of novel hypervalent iodine reagents and their applications to stereoselective synthesis of biologically active natural products

在这个项目中，我们注意到了利用超高压碘（III）试剂激活的Lewis酸类如BF_3·Et_2O和TMSOTf及其对生物活性天然产品合成的应用。我们最近报告了使用苯甲酸（III） bis （三氟乙酸酯） （PIFA）的核物质的核物质替代物。这种反应对硝基、氧、碳和硫核物质的引入是有效的。在这个项目中，活性高水平碘试剂的应用已经开发出了内分子循环化反应，是由谁描述的. i）苯醚的内分子循环化在烷基氮化物侧链中直接获得了奎诺酮亚胺衍生物，使用PIFA-TMSOTf。这一反应也被发现对indoloquinone-imines合成有效果，海洋反肿瘤化合物的关键预测器. ii）利用PIFA-BF_3·Et_2O启用内聚苯偶联反应，以合成良好yields中的淀粉酰化aceae alkaloids和多功能生物化合物的基本结构. iii）利用PIFA-BF_3·Et_2O来合成含有硫酸盐的异环化合物的一种新颖和有效合成方法. iii）利用PIFA-BF_3·Et_2 O来自phenol ethers，承载苯甲基硫烷基侧链已经开发出来。Furthermore，我们找到了一种用于环硫醚氮杂化的新颖方法。Phl=O和TMSN_3允许二氢苯并硫衍生物的α氧化化的组合，在中等年龄下易于芳香化和可检测性。这些发现将为含有硫酸盐的发现提供强大的工具的总合成。

In this project, we focussed our attention on the development of novel reactions using hypervalent iodine (III) reagents activated by Lewis acids such as BF_3・Et_2O and TMSOTf, and their applications to the synthesis of biologically active natural products.We recently reported the nucleophilic substitution of phenol ethers using phenyliodine (III) bis (trifluoroacetate) (PIFA). The reaction is efficient for the introduction of nitrogen, oxygen, carbon, and sulfur nucleophiles to phenol ethers. In this project, the applications of activated hypervalent iodine reagents to intramolecular cyclization reactions have been developed, which are described below.i) The intramolecular cyclization of phenol ethers bearing an alkyl azide side chain directly gave quinone imine derivatives in good yields using PIFA-TMSOTf. This reaction was also found to be effective for the synthesis of indoloquinone-imines, key precursor to marine anti-tumor alkaloids.ii) The intramolecular phenolic coupling reaction using PIFA-BF_3・Et_2O enabled to synthesize the essential structure of amaryllidaceae alkaloids and multi-functionalized biaryl compounds in good yields.iii) A novel and efficient synthesis of sulfur-containing heterocyclic compounds using PIFA-BF_3・Et_2O from phenol ethers bearing benzylthioalkyl side chain was developed.Furthermore, we found a novel method for alpha-azidation of cyclic sulfides. The combination of Phl=O and TMSN_3 allowed alpha-azidation of dihydrobenzothiophen derivatives, which are easily aromatized and labile under oxidative conditions, in moderate yields. These findings will provide powerful tools for the total synthesis of sulfur-containing discorhabdins.