重氮介导的芳甲基骨架多官能团化反应研究

The multi-functionalization of arylmethyl skeleton, which primarily involve the formation of several new chemical bonds, is an area of research that has gained significant attention in modern synthetic chemistry. In particular, the exploitation of direct functionalized benzyl Csp3-H has been investigated extensively owing to its broad applications in the field of organic synthesis. Although pioneering studies have reported quinone methides as a synthon for the construction of multi-functionalized arylmethyl skeleton, the functionality of this approach has been limited by the retaining of oxygen atoms in quinone methides, which render the transformation process monotonous. Viewed as an alternative approach complementary to the conventional uses of quinone methides, aryldiazo possesses promising advantages including simple preparation, high reactivity and its involvement in a wide variety of reactions, has potential utility as an efficient synthon. In addition, the ortho- or para-alkyl aryldiazo are capable in generating quinonehydrazone methide under alkaline conditions, in which the resulting quinonehydrazone can subsequently react with metal to generate metal carbene, followed by migratory insertion and cyclization reaction. Furthermore, the early functionalization of benzyl can also be avoided. In the current proposal, we will systematically develop the diazo-mediated multi-functionalization of arylmethyl skeleton, which is anticipated to achieve high regio-selectivity of the reaction under mild conditions. Further investigation of the present methodology and mechanism will also be conducted to develop methods for preparing related heterocyclic compounds with promising biological activity.

芳甲基骨架的多官能团化反应包含几类新的化学键的生成，尤其是苄基位Csp3-H键的直接官能团化，一直是有机合成领域的研究热点和重点。其中，经由亚甲基醌活性中间体实现芳甲基骨架多官能团化的反应已经被广泛应用于有机合成中。然而，亚甲基醌中的氧原子，在反应中一直保留，转化相对单一。值得关注的是，芳基重氮化合物易于制备，反应活性高，反应类型丰富等优点，已成为一类高效的合成子。此外，邻、对位烷基取代芳香重氮化合物可在碱性条件下生成亚甲基醌腙，进而醌腙可发生多种金属卡宾迁移插入反应，以及环加成等反应；同时，苄基位可直接官能团化，避免了预先官能团化。为此，我们将系统研究重氮介导的芳甲基骨架的多官能团化反应，力求在温和条件下实现反应的高区域选择性，研究其反应机理；并且应用该策略构建一些具有潜在生物活性的杂环化合物。

芳甲基骨架的多官能团化反应包含几类新的化学键的生成，一直是有机合成领域的研究热点和重点。其中，经由亚甲基醌活性中间体实现芳甲基骨架多官能团化的反应已经被广泛应用于有机合成中。然而，亚甲基醌中的氧原子，在反应中一直保留，转化相对单一。值得关注的是，芳基重氮化合物易于制备，反应活性高，反应类型丰富等优点，已成为一类高效的合成子。为此，我们系统研究了重氮介导的若干有机反应，在温和条件下实现了芳基化反应、偶氮化反应，以及四唑酮内盐的合成；同时利用分子内串联环化策略，选择性地实现了芳乙炔的双羰基化、共轭烯炔烃的羰基化-二溴化，以及系列异香豆素和苯并异呋喃酮类天然杂环分子和复杂螺环化合物的高效合成。本项目成功实现了重氮介导的若干新反应，并最终完成了芳甲基骨架的选择性多官能团化，尤其是在若干复杂多元杂环构建方面提出了高效的合成新方法，创新性较高。通过本项目的实施，培养毕业6名硕士研究生；在国际专业期刊上发表SCI论文20篇，国内核心期刊上发表论文2篇；申请发明专利7项，其中授权5项；出版学术专著1部。