过渡金属催化串联反应合成含氨基酸或氟功能化基团的吲哚

Indoles are involved in a variety of nature products, and display diverse biological activities. A large number of indoles have been applied in pharmaceuticals or agricultural chemicals. Therefore, the synthesis and functionalization of indoles are crucial in the field of organic synthesis. This project is designed to develop several novel methods for the synthesis of functionalized group indoles containing amino acids or fluorine atom via transition metal-catalyzed tandem reactions. Firstly, tandem reaction of 3-(2-isocyanoaryl) acrylic acid ester and bis(pinacolato)diboron leading to functionalized indoles containing amino acids will been investigated. Secondly, tandem reaction of 3-(2-isocyanoaryl) acrylic acid ester and double radicals, especially radical aminofluorination of isocyano insertion for the synthesis of fluorinated indoles will also be studied. Moreover, the radical aminofluorination research will be switched to N-2-alkynylaryl amidyl for the preparation of other fluorinated indoles. Finally, the indole products will be converted into further derivatives through chemical methods, which will provide new strategies for the synthesis of related natural products and pharmaceuticals.

吲哚在天然产物中分布广泛，且表现出丰富多样的生物活性。目前已有大量的吲哚应用于药物或农药中。因此，吲哚的合成和功能化在有机合成领域至关重要。本项目旨在开发过渡金属催化的串联反应合成含氨基酸或氟功能化基团的吲哚的新方法。首先，我们将研究3-(2-异氰基芳基)-丙烯酸酯与联硼酸频那醇酯的串联反应合成含氨基酸的吲哚。接下来，研究3-(2-异氰基芳基)-丙烯酸酯与双自由基，特别是异腈插入的胺氟化反应合成含氟的吲哚。然后，研究N-(2-炔基芳基)-酰胺自由基的胺氟化反应合成其它含氟的吲哚。最后，通过化学方法将所得到的吲哚产物进行转化，为吲哚天然产物以及药物的合成提供新策略。

咪唑并[1,2-a]吡啶、咪唑并[2,1-b]噻唑、菲啶、喹啉和苯并呋喃等被认为是“药学偏好”的杂环骨架，表现出丰富多样的生物活性并广泛存在于临床药物或天然产物中。因此，这些杂环化合物的合成和功能化在有机合成领域至关重要。. 在本项目中，我们首先开发了几种新颖的方法，通过直接的C-H官能团化合成了咪唑并[1,2-a]吡啶、咪唑并[2,1-b]噻唑衍生物，并在它们的C-3位引入了氟原子、酯基、亚甲基桥联的双杂环、氰甲基等。接着，我们基于自由基加成/氰基插入/均裂芳基取代串联反应策略，成功构筑了6-位含季碳中心的菲啶骨架，并引入氰基、酯基、酰胺基、羰基、含氟烷基等一系列重要的官能团。最后，我们通过自由基串联反应还分别得到了3-二氟烷基喹啉，甲砜基和羰基双官能团化的苯并呋喃衍生物。这些结果为多样化官能团化的有机化合物的合成提供了多种温和、简便、直接的方法，并有望在药物合成中获得应用。