Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian 116024, P. R. China.
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China.
Org Lett. 2021 Feb 5;23(3):802-807. doi: 10.1021/acs.orglett.0c04030. Epub 2021 Jan 19.
Indole-fused bicyclo[3.2.1]octanes are highly important structural units in natural products and biologically active compounds. However, there has been limited success in the enantioselective synthesis of these skeletons due to the complexity of the structure and the control of the enantioselectivity. Herein an enantioselective construction of indole-fused bicyclo[3.2.1]octanes bearing an all-carbon quaternary bridgehead stereocenter was developed via an aminopalladition-triggered Heck-type reaction. The protocol features mild conditions and good tolerance for a wide range of functional groups. The transformation can also be scaled up to demonstrate its practicability. The mechanistic studies reveal that the formation of an intermediate indol-3-yl palladium species via C-H activation should be ruled out.
吲哚并[3.2.1]辛烷骨架是天然产物和生物活性化合物中非常重要的结构单元。然而，由于结构的复杂性和对对映选择性的控制，这些骨架的对映选择性合成一直没有取得成功。本文通过氨钯化引发的 Heck 型反应，发展了一种具有全碳桥环季碳手性中心的吲哚并[3.2.1]辛烷骨架的对映选择性构建方法。该方法条件温和，对各种官能团具有良好的耐受性。该转化还可以放大规模，证明其实用性。机理研究表明，通过 C-H 活化形成的中间体吲哚-3-基钯物种应该被排除。
