Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
J Am Chem Soc. 2023 Jun 28;145(25):13542-13548. doi: 10.1021/jacs.3c04016. Epub 2023 Jun 12.
The arylethylamine pharmacophore is conserved across a range of biologically active natural products and pharmaceuticals, particularly in molecules that act on the central nervous system. Herein, we present a photoinduced copper-catalyzed azidoarylation of alkenes at a late stage with arylthianthrenium salts, allowing access to highly functionalized acyclic (hetero)arylethylamine scaffolds that are otherwise difficult to access. A mechanistic study is consistent with a -BINAP-Cu-azide () as the photoactive catalytic species. We show the utility of the new method by the expedient synthesis of racemic melphalan in four steps through C-H functionalization.
芳基乙胺药效团存在于一系列具有生物活性的天然产物和药物中，特别是在作用于中枢神经系统的分子中。在此，我们提出了一种在芳基噻蒽鎓盐存在下，用光诱导铜催化的末端烯烃叠氮芳基化反应，从而得到高度官能化的非循环（杂）芳基乙胺支架的方法，否则这些支架难以获得。一项机理研究表明，-BINAP-Cu-叠氮化物（）是光活性催化物种。我们通过 C-H 官能化以四步合成外消旋美法仑，展示了新方法的实用性。
