Copper-Catalyzed Selective Oxidative Cross-Coupling of Tryptophols and Tryptamines To Access Heterocyclic 3a,3a'-Bisindolines

Org Lett. 2022 Apr 15;24(14):2716-2721. doi: 10.1021/acs.orglett.2c00821. Epub 2022 Apr 7.

Abstract

The first example of cyclization cross-coupling of tryptophols and tryptamines has been realized by copper catalysis with air or oxone as the terminal oxidant, resulting in the direct construction of a new class of heterocyclic 3a,3a'-bisindolines in moderate to good yields with high chemoselectivities. A series of mechanistic control experiments were also conducted, indicating that the copper catalyst selectively coordinates with the nitrogen moiety of the tryptamine to initiate the oxidation, and a nucleophilic-alkylation process is proposed for the carbon-carbon bond-forming in the reaction. The novel synthetic strategies and molecular skeletons outlined in this work provide new ideas and concepts for the design of other useful reaction and potential drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon
  • Catalysis
  • Copper*
  • Cyclization
  • Indoles*
  • Molecular Structure
  • Oxidative Stress
  • Tryptamines

Substances

  • Indoles
  • Tryptamines
  • Carbon
  • Copper