Iron-Catalyzed Oxidative Cross-Coupling of Phenols and Tyrosine Derivatives with 3-Alkyloxindoles

J Org Chem. 2021 Dec 17;86(24):18164-18178. doi: 10.1021/acs.joc.1c02435. Epub 2021 Dec 9.


In this study, a novel iron-catalyzed oxidative cross-coupling reaction between phenols and 3-alkyloxindole derivatives is reported. The efficient method, which is based on the FeCl3 catalyst and the t-BuOOt-Bu oxidant in 1,2-dichloroethane at 70 °C, affords 3-alkyl-3-(hydroxyaryl)oxindole compounds with a high degree of selectivity. The generality of the conditions was proven by reacting various substituted phenols, naphthols, and tyrosine derivatives with 3-alkyloxindoles. To apply the chemistry for the conjugation of tyrosine-containing short peptides with oxindolylalanine (Oia) derivatives, the reaction conditions were modified [Fe(O2CCF3)3 catalyst, t-BuOOt-Bu, HFIP, 70 °C], and amino acids with acid-stable N-protecting groups were used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Iron*
  • Oxidative Stress
  • Phenols*
  • Tyrosine


  • Phenols
  • Tyrosine
  • Iron