Visible-Light-Promoted Fe(III)-Catalyzed N-H Alkylation of Amides and N-Heterocycles

J Org Chem. 2022 Aug 5;87(15):9797-9805. doi: 10.1021/acs.joc.2c00854. Epub 2022 Jul 20.

Abstract

The combination of the radical chemistry of ligand-to-metal charge transfer with metal catalysis by a single iron salt helps to realize the visible-light-promoted N-H alkylation of amides and N-heterocycles. A wide variety of amides and nitrogen-containing heterocycles were tolerated in our protocol to give N-alkylated products. The applicability of this protocol was further demonstrated by late-stage alkylation of N-H-containing pharmaceuticals. Moreover, N-H-alkylated α-amino tetrahydrofurans could be transformed into versatile ring-opened amino alcohols under reducing conditions. A mechanistic study revealed that hydrogen atom transfer by a tert-butoxyl radical and a chlorine radical was responsible for the activation of C(sp3)-H precursors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Amides*
  • Catalysis
  • Ferric Compounds*
  • Molecular Structure

Substances

  • Amides
  • Ferric Compounds