Microwave-Assisted Copper(II)-Catalyzed Cascade Cyclization of 2-Propargylamino/Oxy-Arylaldehydes and O-Phenylenediamines: Access to Densely Functionalized Benzo[ f]Imidazo[1,2- d][1,4]Oxazepines and Benzo[ f]Imidazo[1,2- d][1,4]Diazepines

J Org Chem. 2022 Jul 15;87(14):8956-8969. doi: 10.1021/acs.joc.2c00671. Epub 2022 Jun 28.

Abstract

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible O/N-propargylated 2-hydroxy or 2-aminobenzaldehydes and o-phenylenediamines to synthesize densely functionalized imidazo[1,2-d][1,4]oxazepines and imidazo[1,2-d][1,4]diazepines in high yields (up to 93%). This one-pot two-step process was found to be highly atom economical (-H2O, -H2) and operationally simple and enabled the generation of two new heterocycle rings (seven- and five-membered) and three new C-N bonds in a single synthetic operation. These reactions well tolerated a variety of substituents including electron-donating and electron-withdrawing groups and furnished the desired fused heterocycles in high yields under microwave irradiation in a very short reaction time. The mechanism of the established protocol involves sequential imine formation-intramolecular cyclization-air oxidation followed by 7-exo-dig cyclization steps. A comparative study between the microwave-assisted approach and conventional heating was also performed to demonstrate the advantages of the microwave-assisted protocol in terms of high yield and shorter reaction time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines
  • Catalysis
  • Copper*
  • Cyclization
  • Microwaves
  • Oxazepines*
  • Phenylenediamines

Substances

  • Azepines
  • Oxazepines
  • Phenylenediamines
  • Copper