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

Abstract

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible <i>O</i>/<i>N</i>-propargylated 2-hydroxy or 2-aminobenzaldehydes and <i>o</i>-phenylenediamines to synthesize densely functionalized imidazo[1,2-<i>d</i>][1,4]oxazepines and imidazo[1,2-<i>d</i>][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-<i>exo</i>-<i>dig</i> 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.