Microwave-Assisted Intramolecular Ullmann Diaryl Etherification as the Post-Ugi Annulation for Generation of Dibenz[<i>b</i>,<i>f</i>][1,4]oxazepine Scaffold

Abstract

A sequence of the Ugi four-component reaction (U-4CR) and microwave-assisted intramolecular Ullmann etherification has been established for efficient generation of a dibenz[b,f][1,4]oxazepine scaffold. The U-4CR, using 2-aminophenols and 2-bromobenzoic acids or 2-bromobenzaldehydes as the inputs, was carried out in MeOH at 50-60 °C for 2-3 days to form a collection of 22 linear products in 46-90% yields. A microwave-assisted intramolecular Ullmann etherification was then used to transform these acyclic U-4CR products into the cleft-shaped 6/7/6-fused tricyclic heterocycles. The intramolecular Ullmann diaryl ether formation was catalyzed by 10 mol % of CuI and 30 mol % of N,N-dimethylglycine hydrochloride (DMG·HCl) in the presence of Cs₂CO₃ with microwave irradiation (150 °C, 30 min) to furnish dibenz[b,f][1,4]oxazepin-11(10H)-ones and dibenz[b,f][1,4]oxazepin-11(10H)-carboxamides in 64-100% yields.