Assembly of 1,3-Dihydro-2H-3-benzazepin-2-one Conjugates via Ugi Four-Component Reaction and Palladium-Catalyzed Hydroamidation

The Ugi four-component reaction (U-4CR) of a number of 2-aminophenols was carried out with 2-alknylbenzaldehydes, benzyl isocyanide, and 2-chloro-5-nitrobenzoic acid in MeOH under microwave heating (MW, 80 degrees C, 20 min). The reaction mixture was then directly treated with aqueous K2CO3 (MW, 100 degrees C, 10 min) to promote an intramolecular nucleophilic aromatic substitution (SNAr), resulting in the formation of highly functionalized dibenz[b,f][1,4]oxazepin-11(10H)-ones. The N-benzyl amide and arylalkynyl moieties, derived from benzyl isocyanide and 2-alkynylbenzaldehydes, allow for further assembly of 1,3-dihydro-2H-3-benzazepin-2-one scaffold via an intramolecular 7-endo-dig hydroamidation catalyzed by 10 mol% Pd(PhCN)(2)Cl-2 (THF, 60 degrees C, 24 h, 61-74%). This new post-Ugi annulation enables an expeditious access to the C-N bond-linked conjugates of two benzannulated seven-membered-ring heterocycles.