Pyrrolidine/Azepane Ring Expansion via Intramolecular Ullmann-Type Annulation/Rearrangement Cascade: Synthesis of Highly Functionalized 1H-Benzazepines.

ABSTRACT

5-Arylpyrrolidine-2-carboxylates with an ortho-halogen substituent at 5-aryl and an electron-withdrawing group at the C4 position of the pyrrolidine ring were transformed into 1H-benzo[b]azepine-2-carboxylates under Cu(I) promotion and microwave activation. Reaction promoter copper(I) thiophene-2-carboxylate has been generated in situ in the reaction's environment from Cu2O and thiophene-2-carboxylic acid. Functionalized 1H-benzo[b]azepine-2-carboxylates were obtained in racemic and optically active forms in 67-89% yields. Subsequent stereoselective 1,3-dipolar cycloaddition and an Ullmann-type annulation/rearrangement cascade (UARC) ensure a synthetic route to oligomeric optically active benzazepine species with a well-defined 3D-structure.