Phosphine-Catalyzed α-Umpolung-Aldol Reaction for the Synthesis of Benzo[b]azapin-3-ones

A novel phosphine-catalyzed intermolecular cyclization between 2-sulfonamidobenzaldehyes and ynones is reported. This methodology serves as a conduit for the construction of benzo[b]azepin-3-ones in good to excellent yields under mild conditions. The resulting 2-benzylidene moieties are formed exclusively in the E-configuration. Mechanistically, this unusual annulation occurs through a phosphine-catalyzed alpha-umpolung addition, followed by an aldol reaction. One of the benzo[b]azepin-3-one products was converted to the core structure of 3-amino-[a]benzazepin-2-one-1-alkanoic acids, many of which function as angiotensin-converting enzyme inhibitors.