Synthesis of 4-azepanones and heteroaromatic-fused azepines

Two syntheses of versatile intermediate azepinones 2 and 3 are described. A 6-step intramolecular Dieckmann cyclization and decarboxylation led to the intermediate 3 while an alternate 4-step synthesis of 2 was developed and used for scale-up. The highlight of the second synthesis is the one-step per-bromination/elimination protocol from readily available azepinone 13a to provide a versatile scaffold in vinyl bromide 5, which enables SAR around the aryl moiety. An example of the elaboration of the intermediate 2 toward a heteroaryl azepinone is also described.