Synthesis of Furobenzazepinones by an Intramolecular Heck Reaction

Significance

A synthesis of tricyclic lactams, furobenzazepinones using an intramolecular Heck reaction as a key step is reported. The key intermediate 1 was synthesized in six steps from commercially available 2-hydroxyl-3-methoxybenzaldehyde in 30% overall yield. Interestingly, when R² = H, direct intramolecular Heck reaction from intermediate 4 to the product could not be achieved. However, treatment of 2, readily prepared from 1 by treatment with β-chloroacetyl chloride under Heck conditions, gave the targeted compound, via the in situ produced acrylamide 3, which could be isolated. The intramolecular Heck reaction is an unusual 7-endo-trig process. In addition, an intermolecular Heck reaction was achieved by reaction of 2-acetyl-4-bromo-7-methoxybenzo[b]furan with 3-chloro-propionamide showing that alkyl chlorides could be used for the Heck process.