Synthesis of 3-Benzazepines via an Intramolecular Reductive Heck Reaction

Significance

Reported here is a new procedure for the regio- and stereoselective synthesis of 1-substituted 3-benzazepinones via intramolecular reductive Heck reaction. The key substrates were prepared from β-phenethylamines derived from the corresponding 2-bromocinnamic acid. The Z-stereochemistry of the resulting product is due to the expected syn addition. The overall result is a 7-exo-dig process. Higher yields were obtained under high dilution conditions in DMF-H₂O mixtures. The expected advantage over conventional heating (12 h) for microwave conditions (0.25 h) was observed. TMS-substituted acetylenic amides gave low yields due to amide hydrolysis. Some 3-benzazepinones were further reduced ­efficiently to the corresponding 3-benzazepines. Two analogues of benzazocine derivatives (type A) were also prepared in modest yields.