Design and Synthesis of 1‐Benzazepine Derivatives by Strategic Utilization of Suzuki–Miyaura Cross‐Coupling, Aza‐Claisen Rearrangement and Ring‐Closing Metathesis

Abstract

AbstractA new and simple methodology has been realized for the synthesis of 7‐substituted 2,3,4,5‐tetrahydro‐1‐benzazepine derivatives with Suzuki–Miyaura cross‐coupling, aza‐Claisen rearrangement and ring‐closing metathesis (RCM) the key steps. Here, o‐allylacetanilide derivatives were obtained by Suzuki–Miyaura cross‐coupling of the corresponding o‐iodoacetanilides. The o‐allylacetanilides, on N‐allylation under phase‐transfter catalysis conditions, provided diallyl derivatives as suitable precursors for RCM. These diallyl derivatives, on treatment with Grubbs' second‐generation catalyst, gave the 1‐benzazepine derivatives in moderate‐to‐good yields. These RCM products were found to be unstable and so they were hydrogenated to provide stable tetahydro‐1‐benzazepine derivatives 25–28. 1H‐1‐Benzazepin‐2‐one derivatives 44 and 45 were synthesized following a similar sequence. In addition, the aza‐Claisen rearrangement was utilized as a key step in the preparation of RCM precursor 17. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)