Design and synthesis of 1-benzazepine derivatives by strategic utilization of Suzuki-Miyaura cross-coupling, aza-Claisen rearrangement and ring-closing metathesis

Abstract

A 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.