Synthesis of 2,3,4,5-Tetrahydrobenzo[1,4]thiazepines via N‑Acyliminium Cyclization

We report an efficient and scalable synthesis of 7-methoxy-2,3,4,5-tetrahydrobenzo­[1,4]­thiazepine, the core structure of biologically active molecules like JTV-519 and S107. This synthetic route, starting with 4-methoxythiophenol and proceeding via acyliminum cyclization, gives the target product in four steps and 68% overall yield and is a substantial improvement over previously published processes. Nine additional examples of tetrahydrobenzo­[1,4]­thiazepine synthesis via acyliminium ring closure are also presented.