A concise, practical synthesis of 2,3-dihydro-1,5-benzothiazepines

We have developed a domino process involving the Michael addition of 2-aminothiophenols to chalcones, followed by in situ cyclization. Up to 98% chemical yields have been obtained at room temperature by using hexafluoro-2-propanol (HFIP). The reaction was found to be tolerant to a number of electron-withdrawing or electron-releasing substituents on chalcones. In order to access the feasibility of the procedure on larger scale a few experiments have been carried out by recovering and recycling HFIP in subsequent runs. The yield of 2,3-dihydro-1,5-benzothiazepine remained unchanged and only minor amounts of HFIP was added in order to restore identical initial conditions.