Synthesis of 1,5-Benzothiazepines from Aziridines and 2-Aminothiophenol

Significance

Reported is the synthesis of 3-amino-1,5-benzothiazepines by the ring opening of aziridines with 2-aminothiophenol. In preliminary investigations the nitrogen-protecting group was varied and the phenylsulfonyl group shown gave the best yields. In subsequent studies, trans-aziridines were used and shown to react with retention of relative stereochemistry to give one of two different regioisomers in modest yields. When the mesylated aziridine B was used, the previously observed reaction path was followed, with ring opening occurring in preference to substitution of the mesylate. If aziridines C were used, a reaction occurred first at the more reactive tosyl group in preference to the opening of the aziridine ring, to give the opposite regioisomer. Hence, the regiochemistry can be controlled by using either the mesyl or tosyl functionality. The reaction was monitored by NMR spectroscopy and intermediate A was observed, supporting the suggested mechanism.