Enantioselective Synthesis of N-H-Free 1,5-Benzothiazepines

An enantioselective sulfa-Michael-cyclization reaction was developed for the synthesis of 1,5-benzothiazepines with versatile pharmacological activities. The reaction between 2-aminothiophenol and alpha,beta-unsaturated pyrazoleamides gave direct access to N-H-free 1,5-benzothiazepines in the presence of a chiral N,N'-dioxide/Yb(OTf)(3) complex. Excellent enantioselectivities (up to 96% ee) and high yields (up to 99%) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)-(-)-Thiazesim.