Enantioselective Synthesis of N−H‐Free 1,5‐Benzothiazepines

Abstract

Abstract 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 α,β‐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.