Enantioselective Synthesis of N−H‐Free 1, 5‐Benzothiazepines. Issue 3 (29th November 2016)

• Record Type: Journal Article
• Authors: Wang, Guojin; Tang, Yu; Zhang, Yu; Liu, Xiaohua; Lin, Lili; Feng, Xiaoming
• Is Part Of: Chemistry. Volume 23:Issue 3(2017)
• Page Start: 554
• Page End: 557
• Publication Date: 2016-11-29
• Subjects: asymmetric catalysis -- Lewis acid catalysis -- sulfa-Michael reaction -- synthesis design -- α, β-unsaturated pyrazolamide; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201605127
• Languages: English
• ISSNs: 0947-6539

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. Abstract : Go gentle : An enantioselective sulfa‐Michael‐cyclization reaction was developed for the synthesis of 1, 5‐benzothiazepines with versatile pharmacological activities. Excellent enantioselectivities (up to 96 % ee ) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. Furthermore, the reactions were applied to enable the concise synthesis of the chiral drug ( R )‐Thiazesim (see scheme).