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Organocatalytic Asymmetric Sulfa‐Michael Addition of 2‐Aminothiophenols to Chalcones: First Enantioselective Access to 2,3,4,5‐Tetrahydro‐1,5‐benzothiazepines
Author(s) -
Corti Vasco,
Camarero Gonzalez Patricia,
Febvay Julie,
Caruana Lorenzo,
Mazzanti Andrea,
Fochi Mariafrancesca,
Bernardi Luca
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601364
Subject(s) - enantioselective synthesis , chemistry , michael reaction , intramolecular force , diastereomer , amination , reductive amination , catalysis , combinatorial chemistry , organocatalysis , organic chemistry , stereochemistry
1,5‐Benzothiazepine frameworks are highly relevant in medicinal chemistry. Reported catalytic asymmetric approaches to these scaffolds have targeted 2,3‐dihydro‐1,5‐benzothiazepin‐4‐ones but leave the corresponding amines (i.e., 2,3,4,5‐tetrahydro‐1,5‐benzothiazepines) out of reach. Herein, we present the first entry to these important compounds in enantioenriched form. Our approach is based on the catalytic asymmetric sulfa‐Michael addition of 2‐aminothiophenols to trans ‐chalcones, followed by intramolecular reductive amination. Both reactions required careful study to solve several challenging issues. The resulting optimized two‐step protocol afforded a range of 2,3,4,5‐tetrahydro‐1,5‐benzothiazepines as single trans diastereomers in moderate to good yields and enantioselectivities.