Catalytic Enantioselective Synthesis of Protecting-Group-Free 1,5-Benzothiazepines.
A one-pot enantioselective route to N-unprotected 2,3-dihydro-1,5-benzothiazepinones, by an organocatalyzed sulfa-Michael reaction of readily available α,β-unsaturated N-acyl pyrazoles with 2-aminothiophenols followed by silica-gel-catalyzed lactamization, has been developed. The method proceeds under mild conditions at room temperature and it requires only 1 mol % catalyst loading, to give 2-aryl/alkyl-substituted 1,5-benzothiazepines in generally good to excellent yields and enantioselectivities. The process, used for a short synthesis of antidepressant drug (R)-(-)-thiazesim, represents the first method to access enantioenriched unprotected 1,5-benzothiazepines, which are useful for rapid derivatization in drug discovery.
Dipartimento di Chimica e Biologia "A. Zambelli", Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy.
Sara
S
Meninno
Dipartimento di Chimica e Biologia "A. Zambelli", Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy.
Chiara
C
Volpe
Dipartimento di Chimica e Biologia "A. Zambelli", Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy.
Alessandra
http://orcid.org/0000-0003-1132-8610
A
Lattanzi
1,5-benzothiazepine; asymmetric synthesis; enoate equivalent; michael addition; organocatalysis