title: Facile net cycloaddition approach to optically active 1,5-benzothiazepines.
abstract: The 1,5-benzothiazepine moiety is well-known as a versatile pharmacophore, and its derivatives are expected to have antagonism against numerous diseases. Thus, it is desirable to develop a synthetic route that enables facile enantioselective preparation of a wide range of such derivatives. Although the cycloaddition approach could be considered a possible route to these compounds, to date, there has been no precedent of such a protocol. We therefore present the first example of a highly enantioselective net [4 + 3] cycloaddition to afford 1,5-benzothiazepines by utilizing α,β-unsaturated acylammonium intermediates generated by chiral isothiourea catalysts, which undergo two sequential chemoselective nucleophilic attacks by 2-aminothiophenols. This protocol provided cycloadducts in extremely high regioselectivity, with a good-to-excellent stereoselectivity being achieved regardless of the steric and electronic properties of the substrates. This method therefore offers promising synthetic routes for the construction of a library of optically active 1,5-benzothiazepines for assay evaluation.
authors: Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan.
authors: Yukihiro
authors: Y
authors: Fukata
authors: Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan.
authors: Keisuke
authors: K
authors: Asano
authors: Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan.
authors: Seijiro
authors: S
authors: Matsubara
mesh_terms: D002384:Catalysis; D061565:Cycloaddition Reaction; D013237:Stereoisomerism; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry; D013890:Thiourea / Q000031:analogs & derivatives
chemical_list: C106746:1,5-benzothiazepine; D013841:Thiazepines; D013890:Thiourea