%0 Journal Article %A Fukata, Yukihiro %A Asano, Keisuke %A Matsubara, Seijiro %D 2015 %T Facile Net Cycloaddition Approach to Optically Active 1,5‑Benzothiazepines %U https://acs.figshare.com/articles/journal_contribution/Facile_Net_Cycloaddition_Approach_to_Optically_Active_1_5_Benzothiazepines/2172163 %R 10.1021/jacs.5b02537.s001 %2 https://acs.figshare.com/ndownloader/files/3806089 %K sequential chemoselective nucleophilic attacks %K benzothiazepine %K assay evaluation %K cycloaddition approach %K Cycloaddition Approach %K derivative %K acylammonium intermediates %K enantioselective preparation %K chiral isothiourea catalysts %X 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. %I ACS Publications