10.1021/jacs.5b02537.s001
Yukihiro Fukata
Yukihiro
Fukata
Keisuke Asano
Keisuke
Asano
Seijiro Matsubara
Seijiro
Matsubara
Facile
Net Cycloaddition Approach to Optically Active
1,5‑Benzothiazepines
American Chemical Society
2015
sequential chemoselective nucleophilic attacks
benzothiazepine
assay evaluation
cycloaddition approach
Cycloaddition Approach
derivative
acylammonium intermediates
enantioselective preparation
chiral isothiourea catalysts
2015-04-29 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Facile_Net_Cycloaddition_Approach_to_Optically_Active_1_5_Benzothiazepines/2172163
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.