ja5b02537_si_002.cif (30.75 kB)
Facile Net Cycloaddition Approach to Optically Active 1,5‑Benzothiazepines
dataset
posted on 2015-04-29, 00:00 authored by Yukihiro Fukata, Keisuke Asano, Seijiro MatsubaraThe 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.