Y. Yoshida and T. Endo
Tetrahedron Letters 72 (2021) 153086
containing MTBD and DBU showed complete disappearance of –
NH peak of 1a as well as that of TBD (Fig. S2). Nevertheless, the cat-
alytic efficiency of MTBD and DBU is insufficient compared to that
of TBD. The reason could be explained that MTBD and DBU without
containing active protons are not able to sufficiently activate an
epoxy moiety of 1a, and also are not able to smoothly give rise
to the proton transfer from carbamate to epoxy moieties. These
results indicate that superior efficiency of TBD catalyst is due to
specific intermolecular interaction between 1a and TBD based on
a hydrogen bond. Therefore, the intramolecular cyclization of 1a
with TBD immediately proceeds together with a proton transfer
from carbamate moiety to epoxy ring via guanidinium cation of
TBD. Moreover, a basicity of the catalysts might also depend on
the catalytic efficiency, because the reaction rate of the intramolec-
ular cyclization of 1a increased with increasing pKBH+ values
(Fig. 1) [40,41]. On the other hand, an inactivity of DBU-HI is
because of fairly weak interaction between 1a and DBU-HI. In fact,
the broaden peak due to –NH proton of 1a was observed at
8.80 ppm in 1H NMR spectrum of the mixture containing DBU-HI,
although 1H NMR spectra of the mixtures containing the other cat-
alysts never showed the peak of –NH proton in the same range
(Fig. S2). This result indicates that the intramolecular cyclization
scarcely proceeds together with a proton transfer from 1a to
DBU-HI at least under room temperature.
Next, the substituent effects such as electronic and steric effects
for the intramolecular cyclization of glycidyl carbamates having
various functional groups were examined with TBD according to
Scheme 2a. The intramolecular cyclization of 1b having a methoxy
group as an electron donating group proceeded in a high yield,
whereas 1c having a trifluoromethyl group as an electron with-
drawing group exhibited a lower yield than the reaction from 1a
and 1b. As mentioned above, the intramolecular cyclization of phe-
nyl glycidyl carbamate proceeds due to the nucleophilic attack of
the electron-rich nitrogen atom on the carbamate moiety to the
epoxide moiety. Therefore, the phenyl glycidyl carbamates having
electron donating groups exhibits a high yield in this reaction sys-
tem. Moreover, the phenyl glycidyl carbamates having bulky
groups such as ortho-dimethyl (1d) and diisopropyl (1e) groups
afforded the target compounds in moderate yields, because the
nucleophilic attack of the nitrogen atom on the carbamate moiety
to the epoxide moiety is restricted owing to the steric hindrance of
bulky groups. The reaction of glycidyl carbamates having aliphatic
groups such as n-hexyl (1f), cyclohexyl (1 g), and benzyl (1 h)
groups were also performed under the same conditions, however,
all of the glycidyl carbamates were never converted to 2-oxazolidi-
none derivatives. This is because the acidity of the NAH proton on
aliphatic glycidyl carbamates is fairly lower than that of aromatic
glycidyl carbamates owing to the electron donating effect from
the aliphatic functional groups [12–13]. On the basis of these
results, the synthesis of bifunctional 2-oxazolidinone derivatives
was attempted with TBD from aromatic bifunctional glycidyl car-
bamates (3) according to Scheme 2b.
As well as the reaction system of monofunctional phenyl gly-
cidyl carbamates, bifunctional glycidyl carbamates having the aro-
matic groups such as methylene bisphenyl (3j) and
dimethylbiphenyl (3 k) groups afforded successfully the bifunc-
tional 4-hydroxymethyl 2-oxazolidinones (4) in moderate yields.
On the other hand, the bifunctional glycidyl carbamate having
the para-phenylene group (3i) was never converted to the target
compound, because the lone pairs on the nitrogen atoms of both
carbamate moieties were delocalized owing to the conjugate effect
between phenylene and carbamate units. Furthermore, the reac-
tion of the trifunctional glycidyl carbamate having triphenyl-
methane group (5 l) was also performed under standard
conditions according to Scheme 2c, and the trifunctional 4-hydrox-
Scheme 2. Synthesis of 4-hydroxymethyl 2-oxazolidinone derivatives with TBD in
acetone at 25 °C for 24 h from, (a) glycidyl carbamates having various functional
groups, (b) bifunctional glycidyl carbamates having aromatic groups, and (c)
trifunctional glycidyl carbamate.
ymethyl 2-oxazolidinones (6 l) was successfully synthesized in
57% yield.
In summary, we achieved a synthesis of 4-hydroxymethyl 2-
oxazolidinones having various functional groups by the
intramolecular cyclization of glycidyl carbamates with a catalytic
amount of amine at room temperature. Among the amine catalysts,
TBD was significantly effective catalyst for the intramolecular
cyclization of glycidyl carbamates because the carbamate and
3