Quaternary ammonium bromide functionalized polyethylene glycol: A highly efficient and recyclable catalyst for selective synthesis of 5-aryl-2-oxazolidinones from carbon dioxide and aziridines under solvent-free conditions

Article abstract of DOI:10.1021/jo800269v

(Chemical Equation Presented) A quaternary ammonium bromide covalently bound to polyethylene glycol (PEG, MW = 6000), i.e., PEG₆₀₀₀- (NBu₃Br)₂, was found to be an efficient and recyclable catalyst for the cycloaddition reaction of aziridines to CO₂ under mild conditions without utilization of additional organic solvents or cocatalysts. As a result, 5-aryl-2-oxazolidinone was obtained in high yield with excellent regioselectivity. The catalyst worked well for a wide variety of 1-alkyl-2-arylaziridines. Besides, the catalyst could be recovered by centrifugation and reused without significant loss of catalytic activity and selectivity.

Full text of DOI:10.1021/jo800269v

CO2;5 and (iii) insertion of CO2 into the aziridines moiety.6
Methods ii and iii utilizing CO2 as a feedstock, which is an
abundant, nontoxic, and cheap C1 building block, are promising
from a green chemistry perspective.7 In this respect, numerous
homogeneous catalysts have currently been developed for the
cycloaddition reaction of aziridines to CO2, such as a dual-
component system, viz., SalenCr(III)/DMAP6f or Phenol/
DMAP,6g alkali metal halide,6c–e or the tetraalkylammonium
halide system.6d Particularly, iodine was extremely active for
this reaction under supercritical CO2 (scCO2) conditions.6b,h In
addition, the cycloaddition of aziridines to CO2 also proceeded
smoothly under electrochemical reaction conditions.6a Nonethe-
less, toxic organic solvents and cocatalysts are generally required
to achieve high yields, along with a limited substrate scope in
those above-mentioned cases. Therefore, the recyclability of the
catalysts and product separation and developing highly effective
catalysts for regioselective synthesis of 5-substituted-2-oxazoli-
nones are still important issues to be addressed.
Quaternary Ammonium Bromide Functionalized
Polyethylene Glycol: A Highly Efficient and
Recyclable Catalyst for Selective Synthesis of
5-Aryl-2-oxazolidinones from Carbon Dioxide
and Aziridines Under Solvent-Free Conditions
Ya Du, Ying Wu, An-Hua Liu, and Liang-Nian He*
State Key Laboratory and Institute of Elemento-Organic
Chemistry, Nankai UniVersity, Tianjin 300071,
People’s Republic of China
heln@nankai.edu.cn
ReceiVed February 2, 2008
As catalyst recycling is often a vital problem in homogeneous
catalysis efficient recycling concepts have to be developed. To
preserve the benefits of a homogeneous catalyst while co-opting
the primary benefits of a heterogeneous catalyst, one strategy
is to graft the active species onto an insoluble support, whereby
the catalyst can be readily separated from the reaction mixture
by filtration. Notably, An appealing methodology would employ
a CO2-philic support for the reaction such that the supported
catalyst dissolves during the reaction and can precipitate
quantitatively at the separation stage. The most commonly used
parameters to induce the precipitation are temperature, solvent,
polarity, and pH of the solution. In this context, PEG should
be an excellent candidate, being regarded as an environmentally
benign medium for chemical reactions.8 We envisioned that a
functionalized PEG, with a quaternary ammonium salt as a
catalytically active species being covalently grafted onto PEG,
could be utilized as an active and recyclable homogeneous
catalyst for oxazolidinone synthesis from aziridine and CO2. In
A quaternary ammonium bromide covalently bound to
polyethylene glycol (PEG, MW ) 6000), i.e., PEG6000
-
(NBu3Br)2, was found to be an efficient and recyclable
catalyst for the cycloaddition reaction of aziridines to CO2
under mild conditions without utilization of additional
organic solvents or cocatalysts. As a result, 5-aryl-2-oxazo-
lidinone was obtained in high yield with excellent regiose-
lectivity. The catalyst worked well for a wide variety of
1-alkyl-2-arylaziridines. Besides, the catalyst could be re-
covered by centrifugation and reused without significant loss
of catalytic activity and selectivity.
(4) Selected examples for condensation of amino alcohols with carbonyl
derivatives to afford oxazolidinones, see: (a) Crowther, H. L.; McCombie, H.
J. Chem. Soc. 1913, 103, 27. (b) Close, W. J. J. Am. Chem. Soc. 1951, 73, 95.
(c) Ben-Ishai, D. J. Am. Chem. Soc. 1956, 78, 4962. (d) Vo, L.; Ciula, J.;
Gooding, O. W. Org. Process Res. DeV. 2003, 7, 514. Oxazolidinones synthesis
by direct addition of carbon dioxide or carbon monoxide to ꢀ-amino alcohols,
see: (e) Steele, A. B. U.S. Patent 2 868 801, 1959. (f) Lynn, J. W. U.S. Patent
2 975 187, 1961. (g) Yoshida, T; Kambe, N.; Ogawa, A; Sonoda, N. Phosphorus
Sulfur 1988, 38, 137.
Oxazolidinones are important heterocyclic compounds show-
ing a large application as intermediates1 and chiral auxiliaries2
in organic synthesis. Cyclic carbamates like 5-substituted
oxazolidinones are often employed as fragments in biologically
active materials for pharmaceutical and agricultural uses.3 There
are three main synthetic strategies starting from C1 resources:
(i) carbonylation of amino alcohols with phosgene, CO, etc.;4
(ii) reaction of propargylamines or propargylic alcohols with
(5) Selected examples concerning the reaction of propargylamines with carbon
dioxide to afford oxazolidinones, see: (a) Costa, M.; Chiusoli, G. P.; Rizzardi,
M. Chem. Commun. 1996, 1699. (b) Shi, M.; Shen, Y. M. J. Org. Chem. 2002,
67, 16. (c) Feroci, M.; Orsini, M.; Sotgiu, G.; Rossi, L.; Inesi, A. J. Org. Chem.
2005, 70, 7795. (d) Kayaki, Y.; Yamamoto, M.; Suzuki, T.; Ikariya, T. Green
Chem. 2006, 8, 1019. Reaction of propargylic alcohols and amines to give
oxazolidinones, see: (e) Gu, Y. L.; Zhang, Q. H.; Duan, Z. Y.; Zhang, J.; Zhang,
S. G.; Deng, Y. Q. J. Org. Chem. 2005, 70, 7376.
(1) For selected examples with oxazolidinones as intermediates, see: (a)
Watson, R. J.; Batty, D.; Baxter, A. D.; Hannah, D. R.; Owen, D. A.; Montana,
J. G. Tetrahedron Lett. 2002, 43, 683. (b) Aurelio, L.; Brownlee, R. T. C.;
Hughus, A. B. Chem. ReV. 2004, 104, 5823. (c) Shi, Z. D.; Liu, H. P.; Zhang,
M. C.; Yang, D. J.; Burke, T. R., Jr Synth. Commun. 2004, 34, 3883. (d) Makhtar,
T. M.; Wright, G. D. Chem. ReV. 2005, 105, 529. (e) Andreou, T.; Costa, A. M.;
Esteban, L.; Gonzalez, L.; Mas, G.; Vilarrasa, J. Org. Lett. 2005, 7, 4083.
(2) For selected examples using oxazolidinones as chiral auxiliaries, see: (a)
Phoon, C. W.; Abell, C. Tetrahedron Lett. 1998, 39, 2655. (b) Prashad, M.;
Liu, Y. G.; Kim, H. Y.; Repic, O.; Blacklock, T. J. Tetrahedron: Asymmetry
1999, 10, 3479. (c) Gawley, R. E.; Campagna, S. A.; Santiago, M.; Ren, T.
Tetrahedron: Asymmetry 2002, 13, 29.
(6) The insertion of CO2 into the aziridines moiety to give oxazolidinones,
see: (a) Tascedda, P.; Dunach, E. Chem. Commun. 2000, 449. (b) Kawanami,
H.; Ikushima, Y. Tetrahedron Lett. 2002, 43, 3841. (c) Hancock, M. T.; Pinhas,
A. R. Tetrahedron Lett. 2003, 44, 5457. (d) Sudo, A.; Morioka, Y.; Koizumi,
E.; Sanda, F.; Endo, T. Tetrahedron Lett. 2003, 44, 7889. (e) Sudo, T.; Morioka,
Y.; Sanda, F.; Endo, T. Tetrahedron Lett. 2004, 45, 1363. (f) Miller, A. W.;
Nguyen, S. T. Org. Lett. 2004, 6, 2301. (g) Shen, Y. M.; Duan, W. L.; Shi, M.
Eur. J. Org. Chem. 2004, 3080. (h) Kawanami, H.; Matsumoto, H.; Ikushima,
Y. Chem. Lett. 2005, 34, 60. (i) Ihata, O.; Kayaki, Y.; Ikariya, T. Angew. Chem.,
Int. Ed. 2004, 43, 717.
(3) (a) Brickner, S. J. Curr. Pharm. Des. 1996, 2, 175. (b) Barbachyn, M. R.;
Ford, C. W. Angew. Chem, Int. Ed. 2003, 42, 2010. (c) Nilus, A. M. Curr. Opin.
InVest. Drugs. 2003, 4, 149.
(7) Sakakura, T.; Choi, J. C.; Yasuda, H. Chem. ReV. 2007, 107, 2365.
10.1021/jo800269v CCC: $40.75
Published on Web 05/13/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 4709–4712 4709

TABLE 1. Carboxylation of Aziridine into Oxazolidinonea
FIGURE 1. Plot of TOF as a function of CO2 pressure for the reaction
of CO2 and 1a. Reaction conditions: PEG6000(NBu3Br)2 (32.4 mg, 0.005
mmol), 1a (294 mg, 2 mmol), 100 °C, 20 min.
d
entry
1
catalyst
t (min) yield (%)b regio-sel (%)c TOF (h-1
)
5
5
5
5
5
5
5
trace
trace
6
38
71
2e PEG6000
3
4
Bu4NBr
94:6
91:9
93:7
96:4
94:6
92:8
93:7
92:8
92:8
96:4
274
1805
3394
2575
1416
2126
1490
1162
1170
1157
Bu4NBr/PEG6000
PEG6000(NBu3Br)2
I2
5
6f
88
94
7g LiBr
8
9
PEG6000(NBu3Br)2 10
PEG6000(NBu3Br)2 15
89
93
98
97
10 PEG6000(NBu3Br)2 20
11h PEG6000(NBu3Br)2 20
12i PEG6000(NBu3Br)2 20
96
a Reaction conditions: catalyst (0.005 mmol, 0.25 mol % with respect
to 1a), 1a (294 mg, 2 mmol), CO2 8 MPa, 100 °C. b The total yield of
2a and 3a, determined by GC with biphenyl as an internal standard.
c Molar ratio of 2a to 3a. d Turnover frequency (TOF): sum of moles of
2a and 3a produced per mole of catalyst per hour. e PEG (30 mg) alone.
f Catalyst: I2, 2.1 mg, 0.008 mmol, 0.4 mol % relative to 1a. g Catalyst:
LiBr, 1.4 mg, 0.016 mmol, 0.8 mol % with regard to 1a. h The second
run of the catalyst recovered from entry 10 (fresh catalyst). i The third
run of the reused catalyst.
FIGURE 2. Reaction temperature dependence of yield and chemose-
lectivity with PEG6000(NBu3Br)2 as a catalyst. Reaction conditions:
PEG6000(NBu3Br)2 (32.4 mg, 0.005 mmol), 1a (294 mg, 2 mmol), 8
MPa, 20 min.
from changes in the physical properties8 of the reaction mixture,
such as low viscosity and increased solubility for the reactants.
Consequently, the ammonium salt can be considered as the
active species for the reaction and supporting Bu4NBr on the
CO2-expandable polymer8d,9 improves the catalytic activity.
Note that 5-aryl-2-oxazolidinone (2a) was preferentially formed
with high regioselectivities in all cases listed in Table 1. The
major isomer, i.e., 2a, corresponds to the incorporation of CO2
at the more sterically hindered side of the monosubstituted
aziridine; in other words, the more substituted carbon-nitrogen
is predominately carboxylated.
the present work, we would like to report the use of
PEG6000(NBu3Br)2 gave rise to a high yield and regioselectivity
for 5-substituted-2-oxazolidinone synthesis under mild condi-
tions, without the need of any additives. Furthermore, the
catalyst is quite efficacious for a wide scope of substrates under
organic solvent-free conditions.
The cycloaddition reaction of aziridines with CO2 was
conducted in a batch-wise operation in the presence of 0.25
mol % of the catalyst relative to the initial amount of substrate.
1-Ethyl-2-phenylaziridine (1a) was chosen as the standard
substrate to investigate suitable reaction conditions for the
desired reaction. The results are summarized in Table 1. Without
any catalyst or in the presence of 30 mg of PEG6000 alone, the
coupling reaction of 1a/CO2 did not occur at all (entries 1 and
2). Bu4NBr itself showed low catalytic activity in the carboxy-
lation of 1a with CO2 (entry 3). A mixture of Bu4NBr with
PEG6000 has higher catalytic activity than the unsupported
ammonium salt, i.e., Bu4NBr (entry 4 vs 3). Interestingly,
PEG6000(NBu3Br)2 actually has higher catalytic activity than the
unsupported quaternary ammonium (Bu4NBr), even more ef-
fective than the simple physical mixture of Bu4NBr with PEG6000
under the identical conditions (Table 1, entry 5 vs entries 3 and
4). The enhancement of catalytic performance for the PEG-
supported ammonium salt is presumably attributed to the benefits
It is worth mentioning that the turnover frequency (TOF, 3394
h-1) of PEG6000(NBu3Br)2 was attained under reaction conditions
6h
much higher than those of the most active catalysts like I2
and LiBr6e for the aziridine/CO2 reaction (entry 5 vs entries 6
and 7). The only byproducts of this reaction were trace amounts
of 1,4-diethyl-2,5-diphenylpiperazine (4a) and 1,4-diethyl-2,3-
1
diphenylpiperazine (5a) being detected by MS and H NMR
(see the Supporting Information). In other words, excellent
chemoselectivity was attained in this catalytic process.
Shown in Figure 1 is the activity of PEG6000(NBu3Br)2 as a
function of CO2 pressure in the reaction of CO2 and 1a. As is
easily seen, pressure has a great influence on the reaction rate
with variation of CO2 pressure from 1 to 8 MPa. On the other
hand, the reaction rate slightly changes from 8 to 15 MPa.
However, the reaction rate dramatically decreases with further
increase in CO2 pressure. Excessive CO2 pressure may cause a
low concentration of aziridine in the vicinity of the catalyst,
thus resulting in a low reaction rate.10
(8) (a) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Tocco, G.
Org. Lett. 2000, 2, 1737. (b) Heldebrant, D. J.; Jessop, P. G. J. Am. Chem. Soc.
2003, 125, 5600. (c) Reetz, M. T.; Wiesenhofer, W. Chem. Commun. 2004, 2750.
(d) Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D. Green Chem. 2005,
7, 64. (e) Du, Y; Wang, J. Q.; Chen, J. Y.; Cai, F.; Tian, J. S.; Kong, D. L.; He,
L. N. Tetrahedron Lett. 2006, 47, 1271. (f) Zhou, H. F.; Fan, Q. H.; Tang, W. J.;
Xu, L. J.; He, Y. M.; Deng, G. J.; Zhao, L. W.; Gu, L. Q.; Chan, A. S. C. AdV.
Synth. Catal. 2006, 348, 2172. (g) Tian, J. S.; Miao, C. X.; Wang, J. Q.; Cai, F.;
Du, Y.; Zhao, Y.; He, L. N. Green Chem. 2007, 9, 566.
Figure 2 shows the temperature dependence on the yield of
oxazolidinones. The yield of 2a increases sharply with a
(9) Jessop, P.; Wyne, D. C.; Dehaai, S.; Nakawatase, D. Chem. Commun.
2000, 693.
(10) Lu, X. B.; Xiu, J. H.; He, R.; Jin, K.; Luo, L. M.; Feng, X. J. Appl.
Catal. A 2004, 275, 73.
4710 J. Org. Chem. Vol. 73, No. 12, 2008

SCHEME 1. A Putative Mechanism
TABLE 2. Substrate Scopea
achieved within about 20 min (entries 1, 2, 4, and 5, Table 2).
However, 2-phenylaziridine (1c) displayed a relatively low
selectivity probably due to the formation of self-oligomers as
detected by GC-MS (entry 3). The substrates 1g-n bearing a
branched alkyl group at the nitrogen atom showed in slower
reaction rate, presumably due to the steric interactions in terms
of reaction mechanistic consideration (Scheme 1). Nonetheless,
excellent results except for 1g were also obtained at a prolonged
reaction time (entries 7-14). With regard to regioselectivity,
the nature of the R1 group is a crucial factor in dominating the
selectivity of the reaction, as has been previously reported.6b If
R1 is an aryl group, product 2 is favored, whereas if R1 is an
alkyl group, product 3 is favored. It seems to be shown that the
regioselectivity can be significantly enhanced from 86:14 (2:3)
to an exclusive generation of 2 (entries 3 and 7-10) as the alkyl
substituent at the nitrogen atom is augmented. On the other hand,
an electron-donating group on the C1-aryl group gave a faster
reaction rate than the presence of an electron-withdrawing group
(entry 13 vs 14) to accelerating this reaction. Interestingly, the
4-substituted oxazolidinone 3o was preferentially produced in
a molar ratio of 80:20 (3o to 2o) when R1 at the carbon atom
is an alkyl group, which would be explained by the proposed
mechanism as outlined in Scheme 1 (entry 15). It is also noted
that 1,2,4,5-tetraphenylpiperazine and 1,2,3,4-tetraphenylpip-
erazine were formed, as detected by LC-MS, when both R and
R1 in the substrate 1 are phenyl groups (entry 16).
On the basis of the experiment results, a possible mechanism
for the PEG6000(NBu3Br)2-catalyzed cycloaddition of CO2 with
aziridine was proposed as shown in Scheme 1. This proposal is
analogous to that of the LiI-catalyzed version for the same
reaction.6c The mechanism involves three steps: coordination
of CO2 to aziridine (step I), then ring opening of the aziridine
through two different pathways as represented by paths a and
b mainly depending on the nature of the R1 group with alkyl
substitution at the N-position (step II), and subsequent cycliza-
tion via an intramolecular nucleophilic attack leading to
oxazolidinones and regeneration of the catalyst (step III). In
this respect, the following observation supports our hypothesis.
The rate dependence on the steric effect of the R group on the
nitrogen atom shown in Table 2 implies that the coordination
of CO2 to the aziridine(I) is a reversible step in the catalytic
cycle and the substrates with less sterically hindered R would
be favorable for the coordination with CO2, thus resulting in
higher reaction rate compared with those substrates with more
sterically hindered R. This proposed mechanism could also
account for the effect of the R1 substituent on the selective
formation of 2 or 3. As deduced from Scheme 1, if R1 is an
aryl group, the intermediate A would be more stable than B
and thus 2 would be predominantly formed; in contrast, if R1
is an alkyl group, B would be favored, which in turn results in
dominantly producing 3. Furthermore, the reaction of (S)-1-
conv
isolated
regioselectivity
(%)d
entry
substrate
time
(%)b
yield (%)c
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
20 min
15 min
15 min
20 min
25 min
45 min
72 h
>99
>99
>99
99
>99
>99
50
>99
>99
>99
>99
97
>99
>99
99
95
83
59
89
94
>99
49
96
93
91
88
94
94
95
88
92:8
93:7
86:14
93:7
91:9
96:4
100
99:1
96:4
91:9
94:6
99:1
99:1
100
24 h
14h
9
10
11
12
13
14
15
16e
1j
1k
1l
1m
1n
1o
1p
12 h
11 h
10 h
10 h
15 h
1 h
24 h
20:80
100
a Reaction conditions: PEG6000(NBu3Br)2 (32.4 mg, 0.005 mmol),
substrate (2 mmol), CO2 8 MPa, 100 °C. b Determined by GC. c The total
yield of 2 and 3. d Molar ratio of 2 to 3. e 1,2,4,5-Tetraphenylpiperazine and
1,2,3,4-tetraphenylpiperazine were detected by LC-MS.
temperature increase from 60 to 100 °C, with no significant
change in yield observed from 100 to 120 °C. A further increase
in temperature causes a slight decrease in the chemoselectivity,
due to facile formation of piperazines 4a and 5a at a higher
temperature. Accordingly, 100 °C is suitable for conducting the
reaction at a reasonable rate.
It is worth mentioning that variation of temperature and
pressure had no influence on the regioselectivity of 2a ,which
remained over 92% in all cases. Furthermore, the catalyst
PEG6000(NBu3Br)2 can be recovered by centrifugation11and
reused for the next run with excellent activity (entries 11 and
12, Table 1).
To demonstrate the utility and generality of this approach,
we examined the cycloaddition reactions of various aziridines
(1a-p) with CO2 by performing the reaction under the given
conditions. The results are listed in Table 2. It is found that the
reactions of aziridines (1a, 1b, 1d, and 1e) bearing alkyl groups
at the nitrogen atom proceeded smoothly and good yields were
(11) After the reaction, Et2O (2 × 4 mL) was added to the reaction mixture;
the catalyst was then precipitated and separated by centrifugation.
J. Org. Chem. Vol. 73, No. 12, 2008 4711

SCHEME 2. Carboxylation of (S)-1-Butyl-2-phenylaziridine
into Oxazolidinone
Experimental Section
General Procedure for Carboxylation of Aziridine with
CO2. A 25 mL autoclave reactor was charged with catalyst
PEG6000(NBu3Br)2 (32.4 mg, 0.005 mmol) and aziridine (2 mmol).
CO2 was introduced into the autoclave and then the mixture was
stirred at 100 °C for 5 min to allow equilibration. Finally, the
pressure was adjusted to 8 MPa and the mixture was stirred
continuously. When the reaction was finished, the reactor was
cooled in ice-water and CO2 was ejected slowly. An aliquot of
sample was taken from the resultant mixture and dissolved in
CH2Cl2 for GC analysis. The residue was purified by column
chromatography on silica gel (200-300 mesh, eluting with 8:1 to
1:1 petroleum ether/ethyl acetate) to afford the desired product.
The products were further identified by NMR and MS (see the
Supporting Information), which are consistent with those reported
in the literature6f,15 and in good agreement with the assigned
structures.
butyl-2-phenylaziridine (S-1e)12 with CO2 in the presence of
0.25 mol % PEG6000(NBu3Br)2 (Scheme 2) affords S-2e in
91.4% yield and S-3e in 8.6% yield with retention of
stereochemistry,13,14 further supporting the above mechanism
where there is a double inversion of stereochemistry at the chiral
carbon center, which is attacked. In addition, Scheme 1 can
also be used to rationalize the dependence of the reaction on
CO2 pressure in the range of 1 to 8 MPa (Figure 1). As Scheme
1 suggests, the coordination of CO2 with aziridine would be a
reversible step in the catalytic cycle. Therefore, a higher CO2
pressure could be favorable for the CO2 coordination leading
to the desired product and suppressing the formation of 4a and
5a.
In conclusion, we developed an efficient and recyclable
catalyst for high selective synthesis of 5-substituted-2-oxazo-
lidinones from CO2 and various aziridines without any added
organic solvents or cocatalysts. It is also found that selective
formation 5-substituted-2-oxazolidinone 2 or 4-substituted
isomer 3 relies on R1 at the carbon of the substrate when R is
a fixed alkyl group. To our knowledge, the PEG-supported
ammonium catalyst system is one of the most efficient catalyst
systems to date for this carboxylation reaction under mild
conditions. One of the salient features of this protocol would
be that the catalyst can be readily recovered by centrifugation
and reused with retention of high catalytic activity and regi-
oselectivities. This process represents a pathway for the
environmentally benign chemical fixation of CO2 to afford
5-substituted-2-oxazolidinones.
3-Ethyl-5-phenyloxazolidin-2-one (2a). Colorless liquid; 1H
3
NMR (300 MHz, CDCl3) δ 1.17 (t, J ) 7.2 Hz, 3H), 3.29-3.45
3
3
(m, 3H), 3.92 (t, J ) 8.7 Hz, 1H), 5.48 (t, J ) 7.8 Hz, 1H),
7.34-7.42 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 12.4, 38.8, 51.5,
74.2, 125.4, 128.6, 128.8, 138.8, 157.5; MS (ESI) calcd for
C11H13NO2 191.09, found 192.29 (M + H)+, 214.38 (M + Na)+,
405.01 (2 M + Na)+; HRMS calcd for C11H13NO2 (M + H)+
192.1019, found 192.1015.
3-Ethyl-4-phenyloxazolidin-2-one (3a). Colorless liquid; 1H
3
NMR (400 MHz, CDCl3) δ 1.05 (t, J ) 7.2 Hz, 3H), 2.79-2.88
(m, 1H), 3.48-3.57 (m, 1H), 4.10 (t, 3J ) 8.0 Hz, 1H), 4.62 (t, 3J
) 8.8 Hz, 1H), 4.81 (t, 3J ) 7.2 Hz, 1H), 7.30-7.44 (m, 5H); 13
C
NMR (75 MHz, CDCl3) δ 12.1, 36.8, 59.3, 69.7, 126.9, 129.0,
129.2, 137.8, 158.1; MS (ESI) calcd for C11H13NO2 191.09, found
192.29 (M + H)+, 214.38 (M + Na)+, 405.01 (2 M + Na)+; HRMS
calcd for C11H13NO2 (M + H)+ 192.1019, found 192.1015.
Acknowledgment. Financial support from National Science
Foundation (Grant Nos. 20421202 and 20672054) and the 111
project (B06005) and the Tianjin Natural Science Foundation
is gratefully acknowledged. We also thank the referees for their
valuable suggestions.
(12) (S)-1-Butyl-2-phenylaziridine (S-1e) was synthesized according to a
literature procedure: Calet, S.; Urso, F.; Alper, H. J. Am. Chem. Soc. 1989, 111,
931.
(13) The reaction of (S)-1-butyl-2-phenylaziridine (S-1e) with CO2 in the
presence of 0.25 mol % catalyst affords (S)-3-butyl-5-phenyloxazolidione (S-
2e) in 96.7% ee with 91.4% yield and (S)-3-butyl-4-phenyloxazolidione (S-3e)
in 97.5% ee with 8.6% yield. The enantiomeric excess of S-2e and S-3e was
determined by HPLC, using Agilent 1100 series with a chiralcel AD-H (hexane/
isopropyl alcohol 95:5, 220 nm) at room temperature. The retention times of
S-2e and R-2e are 14.87 and 16.39 min, and the retention times of S-3e and
R-3e are 21.24 and 23.51 min, respectively.
Supporting Information Available: General experimental
methods, experimental procedures, and characterization for
aziridines, oxazolidinones, and piperazines and copies of NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO800269V
(14) The absolute configuration is S, as compared the optical rotation value
with the literature data.14a,b The optical rotation values were recorded with Perkin-
Elmer Instruments (model 341) [R]20 +13.6 (c 1.5, CHCl3) and [R]20 +31.1
D
D
(c 0.8, CHCl3) for the (+)-2e and (+)-3e, respectively. (a) Claude, A.; Francois,
C.; Louis, H.; Olivier, V. Tetrahedron Lett. 1993, 34, 4509–4512. (b) Tanis,
S. P.; Evans, B. R.; Nieman, J. A.; Parker, T. T.; Taylor, W. D.; Heasley, S. E.;
Herrinton, P. M.; Perrault, W. R.; Hohler, R. A.; Dolak, L. A.; Hester, M. R.;
Seest, E. P. Tetrahedron: Asymmetry, 2006, 17, 2154–2182.
(15) (a) Bergmann, E. D.; Goldschomidt, Z. J. Med. Chem. 1968, 11, 1121.
(b) Herweh, J. E. J. Org. Chem. 1968, 33, 4029. (c) Das, J. Synth. Commun.
1988, 18, 907. (d) Orito, K.; Miyazawa, M.; Nakamura, T.; Horibata, A.; Ushito,
H.; Nagasaki, H.; Yuguchi, M.; Yamashitan, S.; Yamazaki, T.; Tokuda, M. J.
Org. Chem. 2006, 71, 5951.
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