Synthesis of 2-oxazolidinone by N-heterocyclic carbene-catalyzed carboxylative cyclization of propargylic amine with CO2

Article abstract of DOI:10.1016/j.tetlet.2016.02.027

By employing N-heterocyclic carbenes as catalysts, the carboxylative cyclization of propargylic amine proceeded under 0.6 MPa of CO₂ to afford the corresponding 2-oxazolidinone at 90 °C in 2-propanol. Among N-heterocyclic carbenes, 1,3-di-t-but

Full text of DOI:10.1016/j.tetlet.2016.02.027

Accepted Manuscript
Synthesis of 2-oxazolidinone by N-heterocyclic carbene–catalyzed carboxyla-
tive cyclization of propargylic amine with CO2
Ken-ichi Fujita, Akira Fujii, Junichi Sato, Shun-ya Onozawa, Hiroyuki Yasuda
PII:
S0040-4039(16)30138-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.02.027
TETL 47300
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 December 2015
3 February 2016
9 February 2016
Please cite this article as: Fujita, K-i., Fujii, A., Sato, J., Onozawa, S-y., Yasuda, H., Synthesis of 2-oxazolidinone
by N-heterocyclic carbene–catalyzed carboxylative cyclization of propargylic amine with CO2, Tetrahedron
Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.02.027
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

1
Tetrahedron Letters
Synthesis of 2-oxazolidinone by N-heterocyclic carbene–catalyzed carboxylative
cyclization of propargylic amine with CO2
Ken-ichi Fujita, a,* Akira Fujii,a Junichi Sato,b Shun-ya Onozawa,a Hiroyuki Yasudaab
aNational Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
bGraduate School of Science and Engineering, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
By employing N-heterocyclic carbenes as catalysts, the carboxylative cyclization of propargylic
amine proceeded under 0.6 MPa of CO2 to afford the corresponding 2-oxazolidinone at 90 ºC in
2-propanol. Among N-heterocyclic carbenes, 1,3-di-t-butylimidazol-2-ylidene was the most
effective catalyst for the reaction, providing 2-oxazolidinone in a maximum chemical yield of
99%.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
N-Heterocyclic carbene
Catalyst
Carbon dioxide
Carboxylative cyclization
2-Oxazolidinone
Carbon dioxide (CO2) has drawn much attention from the
viewpoint of global warming and is one of the most promising
alternatives to phosgene, which has high toxicity, as a C1
building block.1 The development of green processes based on
the chemical fixation of CO2 has received a great deal of interest
in recent years because CO2 can be used as a safe, inexpensive,
and renewable resource to produce useful organic compounds.2
One of the useful methods in which CO2 has been utilized as a
substrate is through the carboxylative cyclization of propargylic
amines with CO2 to provide 2-oxazolidinones.3 For example, this
conversion has been found to be catalyzed by organometallic
complexes of noble metals such as ruthenium,4 palladium,5
silver,6 and gold.7 In particular, an N-heterocyclic carbene
(NHC)–gold(I) complex afforded high catalytic activity across a
wide range of carboxylative cyclizations of propargylic amines
with CO2.7a,c,d
The chemistry of NHCs has attracted attention because of the
rapid development of general synthetic methods and because of
their potential as organocatalysts for wide applications in the
field of catalytic organic syntheses.8 For example, NHCs are used
as metal-free catalysts for organic syntheses such as benzoin
condensation, transesterification, and cyanosilylation.9 This is
because their unique electronic and steric properties can be finely
tuned by varying their substituent patterns. We report herein the
NHC-catalyzed carboxylative cyclization of propargylic amine
with CO2 to provide 2-oxazolidinones. In a screening of various
NHCs as catalysts, 5 mol% of 1,3-di-t-butylimidazol-2-ylidene
(ItBu) was found to be the most effective catalyst for the
carboxylative cyclization of propargylic amine with CO2. Metal-
free carboxylative cyclizations of propargylic amine with CO2
previously reported.10,11 From the perspective of green chemistry,
the chemical fixation of CO2 promoted by a metal-free catalyst is
a very attractive field, as CO2 is naturally abundant and less
reactive.12
We have examined the carboxylative cyclization of
propargylic amine 1a with CO2 to provide 2-oxazolidinone 2a
through the use of various NHCs as catalysts, as shown in Table
1. First, by the stirring of a 2-propanol solution of propargylic
amine 1a at 90 ºC for 24 h in a sealed autoclave under 0.6 MPa
of CO2 in the absence of an NHC, the chemical yield of 2-
oxazolidinone 2a was very low (4%; Table 1, entry 1). Next, by
employing 10 mol% of various NHCs as catalysts, 2-
oxazolidinone 2a was detected in all cases (Table 1, entries 2–5).
It was found that 1,3-bis(2,6-diisopropylphenyl)imidazole-2-
ylidene (IPr) afforded a much higher chemical yield of 2a than
1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene
(SIPr)
(Table 1, entries 2 and 3). By the optimization of the substituent
on nitrogen in the imidazolylidene ring, 1,3-di-t-butylimidazol-2-
ylidene (ItBu) was found to be the most effective catalyst for the
carboxylative cyclization of propargylic amine 1a with CO2,
providing 2-oxazolidinone 2a in a 95% chemical yield (Table 1,
entry 5). Furthermore, by the examination of the amount of ItBu
as a catalyst, 5 mol% of ItBu even promoted the carboxylative
cyclization of propargylic amine 1a with CO2 to provide 2-
oxazolidinone 2a in a 97% chemical yield (Table 1, entry 6).
We then optimized the solvent for the carboxylative
cyclization of propargylic amine 1a with CO2 (Table 2). By
employing 5 mol% of ItBu, which afforded the highest chemical
yield in Table 1, the carboxylative cyclization of 1a was carried
out at 90 ºC for 24 h under 0.6 MPa of CO2 in each solvent. First,
when the carboxylative cyclization was carried out in methanol
or ethanol, the chemical yield of 2-oxazolidinone 2a was low in
either case (Table 2, entries 1 and 2). This is probably because
ItBu is partially deactivated by methanol or ethanol due to O–H

2
Tetrahedron
insertion of ItBu.13 On the other hand, by carrying out the
Table 2 Optimization of solvent for carboxylative cyclization
of propargylic amine 1a.
carboxylative cyclization in toluene, 2-oxazolidinone 2a was
obtained in a fair chemical yield (80%; Table 2, entry 5). By
carrying out the carboxylative cyclization in 2-propanol, 2-
oxazolidinone 2a was obtained in the highest chemical yield
(97%; Table 2, entry 3).
Table 1 Carboxylative cyclization of propargylic amine 1a
catalyzed by various NHCs.
Entry
Solvent
MeOH
EtOH
Yield (%)a
1
2
3
4
5
6
30
55
97
92
80
0
iPrOH
t-BuOH
Toluene
CH2Cl2
Determined by the integration of 1H NMR absorptions referring to an
a
internal standard.
Entry
1
NHC catalyst
none
x (mol%)
Yield (%)b
Table
3
Optimization of reaction temperature for
carboxylative cyclization of propargylic amine 1a.
0
4
2
3
(SIPr)
(IPr)
10
10
33
82
Entry
Temp. (ºC)
70
80
90
100
Yield (%)a
1
2
3
20
80
97
82
4
a
Determined by the integration of 1H NMR absorptions referring to an
internal standard.
4
(IMes)
(ItBu)
10
74
Finally, we performed the carboxylative cyclization of various
propargylic amines 1 under 0.6 MPa of CO2 by employing 5
mol% of ItBu as a catalyst, as shown in Table 4. The introduction
of a methoxy group at the phenyl group in R1 decreased the
reactivity of the triple bond (48%; Table 4, entry 2). Even though
the reaction time of the carboxylative cyclization of 1b extended
to 48 h at 90 ºC, the chemical yield of the corresponding 2-
oxazolidinone 2b was 86% (Table 4, entry 3). In contrast, the
introduction of a cyano group at the phenyl group in R1 enhanced
the reactivity of the triple bond. 1c was converted to 2c at 70 ºC
only for 4 h (91%; Table 4, entry 4). Then, in the case of the
methyl or ethyl group in R1, the corresponding 2-oxazolidinone
was not obtained in either case (Table 4, entries 6 and 7). On the
other hand, the reaction of a substrate having a terminal alkyne
unit 1g or 1h was carried out at 90 ºC for 24 h to provide the
corresponding 2-oxazolidinone 2g or 2h in an excellent chemical
yield in both cases (Table 4, entries 8 and 9).
Figure 1 shows a plausible mechanism for the efficient
carboxylative cyclization of propargylic amine 1. CO2 is initially
trapped by ItBu to form the ItBu–CO2 adduct 3 in situ,14 which
then reacts with propargylic amine 1 to afford 4.12 Then, the
intramolecular cyclization of 4 produces 2-oxazolidinone 2 with
the regeneration of ItBu. The intermolecular nucleophilic attack
of the ItBu–CO2 adduct 3 on substrate 1 is a possible rate-
determining step in the catalytic cycle. Consequently, propargylic
amine 1b showed low reactivity caused by an electron-donating
group such as a methoxy group at the phenyl group in R1 which
retarded the nucleophilic attack of 3 on the triple bond of 1b
(Table 4, entries 2 and 3). In the case of the alkyl group in R1, the
reactivity is absent probably because the electron density of the
5
6
10
5
95
97
78
ItBu
ItBu
7
2
a
Reaction conditions: Indicated amount of an NHC catalyst, 1a (1 equiv),
iPrOH (1 M based on 1a), carried out at 90 ºC for 24 h in a sealed autoclave
under 0.6 MPa of CO2.
b
Determined by the integration of 1H NMR absorptions referring to an
internal standard.
We subsequently examined the carboxylative cyclization of
propargylic amine 1a with CO2 in 2-propanol at various reaction
temperatures, as shown in Table 3. By carrying out the
carboxylative cyclization of propargylic amine 1a at 70 ºC, 2-
oxazolidinone 2a was obtained in a poor chemical yield (20%;
Table 3, entry 1). The carboxylative cyclization was carried out
at 90 ºC to afford 2-oxazolidinone 2a in the highest chemical
yield (97%; Table 3, entry 3).

3
Table 4 Carboxylative cyclization of various propargylic amines 1 for the synthesis of 2-oxazolidinone 2.
Entry
R1
R2
Substrate
1a
Temp. (ºC)
Time (h)
Product
2a
Yield (%)a
1
2
3
4
5
6
7
8
9
C6H5
CH3
90
90
90
70
90
90
90
90
90
24
24
48
4
97
48
86
91
89
0
4-CH3OC6H4
4-CH3OC6H4
4-CNC6H4
C6H5
CH3
1b
2b
CH3
1b
2b
CH3
1c
2c
C6H5CH2
C6H5CH2
C6H5CH2
CH3
24
24
24
24
24
1d
2d
CH3
1e
2e
C2H5
0
1f
2f
H
91
99
1g
2g
H
C6H5CH2
1h
2h
a Determined by the integration of 1H NMR absorptions referring to an internal standard.
3.
4.
(a) Pulla, S.; Felton, C. M.; Ramidi, P.; Gartia, Y.; Ali, N.; Nasini,
U. B.; Ghosh, A. J. CO2 Utilization 2013, 2, 49–57. (b) Maggi, R.;
Bertolotti, C.; Orlandini, E.; Oro, C.; Sartori, G.; Selva, M.
Tetrahedron Lett. 2007, 48, 2131–2134. (c) Kayaki, Y.;
Yamamoto, M.; Suzuki, T.; Ikariya, T. Green Chem. 2006, 8,
1019–1021. (d) Feroci, M.; Orsini, M.; Sotgiu, G.; Rossi, L.; Inesi,
A. J. Org. Chem. 2005, 70, 7795–7798.
triple bond of 1e or 1f increases due to the inductive effect of the
alkyl group (Table 4, entries 6 and 7). On the other hand, by the
introduction of an electron-withdrawing group such as a cyano
group at the phenyl group in R1, the reactivity of the triple bond
is enhanced due to decrease in the electron density of the triple
bond of 1c (Table 4, entry 4).
Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. Tetrahedron
Lett. 1987, 28, 4417–4418.
5.
6.
Shi, M.; Shen, Y.-M. J. Org. Chem. 2002, 67, 16–21.
(a) Yoshida, M.; Mizuguchi, T.; Shishido, K. Chem. Eur. J. 2012,
18, 15578–15581. (b) Kikuchi, S.; Yoshida, S.; Sugawara, Y.;
Yamada, W.; Cheng, H.-M.; Fukui, K.; Sekine, K.; Iwakura, I.;
Ikeno, T.; Yamada, T. Bull. Chem. Soc. Jpn. 2011, 84, 698–717.
(c) Yoshida, S.; Fukui, K.; Kikuchi, S.; Yamada, T. Chem. Lett.
2009, 38, 786–787.
7.
8.
(a) Hase, S.; Kayaki, Y.; Ikariya, T. ACS Catal. 2015, 5, 5135–
5140. (b) Yuan, R.; Lin, Z. ACS Catal. 2015, 5, 2866–2872. (c)
Fujita, K.; Sato, J.; Inoue, K.; Tsuchimoto, T.; Yasuda, H.
Tetrahedron Lett. 2014, 55, 3013–3016. (d) Hase, S.; Kayaki, Y.;
Ikariya, T. Organometallics 2013, 32, 5285–5288.
For reviews on NHCs, (a) Nelson, D. J.; Nolan, S. P. Chem. Soc.
Rev. 2013, 42, 6723–6753. (b) Ranganath, K. V. S.; Onitsuka, S.;
Kumar, A. K.; Inanaga, J. Catal. Sci. Technol. 2013, 3, 2161–
2181. (c) de Fremont, P.; Marion, N.; Nolan, S. P. Coord. Chem.
Rev. 2009, 253, 862–892. (d) Kuhl, O. Chem. Soc. Rev. 2007, 36,
592–607. (e) Crudden, C. M.; Allen, D. P. Coord. Chem. Rev.
2004, 248, 2247–2273.
9.
For reviews on the use of NHCs as metal-free catalysts, (a) Fevre,
M.; Pinaud, J.; Gnanou, Y.; Vignolle, J.; Taton, D. Chem. Soc.
Rev. 2013, 42, 2142–2172. (b) Bugaut, X.; Glorius, F. Chem. Soc.
Rev. 2012, 41, 3511–3522. (c) Enders, D.; Niemeier, O.; Henseler,
A. Chem. Rev. 2007, 107, 5606–5655. (d) Marion, N.; Díez-
Gonzalez, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988–
3000.
Figure 1 Plausible mechanism of carboxylative cyclization of propargylic
amine 1 catalyzed by the ItBu–CO2 adduct.
In summary, by employing N-heterocyclic carbenes as
catalysts, the carboxylative cyclization of propargylic amine with
CO2 proceeded to afford the corresponding 2-oxazolidinone. In
particular, 1,3-di-t-butylimidazol-2-ylidene was the most
effective catalyst for the reaction, providing 2-oxazolidinone in a
maximum chemical yield of 99%.
10. A previous report on the carboxylative cyclization of propargylic
amine with CO2 catalyzed by 10 mol% of a superbase: Costa, M.;
Chiusoli, G. P.; Taffurelli, D.; Dalmonego G. J. Chem. Soc.
Perkin Trans. 1 1998, 1541–1546.
11. Previous reports on the carboxylative cyclization of propargylic
amine with CO2 in the ionic liquid, which was not catalytic
conversion: (a) Hu, J.; Ma, J.; Zhu, Q.; Zhang, Z.; Wu, C.; Han, B.
Angew. Chem., Int. Ed. 2015, 54, 5399–5403. (b) Hu, J.; Ma, J.;
Zhu, Q.; Zhang, Z.; Zhou, H.; Lu, W.; Han, B. Green Chem. 2015,
17, 1219–1225.
12. A previous report on an NHC–catalyzed carboxylative cyclization
of propargylic alcohol with CO2: Kayaki, Y.; Yamamoto, M.;
Ikariya, T. Angew. Chem., Int. Ed. 2009, 48, 4194–4197.
13. Moss, R. A. Chem. Eng. News 1969, 47, 50–59.
14. Ausdall, B. R. V.; Glass, J. L.; Wiggins, K. M.; Aarif, A. M.;
Loue, J. J. Org. Chem. 2009, 74, 7935–7942.
References and notes
1.
2.
(a) Yang, L.; Wang, H. ChemSusChem 2014, 7, 962–998. (b)
Sakakura, T.; Choi, J.-C.; Yasuda, H. Chem. Rev. 2007, 107,
2365–2387.
(a) Omae, I. Coord. Chem. Rev. 2012, 256, 1384–1405. (b)
Huang, K.; Sun, C.-L.; Shi, Z.-J. Chem. Soc. Rev. 2011, 40, 2435–
2452. (c) Cokoja, M.; Bruckmeier, C.; Rieger, B.; Herrmann, W.
A.; Kuhn, F. E. Angew. Chem., Int. Ed. 2011, 50, 8510–8537. (d)
Riduan, S. N.; Zhang, Y. Dalton Trans., 2010, 39, 3347–3357.
Click here to remove instruction text...

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Synthesis of 2-oxazolidinone by N-heterocyclic
carbene–catalyzed carboxylative cyclization of
propargylic amine with CO2
Leave this area blank for abstract info.
Ken-ichi Fujita,* Akira Fujii, Junichi Sato,
Shun-ya Onozawa, Hiroyuki Yasuda