Aqueous media carboxylative cyclization of propargylic amines with CO 2 catalyzed by amphiphilic dendritic N-heterocyclic carbene-gold(I) complexes

Article abstract of DOI:10.1016/j.tetlet.2014.03.074

We prepared amphiphilic dendritic N-heterocyclic carbene (NHC)-gold(I) complexes having poly(ethylene glycol) units at the peripheral layer. By employing 1 mol % of the dendritic NHC-gold(I) catalyst, the aqueous media carboxylative cyclization of proparg

Full text of DOI:10.1016/j.tetlet.2014.03.074

Tetrahedron Letters 55 (2014) 3013–3016
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Aqueous media carboxylative cyclization of propargylic amines
with CO2 catalyzed by amphiphilic dendritic N-heterocyclic
carbene–gold(I) complexes
a
b
b
a
Ken-ichi Fujita a, , Junichi Sato , Kensuke Inoue , Teruhisa Tsuchimoto , Hiroyuki Yasuda
⇑
a National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
b Department of Applied Chemistry, School of Science and Technology, Meiji University, Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
We prepared amphiphilic dendritic N-heterocyclic carbene (NHC)–gold(I) complexes having poly(ethyl-
ene glycol) units at the peripheral layer. By employing 1 mol % of the dendritic NHC–gold(I) catalyst, the
aqueous media carboxylative cyclization of propargylic amines proceeded smoothly to provide the
corresponding 2-oxazolidinone under atmospheric pressure of CO2 at room temperature.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 10 February 2014
Revised 14 March 2014
Accepted 18 March 2014
Available online 24 March 2014
Keywords:
NHC–gold(I) complex
Carbon dioxide
Propargylic amine
2-Oxazolidinone
Development of green processes based on chemical fixation of
carbon dioxide (CO2) has received a great deal of interest in recent
years because CO2 could be used as a safe, inexpensive, and renew-
able C1 building block to produce useful organic compounds.1 One
useful method in which CO2 has been utilized as a substrate is
through the carboxylative cyclization of propargylic amines with
CO2 to provide 2-oxazolidinones. For example, the carboxylative
cyclization of propargylic amines has been found to proceed in
the presence of organometallic complexes of ruthenium and palla-
dium as catalysts under high CO2 pressure.2 Even in the absence of
catalysts, this conversion has been successfully achieved under
supercritical CO2.3 Recently, it was reported that N-heterocyclic
carbene (NHC)–gold(I) complexes or silver acetate can catalyze
the carboxylative cyclization of propargylic amines under atmo-
spheric pressure of CO2.4
Dendrimers are fascinating molecules due to their unique
physical and chemical properties caused by their well-defined
hyperbranched frameworks.5 Metallodendrimers with a functional
or catalytic site at their core have received considerable attention.6
Their solubility and physical properties can be altered by
peripheral modification.7 For example, by the introduction of
hydrophilic groups to the peripheral layer of a hydrophobic den-
dron, metal core dendrimers can become water-soluble8 and afford
unique catalytic activity.9 We wish to report herein the synthesis
of amphiphilic dendritic NHC–gold(I) complexes having poly(eth-
ylene glycol) units at the peripheral layer, their application as
catalysts to the aqueous media carboxylative cyclization of propar-
gylic amines under atmospheric pressure of CO2, and reuse of the
catalyst in the sequential carboxylative cyclization by the succes-
sive addition of the propargylic amine. From the perspective of
green chemistry, chemical fixation of CO2 carried out in water is
a very attractive field, as water is an environmentally benign
solvent.10
The first- and the second-generation NHC–gold(I) core dendri-
mers having the tri(ethylene glycol) unit 2Gn[TEG] were synthe-
sized as follows (Fig. 1, Scheme 1). A suspension of imidazole,
poly(benzyl ether) dendritic bromide Gn[TEG]–Br,8a and CsF–cel-
ite11 in N,N-dimethylformamide (DMF) was stirred at 90 °C for
24 h. A mixture of the obtained dendritic imidazolium bromide
1Gn[TEG] and silver(I) oxide in 1,2-dichloroethane was stirred at
70 °C, and then stirred further after the addition of AuCl(SMe2) to
the reaction mixture at room temperature to provide the corre-
sponding NHC–gold(I) core dendrimer 2Gn[TEG]. All transforma-
tions were carried out in good chemical yields in both generations.
We then examined catalytic activity of the dendrimer 2Gn[TEG]
(n = 1, 2) by performing the carboxylative cyclization of propargy-
lic amines with CO2 (Table 1). The procedure employed herein was
Ikariya’s synthetic sequence.4a Their result with the use of
AuCl(IPr) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)
as a catalyst is shown in Table 1, entry 1.
⇑
Corresponding author. Tel.: +81 29 861 9352; fax: +81 29 861 4577.
E-mail address: k.fujita@aist.go.jp (K. Fujita).
http://dx.doi.org/10.1016/j.tetlet.2014.03.074
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

3014
K. Fujita et al. / Tetrahedron Letters 55 (2014) 3013–3016
derivatives have higher solubility in a polar protic solvent by low-
O X
ering the temperature.12 The fair chemical yield in entry 3 was
probably due to good solubility of 2G1[TEG] in methanol at room
temperature. We subsequently performed this carboxylative cycli-
zation catalyzed by the second-generation catalyst 2G2[TEG].
However the chemical yield of 4a when using 2G2[TEG] was some-
what lower than that with the use of the first-generation
2G1[TEG], probably due to steric hindrance of the second-genera-
tion dendron (Table 1, entries 3 and 4). Next, by employing the
first-generation 2G1[TEG] in water, the aqueous media carboxyla-
tive cyclization proceeded smoothly to provide 4a in a shorter time
(24 h, 85%; Table 1, entry 5). However, also in these cases carried
out in water, the chemical yield for the second-generation
2G2[TEG] was somewhat lower than that for the first-generation
2G1[TEG] (Table 1, entries 5 and 6). On the other hand, by employ-
ing AuCl(IPr) as a catalyst in water at room temperature, the chem-
ical yield of 4a was poor (2%; Table 1, entry 7). Under these
reaction conditions, even with the addition of 8 mol % of tri(ethyl-
ene glycol) dimethyl ether with the same amount of TEG moieties
of 2G1[TEG], 4a was obtained in only 1% yield (Table 1, entry 8).
From these results, it can be concluded that the inclusion of
NHC–gold(I) complex with an amphiphilic dendrimer is essential
to the aqueous media carboxylative cyclization of propargylic
amines with CO2.
O
O
O X
O X
O X
O X
CH2
G2[X]:
G1[X]:
CH2
O X
X (CH2CH2O)3CH3 (TEG)
Figure 1. Structural formulas of Gn[X] dendrons (n = 1, 2).
Gn[TEG]-Br
CsF–Celite
Gn[TEG] N+ N Gn[TEG]
N
NH
DMF, 90 ºC, 24 h
Br–
Gn[TEG]
G1: 95%
G2: 98%
1
Ag2O
AuCl(SMe2)
N
N
Gn[TEG]
Gn[TEG]
ClCH2CH2Cl
70 ºC, 5 h
rt, 3 h
Au
Cl
Gn[TEG]
We next synthesized the first-generation of other amphiphilic
dendritic NHC–gold(I) catalysts having either penta(ethylene
glycol) or dodeca(ethylene glycol) units at the peripheral layer
2G1[PEG] and 2G1[DEG], which were prepared according to the
procedure similar to that used for 2G1[TEG] (Scheme 2).13 All
transformations were carried out in fair chemical yields for both
catalysts.14
2
G1: 91%
G2: 85%
Scheme 1. Preparation of 2Gn[TEG] (n = 1, 2).
G1[X]-Br
Table 1
CsF–Celite
Carboxylative cyclization of propargylic amine 3a with CO2 catalyzed by 2Gn[TEG]a
G1[X] N+ N G1[X]
N
NH
DMF, 90 ºC, 24 h
Ph
Br–
G1[X]
2Gn[TEG] (2 mol%)
CO2 (0.1 MPa)
1
Ph
X (CH CH O) CH (PEG)
=
2
2
5
3
O
N
HN
PEG: 94%
DEG: 73%
Solvent, Temp.
(CH2CH2O)12CH3 (DEG)
O
3a
4a
Ag2O
AuCl(SMe2)
rt, 3 h
G1[X]
N
N G1[X]
Entry
Au catalyst
Solvent
Temp. (°C)
Time (h)
Yieldb (%)
ClCH2CH2Cl
70 ºC, 24 h
1c
2
3
4
5
AuCl(IPr)
2G1[TEG]
2G1[TEG]
2G2[TEG]
2G1[TEG]
2G2[TEG]
AuCl(IPr)
AuCl(IPr)
MeOH
MeOH
MeOH
MeOH
H2O
H2O
H2O
H2O
40
40
rt
rt
rt
rt
rt
rt
48
48
48
48
24
24
24
24
76
47
82
73
85
72
2
Au
Cl
2G1[X]
PEG: 90%
DEG: 92%
6
7
8d
1
Scheme 2. Preparation of 2G1[X].
a
Reaction conditions: 2Gn[TEG] (2 mol %), 3a (0.8 mmol), solvent (1 M based on
3a), carried out at 40 °C or at room temperature for the indicated time under
atmospheric pressure of CO2 (0.1 MPa).
As shown in Table 2, by employing three amphiphilic dendritic
NHC–gold(I) catalysts 2G1[X] (X = TEG, PEG, DEG), respectively, the
aqueous media carboxylative cyclization of 3a with CO2 was car-
ried out at room temperature for 24 h. As a result, the dendritic
NHC–gold(I) catalyst having the penta(ethylene glycol) unit
2G1[PEG] afforded the highest chemical yield (Table 2, entries 3
and 4). Even in the case of using 1 mol % of the catalyst, 2G1[PEG]
afforded a fair chemical yield of 4a (82%; Table 2, entry 4).
We subsequently performed the aqueous media carboxylative
cyclization of various propargylic amines by employing 1 mol %
of the dendritic NHC–gold(I) catalysts having penta(ethylene
glycol) units 2G1[PEG], as shown in Table 3.15 In the cases of the
internal propargylic amines except for 3a, the carboxylative
cyclization reactions were carried out for 48 h to provide the
corresponding 2-oxazolidinones 4 in acceptable chemical yields
b
Determined by integration of 1H NMR absorptions referring to an internal
standard.
c
Cited from Ref. 4a.
d
Carried out in the presence of 8 mol % of tri(ethylene glycol) dimethyl ether.
First, by employing 2 mol % of the first-generation catalyst
2G1[TEG], the carboxylative cyclization of N,N-methyl(3-phenyl-
propargyl) amine 3a was carried out under atmospheric pressure
of CO2 (0.1 MPa) in methanol at 40 °C for 48 h. However in this
case, the reaction proceeded heterogeneously to provide the
corresponding 2-oxazolidinone 4a in a rather low chemical yield
(47%; Table 1, entry 2). In contrast, by employing 2G1[TEG] as a
catalyst at room temperature, 4a was obtained in a fair chemical
yield (82%; Table 1, entry 3). Generally, poly(ethylene glycol)

K. Fujita et al. / Tetrahedron Letters 55 (2014) 3013–3016
3015
Table 2
Table 4
Aqueous media carboxylative cyclization of propargylic amine 3a with CO2 catalyzed
Sequential carboxylative cyclization by the successive addition of 3aa
by 2G1[X]a
2G1[PEG] (1 mol%)a
CO2 (0.1 MPa)
Ph
Ph
2G1[X] (x mol%)
Ph
O
N
CO2 (0.1 MPa)
Ph
HN
H2O, rt
O
N
HN
H2O, rt, 24 h
O
3a
4a
O
X=(CH2CH2O)3CH3 (TEG)
(CH2CH2O)5CH3 (PEG)
(CH2CH2O)12CH3 (DEG)
3a
4a
Entry
Successive addition of 3ab
Time (h)
Yieldc (%)
TON
1
2
3
—
24
48
72
82
87
70
82
174
210
After 24 h
After 24 and 48 h
Entry
X
2G1[X] (x mol %)
Yieldb (%)
1
2
3
4
5
6
TEG
TEG
PEG
PEG
DEG
DEG
2
1
2
1
2
1
85
60
87
82
84
72
a
b
c
The initial reaction conditions were the same as those indicated in Table 2.
3a (0.8 mmol) was added successively.
Based on total volume of 3a. Determined by integration of 1H NMR absorptions
referring to an internal standard.
a
Reaction conditions: 2G1[X] (1 or 2 mol %), 3a (0.8 mmol), H2O (1 M based on
these results, it can be concluded that 2G1[PEG] maintains its cat-
alytic activity after the initial and second round carboxylative
cyclizations of 3a, and that the catalyst 2G1[PEG] can be reused
by the successive addition of 3a.
3a), carried out at room temperature for 24 h under atmospheric pressure of CO2
(0.1 MPa).
b
Determined by integration of 1H NMR absorptions referring to an internal
standard.
In summary, by employing amphiphilic dendritic NHC–gold(I)
catalysts, the aqueous media carboxylative cyclization of propargy-
lic amines with CO2 proceeded at room temperature to provide the
corresponding 2-oxazolidinones in acceptable chemical yields.
Furthermore, the dendritic NHC–gold(I) catalyst could be reused
in the sequential carboxylative cyclization by the successive addi-
tion of the propargylic amine.
Table 3
Aqueous media carboxylative cyclization of various propargylic amines with CO2
catalyzed by 2G1[PEG]a
R1
2G1[PEG] (1 mol%)
References and notes
R1
CO2 (0.1 MPa)
O
N
HN R2
R2
H2O, rt
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Shi, Z.-J. Chem. Soc. Rev. 2011, 40, 2435–2452; (c) Sakakura, T.; Choi, J.-C.;
Yasuda, H. Chem. Rev. 2007, 107, 2365–2387.
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Sekine, K.; Iwakura, I.; Ikeno, T.; Yamada, T. Bull. Chem. Soc. Jpn. 2011, 84, 698–
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5. (a)Dendrimers and Other Dendritic Polymers; Fréchet, J. M. J., Tomalia, D. A., Eds.;
John Wiley & Sons: New York, 2001; (b) Newkome, G. R.; Moorefield, C. N.;
Vogtle, F. Dendrimers and Dendrons; Wiley-VCH: Weinheim, 2001; (c) Chase, P.
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4016–4054; (d) Fréchet, J. M. J. J. Polym. Sci., Part A: Polym. Chem. 2003, 41,
3713–3725.
O
4
3
Entry Substrate R1
R2
Time (h) Product Yieldb (%)
1
2
3
3a
3b
3c
3d
3e
C6H5
CH3
24
48
4a
4b
4c
4d
4e
82
87
74
72
49
4-CH3C6H4 CH3
CH3
C2H5
H
C6H5CH2 48
C6H5CH2 48
4
5c
CH3
72
a
The reaction conditions were the same as those indicated in Table 2.
b
Determined by integration of 1H NMR absorptions referring to an internal
standard.
c
2 mol % of 2G1[PEG] was used.
6. (a) Fujita, K.; Yamazaki, M.; Ainoya, T.; Tsuchimoto, T.; Yasuda, H. Tetrahedron
2010, 66, 8536–8543; (b) Fujita, K.; Ainoya, T.; Tsuchimoto, T.; Yasuda, H.
Tetrahedron Lett. 2010, 51, 808–810; (c) Benito, J. M.; de Jesús, E.; de la Mata, F.
J.; Flores, J. C.; Gómez, R. Chem. Commun. 2005, 5217–5219; (d) Helms, B.;
Liang, C. O.; Hawker, C. J.; Fréchet, J. M. J. Macromolecules 2005, 38, 5411–5415;
(e) Fujiwara, T.; Obora, Y.; Tokunaga, M.; Sato, H.; Tsuji, Y. Chem. Commun.
2005, 4526–4528.
7. (a) Helms, B.; Fréchet, J. M. J. Adv. Synth. Catal. 2006, 348, 1125–1148; (b) Reek,
J. N. H.; Arevalo, S.; van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.
Adv. Catal. 2006, 49, 71–151; (c) Grayson, S. M.; Fréchet, J. M. J. Chem. Rev. 2001,
101, 3819–3867; (d) Astruc, D.; Chardac, F. Chem. Rev. 2001, 101, 2991–3023.
8. (a) Fujita, K.; Kujime, M.; Muraki, T. Bull. Chem. Soc. Jpn. 2009, 2, 261–266;
(b) Hattori, H.; Fujita, K.; Muraki, T.; Sakaba, A. Tetrahedron Lett. 2007, 48,
6817–6820; (c) Gong, L.-Z.; Pu, L. Tetrahedron Lett. 2001, 42, 7337–7340.
9. (a) Fujihara, T.; Yoshida, S.; Terao, J.; Tsuji, Y. Org. Lett. 2009, 11, 2121–2124; (b)
Fujihara, T.; Yoshida, S.; Ohta, H.; Tsuji, Y. Angew. Chem., Int. Ed. 2008, 47, 8310–
8314.
10. (a) Li, C.-J.; Chen, L. Chem. Soc. Rev. 2006, 35, 68–82; (b) Li, C.-J. Chem. Rev. 2005,
105, 3095–3165.
11. Lee, J. C.; Choi, Y. Synth. Commun. 1998, 28, 2021–2026.
12. (a) Bailey, F. E.; Koleske, J. V. Poly(ethylene oxide); Academic Press: New York,
1976; (b) Bergbreiter, D. E.; Zhang, L.; Mariagnanam, V. M. J. Am. Chem. Soc.
1993, 115, 9295–9296.
13. Preparation of 2G1[PEG]: A suspension of 1G1[PEG] (672 mg, 0.505 mmol) and
silver(I) oxide (151.8 mg, 0.655 mmol) in 1,2-dichloroethane (5 mL) was
stirred at 70 °C for 24 h under an argon atmosphere. After cooling to room
temperature, AuCl(SMe2) (149 mg, 0.506 mmol) was added to the reaction
(Table 3, entries 2–4). The reaction of a substrate having a terminal
alkyne unit, N-methylpropargylamine 3e, gave the corresponding
2-oxazolidinone 4e in a rather low chemical yield, even when
the reaction was carried out for 72 h through the use of 2 mol %
of 2G1[PEG] (49%; Table 3, entry 5).16–18
Finally, the reusability of the catalyst 2G1[PEG] was examined
in the sequential carboxylative cyclization by the successive addi-
tion of the propargylic amine 3a (Table 4). The carboxylative cycli-
zation of 3a catalyzed by 1 mol % of 2G1[PEG] was carried out at
room temperature for 24 h to provide the corresponding 2-oxazo-
lidinone 4a in an 82% chemical yield, as mentioned above (Table 4,
entry 1). In a separate run, after 3a was initially reacted with CO2
through the use of 1 mol % of 2G1[PEG] for 24 h, 3a was subse-
quently added to the reaction mixture, and the reaction was con-
tinued for 24 h (total 48 h). As a result, 4a was obtained in an
87% chemical yield (TON 174; Table 4, entry 2). In the run of entry
3, the further successive addition of 3a after 48 h allowed us to
obtain 4a in a 70% chemical yield (TON 210; Table 4, entry 3). From

3016
K. Fujita et al. / Tetrahedron Letters 55 (2014) 3013–3016
mixture. The resulting mixture was stirred at room temperature for 3 h under
with CO2 proceeded by the stirring of the resulting mixture at room
temperature. After 24–48 h, methanol and dichloromethane were added to
homogenize the reaction mixture. The chemical yield was determined by
integrating 1H NMR absorptions referring to an internal standard (3-
hydroxybenzyl alcohol (1 mmol)), which was added to the homogenized
aqueous solution.
an argon atmosphere. The reaction mixture was concentrated to dryness, and
the residue was filtered through Celite to remove insoluble materials. After
evaporation of the filtrate, the residue was purified with silica gel column
chromatography (ethyl acetate–methanol = 3:1 as an eluent) to obtain
2G1[PEG] (669 mg, 0.452 mmol) in a 90% yield.
14. Selected data: 2G1[PEG] Pale yellow oil; IR (neat) 2872, 1594, 1447, 1349, 1298,
16. As an example of a primary amine, 1-ethynylcyclohexylamine did not afford
the corresponding 2-oxazolidinone.
1246, 1119, 949, 851 cmÀ1 1H NMR (400 MHz; CDCl3) d 6.87 (s, 2 H), 6.49 (d,
;
J = 2.1 Hz, 4 H), 6.45 (t, J = 2.1 Hz, 2H), 5.26 (s, 4 H), 4.09 (t, J = 4.7 Hz, 8 H), 3.83
(t, J = 4.7 Hz, 8 H), 3.73–3.62 (m, 56 H), 3.56–3.52 (m, 8 H), 3.37 (s, 12 H); 13C
NMR (100 MHz; CDCl3) d 171.2, 160.4, 136.9, 120.9, 107.1, 101.5, 71.9, 70.7,
17. 2-Oxazolidinones 4a,4a 4c,19 4d,19 and 4e4a are known compounds, and their
NMR spectra are in accordance with those reported in the literature.
18. Compound 4b White powder; mp 133.4–134.5 °C; IR (KBr) 2916, 2862, 1782,
70.6, 70.5, 70.5, 70.5, 69.5, 67.6, 59.0, 55.2; Anal. Calcd for C61H104AuClN2O24
C, 49.44; H, 7.07; N, 1.89; Cl, 2.39. Found: C, 49.54; H, 7.09; N, 1.77; Cl, 2.21.
15. General procedure: To Schlenk-tube were successively added 2G1[PEG]
:
1697, 1435, 1412, 1273, 1088, 1034, 841 cmÀ1 1H NMR (400 MHz; CDCl3) d
;
7.45 (d, J = 8.1 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 2 H), 5.48 (t, J = 2.0 Hz, 1 H), 4.31 (d,
J = 2.0 Hz, 2 H), 2.99 (s, 3 H), 2.33 (s, 3 H); 13C NMR (100 MHz; CDCl3) d 155.7,
140.8, 136.5, 130.6, 129.1, 128.0, 102.7, 50.7, 30.3, 21.1; Anal. Calcd for
a
(0.008 mmol), degassed water (0.8 mL) and a propargylic amine (0.8 mmol)
under an argon atmosphere, and the inside of the Schlenk-tube was replaced
with CO2 (0.1 MPa). The carboxylative cyclization of the propargylic amine
C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.95; H, 6.44; N, 6.79.
19. Yoshida, M.; Mizuguchi, T.; Shishido, K. Chem. Eur. J. 2012, 18, 15578–15581.