Carboxylative cyclization of propargylic amines with CO2 catalyzed by dendritic N-heterocyclic carbene-gold(I) complexes

Article abstract of DOI:10.1016/j.tet.2016.01.016

We prepared several of a new type of dendritic N-heterocyclic carbene (NHC)-gold(I) complex. In particular, by employing an amphiphilic dendritic NHC-gold(I) complex having penta(ethylene glycol) units at the peripheral layer as a catalyst, the aqueous me

Full text of DOI:10.1016/j.tet.2016.01.016

Tetrahedron 72 (2016) 1205e1212
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Carboxylative cyclization of propargylic amines with CO2 catalyzed
by dendritic N-heterocyclic carbeneegold(I) complexes
,
b
c
b
Ken-ichi Fujita a , Kensuke Inoue , Junichi Sato , Teruhisa Tsuchimoto ,
*
Hiroyuki Yasuda a
,
c
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
c Graduate School of Science and Engineering, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
We prepared several of a new type of dendritic N-heterocyclic carbene (NHC)egold(I) complex. In par-
ticular, by employing an amphiphilic dendritic NHCegold(I) complex having penta(ethylene glycol) units
at the peripheral layer as a catalyst, the aqueous media carboxylative cyclization of propargylic amines
proceeded smoothly to provide the corresponding 2-oxazolidinone at room temperature under atmo-
spheric pressure of CO2.
Received 1 December 2015
Received in revised form 5 January 2016
Accepted 8 January 2016
Available online 11 January 2016
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
NHCegold(I) complex
Carbon dioxide
Propargylic amine
2-Oxazolidinone
1. Introduction
a functional or catalytic site at their core, have received consider-
able attention because of their unique selectivity and reactivity
The chemical fixation of carbon dioxide (CO2) into valuable or-
ganic molecules has received much attention in synthetic organic
chemistry in recent years because CO2 is a safe, inexpensive, and
renewable C1 resource.1 Although CO2, as the most oxidized carbon
derivative, is much less reactive, its application to organic synthesis
has been considered one of the most challenging research topics.
One of the useful transformations in which CO2 has been utilized as
a substrate is through the carboxylative cyclization of propargylic
amines with CO2 to provide 2-oxazolidinones.2 For example, the
carboxylative cyclization of propargylic amines has been found to
proceed in the presence of organometallic complexes of ruthenium
and palladium as catalysts under 4e5 MPa of CO2.3 Very recently,
we have reported that N-heterocyclic carbene (NHC), which is
metal-free, can also catalyze the carboxylative cyclization of
propargylic amines to provide 2-oxazolidinones under 0.6 MPa of
CO2.4 Moreover, even under atmospheric pressure of CO2,
NHCegold(I) complexes or silver acetate can promote the carbox-
ylative cyclization of propargylic amines.5
caused by a specific reaction field constructed by the dendron.7
Moreover, their solubilities and physical properties can be altered
by peripheral modification.8 For example, by the introduction of
hydrophilic groups to the peripheral layer of a hydrophobic den-
dron, metal core dendrimers can become water-soluble9 and afford
unique catalytic activity.10 In this paper, we report the synthesis of
novel NHCegold(I) core dendrimers having a poly(benzyl ether)
dendron with the modification of the peripheral layer 1Gn[X]
(X¼Me, TEG, PEG, and DEG; Fig. 1), and their application as catalysts
to the carboxylative cyclization of propargylic amines under at-
mospheric pressure of CO2.11 In particular, by employing amphi-
philic dendritic NHCegold(I) complexes having poly(ethylene
glycol) units at the peripheral layer as catalysts, the aqueous media
carboxylative cyclization of propargylic amines proceeded
smoothly to provide 2-oxazolidinones at room temperature. From
the perspective of green chemistry, the chemical fixation of CO2
carried out in water is a very attractive field, as water is an envi-
ronmentally benign solvent.12
Dendrimers are fascinating molecules due to their unique
physical and chemical properties caused by their well-defined
hyperbranched frameworks.6 Metallodendrimers, which have
2. Results and discussion
NHCegold(I) core dendrimers having
a methyl group or
a tri(ethylene glycol) unit at the peripheral layer 1Gn[X] (X¼Me,
* Corresponding author. E-mail address: k.fujita@aist.go.jp (K. Fujita).
TEG; n¼1e3) were synthesized as follows (Table 1). A suspension
http://dx.doi.org/10.1016/j.tet.2016.01.016
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

1206
K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
Fig. 1. Structural formulas of 1Gn[X] and Gn[X] dendrons (n¼1e3).
of imidazole, poly(benzyl ether) dendritic bromide 2Gn[X], and
CsFeCeliteÒ13 in N,N-dimethylformamide (DMF) was stirred at
90 ꢀC for 24 h to afford the corresponding dendritic imidazolium
bromide 3Gn[X]. A mixture of 3Gn[X] and silver(I) oxide in 1,2-
dichloroethane was stirred at 70 ꢀC till the complete consump-
tion of 3Gn[X], which was detected by 1H NMR. The reaction times
are shown in Table 1. By the subsequent addition of AuCl(SMe2)
and the stirring of the reaction mixture at room temperature for
3 h, the corresponding NHCegold(I) core dendrimers 1Gn[X] were
obtained. Transformations were carried out in good chemical
yields in all cases.
We then examined the catalytic activity of the NHCegold(I) core
dendrimer having a methyl group at the peripheral layer 1Gn[Me]
(n¼1e3) by performing the carboxylative cyclization of propargylic
amines with CO2 (Table 2). The procedure employed herein was
Ikariya’s synthetic sequence.5c Table 2, entry 1 shows their results
with use of AuCl(IPr) (IPr¼1,3-bis(2,6-diisopropylphenyl)imidazol-
2-ylidene) as a catalyst.
First, by employing 2 mol % of the first-generation dendritic
catalyst 1G1[Me], the carboxylative cyclization of N,N-methyl(3-
phenylpropargyl) amine 4a was carried out under atmospheric
pressure of CO2 (0.1 MPa) in methanol at 40 ꢀC for 48 h. The reaction
proceeded homogeneously to provide the corresponding 2-
oxazolidinone 5a in a 59% chemical yield (Table 2, entry 2).14 The
carbonecarbon double bond of 5a was found to be in the Z con-
figuration by NMR referring to the previously reported literature.5c
On the other hand, by employing the second-generation 1G2[Me]
as a catalyst, 2-oxazolidinone 5a was obtained in a 75% chemical
yield (Table 2, entry 3). This improvement of the chemical yield of
5a is probably due to a specific catalytic environment constructed
by the dendron.15 However, when the third-generation 1G3[Me]
was used as a catalyst, the chemical yield of 5a somewhat de-
creased, contrary to our expectations (67%; Table 2, entry 4).
Next, we examined the catalytic activity of the amphiphilic
NHCegold(I) core dendrimer having the tri(ethylene glycol) unit
1Gn[TEG] (n¼1e3) (Table 3). By employing 2 mol % of the first-
generation 1G1[TEG] as a catalyst, the carboxylative cyclization of
propargylic amine 4a with CO2 heterogeneously proceeded in
methanol at 40 ꢀC for 48 h to provide the corresponding 2-
oxazolidinone 5a in a 47% chemical yield (Table 3, entry 1). On
Table 1
Preparation of 1Gn[X] (X¼Me, TEG; n¼1e3)
Table 2
Carboxylative cyclization of propargylic amine 4a with CO2 catalyzed by 1Gn[Me]a
Entry
Au catalyst
Yield (%)b
1c
2
3
AuCl(IPr)
1G1[Me]
1G2[Me]
1G3[Me]
76
59
75
67
Entry
Gn[X]
Time (h)
Yield of 1Gn[X] (%)a
1
2
3
4
5
6
G1[Me]
G2[Me]
G3[Me]
G1[TEG]
G2[TEG]
G3[TEG]
3
20
48
3
5
24
78
81
86
91
85
94
4
a
Reaction conditions: Au catalyst (2 mol %), 4a (0.8 mmol), methanol (1M based
on 4a), carried out at 40 ꢀC for 48 h under atmospheric pressure of CO2 (0.1 MPa).
b
Determined by integration of 1H NMR absorptions referring to an internal
standard.
a
c
Isolated yield.
Cited from Ref. 5c.

K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
1207
Table 3
Carboxylative cyclization of propargylic amine 4a with CO2 catalyzed by 1Gn[TEG]a
Table 4
a
Aqueous media carboxylative cyclization of propargylic amine 4a with CO2
Yield (%)b
Entry
Au catalyst
Solvent
Temp (oC)
Time (h)
Yield (%)b
Entry
Au catalyst
1
2
3
4
1G1[TEG]
1G2[TEG]
1G1[TEG]
1G1[TEG]
1G1[Me]
1G1[Me]
AuCl(IPr)
AuCl(IPr)
1G2[TEG]
1G3[TEG]
1G1[TEG]
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
iPrOH
40
40
rt
rt
40
rt
40
rt
rt
rt
rt
48
48
24
48
48
48
48
48
48
48
48
47
29
67
82
59
10
76
59
73
71
62
1
2
3
4
1G1[TEG]
1G2[TEG]
1G3[TEG]
AuCl(IPr)
1G1[Me]
AuCl(IPr)
1G1[Me]
85
72
24
2
1
1
5
5
6c
7c
6
7c
8
1
a
The reaction conditions were the same as those indicated in Table 2.
9
10
11
b
Determined by integration of 1H NMR absorptions referring to an internal
standard.
c
Carried out in the presence of 8 mol % of tri(ethylene glycol) dimethyl ether.
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
Cited from Ref. 5c.
1G1[TEG], 5a was obtained in only 1% yields in both cases (Table 4,
entries 6 and 7). From these results, it can be concluded that the
inclusion of the NHCegold(I) complex with an amphiphilic den-
drimer is essential to the aqueous media carboxylative cyclization
of propargylic amines with CO2.
the other hand, the chemical yield of 5a when the second-
generation 1G2[TEG] was used was lower than that when the
first-generation 1G1[TEG] was used, probably due to the low sol-
ubility of the second-generation 1G2[TEG] in methanol, contrary to
our expectations (Table 3, entries 1 and 2). Next, by employing the
first-generation 1G1[TEG] as a catalyst at room temperature, the
chemical yield of 5a increased (24 h: 67%, 48 h: 82%; Table 3, entries
3 and 4). In contrast, when 1G1[Me] or AuCl(IPr) was used as
a catalyst, the chemical yield of 5a decreased as a result of the re-
duced reaction temperature in both cases (Table 3, entries 5e8).
Generally, poly(ethylene glycol) derivatives have higher solubility
in a polar protic solvent when the temperature is reduced.16 The fair
chemical yields in entries 3 and 4 in Table 3, carried out at room
temperature, were probably attributable to the good solubility of
1G1[TEG] in methanol when the reaction temperature is reduced.
We then employed the second- or third-generation 1Gn[TEG] as
a catalyst at room temperature. The chemical yield of 5a was
somewhat decreased by the increase in the generation number of
1Gn[TEG] (Table 3, entries 9 and 10). Finally, by carrying out the
reaction using the first-generation 1G1[TEG] as a catalyst in 2-
propanol, 5a was obtained in a 62% chemical yield (Table 3, entry
11), which was lower than that when methanol was used (82%;
Table 3, entry 4).
We next synthesized the first-generation of other amphiphilic
dendritic NHCegold(I) catalysts having either penta(ethylene gly-
col) or dodeca(ethylene glycol) units at the peripheral layer 1G1
[PEG] and 1G1[DEG]. The first-generation dendritic bromide having
the penta(ethylene glycol) units 2G1[PEG] and the first-generation
dendritic bromide having the dodeca(ethylene glycol) units 2G1
[DEG] were prepared using the previously reported synthetic pro-
cedures,9a,10a as shown in Scheme 1 and Scheme 2, respectively.
1G1[PEG] and 1G1[DEG] were prepared according to a procedure
similar to that used for 1G1[TEG] (Scheme 3). All transformations
were carried out in good chemical yields for both catalysts.
As shown in Table 5, by employing three amphiphilic dendritic
NHCegold(I) catalysts 1G1[X] (X¼TEG, PEG, and DEG), the aqueous
MsCl, Et3N
MsO(CH2CH2O)5CH3
HO(CH2CH2O)5CH3
THF
rt, 7 h
6[PEG]
Ms:CH3SO2
OH
We subsequently performed the carboxylative cyclization in
water by using an amphiphilic dendritic NHCegold(I) complex 1Gn
[TEG] as a catalyst (Table 4). By employing the first-generation 1G1
[TEG] in water, the aqueous media carboxylative cyclization pro-
ceeded smoothly to provide 5a for 24 h in an 85% chemical yield
(Table 4, entry 1). However, when the various generation 1Gn[TEG]
were used in the aqueous media carboxylative cyclization, the
chemical yield of 5a decreased by the increase in the generation
number of 1Gn[TEG] (G2: 72%, G3: 24%; Table 4, entries 2 and 3). As
a result, the first-generation 1G1[TEG] smoothly catalyzed the
aqueous media carboxylative cyclization of 4a to provide 5a in the
highest chemical yield. In contrast, by employing AuCl(IPr) or the
NHCegold(I) core dendrimer having a methyl group at the pe-
ripheral layer 1G1[Me] as a catalyst in water at room temperature,
the chemical yields of 5a were 2% and 1%, respectively (Table 4,
entries 4 and 5). Under the same reaction conditions as in entries 4
and 5 in Table 4, even with the addition of 8 mol % of tri(ethylene
glycol) dimethyl ether using the same amount of TEG moieties of
HO
O(CH2CH2O)5CH3
O(CH2CH2O)5CH3
OH
K2CO3, 18-Crown-6
DMF
HO
80 ºC, 22 h
7[PEG]
86%
O(CH2CH2O)5CH3
CBr4, PPh3
THF
Br
rt, 10 min
O(CH2CH2O)5CH3
2G1[PEG]
76%
Scheme 1. Preparation of 2G1[PEG].

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K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
Table 5
Aqueous media carboxylative cyclization of propargylic amine 4a with CO2 catalyzed
by 1G1[X]a
Entry
X
1G1[X] (x mol %)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
TEG
TEG
PEG
PEG
PEG
PEG
DEG
DEG
DEG
2
1
2
1
1
0.5
2
1
1
24
24
24
24
15
24
24
24
15
85
60
87
82
72
17
84
77
61
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.
Finally, we performed the aqueous media carboxylative cycli-
zation of various propargylic amines by employing the dendritic
NHCegold(I) catalyst having penta(ethylene glycol) units 1G1
[PEG], as shown in Table 6. When the internal propargylic amines
were used, except for 4a, the carboxylative cyclization reactions
were carried out for 48 h through the use of 1 mol % of 1G1[PEG] to
Scheme 2. Preparation of 2G1[DEG].
provide the corresponding 2-oxazolidinones
5 in acceptable
chemical yields (Table 6, entries 2e5). The reactions of substrates
having terminal alkyne units 4f and 4g gave the corresponding 2-
oxazolidinone 5f and 5g, respectively, in low chemical yields,
even when the reactions were carried out through the use of 2 mol
% of 1G1[PEG] (20% and 49%; Table 6, entries 6 and 7). On the other
hand, primary amine 4h did not afford the corresponding 2-
oxazolidinone.
Table 6
Aqueous media carboxylative cyclization of various propargylic amines with CO2
catalyzed by 1G1[PEG]a
Entry Substrate R1
R2
1G1[PEG] Time (h) Product Yield (%)b
(x mol %)
Scheme 3. Preparation of 1G1[X] (X¼PEG, DEG).
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
C6H5
4-CH3C6H4 CH3
CH3
CH3
C2H5
H
CH3
1
1
1
24
48
48
48
48
48
72
5a
5b
5c
5d
5e
5f
82
87
74
63
72
20
49
C6H5CH2
(CH3)2CH 1
C6H5CH2
C6H5CH2
CH3
media carboxylative cyclization of 4a with CO2 was carried out at
room temperature for 15e24 h. As result, the dendritic
1
2
2
a
NHCegold(I) catalyst having the penta(ethylene glycol) unit 1G1
[PEG] afforded the highest chemical yield of 5a (Table 5, entries
3e5). Even when 1 mol % of the catalyst was used, 1G1[PEG]
afforded a good chemical yield of 5a (82%; Table 5, entry 4). How-
ever when 0.5 mol % of 1G1[PEG] was used as a catalyst, the
chemical yield of 5a decreased significantly (17%; Table 5, entry 6).
In addition, from the results of entries 5 and 9 in Table 5, a reaction
time of 15 h was insufficient to promote the carboxylative cycli-
zation of 4a.
4g
H
5g
8
4h
2
72
5h
0
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.

K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
1209
3. Conclusion
13C NMR (100 MHz; CDCl3)
d
160.9, 160.4, 138.8, 137.3, 134.7, 121.5,
107.9, 105.3, 103.1, 100.0, 70.2, 55.3, 53.4; Anal. Calcd for
C53H57BrN2O12: C, 64.05; H, 5.78; N, 2.82; Br, 8.04%. Found: C,
64.08; H, 5.80; N, 2.71; Br, 7.87%.
By employing an amphiphilic dendritic NHCegold(I) catalyst,
the carboxylative cyclization of propargylic amines proceeded even
at room temperature in methanol to provide the corresponding 2-
oxazolidinone under atmospheric pressure of CO2. Furthermore, on
the basis of the amphiphilicity of the dendritic NHCegold(I) cata-
lyst, the aqueous media carboxylative cyclizations of various
propargylic amines proceeded at room temperature. Thus, the
chemical fixation of CO2 could be performed in water at room
temperature.
4.2.3. 1,3-Bis[3,5-bis{3,5-bis(3,5-dimethoxybenzyloxy)benzyloxy}
benzyl]imidazolium bromide (3G3[Me]). White powder; mp 62e64 ꢀC;
IR (KBr) 2998, 2938, 2838, 1598, 1458, 1374, 1324, 1156, 1052,
834 cmꢁ1 1H NMR (400 MHz; CDCl3)
; d 11.01 (s, 1H, Im), 6.64 (d,
J¼2.1 Hz, 2H, Im), 6.60e6.51 (m, 26H, ArH), 6.38 (t, J¼2.2 Hz, 8H, ArH),
5.33 (s, 4H, NCH2Ar), 4.97 (s, 8H, OCH2Ar), 4.95 (s, 16H, OCH2Ar), 3.76
(s, 48H, OCH3); 13C NMR (100 MHz; CDCl3)
d 161.0, 160.4, 160.0, 139.1,
4. Experimental
4.1. General
138.9, 137.7, 134.7, 121.3, 107.7, 106.5, 105.2, 103.2, 101.7, 99.9, 70.1, 70.0,
55.3, 53.5; Anal. Calcd for C117H121BrN2O28: C, 67.46; H, 5.85; N, 1.34;
Br, 3.84%. Found: C, 67.55; H, 5.91; N, 1.24; Br, 3.82%.
Kieselgel 60 F254 (Merck) was used for TLC, and Wakogel C-300
(Wako) was used for silica gel column chromatography. Degassed
solvent was prepared by freeze-pump-thaw cycling of commer-
cially available dry solvents for the carboxylative cyclization of
propargylic amines 4. Propargylic amine 4g, other reagents, and dry
solvents were commercially available and were used as received.
Propargylic amines 4 except for 4b and 4g were prepared by the
method in the literature (4a,5c 4c,5e 4d,5c 4e,17 4f,5e 4h5e). Dendritic
bromides 2Gn[X] (X¼Me,18 TEG;19 n¼1e3) were prepared by our
previously reported synthetic procedures.9a
Microanalyses were performed with a CE Instruments EA1110
elemental analyzer. IR spectra were recorded on a Shimadzu IR
Prestige-21 FT-IR spectrophotometer. 1H and 13C NMR spectra were
measured with a Bruker Avance III 400 spectrometer (1H: 400 MHz,
13C: 100 MHz). Chemical shifts were reported as ppm downfield
4.2.4. 1,3-Bis(3,5-bis[2-{2-(2-methoxyethoxy)ethoxy}ethoxy]benzyl)
imidazolium bromide (3G1[TEG]). Colorless oil; IR (Neat) 3064,
2877, 1598, 1447, 1351, 1300, 1123, 949, 851, 763 cmꢁ1 1H NMR
;
(400 MHz; CDCl3)
d
10.53 (s, 1H, Im), 7.32 (d, J¼4.0 Hz, 2H, Im), 6.63
(d, J¼2.0 Hz, 4H, ArH), 6.47 (t, J¼1.7 Hz, 2H, ArH), 5.42 (s, 4H,
NCH2Ar), 4.11 (t, J¼4.6 Hz, 8H, OCH2CH2), 3.82 (t, J¼4.6 Hz, 8H,
CH2CH2O), 3.75e3.70 (m, 8H, CH2CH2O), 3.70e3.62 (m, 16H,
OCH2CH2O), 3.57e3.52 (m, 8H, CH2CH2O), 3.37 (s, 12H, OCH3); 13C
NMR (100 MHz; CDCl3)
71.7, 70.6, 70.5, 70.4, 70.3, 69.4, 67.7, 58.8, 53.3; Anal. Calcd for
45H73BrN2O16$H2O: C, 54.27; H, 7.59; N, 2.81; Br, 8.02%. Found: C,
d 160.4,137.0,134.7,134.6,121.7,107.7,102.3,
C
54.50; H, 7.70; N, 2.72; Br, 8.02%.
4.2.5. 1,3-Bis{3,5-bis(3,5-bis[2-{2-(2-methoxyethoxy)ethoxy}ethoxy]
benzyloxy)benzyl}imidazolium bromide (3G2[TEG]). Colorless oil; IR
from TMS as an internal standard in
d
units. Coupling constants (J)
(Neat) 2876, 1595, 1447, 1351, 1299, 1248, 1174, 848, 763, 684 cmꢁ1
;
were given in hertz (Hz). Melting points were determined on
a Yanaco MP-500D, and were uncorrected.
1H NMR (400 MHz; CDCl3)
d
10.83 (s, 1H, Im), 7.07 (d, J¼1.2 Hz, 2H,
Im), 6.63 (d, J¼2.0 Hz, 4H, ArH), 6.57 (d, J¼2.0 Hz, 10H, ArH), 6.43 (t,
J¼2.2 Hz, 4H, ArH), 5.43 (s, 4H, NCH2Ar), 4.99 (s, 8H, OCH2Ar), 4.10
(t, J¼4.8 Hz, 16H, OCH2CH2), 3.83 (t, J¼4.8 Hz, 16H, CH2CH2O),
3.75e3.70 (m, 16H, OCH2CH2), 3.69e3.62 (m, 32H, OCH2CH2O),
3.56e3.51 (m, 16H, CH2CH2O), 3.56 (s, 24H, OCH3); 13C NMR
4.2. Synthesis of a dendritic imidazolium bromide 3Gn[X]
from imidazole and 2Gn[X] (Table 1 and Scheme 3): typical
procedure
(100 MHz; CDCl3)
d 160.5, 160.1, 138.9, 137.6, 135.0, 121.9, 107.8,
A dry N,N-dimethylformamide suspension (7 mL) of imidazole
(341.4 mg, 5.015 mmol), 3,5-dimethoxybenzylbromide 2G1[Me]
(2.439 g, 10.55 mmol) and CsF-CeliteÒ13 (3.889 mmol/g: 1.426 g,
5.546 mmol) was stirred at 90 ꢀC for 24 h under an argon atmo-
sphere. After 1H NMR was used to detect the completion of the
reaction, the reaction mixture was filtered with CeliteÒ to remove
inorganic salts, and the filtrate was evaporated to dryness. The
residue was purified with silica gel column chromatography
(dichloromethane/methanol¼10/1 as eluent) to obtain a dendritic
imidazolium bromide 3G1[Me] (1.957 g, 4.355 mmol) in an 87%
yield.
106.2, 103.3, 101.3, 72.0, 70.8, 70.7, 70.6, 70.2, 69.7, 67.6, 59.0, 53.5;
Anal. Calcd for C101H153BrN2O36$H2O: C, 58.63; H, 7.55; N, 1.35; Br,
3.86%. Found: C, 58.59; H, 7.55; N, 1.28; Br, 4.08%.
4.2.6. 1,3-Bis[3,5-bis{3,5-bis(3,5-bis[2-{2-(2-methoxyethoxy)ethoxy}
ethoxy]benzyloxy)benzyloxy}benzyl]imidazolium bromide (3G3[TEG]).
Colorless oil; IR (Neat) 2876, 1593, 1447, 1350, 1298, 1247, 1173, 950,
845, 684 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d 10.93 (s, 1H, Im), 7.09 (d,
J¼1.4 Hz, 2H, Im), 6.66 (d, J¼2.4 Hz, 12H, ArH), 6.57 (d, J¼2.0 Hz, 18H,
ArH), 6.53 (t, J¼2.0 Hz, 4H, ArH), 6.43 (t, J¼2.2 Hz, 8H, ArH), 5.39 (s, 4H,
NCH2Ar), 4.99 (s, 8H, OCH2Ar), 4.95 (s, 16H, OCH2Ar), 4.09 (t, J¼4.8 Hz,
32H, OCH2CH2), 3.82 (t, J¼4.6 Hz, 32H, CH2CH2O), 3.73e3.68 (m, 32H,
OCH2CH2), 3.68e3.61 (m, 64H, OCH2CH2O), 3.55e3.50 (m, 32H,
4.2.1. 1,3-Bis(3,5-dimethoxybenzyl)imidazolium bromide (3G1[Me]).
White powder; mp 155e157 ꢀC; IR (KBr) 3129, 3018, 2997, 2976,
CH2CH2O), 3.35 (s, 48H, OCH3); 13C NMR (100 MHz; CDCl3)
d 160.4,
1601, 1480, 1356, 1214, 1169, 833 cmꢁ1
;
1H NMR (400 MHz; CDCl3)
160.04, 160.00,139.0,138.9,137.7, 134.9, 121.6, 107.8, 106.5, 106.1,102.9,
101.6, 101.1, 71.9, 70.7, 70.6, 70.5, 70.1, 70.0, 69.6, 67.5, 58.9, 53.4; Anal.
Calcd for C213H313BrN2O76: C, 60.95; H, 7.52; N, 0.67; Br, 1.90%. Found:
C, 60.61; H, 7.53; N, 0.61; Br, 1.69%.
d
10.99 (s, 1H, Im), 7.16 (d, J¼1.6 Hz, 2H, Im), 6.62 (d, J¼2.2 Hz, 4H,
ArH), 6.44 (t, J¼2.0 Hz, 2H, ArH), 5.44 (s, 4H, NCH2Ar), 3.80 (s, 12H,
OCH3); 13C NMR (100 MHz; CDCl3)
161.3, 136.9, 134.9, 121.9, 106.7,
d
101.1, 55.6, 53.2; Anal. Calcd for C21H25BrN2O4: C, 56.13; H, 5.61; N,
6.23; Br, 17.78%. Found: C, 56.31; H, 5.60; N, 6.09; Br, 17.56%.
4.2.7. 1,3-Bis{3,5-bis(2,5,8,11,14-pentaoxahexadecane-16-yloxy)ben-
zyl}imidazolium bromide (3G1[PEG]). Colorless oil; IR (Neat) 2873,
4.2.2. 1,3-Bis{3,5-bis(3,5-dimethoxybenzyloxy)benzyl}imidazolium
bromide (3G2[Me]). White powder; mp 65e67 ꢀC; IR (KBr) 2998,
2940, 2839, 1599, 1458, 1432, 1206, 1157, 1053, 835 cmꢁ1; 1H NMR
1598, 1450, 1350, 1300, 1249, 1118, 950, 852, 764, 681 cmꢁ1 1H
;
NMR (400 MHz; CDCl3)
d 10.89 (s, 1H, Im), 7.15 (s, 2H, Im), 6.66 (d,
J¼2.0 Hz, 4H, ArH), 6.50 (t, J¼2.0 Hz, 2H, ArH), 5.41 (s, 4H, NCH2Ar),
4.13 (t, J¼4.4 Hz, 8H, OCH2CH2), 3.84 (t, J¼4.6 Hz, 8H, CH2CH2O),
3.75e3.61 (m, 56H, OCH2CH2O), 3.57e3.52 (m, 8H, CH2CH2O), 3.37
(400 MHz; CDCl3)
d
10.66 (s, 1H, Im), 7.08 (d, J¼1.2 Hz, 2H, Im), 6.67
(d, J¼2.0 Hz, 4H, ArH), 6.60e6.52 (m, 10H, ArH), 6.40e6.36 (m, 4H,
ArH), 5.40 (s, 4H, NCH2Ar), 4.96 (s, 8H, OCH2Ar), 3.76 (s, 24H, OCH3);
(s, 12H, OCH3); 13C NMR (100 MHz; CDCl3)
d 160.4, 137.1, 134.7,

1210
K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
121.8, 107.7, 102.3, 71.7, 70.5, 70.3, 70.2, 69.4, 67.6, 58.8, 53.3; Anal.
Calcd for C61H105BrN2O24: C, 55.07; H, 7.96; N, 2.11; Br, 6.01%.
Found: C, 55.06; H, 8.07; N, 1.99; Br, 5.94%.
Anal. Calcd for C117H120AuClN2O28: C, 62.89; H, 5.41; N, 1.25; Cl,
1.59%. Found: C, 62.87; H, 5.40; N, 1.08; Cl, 1.47%.
4.3.4. Chloro{1,3-bis(3,5-bis[2-{2-(2-methoxyethoxy)ethoxy}ethoxy]
benzyl)imidazol-2-ylidene}gold(I) (1G1[TEG]). Pale yellow oil; IR
(Neat) 3102, 2876, 1735, 1598, 1451, 1351, 1298, 1244, 1125,
4.2.8. 1,3-Bis{3,5-bis(2,5,8,11,14,17,20,23,26,29,32,35-
dodecaoxaheptatriacontan-37-yloxy)benzyl}imidazolium bromide (3G1
[DEG]). Colorless oil; IR (Neat) 2872, 1598, 1447, 1349, 1300, 1250,
850 cmꢁ1 1H NMR (400 MHz; CD3OD)
; d 7.31 (s, 2H, Im), 6.56 (d,
1134, 951, 851, 764 cmꢁ1
;
1H NMR (400 MHz; CDCl3)
d
10.89 (s, 1H,
J¼2.1 Hz, 4H, ArH), 6.44 (t, J¼2.1 Hz, 2H, ArH), 5.24 (s, 4H, NCH2Ar),
4.06 (t, J¼4.6 Hz, 8H, OCH2CH2), 3.78 (t, J¼4.6 Hz, 8H, CH2CH2O),
3.68e3.57 (m, 24H, OCH2CH2O), 3.52e3.48 (m, 8H, CH2CH2O), 3.32
Im), 7.36 (s, 2H, Im), 6.73 (s, 4H, ArH), 6.49 (s, 2H, ArH), 5.44 (s, 4H,
NCH2Ar), 4.15 (t, J¼4.4 Hz, 8H, OCH2CH2), 3.84 (t, J¼4.6 Hz, 8H,
CH2CH2O), 3.77e3.44 (m, 176H, OCH2CH2O), 3.38 (s, 12H, OCH3); 13C
(s, 12H, OCH3); 13C NMR (100 MHz; CD3OD)
d 171.6, 161.7, 139.9,
NMR (100 MHz; CDCl3)
70.5, 70.3, 69.5, 67.7, 58.9, 53.3; Anal. Calcd for
117H217BrN2O52$5.5H2O: C, 52.77; H, 8.63; N, 1.05%. Found: C, 52.39;
d
160.4, 137.2, 134.9, 121.9, 107.7, 102.5, 71.8,
123.0, 107.8, 102.7, 73.0, 71.7, 71.6, 71.4, 70.7, 68.8, 59.1, 55.8; Anal.
Calcd for C45H72AuClN2O16: C, 47.85; H, 6.43; N, 2.48; Cl, 3.14%.
Found: C, 47.65; H, 6.43; N, 2.31; Cl, 2.81%.
C
H, 8.38; N, 0.83%.
4.3.5. Chloro[1,3-bis{3,5-bis(3,5-bis[2-{2-(2-methoxyethoxy)ethoxy}
ethoxy]benzyloxy)benzyl}imidazol-2-ylidene]gold(I) (1G2[TEG]). Pale
yellow oil; IR (Neat) 2873, 1594, 1447, 1351, 1298, 1174, 1069,
846 cmꢁ1; 1H NMR (400 MHz; CD3OD)
d 7.17 (s, 2H, Im), 6.55e6.48
4.3. Synthesis of a dendritic NHCeGold(I) complex 1Gn[X]
from 3Gn[X] (Table 1 and Scheme 3): typical procedure
(m,14H, ArH), 6.41 (t, J¼2.1 Hz, 4H, ArH), 5.18 (s, 4H, NCH2Ar), 4.88 (s,
8H, OCH2Ar), 4.04 (t, J¼4.6 Hz, 16H, OCH2CH2), 3.76 (t, J¼4.6 Hz, 16H,
CH2CH2O), 3.66e3.62 (m, 16H, OCH2CH2), 3.61e3.55 (m, 32H,
A suspension of a dendritic imidazolium bromide 3G1[Me]
(300.2 mg, 0.668 mmol) and silver(I) oxide (77.8 mg, 0.336 mmol)
in dry 1,2-dichloroethane (25 mL) was stirred at 70 ꢀC for 3 h under
an argon atmosphere. The completion of the reaction was detected
by 1H NMR. After the reaction mixture was cooled to room tem-
perature, AuCl(SMe2) (196.3 mg, 0.666 mmol) was added. The
resulting mixture was stirred at room temperature for 3 h under an
argon atmosphere. The mixture was then concentrated to dryness,
and the residue was filtered through CeliteÒ to remove insoluble
materials. After evaporation of the filtrate, the residue was purified
with silica gel column chromatography (hexane/ethyl acetate¼1/1
as eluent) to obtain a dendritic NHCegold(I) complex 1G1[Me]
(314.3 mg, 0.523 mmol) in a 78% yield.
OCH2CH2O), 3.50e3.46 (m, 16H, CH2CH2O), 3.30 (s, 24H, OCH3); 13
C
NMR (100 MHz; CD3OD) d 171.6, 161.5, 161.4, 140.9, 140.0, 123.1, 108.2,
107.2, 103.4, 102.1, 73.0, 71.7, 71.6, 71.4, 71.0, 70.8, 68.8, 59.2, 55.7;
Anal. Calcd for C101H152AuClN2O36$2H2O: C, 54.19; H, 7.02; N,1.25; Cl,
1.58%. Found: C, 53.86; H, 6.91; N, 1.10; Cl, 1.47%.
4.3.6. Chloro(1,3-bis[3,5-bis{3,5-bis(3,5-bis[2-{2-(2-methoxyethoxy)
ethoxy}ethoxy]benzyloxy) benzyloxy}benzyl]imidazol-2-ylidene)gold(I)
(1G3[TEG]). Pale yellow oil; IR (Neat) 2876, 1594, 1447, 1350, 1298,
1174, 1069, 845 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d 6.89 (s, 2H, Im),
6.66 (d, J¼2.0 Hz, 8H, ArH), 6.58 (d, J¼2.0 Hz, 16H, ArH), 6.56 (t,
J¼2.0 Hz, 2H, ArH), 6.54 (t, J¼2.2 Hz, 4H, ArH), 6.53 (t, J¼2.2 Hz, 4H,
ArH), 6.44 (t, J¼2.2 Hz, 8H, ArH), 5.26 (s, 4H, NCH2Ar), 4.95 (s, 24H,
OCH2Ar), 4.09 (t, J¼4.8 Hz, 32H, OCH2CH2), 3.82 (t, J¼4.8 Hz, 32H,
CH2CH2O), 3.74e3.69 (m, 32H, OCH2CH2), 3.68e3.61 (m, 64H,
4.3.1. Chloro{1,3-bis(3,5-dimethoxybenzyl)imidazol-2-ylidene}
gold(I) (1G1[Me]). White powder; mp 174e176 ꢀC; IR (KBr) 2944,
OCH2CH2O), 3.55e3.51 (m, 32H, CH2CH2O), 3.36 (s, 48H, OCH3); 13
C
2839, 1600, 1454, 1419, 1357, 1300, 1208, 1164, 1070, 785, 697 cmꢁ1
;
1H NMR (400 MHz; CDCl3)
ArH), 5.29 (s, 4H, NCH2Ar), 3.78 (s, 12H, OCH3); 13C NMR (100 MHz;
CDCl3) 171.5, 161.3, 137.1, 120.9, 106.1, 100.4, 55.5, 55.2; Anal. Calcd
d
6.88 (s, 2H, Im), 6.50e6.39 (m, 6H,
NMR (100 MHz; CDCl3)
d 171.1, 160.3, 160.1, 139.0, 138.9, 137.4, 121.1,
107.1, 106.5, 106.1, 101.9, 101.6, 101.1, 71.9, 70.8, 70.6, 70.5, 70.1, 70.0,
69.6, 67.5, 59.0, 55.1; Anal. Calcd for C213H312AuClN2O76: C, 58.82; H,
7.23; N, 0.64; Cl, 0.82%. Found: C, 59.09; H, 7.32; N, 0.54; Cl, 0.80%.
d
for C21H24AuClN2O4$0.3H2O: C, 41.60; H, 4.09; N, 4.62; Cl, 5.85%.
Found: C, 41.54; H, 3.88; N, 4.33; Cl, 6.23%.
4.3.7. Chloro[1,3-bis{3,5-bis(2,5,8,11,14-pentaoxahexadecane-16-
yloxy)benzyl}imidazol-2-ylidene]gold(I) (1G1[PEG]). Pale yellow oil;
IR (Neat) 2872,1594,1447, 1349,1298,1246,1119, 949, 851 cmꢁ1; 1H
4.3.2. Chloro[1,3-bis{3,5-bis(3,5-dimethoxybenzyloxy)benzyl}imida-
zol-2-ylidene]gold(I) (1G2[Me]). White powder; mp 132e134 ꢀC; IR
(KBr) 2998, 2938, 2838, 1599, 1459, 1430, 1349, 1154, 1056,
NMR (400 MHz; CDCl3)
d
6.87 (s, 2H, Im), 6.49 (d, J¼2.1 Hz, 4H,
834 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d 6.79 (s, 2H, Im), 6.57e6.50
ArH), 6.45 (t, J¼2.1 Hz, 2H, ArH), 5.26 (s, 4H, NCH2Ar), 4.09 (t,
J¼4.7 Hz, 8H, OCH2CH2), 3.83 (t, J¼4.7 Hz, 8H, CH2CH2O), 3.73e3.62
(m, 56H, OCH2CH2O), 3.56e3.52 (m, 8H, CH2CH2O), 3.37 (s, 12H,
(m, 14H, ArH), 6.40 (t J¼2.0 Hz, 4H, ArH), 5.26 (s, 4H, NCH2Ar), 4.95
(s, 8H, OCH2Ar), 3.79 (s, 24H, OCH3); 13C NMR (100 MHz; CDCl3)
OCH3); 13C NMR (100 MHz; CDCl3)
d 171.2, 160.4, 136.9, 120.9, 107.1,
d
171.5,161.0,160.3,138.9,137.1,120.9,107.2,105.2,102.2,100.0, 70.1,
101.5, 71.9, 70.7, 70.6, 70.54, 70.53, 70.47, 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%.
55.4, 55.1; Anal. Calcd for C53H56AuClN2O12: C, 55.57; H, 4.93; N,
2.45; Cl, 3.10%. Found: C, 55.43; H, 4.86; N, 2.23; Cl, 3.07%.
4.3.3. Chloro(1,3-bis[3,5-bis{3,5-bis(3,5-dimethoxybenzyloxy)ben-
zyloxy}benzyl]imidazol-2-ylidene)gold(I) (1G3[Me]). White powder;
mp 67e69 ꢀC; IR (KBr) 2998, 2937, 2838, 1594, 1456, 1374, 1324,
4.3.8. Chloro[1,3-bis{3,5-bis(2,5,8,11,14,17,20,23,26,29,32,35-
dodecaoxaheptatriacontan-37-yloxy)benzyl}imidazol-2-ylidene]
gold(I) (1G1[DEG]). Pale yellow oil; IR (Neat) 2873, 1597, 1451, 1349,
1205, 1157, 1053, 833 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d 6.75 (s, 2H,
1298, 1248, 1118, 950, 851 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d 6.89
Im), 6.63 (d, J¼2.0 Hz, 8H, ArH), 6.56 (d, J¼2.4 Hz, 16H, ArH), 6.54 (t,
J¼2.2 Hz, 4H, ArH), 6.51 (t, J¼2.0 Hz, 2H, ArH), 6.45 (t, J¼2.0 Hz, 4H,
ArH), 6.39 (t, J¼2.2 Hz, 8H, ArH), 5.20 (s, 4H, NCH2Ar), 4.96 (s, 16H,
OCH2Ar), 4.92 (s, 8H, OCH2Ar), 3.76 (s, 48H, OCH3); 13C NMR
(s, 2H, Im), 6.49 (d, J¼2.0 Hz, 4H, ArH), 6.45 (d, J¼2.0 Hz, 2H, ArH),
5.26 (s, 4H, NCH2Ar), 4.09 (t, J¼4.4 Hz, 8H, OCH2CH2), 3.83 (t,
J¼4.6 Hz, 8H, CH2CH2O), 3.77e3.44 (m, 176H, OCH2CH2O), 3.38 (s,
12H, OCH3); 13C NMR (100 MHz; CDCl3)
d 171.0, 160.3, 136.9, 120.9,
(100 MHz; CDCl3)
d 171.4, 160.9, 160.2, 160.0, 139.1, 139.0, 137.3,
107.0, 101.4, 71.9, 70.9, 70.7, 70.5, 69.5, 67.5, 59.0, 55.2; Anal. Calcd
120.9, 107.0, 106.3, 105.2, 102.1, 101.7, 99.9, 70.0, 55.7, 55.3, 55.0;

K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
1211
for C117H216AuClN2O52: C, 51.75; H, 8.02; N, 1.03; Cl, 1.31%. Found: C,
51.63; H, 8.11; N, 0.91; Cl, 1.31%.
A dry N,N-dimethylformamide suspension (160 mL) of 3,5-
dihydroxybenzyl alcohol (3.334 g, 23.79 mmol), the above-
obtained crude 6[PEG], anhydrous potassium carbonate (8.361 g,
60.50 mmol), and 18-crown-6 (3.145 g, 11.90 mmol) was stirred at
80 ꢀC for 22 h under an argon atmosphere. The completion of the
reaction was detected by 13C NMR. The reaction mixture was fil-
tered with CeliteÒ to remove inorganic salts, and the filtrate was
evaporated to dryness. The residue was purified with silica gel
column chromatography (ethyl acetate/methanol¼10/1 as eluent)
to obtain the first-generation dendritic alcohol 7[PEG] (12.464 g,
20.476 mmol) in an 86% yield.
4.4. Synthesis of a propargylic amine (4b)
To a dry diethylamine solution (7 mL) of 4-iodotoluene (3.502 g,
16.06 mmol), PdCl2(PPh3)2, (225.2 mg, 0.3208 mmol), and copper(I)
iodide (31.4 mg, 0.165 mmol) was slowly added a dry diethylamine
solution (3 mL) of N-methylpropargylic amine (1.285 g,
17.66 mmol) at 0 ꢀC under an argon atmosphere. The resulting
mixture was stirred at room temperature for 20 h under an argon
atmosphere. After the complete consumption of 4-iodotoluene was
confirmed by 1H NMR, the reaction mixture was filtered with
CeliteÒ to remove inorganic salts, and the filtrate was evaporated to
dryness. The residue was purified with silica gel column chroma-
tography (ethyl acetate/hexane¼1/1 as eluent) and with distillation
by Kugelrohr (100 ꢀC/0.22 hPa) to obtain a propargylic amine 4b
(1.888 g, 11.86 mmol) in a 74% yield.
4.6.1. {3,5-Bis(2,5,8,11,14-pentaoxahexadecane-16-yloxy)phenyl}
methanol (7[PEG]). Colorless oil; IR (Neat) 3466, 2873, 1596, 1450,
1350, 1294, 1249, 1170, 1118, 949, 848 cmꢁ1 1H NMR (400 MHz;
;
CDCl3)
d
6.54 (d, J¼2.2 Hz, 2H, ArH), 6.40 (t, J¼2.2 Hz, 1H, ArH), 4.60
(d, J¼6.2 Hz, 2H, CH2Ar), 4.11 (t, J¼4.8 Hz, 4H, OCH2CH2), 3.83 (t,
J¼4.8 Hz, 4H, CH2CH2O), 3.74e3.70 (m, 4H, OCH2CH2), 3.69e3.61
(m, 24H, OCH2CH2O), 3.56e3.52 (m, 4H, CH2CH2O), 3.37 (s, 6H,
4.4.1. N-Methyl-3-(40-methylphenyl)-2-propynylamine (4b). Pale yellow
OCH3), 2.27 (t, J¼3.1 Hz, 1H); 13C NMR (100 MHz; CDCl3)
d 160.0,
oil; IR (Neat) 3325, 3279, 2924, 2793, 1504, 1443, 1327, 1111, 826,
143.7, 105.4, 100.7, 71.9, 70.8, 70.62, 70.60, 70.59, 70.57, 70.55,
70.48, 69.7, 67.5, 65.0, 59.0; Anal. Calcd for C29H52O13: C, 57.22; H,
8.61%. Found: C, 57.20; H, 8.70%.
756 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d
7.31 (d, J¼8.1 Hz, 2H, ArH), 7.09
(d, J¼8.1 Hz, 2H, ArH), 3.59 (s, 2H, CH2), 2.52 (s, 3H, ArCH3), 2.33 (s, 3H,
NCH3); 13C NMR (100 MHz; CDCl3)
138.0, 131.5, 129.0, 120.2, 86.7, 83.7,
d
40.8, 35.4, 21.4; Anal. Calcd for C11H13N: C, 82.97; H, 8.23; N, 8.80%.
Found: C, 82.61; H, 8.32; N, 8.64%.
4.7. Synthesis of the first-generation dendritic bromide
(2G1[PEG])
4.5. Carboxylative cyclization of propargylic amines with CO2:
General procedure
To a dry tetrahydrofuran solution (16 mL) of the first-generation
dendritic alcohol 7[PEG] (3.461 g, 5.685 mmol) and carbon tetra-
bromide (2.348 g, 7.079 mmol) was added triphenylphosphine
(1.867 g, 7.079 mmol), and the resulting mixture was stirred at
room temperature for 10 min under an argon atmosphere. After the
complete consumption of 7[PEG] was confirmed by TLC, the re-
action mixture was filtered with CeliteÒ, and the filtrate was
evaporated to dryness. The residue was purified with silica gel
column chromatography (ethyl acetate/methanol¼10/1 as eluent)
to obtain the first-generation dendritic bromide 2G1[PEG] (2.905 g,
4.325 mmol) in a 76% yield.
To a Schlenk tube were successively added an NHCegold(I)
complex 1Gn[X] (0.008 mmol), degassed solvent (0.8 mL), and
a propargylic amine 4 (0.8 mmol) under an argon atmosphere. The
interior of the Schlenk tube was then replaced with CO2 (0.1 MPa).
The carboxylative cyclization of the propargylic amine with CO2
proceeded by the stirring of the resulting mixture at the indicated
temperature. After 15e72 h, methanol and dichloromethane were
added to homogenize the reaction mixture. The chemical yield of 2-
oxazolidinone 5 was determined by integrating 1H NMR absorp-
tions referring to an internal standard (3-hydroxybenzyl alcohol
(1 mmol)), which was added to the homogenized reaction mixture.
2-oxazolidinones 5 except for 5b are known compounds, and
their NMR spectra are in accordance with those reported in the
literature (5a,5c 5c,16 5d,5c 5e,16 5f,16 5g5c).
4.7.1. 3,5-Bis(2,5,8,11,14-pentaoxahexadecane-16-yloxy)benzyl bro-
mide (2G1[PEG]). Colorless oil; IR (Neat) 2873, 1595, 1449, 1349,
1297, 1249, 1177, 1108, 949, 850 cmꢁ1 1H NMR (400 MHz; CDCl3)
;
d
6.55 (d, J¼2.2 Hz, 2H, ArH), 6.42 (t, J¼2.2 Hz, 1H, ArH), 4.39 (s, 2H,
CH2Ar), 4.10 (t, J¼4.8 Hz, 4H, OCH2CH2), 3.84 (t, J¼4.8 Hz, 4H,
CH2CH2O), 3.74e3.70 (m, 4H, OCH2CH2), 3.69e3.62 (m, 24H,
OCH2CH2O), 3.56e3.53 (m, 4H, CH2CH2O), 3.38 (s, 6H, OCH3); 13C
4.5.1. (Z)-5-(40-Methylbenzylidene)-3-methyl-1,3-oxazolidin-2-one
(5b). White powder; mp 133.4e134.5 ꢀC; IR (KBr) 2916, 2862, 1782,
NMR (100 MHz; CDCl3)
70.70, 70.68, 70.67, 70.60, 69.7, 67.7, 59.1, 33.6; Anal. Calcd for
29H51BrO12: C, 51.86; H, 7.65; Br, 11.90%. Found: C, 51.95; H, 7.69;
d 160.1, 139.7, 108.0, 101.8, 72.0, 70.9, 70.72,
1697, 1435, 1412, 1273, 1088, 1034, 841 cmꢁ1 1H NMR (400 MHz;
;
CDCl3)
(t, J¼2.0 Hz, 1H, CH), 4.31 (d, J¼2.0 Hz, 2H, CH2), 2.99 (s, 3H, NCH3),
2.33 (s, 3H, ArCH3); 13C NMR (100 MHz; CDCl3)
155.7, 140.8, 136.5,
d
7.45 (d, J¼8.1 Hz, 2H, ArH), 7.13 (d, J¼8.0 Hz, 2H, ArH), 5.48
C
Br, 11.66%.
d
130.6, 129.1, 128.0, 102.7, 50.7, 30.3, 21.1; Anal. Calcd for C12H13NO2:
C, 70.92; H, 6.45; N, 6.89%. Found: C, 70.95; H, 6.44; N, 6.79%.
4.8. Synthesis of the first-generation dendritic methyl ben-
zoate (8)
4.6. Synthesis of the first-generation dendritic alcohol (7[PEG])
To a dry tetrahydrofuran solution (50 mL) of dodeca(ethylene
glycol) monomethyl ether (12.976 g, 23.147 mmol) and triethyl-
amine (3.480 g, 34.39 mmol), a dry tetrahydrofuran solution
(25 mL) of methanesulfonyl chloride (2.595 g, 22.66 mmol) was
slowly added under an argon atmosphere. The resulting solution
was stirred at room temperature for 3 h under an argon atmo-
sphere. After the completion of the reaction was detected by 1H
NMR, the reaction mixture was filtered with CeliteÒ to remove
insoluble materials using dichloromethane, and the filtrate was
evaporated to dryness to afford crude 6[DEG].
To a dry tetrahydrofuran solution (50 mL) of penta(ethylene
glycol) monomethyl ether (10.348 g, 41.015 mmol) and triethyl-
amine (8.358 g, 82.60 mmol), a dry tetrahydrofuran solution
(40 mL) of methanesulfonyl chloride (7.079 g, 61.80 mmol) was
slowly added under an argon atmosphere. The resulting solution
was stirred at room temperature for 7 h under an argon atmo-
sphere. After 1H NMR detected the completion of the reaction, the
reaction mixture was filtered with CeliteÒ to remove insoluble
materials by use of dichloromethane, and the filtrate was evapo-
rated to dryness to afford crude 6[PEG].
A dry N,N-dimethylformamide suspension (80 mL) of methyl
3,5-dihydroxybenzoate (1.608 g, 9.563 mmol), the above-obtained

1212
K. Fujita et al. / Tetrahedron 72 (2016) 1205e1212
crude 6[DEG], anhydrous potassium carbonate (3.308 g,
23.934 mmol), and 18-crown-6 (545.9 mg, 2.065 mmol) was stirred
at 70 ꢀC for 15 h under an argon atmosphere. The completion of the
reaction was detected by 13C NMR. The reaction mixture was fil-
tered with CeliteÒ to remove inorganic salts, and the filtrate was
evaporated to dryness. The residue was purified with silica gel
column chromatography (ethyl acetate/methanol¼15/1, followed
by chloroform/methanol¼10/1, as eluent) to obtain the first-
generation dendritic methyl benzoate 8 (11.692 g, 9.328 mmol) in
a 98% yield.
reduced pressure, and the residue was purified with silica gel col-
umn chromatography (chloroform/methanol¼15/1 as eluent) to
obtain the first-generation dendritic bromide 2G1[DEG] (951.9 mg,
0.739 mmol) in a 92% yield.
4.10.1. {3,5-Bis(2,5,8,11,14,17,20,23,26,29,32,35-dodecaoxahepta-
triacontan-37-yloxy)benzyl bromide (2G1[DEG]). Colorless oil; IR
(Neat) 2873, 1595, 1452, 1349, 1298, 1249, 1107, 950, 848 cmꢁ1; 1H
NMR (400 MHz; CDCl3)
d
6.55 (s, 2H, ArH), 6.42 (t, J¼2.2 Hz, 1H,
ArH), 4.39 (s, 2H, CH2Ar), 4.10 (t, J¼4.8 Hz, 4H, OCH2CH2), 3.84 (t,
J¼5.0 Hz, 4H, CH2CH2O), 3.76e3.60 (m, 84H, OCH2CH2O), 3.57e3.53
(m, 4H, CH2CH2O), 3.38 (s, 6H, OCH3); 13C NMR (100 MHz; CDCl3)
4.8.1. Methyl 3,5-bis(2,5,8,11,14,17, 20,23,26,29, 32,35-
dodecaoxaheptatriacontan-37-yloxy) benzoate (8). Colorless oil; IR
(Neat) 2873, 1718, 1594, 1447, 1349, 1301, 1247, 1102, 950, 854,
d
159.8, 139.5, 107.7, 101.5, 71.8, 70.7, 70.5, 70.42, 70.37, 69.5, 67.4,
58.9, 33.5; Anal. Calcd for C57H107BrO$1.5H2O: C, 52.05; H, 8.43, Br,
6.07%. Found: C, 52.20; H, 8.26; Br, 5.74%.
770 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d
7.19 (d, J¼2.4 Hz, 2H, ArH),
6.69 (t, J¼2.2 Hz, 1H, ArH), 4.14 (t, J¼4.8 Hz, 4H, OCH2CH2), 3.89 (s,
3H, CH3O), 3.85 (t, J¼4.8 Hz, 4H, CH2CH2O), 3.76e3.50 (m, 88H,
References and notes
OCH2CH2O), 3.38 (s, 6H, OCH3); 13C NMR (100 MHz; CDCl3)
d 166.5,
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52.0; Anal. Calcd for C58H108
C, 55.12; H, 8.73%.
O28$0.5H2O: C, 55.18; H, 8.70%. Found:
4.9. Synthesis of the first-generation dendritic alcohol (7[DEG])
A solution of the first-generation dendritic methyl benzoate 8
(5.069 g, 4.044 mmol) in dry tetrahydrofuran (10 mL) was added
dropwise via an addition funnel to a cooled flask containing a sus-
pension of lithium aluminum hydride (184.6 mg, 4.864 mmol) in
dry tetrahydrofuran (40 mL) under an argon atmosphere. The
resulting mixture was stirred at 50 ꢀC for 3 h under an argon at-
mosphere. The excess hydride was quenched with a 1:1 mixture
(ca. 2 g) of pulverized sodium sulfate decahydrate and CeliteÒ in an
ice bath. The reaction mixture was filtered with CeliteÒ to remove
insoluble materials by using dichloromethane, and the filtrate was
dried over anhydrous magnesium sulfate. The solution was con-
centrated under reduced pressure, and the residue was purified
with silica gel column chromatography (chloroform/methanol¼10/
1, as eluent) to obtain the first-generation dendritic alcohol 7[DEG]
(1.960 g, 0.864 mmol) in a 96% yield.
4. Fujita, K.; Sato, J.; Onozawa, S.; Yasuda, H. Chem. Soc. Jpn. 2014, 3 94th Annual
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848 cmꢁ1; 1H NMR (400 MHz; CDCl3)
d
6.54 (d, J¼2.4 Hz, 2H, ArH),
6.40 (t, J¼2.2 Hz, 1H, ArH), 4.60 (d, J¼6.0 Hz, 2H, OCH2Ar), 4.11 (t,
J¼5.0 Hz, 4H, OCH2CH2), 3.84 (t, J¼4.8 Hz, 4H, CH2CH2O), 3.76e3.58
(m, 84H, OCH2CH2O), 3.57e3.53 (m, 4H, CH2CH2O), 3.38 (s, 6H,
OCH3); 13C NMR (100 MHz; CDCl3)
d
159.7, 143.6, 105.0, 100.3, 72.3,
71.6, 70.7, 70.5, 70.3, 69.4, 67.2, 64.5, 58.8; Anal. Calcd for
57H108O27: C, 55.87; H, 8.88%. Found: C, 55.63; H, 9.01%.
C
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anti fashion.5aec
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was stirred at room temperature for 3 h under an argon atmo-
sphere. After the reaction mixture was poured into water (10 mL),
the product was extracted with chloroform three times. The com-
bined organic layers were washed with brine then dried over an-
hydrous sodium sulfate. The solution was concentrated under
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