Synthesis of surface-active N-heterocyclic carbene ligand and its Pd-catalyzed aqueous Mizoroki–Heck reaction

Article abstract of DOI:10.1016/j.tet.2016.05.053

A surface-active N-heterocyclic carbene (NHC) ligand with an octaethylene glycol monomethyl ether and n-dodecyl chain was synthesized. The NHC and its Pd complex behaved as a general surfactant, and hydrophobic oily substrates such as iodobenzene and styrene were emulsified in water, resulting in the acceleration of the Mizoroki–Heck reaction under heterogeneous conditions. Our results demonstrated that the reactive emulsion interface rendered by the surface-active NHC is effective for the aqueous Mizoroki–Heck reaction.

Full text of DOI:10.1016/j.tet.2016.05.053

Accepted Manuscript
Synthesis of surface-active N-heterocyclic carbene ligand and its Pd-catalyzed
aqueous Mizoroki–Heck reaction
Toshiaki Taira, Takaya Yanagimoto, Kenichi Sakai, Hideki Sakai, Akira Endo,
Tomohiro Imura
PII:
S0040-4020(16)30460-4
10.1016/j.tet.2016.05.053
TET 27780
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 3 March 2016
Revised Date: 18 May 2016
Accepted Date: 20 May 2016
Please cite this article as: Taira T, Yanagimoto T, Sakai K, Sakai H, Endo A, Imura T, Synthesis of
surface-active N-heterocyclic carbene ligand and its Pd-catalyzed aqueous Mizoroki–Heck reaction,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.05.053.
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Synthesis of surface-active N-heterocyclic
carbene ligand and its Pd-catalyzed aqueous
Mizoroki–Heck reaction
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Toshiaki Tairaa,*, Takaya Yanagimotob, Kenichi Sakaib, Hideki Sakaib, Akira Endoa and Tomohiro Imuraa,
aResearch Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and
Technology (AIST), Central 5-2, 1-1 Higashi,Tsukuba, Ibaraki 305-8565, Japan
bFaculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510,
Japan

1
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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of surface-active N-heterocyclic carbene ligand and its Pd-catalyzed
aqueous Mizoroki–Heck reaction
Toshiaki Tairaa,*, Takaya Yanagimotob, Kenichi Sakaib, Hideki Sakaib, Akira Endoa and Tomohiro Imuraa,
aResearch Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-2, 1-1
Higashi,Tsukuba, Ibaraki 305-8565, Japan
bFaculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A surface-active N-heterocyclic carbene (NHC) ligand with an octaethylene glycol monomethyl
ether and n-dodecyl chain was synthesized. The NHC and its Pd complex behaved as a general
surfactant, and hydrophobic oily substrates such as iodobenzene and styrene were emulsified in
water, resulting in the acceleration of the Mizoroki–Heck reaction under heterogeneous
conditions. Our results demonstrated that the reactive emulsion interface rendered by the
surface-active NHC is effective for the aqueous Mizoroki–Heck reaction.
Available online
Keywords:
N-heterocyclic carbene
Surface activity
2009 Elsevier Ltd. All rights reserved.
Aqueous reaction
Palladium catalyst
Mizoroki–Heck reaction
cross-coupling reactions.9 The enhancement of the reaction rate
using micelles under pseudo-homogeneous conditions is
1. Introduction
The use of water as a green solvent in chemical reactions is of
significance as it is the most abundant, nontoxic, and
environmentally friendly solvent.1 Several reactions conducted in
water exhibit efficiency higher than those obtained for reactions
conducted in common organic solvents.2 Multicomponent
reactions, such as the Diels–Alder reaction and the Claisen
rearrangement of hydrophobic compounds, have been found to
be accelerated in water as compared to common organic
solvents.3 They are presented that insoluble reactants are
vigorously stirred in an aqueous suspension for increasing the
interfacial area. For improving the solubility of reactants,
typically, phase-transfer catalysts, polymers, crown ethers, and
surfactants are added into aqueous or multiphase media.4-7
Among these additives, surfactants are one of the useful
candidates because they not only solubilize reactants but also
emulsify them for providing an interface between water and the
reactants, which plays a role in accelerating the rate of the
reaction.8
primarily attributed to the increase in the local concentration of
the reactants on the surface as well as inside the micelles.10
Surfactants also form emulsions, which are immiscible
colloidal suspensions under heterogeneous conditions. The same
rate enhancement is also observed for emulsions because they
also contain dispersed oil and continuous water phases with a
large interfacial area. Kobayashi et al. have reported a Lewis-
acid–surfactant-combined catalyst (LASC), which forms
emulsion droplets in the presence of oily substrates in water.11
They have observed that several carbon–carbon bond-forming
reactions, such as Aldol, allylation, and Mannich-type reactions,
proceed under emulsion conditions. Excellent catalytic
performance is attributed to the assembly of the catalyst
combined with a surfactant at the interface of emulsions,
resulting in the formation of a reactive emulsion interface.
N-Heterocyclic carbene (NHC) ligands have attracted
significant interest as the most attractive ligand for transition-
metal-catalyzed reactions in water.12-15 As compared to
conventional phosphine ligands, which are typically sensitive to
water and air, NHCs exhibit superior bonding robustness.16 Since
the first report of a water-soluble sulfonate-functionalized NHC
ligand, a number of hydrophilic-functionalized NHC ligands
Lipshutz et al. have reported that the addition of surfactants,
such as sodium dodecyl sulfate (SDS), polyoxyethanyl α-
tocopheryl sebacate, and DL-α-tocopherol methoxypolyethylene
glycol succinate, together with hydrophobic organometallic
catalysts in water facilitates several types of reactions including
———
 Corresponding authors. Tel.: +81-29-861-4738; fax: +81-29-861-4457; e-mail: t-imura@aist.go.jp (T. Imura)
Tel.: +81-29-861-3400; fax: +81-29-861-4457; e-mail: t-taira@aist.go.jp (T. Taira)

2
Tetrahedron
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have been reported, with focus on increasing their solubilities in
resonance at  = 10.46 ppm was observed in the 1H NMR
spectrum of 1 in CDCl3. A resonance was also observed at  =
137.3 ppm in the 13C{1H} NMR spectrum, corresponding to the
NCN carbon atom; this result further confirms the formation of 1.
1 is soluble in both water and organic solvents such as DMSO,
DMF, acetone, chloroform, and CH2Cl2, indicative of its
amphiphilic nature. Next, the formation of its Pd complex was
confirmed by treating 0.5 equiv. of Pd(OAc)2 with 1 in water or
THF; a clear, pale yellow solution was obtained. In the 13C{1H}
NMR spectrum, a characteristic 2-C resonance at  = 168.6 ppm
was observed. The chemical shift is well consistent with those of
typical NHC-Pd complexes, where the value of PdC signals
range from ca. 158–185 ppm.19 It should be noted that there are
no signal corresponding to free carbene signal above 200 ppm,
indicating that carbene does not dissociate from Pd. Two sets of
peaks at 123.6 and 122.4 ppm, were observed, corresponding to
cis/trans and/or syn/anti isomers. A peak of m/z 1503.51 was
observed in the MALDI-TOF MS spectrum, corresponding to a
[M + H]+ fragment (calcd: 1503.91); this result also supports the
formation of [PdBr2(NHC)2] (1-Pd). Peaks were also observed a
peak of m/z 1104.73 and 1992.77, attributed to Pd oligomers.20
These results imply that 1-Pd is formed as a mixture.
water.17 Although the approach is successful, the NHCs are not
expected to form a reactive interface in water as they remain in
the aqueous phase even with the use of the surfactant; hence such
systems are not completely utilized the potential of them. To the
best of our knowledge, no studies have been reported on surface-
active NHC ligands, even though such ligands are expected to
exhibit dual functions as both a surfactant and ligand, which are
soluble in water and form emulsions. Surface-active NHC can be
expected to facilitate aqueous cross-coupling reactions, because
the reaction commonly requires a hydrophilic base together with
hydrophobic substrates; surface-active NHC should play a role to
smoothly contact the reactants on the emulsion interface.
In this study, a surface-active NHC ligand having an
oligoethylene glycol monomethyl ether and n-dodecyl chain 1
was synthesized, and its surface properties such as surface
tension, micellization, and emulsification were evaluated. 1 was
demonstrated to form a stable oil-in-water (O/W) emulsion with
oily substrates, resulting in the acceleration of the Mizoroki–
Heck reaction under heterogeneous conditions.
2. Results and Discussion
2.1. Synthesis
2.2. Surface properties
The surface activities of the designed NHC 1 in water were
confirmed by the Wilhelmy plate method (Fig. 1 and Table 1). In
Fig. 1, the surface tension of water decreased with increasing
concentration of 1 from 72.2 to 27.6 mN/m, indicating that 1
behaves as a surfactant in water. Typically, it is believed that
Although typical NHCs contain aryl substituents such as IPr,
IMes, SiPr, and SiMes, which impart electronic and steric
properties, an NHC with less bulky substituents such as an
oligoethylene glycol monomethyl ether and n-dodecyl chain as
the hydrophilic and hydrophobic parts, respectively, was
synthesized; its structure was similar to that of the commonly
used nonionic surfactants: octaethylene glycol monododecyl
ether (C12EO8). As the nonionic nature of oligoethylene glycol
also positively affects catalytic performance in cross-coupling
reactions,18 favorable activity would be expected for such a less
sterically hindered NHC. Scheme 1 shows the synthesis of
asymmetric N,N′-substituted imidazolium salt 1 with hydrophilic
and hydrophobic parts by subsequent reactions of imidazole.
First, imidazole was treated with 1-bromododecane in the
presence of NaOH, affording 1-dodecylimidazole in 86% yield.
Second, equimolar amounts of 1-dodecylimidazole and
Br(CH2CH2O)8CH3 were mixed under neat conditions at 100 °C,
affording 1 in 62% yield. An analogous NHC precursor 2 having
methyl and n-dodecyl substituents was also synthesized by
treating 1-methylimidazole with 1-bromododecane. The MALDI-
TOF MS spectrum of 1 exhibited a peak of m/z 603.46,
corresponding to the [M − Br]+ fragment. A characteristic 2-H
40
35
30
25
▲ : 1
● : 1-Pd
20
10-4
10-3
10-2
Concentration (M)
Fig.1. Relationship between surface tension and
concentration of 1 (square) and 1-Pd prepared in situ (circle)
at 25 oC.
Table 1. Surface properties of 1 and 1-Pd prepared in
situ at 25 °C.a)
Averaged diameter
Compound
CMC (M)

CMC (mN/m)
(nm)b)
1
3.9 × 10−3
1.2 × 10−3
27.6
33.2

31.9  10.8
1-Pd
Scheme 1. i) 1.0 equiv. bromododecane and 50% NaOH
aq., ii) 1.0 equiv. Br(CH2CH2O)8CH3, 100 °C, iii) 0.5 equiv.
Pd(OAc)2.
aThe activity coefficient was fixed as 1. bAverage diameter of micelles
was determined by DLS measurements.

3
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addition of 1 and 1-Pd above their CMC (30 mM) led to the
Table 2. Interfacial tension of water–iodobenzene and
decrease of the interfacial tension to 5.6 and 13.1 mN/m,
respectively. By the addition of 1 and 1-Pd, the interfacial tension
of water–styrene also decreased to 4.5 mN/m and 11.8 mN/m,
respectively. These results clearly indicate that both 1 and 1-Pd
exhibit the ability to decrease interfacial tension. Indeed, surface-
active NHC 1 and its Pd complex mixture (1-Pd) formed
emulsions from the mixture of iodobenzene, styrene, and water,
where Pd centers can align between the oil and water phases to
form a reactive interface.
water–styrene interfaces at 25 °Ca),b)
surface-active compound
Iodobenzene
(mN/m)
34.6
Styrene
(mN/m)
33.4
none
1
5.6
4.5
1-Pdc)
13.1
11.8
a[surface-active compound] = 30 mM. bref. 20 c1-Pd was prepared in situ
and measured as a mixture.
when such a surface-active compound is adsorbed at the air–
water interface, the alkyl chain is directed out of water, whereas
the hydrophilic part is directed in water. When the interface is
completely occupied by 1, the excess molecules of 1 start to
aggregate into micelles in water. Dynamic light scattering (DLS)
measurements of aqueous solution of 1 (10 mM) confirm the
formation of micelles with a hydrodynamic diameter of 2.5 ± 0.3
nm. Fig. 1 plots the surface tension versus concentration; the
critical micelle concentration (CMC) of 1 was determined from
this plot. The CMC obtained from the intersection of the two
fitted lines was 3.9 × 10−3 M.21 The addition of 0.5 eq. of
Pd(OAc)2 to 1 produced 1-Pd as a mixture, which also exhibits
an ability to decrease surface tension. NHC-Pd catalysts are
known to form several isomers;12 hence, we also studied the
surface activities of the mixture of 1-Pd. The CMC of 1-Pd was
determined to be 1.2 × 10−3 M. The micelle size of 1-Pd was
greater than that of 1, suggesting that the complexation of Pd
with 1 promotes the association of molecules in water. The CMC
values of 1 and 1-Pd were less than that of SDS (8.3 mM) but
greater than that of cetyltrimethylammonium bromide (CTAB,
0.9 mM).20 The CMC of 1-Pd was less than that of 1, attributed to
the shielding of electropositive repulsion between imidazolium
moieties. The CMC (33.2 mN/m) of 1-Pd was greater than that of
1 as the introduction of Pd between the hydrophilic and
hydrophobic parts of 1 led to the increase of steric bulk at the
air–water interface. Indeed, the micelle size of 1-Pd was
relatively greater (31.9  10.8 nm) than that of 1. The solubility
of hydrophobic substrates within the micelle of 1 was confirmed
2.3. Aqueous Mizoroki–Heck reactions
Next, 1 was applied for the aqueous Mizoroki–Heck reactions
(Table 3). First, as a typical protocol, the reaction in DMF
afforded with quantitative conversion after 24 h and the product
was isolated in 95% yield (entry 1). Hence, we fixed the
concentration of 1 above the CMC (30 mM) in water; then, the
amounts of Pd(OAc)2 and 1 were also fixed to be 3.0 mol% for
the substrates. The aqueous cross-coupling reaction of
iodobenzene and styrene was conducted via in situ generation of
1-Pd (as a mixture) in the presence of NEt3 (Table 3, entry 2).
The solution formed an O/W emulsion, and with the vigorous
stirring of the emulsion at 70 °C for 24 h, stilbene was obtained
with quantitative conversion and the product was isolated in 96%
yield. By decreasing the amount of water, the conversion at 3 h
gradually decreased (89% for 0.6 mL, 60% for 0.2 mL, 58% for
0.006 mL, and 20% without water, respectively). These results
clearly demonstrate that surface-active NHC 1 retains its activity
under aqueous condition and facilitates the Mizoroki–Heck
reaction. In contrast, a reaction using a similar less bulky NHC
ligand 2 without the hydrophilic octaethylene glycol moiety
afforded stilbene in only 15% (entry 4). On the other hand, the
catalytic performance of 2 in DMF was relatively low (52%,
entry 3), while the significant difference of conversion between
the reaction in organic and aqueous solvent were observed. Other
control experiments using common NHC ligands such as 1,3-
dimethylimidazolium iodide (IDM, entry 5) and 1,3-bis(2,6-
diisopropylphenyl)imidazolium chloride (IPr, entry 6) provided
stilbene only 33 and 85% yield, respectively. These results
indicate that a conventional NHC and its Pd catalyst are not
suitable for aqueous reactions.
1
by H NMR measurements (Fig. S-9). Iodobenzene and styrene,
as oily compounds, were chosen as model substrates in this study
because they are miscible with each other and are substrates most
typically used in the Mizoroki–Heck reaction. In the absence of
1, iodobenene and styrene exhibited partial solubility in D2O
below 0.23 and 0.77 mM, respectively. Mixing of 1 above the
CMC (30 mM) led to the solubilization of the hydrophobic
substrates within the micelles, thereby increasing solubility to
5.42 and 7.04 mM, respectively.
Table 3. Scope of Mizoroki-Heck reactions between
iodobenzene and styrenea)
The interfacial tension between water and each substrate used
in the cross-coupling reaction was investigated. Iodobenzene and
styrene, as oily compounds, were chosen as model substrates in
this study because they are miscible with each other and are the
most typical substrates used in the Mizoroki–Heck reaction.
Table 2 shows the values of interfacial tension at the interfaces of
water–iodobenzene and water–styrene in the absence or presence
of surface-active compounds. In the absence of the surface-active
compound, the interfacial tension of iodobenzene exhibited a
high value of 34.6 mN/m; hence, they are immisible.22 The
entry ligand
solventb)
DMF
water
DMF
water
water
water
Conv. (%)c)
Yield (%)d)
1
2
3
4
5
6
1
1
>99
>99
60
95
96
52
15
33
85
2
2
17
IDMe)
IPrf)
46
93
aiodobenzene (0.54 mmol), styrene (0.78 mmol), NEt3 (0.69 mmol),
Pd(OAc)2 (0.018 mmol), ligand, or surfactant (0.018 mmol) were mixed
b
in a solvent for 24 h at 70 °C. the amount of solvents were set to be
c
d
1mL for DMF and 0.6 mL for water. Conversions after 24 h. Isolated
yields. iodide.
e1,3-dimethylimidazolium f1,3-bis(2,6
diisopropylphenyl)imidazolium chloride.
-

4
Tetrahedron
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For evaluating the catalytic performance of 1, the reaction
Table 4. Substrate scope in aqueous Mizoroki-Heck
reactions.a)
profile was also studied (Fig. 2). From the results obtained,
undoubtedly, 1 is found to be the most active, with total
conversion occurring within 5 h, while 2 affords stilbene in 17%.
When a surface-active compound such as SDS was added to 2 for
forming O/W emulsions similar to the case of 1, a moderate
conversion of 40% was observed for the mixture. Lipshutz et al.
have reported that mixing the NHC-Pd catalyst and surfactant
facilitates the aqueous Mizoroki–Heck reactions.9 In the case of
the reaction in DMF, 1 affords stilbene 53% after 5 h and
required 24 h to consume iodobenzene quantitatively (Fig. S-10).
These results suggest that the alignment of the Pd centers at the
interface of emulsions with a large reaction area plays a
significant role for the reaction. Fig. 3 shows the visual
appearance during the reaction. An hour after the reaction began,
the mixture separated into a suspended aqueous phase, and the oil
phase with a solid precipitate of stilbene was obtained. Finally,
residual oil was completely consumed, and the solid part was
separated by simple filtration, affording stilbene as the pure
product. Unfortunately, the Pd catalyst generated in situ resulted
in the formation of a mixture of isomers as well as Pd black after
treatment at 70 °C for 24 h; thus, it exhibits low recyclability.
Further approaches for synthesizing a more stable surface-active
NHC-Pd catalyst have been conducted, which can be recycled
after the reaction.
Given that 1 can efficiently catalyze aqueous Mizoroki-Heck
reaction of iodobenzene and styrene, it was then utilized to
aReactions carried out at 70 oC for 24 h using aryl halide (1 equiv),
olefin (2 equiv), triethylamine (3 equiv), 1 (3 mol%, 30mM), and
Pd(OAc)2 (3 mol %). bIsolated yield. cNo reaction. dNMR yield.
100
● : 1
■ : 2 + SDS
▲ : 2
expand the catalytic scope towards various aryl halides and
olefins (Table 4). A reaction of bromobenzene with styrene
(entry 1) afforded stilbenes in low yield (35%) and that of
chlorobenzene did not proceeded (entry 2), likely due to the
nature of substituent on the aromatic ring (I > Br >> Cl). Under
the optimized condition, both electron-rich (entry 3) and
electron-poor (entry 4) aryl iodides reacted with styrene leading
to good yield (77 and 87%, respectively). Reactions between
acrylates and aryl iodides were also performed, where acrylates
are less reactive coupling partners relative to styrene. The
coupling reactions of methyl acrylate with aryl iodides (entries 5
and 6) also provided methyl cinnamates in 91 and 89%,
respectively.
80
60
40
20
0
0
1
2
3
4
t (h)
3. Conclusions
Fig.2. Concentration versus time profile for the Mizoroki–
Heck reaction: triangle; 2, square; mixture of 2 and SDS,
circle; 1.
In this study, surface-active NHC ligand 1 bearing an
octaethylene glycol monomethyl ether and n-dodecane chain was
synthesized for the first time. 1 behaved as a typical surfactant,
demonstrating the ability to decrease surface tension as well as to
form micelles in water. Interestingly, the CMC value decreased
after complexation with Pd(OAc)2. Furthermore, 1 and 1-Pd
decreased the interfacial tension of water–iodobenzene and
water–styrene, thus providing their stable O/W emulsions. The
utility of the catalyst thus developed was demonstrated in the
aqueous Mizoroki–Heck reaction, affording stilbene, which was
separated by simple filtration, in a conversion of greater than
99%. We revealed that the scope of our methodology can be
extended to various aryl halides and olefins. All these
observations imply that 1, exhibiting dual functions as a ligand
and surfactant, is crucial for facilitating aqueous Mizoroki–Heck
reaction. The operationally simple process without addition of
unnecessary additional surfactants allows the reactions to take
place under environmentally attractive conditions. Furthermore,
the functionalization of NHC with the aim of exhibiting surface
Fig.3. Visual observation of the Mizoroki–Heck reaction:
(a) mixture of the aqueous solution of 1, iodobenzene, and
styrene (t = 0), (b) after the addition of Pd(OAc)2 and NEt3, t
= 1 h, (c) t = 24 h.

5
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activities demonstrates potential applications for not only the
Mizoroki–Heck reactions but also various organometallic
reactions.
δC (100 MHz, CDCl3) 168.6, 137.4, 123.6, 122.4, 120.9, 120.3,
70.4, 70.3, 70.1, 69.2, 58.9, 50.9, 50.8, 49.9, 49.6, 31.8, 30.8,
30.7, 30.2, 29.6, 29.5 (2C), 29.3 (2C), 29.0, 26.4, 26.2, 22.6,
14.0; m/z (MALDI-TOFMS) 1503.51 (MH+).
4.4. Surface tension measurements
4. Experimental
4.1. General
The surface tension of the solutions of 1 and 1-Pd was
determined by the Wilhelmy plate method at 25 °C using a DY-
500 surface tension meter (Kyowa Kaimen Kagaku Co., Japan);
its accuracy was intermittently checked using ultrapure water.
The Pt plate was cleaned by flaming, and glassware was rinsed
using tap and ultrapure water.
All reagents purchased from commercial sources were used
without further purification. Ultrapure water was obtained using
a Millipore (Milli Q) apparatus. NMR spectra were recorded in
CDCl3 on an NMR Avance III 400MHz NMR spectrometer
(Bruker BioSpin K.K.) using tetramethylsilane (TMS) as the
reference. All spectra were recorded at 298 K and analyzed using
4.5. Interfacial tension measurements
the
Topspin
3.1
software.
Matrix-assisted
laser
The interfacial tension of water–oil substrates was determined
by the pendant-drop method at 25 °C; these measurements were
carried out using an automatic interfacial tensiometer (DM500;
Kyowa Interface Science, Japan) and drop shape analysis
software (FAMAS ver. 2.01.19). Water-dissolved 1 or 1-Pd was
used as the drop phase, and the drop was formed at the tip of the
syringe by forcing the solution out by using a set screw. For
interfacial tension measurements of water–iodobenzene, a reverse
needle was used because of the high density of the oil. Drop
shape analysis was performed as follows: first, a drop profile was
extracted from the drop image; second, a curve-fitting program
was used to compare the experimental drop profile with the
theoretical profile; finally, the corresponding interfacial tension
value was obtained.24
desorption/ionization time-of-flight mass spectra (MALDI-
TOFMS) were recorded on an Autoflex series MALDI-TOF
(Bruker Daltonics, USA), where 2,5-dihydroxybenzoic acid and
sinapic acid were used as the matrices. HRMS spectra were
recorded on a JMS-S3000 Spiral TOF system (JEOL, Japan)
using NaI as the calibration standard. Dynamic light scattering
(DLS) measurements were performed on a DLS-7000 instrument
(Otsuka Electronics Co., Japan) using a wavelength of 488 nm
and an Ar laser of 75 mW as the light source at 25 °C. The time-
dependent correlation function of the scattered light intensity was
measured at a scattering angle of 30°. In this study, particle size
distributions were determined by the histogram method. The
purification of products was performed by silica-gel column
chromatography using Wako gel C-200 (75–150 μm, Wako Pure
Chemical Industries Co., Japan). TLC was performed using
silica-gel 70F254 plates (Wako Pure Chemical Industries Co.,
Japan) and were visualized using UV light (254 nm) and I2. 1-
Dodecylimidazole and octaethylene glycol monomethyl ether
bromide were synthesized according to a previously reported
method.23
4.6. Light scattering measurements
The sizes of 1 and 1-Pd assemblies were evaluated by
dynamic light scattering (DLS). A DLS-7000 (Otsuka Electronics
CO., Japan) instrument was employed using a He–Ne laser
(wavelength: 633 nm) at scattering angles of 30 and 90°. The
aqueous solution was passed through a polyvinylidene difluoride
(PVDF) membrane filter (0.45 μm) three times. DLS intensity
data were processed using the instrument software for obtaining
the hydrodynamic diameter, polydispersity index, and mass
diffusion coefficient (D) of the samples. D was derived from the
decay time (c) of the intensity correlation function as D =
4.2. Synthesis of surface-active N-heterocyclic ligand 1
1-Dodecylimidazole (0.532 g, 2.25 mmol) and octaethylene
glycol monomethyl ether bromide (1.00 g, 2.24 mmol) were
added into a test tube and charged with a stir bar. The mixture
was stirred at 100 °C for 2 days. The crude product was purified
by silica-gel chromatography (Rf = 0.49, CHCl3/acetone/MeOH =
6/2/2) to afford 1 (0.930 g, 1.36 mmol, 61%). Pale yellow oil; Rf
(Et2O/CH2Cl2= 3/7) 0.43; δH (400 MHz CDC13): 10.46 (1H, s,
imidazole), 7.81 (1H, s, imidazole), 7.21 (1H, s, imidazole), 4.69
(2H, t, J 4.0 Hz, NCH2), 4.26 (2H, t, J 8.0 Hz, NCH2), 3.94 (2H,
t, J = 4.0 Hz, CH2), 3.74–3.52 (28H, m, CH2), 3.39 (3H, s, CH3),
1.90 (2H, t, J 8.0 Hz, CH2), 1.44–1.15 (18H, m, CH2), 0.87 (3H,
t, J 8.0 Hz, CH3); δC (100 MHz, CDCl3) 137.3, 123.9, 121.1,
71.8, 70.4, 70.3, (2CH2), 70.2, 69.1, 59.0, 50.0, 49.6, 31.9, 30.3,
29.6, 29.5, 29.4, 29.3, 29.0, 26.3, 22.6, 14.1; m/z (MALDI-
TOFMS) 603.46 ([M-Br]+); HRMS (MALDI-TOF): [M − Br]+,
found 603.4560. C32H63N2O8 calculated 603.4584.
2
(2kL c)−1, where kL is the scattering wave vector. The
hydrodynamic mass-diffusion coefficient D0 was obtained as the
limit of D as kL tended to zero. D0 was observed to obey the
Stokes–Einstein relation, D0 = kT/6RH, where k is the
Boltzmann constant, T is the absolute temperature, is the
viscosity of the solvent, and RH is the hydrodynamic radius.25
4.7. General procedure for the aqueous Mizoroki–Heck
reaction
NHC ligand (0.018 mmol), aryl halide (0.54 mmol), and olefin
(0.78 mmol) were added to a test tube equipped with a stir bar
and capped with a silicone septum. 600 μL of water was then
added and vortexed for several seconds. Pd(OAc)2 (4.0 mg, 0.018
mmol) and triethylamine (95 μL, 0.69 mmol) were added, and the
mixture was vigorously stirred (1200 rpm) at 70 °C. Conversion
4.3. Preparation of NHC-Pd complex 2
1
was monitored by H-NMR spectroscopy based on the signal
A 25 mL Schlenk flask was charged with palladium acetate
(22.5 mg, 0.100 mmol), 1 (136.8 mg, 0.200 mmol), 5 mL water
or THF, and a stir bar. The mixture was stirred at 45 °C for 24 h.
The volatiles were removed in vacuo, and 1-Pd was obtained as a
mixture of isomers. Brown oil; δH (400 MHz CDC13) 7.78 (1H, s,
imidazole), 7.65 (1H, s, imidazole), 7.22 (1H, s, imidazole), 7.05
(1H, s, imidazole), 7.04 (1H, s, imidazole), 4.62 (2H, m, CH2),
4.43 (2H, m, CH2), 4.26 (2H, m, CH2), 4.03 (2H, m, CH2), 3.89
(2H, m, CH2), 3.61–3.82 (52H, CH2), 3.57 (4H, t, J 8.0 Hz, CH2),
3.39 (6H, s, CH3), 1.19-1.48 (36H, CH2), 0.84–0.94 (3H, s, CH3);
intensities. After completion of the reaction, the mixture was
cooled to room temperature and filtered, and the remaining solid
was washed with ethyl acetate. After washing the ethyl acetate
with brain, the organic phase was extracted and dried over
MgSO4. The organic solvent was evaporated to obtain the crude
product. For further purification it was purified through column
chromatography (hexane/ethyl acetate).
Acknowledgments

6
Tetrahedron
ACCEPTED MANUSCRIPT
12. Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009,
This study was supported by the Ministry of Education,
109, 3612.
Culture, Sports, Science and Technology, Japan through a Grant-
in-Aid for Scientific Research for Young Scientists (B) (grant
number 26810054). We are grateful to Dr. Hiroaki Sato of our
institute for HRMS measurements.
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