Supramolecular reactor in an aqueous environment: Aromatic cross Suzuki coupling reaction at room temperature

Article abstract of DOI:10.1021/jo051398q

We have investigated supramolecular reactors for the Suzuki coupling reactions of aryl halides with phenyl boronic acids by using self-assembly of amphiphilic rod-coil molecules in aqueous solution at room temperature. All the rod-coil molecules synthesized in this work showed to self-assemble into discrete micelles consisting of aromatic rod bundles encapsulated by hydrophilic poly-(ethylene oxide) coils. We present a comparative study of rod-coil molecules' efficiency as supramolecular reactors for Suzuki coupling reaction. The closed-packed aromatic bundles play an efficient role in supramolecular reactors for the coupling reactions at room temperature. The supramolecular reactor based on hexa-p-phenylene confers unprecedented activity, allowing reactions to be performed at very low catalyst levels, without conventional heating or microwave.

Full text of DOI:10.1021/jo051398q

Supramolecular Reactor in an Aqueous Environment: Aromatic
Cross Suzuki Coupling Reaction at Room Temperature
Ja-Hyoung Ryu, Cheong-Jin Jang, Yong-Sik Yoo, Sung-Gon Lim, and Myongsoo Lee*
Center for Supramolecular Nano-Assembly and Department of Chemistry, Yonsei University,
Seoul 120-749, Korea
mslee@yonsei.ac.kr
Received July 7, 2005
We have investigated supramolecular reactors for the Suzuki coupling reactions of aryl halides
with phenyl boronic acids by using self-assembly of amphiphilic rod-coil molecules in aqueous
solution at room temperature. All the rod-coil molecules synthesized in this work showed to self-
assemble into discrete micelles consisting of aromatic rod bundles encapsulated by hydrophilic poly-
(ethylene oxide) coils. We present a comparative study of rod-coil molecules’ efficiency as
supramolecular reactors for Suzuki coupling reaction. The closed-packed aromatic bundles play
an efficient role in supramolecular reactors for the coupling reactions at room temperature. The
supramolecular reactor based on hexa-p-phenylene confers unprecedented activity, allowing
reactions to be performed at very low catalyst levels, without conventional heating or microwave.
Introduction
chemically active, the chemical reaction is much faster
than in general condition. The confinement of the reac-
tant in the hollow capsules makes very high local
concentration or the preorganization similar to the
product, which provides a microenvironment to enhance
chemical reactivity. The encapsulation of reactants within
the supramolecular cage realizes the following function-
alities such as the stabilization of intermediates,4 new
Well-ordered supramolecular materials with nanom-
eter-scale architectures have shown a variety of func-
tionalities in material science, biochemistry, and catalyst
science.1 Rational molecular design can create self-
assembled nanostructures through noncovalent intermo-
lecular forces such as hydrogen bonding, coordination
bonding, van der Waals interactions, and π-π interac-
tions.2 For example, the self-assembly of bowl-shape
molecules can lead to a capsule formation with a hollow
inner space that has a specific chemical environment
different from outside.3 Some guest molecules are encap-
sulated in the capsule and, if the guest molecules are
(2) (a) Lee, M.; Cho, B.-K.; Zin, W.-C. Chem. Rev. 2001, 101, 3869-
3892. (b) Klok, H.-A.; Lecommandoux, S. Adv. Mater. 2001, 13, 1217-
1229. (c) Stupp, S. I.; Pralle, M. U.; Tew, G. N.; Li, L.; Sayar, M.;
Zubarev, E. R. MRS Bull. 2000, 42-48. (d) Loos, K.; Munoz-Guerra,
S. Microstructure and Crystallization of Rigid-Coil Comblike Polymers
and Block Copolymers. In Supramolecular Polymers; Marcel Dekker:
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* To whom correspondence should be addressed. Fax: 82-2-393-
6096.
(1) (a) Lehn, J.-M. Supramolecular Chemistry: Concepts and Per-
spectives; VCH: Weinheim, Germany, 1995. (b) Vriezema, D. M.;
Aragone`s, M. C.; Elemans, J. A. A. W.; Cornelissen, J. J. L. M.; Rowan,
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10.1021/jo051398q CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/30/2005
8956
J. Org. Chem. 2005, 70, 8956-8962

Aromatic Cross Suzuki Coupling Reaction at r.t.
formation of conformational isomers,5 and templates
themselves.6
In a rod-coil molecular system, consisting of a flexible
coil and a rigid block, the anisotropic orientation of the
rod segments and the repulsion between the covalently
connected blocks lead to self-organization into a wide
variety of aggregation structures.7 The careful selection
of the type and relative length of the respective blocks
can give rise to a variety of the well-defined supramo-
lecular structures in nanometer-scale dimensions. An-
other interesting feature of rod-coil molecules is their
amphiphilic characteristic that shows a strong tendency
of their lipophilic and lipophobic segments to separate
in space into distinct nanodomains.8 Depending on the
solvent content and polarity, rod-coil molecules self-
assemble into different aggregated structures via mutual
interactions between block segments and solvent.
Amphiphilic rod-coil molecules based on poly(ethylene
oxide) (PEO) coils, when dissolved in an aqueous medium,
can self-organize into aggregates consisting of a rod
bundle surrounded by hydrophilic PEO chains.9 An
important property of the aggregates is the ability to
entrap solvophobic aromatic molecules through intermo-
lecular interactions including hydrophobic interactions
and π-π interactions.10 These secondary forces would
provide a nanoenvironment suitable for the confinement
of aromatic guest molecules within the rod bundle.
Accordingly, micellar aggregates of amphiphilic rod-coil
molecules based on poly(ethylene oxide) coils raise the
possibility of the use as containers for aromatic coupling
reactions in aqueous media.
FIGURE 1. CONTIN size distributions of micellar aggrega-
tions of 1 (i), 2 (ii), 3 (iii), and 4 (iv) (2 × 10-4 g/mL in H2O) in
water.
this reaction is expected to have both economical and
environmental advantages.13
In this article, we report room-temperature Suzuki
coupling reactions of aryl halides with aryl boronic acids
in an aqueous environment by using a variety of the
aromatic rod bundles as supramolecular reactors. The
amphiphilic rod-coil molecules consist of poly(ethylene
oxide) with the number of repeating units of 17 as coil
segments and rigid rods based on hexa-p-phenylene (1),
hexa-p-phenylene with dimethyl group (2), tetra-p-phe-
nylene (3), and perylene (4).
Recently, we have demonstrated that the aromatic
bundle of the micelle can be used as an efficient su-
pramolecular reactor for the Pd-catalyzed Suzuki cross
coupling reaction of a wide range of aryl halides with
phenyl boronic acids in an aqueous environment.11 The
Suzuki coupling reactions can take place within aromatic
bundles in aqueous media at room temperature because
this confined environment would lead to a highly con-
centrated reaction site that lowers the energy barrier for
the coupling reaction.12 The use of water as a solvent for
Results and Discussion
Synthesis and Characterization of Rod-Coil Mol-
ecules (1-4). The synthesis of the rod-coil molecules
consisting of poly(ethylene oxide) with the number of
repeating units of 17 and aromatic blocks is outlined in
Scheme 1. 1 and 2, with hexa-p-phenylene rod, were
synthesized from cross coupling of 7 with corresponding
boronic acids respectively and 3 was from homo coupling
of 7.11 Poly(ethylene oxide) was attached to the perylene
to give rise to compound 4. All of the resulting rod-coil
molecules were purified by silica gel column chromatog-
raphy and subsequent prep-HPLC until the polydipersity
index remained constant as described in the Experimen-
tal Section. The rod-coil molecules were characterized
(5) Timmerman, P.; Verboom, W.; van Veggel, F. C. J. M.; van
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Chem., Int. Ed. 2003, 42, 772-776. (b) Lee, M.; Jang, D.-W.; Kang,
Y.-S.; Zin, W.-C. Adv. Mater. 1999, 11, 1018-1021. (c) de Gans, B. J.;
Wiegand, S.; Zubarev, E. R.; Stupp, S. I. J. Phys. Chem. B 2002, 106,
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Soc. 2000, 122, 10201-10205.
1
by H and 13C NMR spectroscopies, elemental analysis,
MALDI-TOF mass spectroscopy, and gel-permeation
chromatography (GPC) and shown to be in full agreement
with the structures presented.
The amphiphilic molecules based on elongated rods
display aggregation behavior in aqueous media. Dynamic
light scattering study in aqueous solutions showed that
all the rod-coil molecules self-assemble into micellar
(9) (a) Wang, H.; You, W.; Yu, L.; Wang, H. H. Chem. Eur. J. 2004,
10, 986-993. (b) Kilbinger, A. F. M.; Schenning, A. P. H. J.; Goldoni,
F.; Feast, W. J.; Meijer, E. W. J. Am. Chem. Soc. 2000, 122, 1820-
1821.
(12) (a) Hof, F.; Rebek Jr, J. Proc. Natl. Acad. Sci. 2002, 99, 4775-
4777. (b) Kang, J.; Rebek, J., Jr. Nature 1997, 385, 3650-3656. (c)
Heemstra, J. M.; Moore, J. S. J. Am. Chem. Soc. 2004, 126, 1648-
1649. (d) Friedler, D.; Bergman, R. G.; Raymond, K. N. Angew. Chem.,
Int. Ed. 2004, 43, 6748-6751.
(13) (a) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64,
3384-3388. (b) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4, 2997-3000.
(c) Bumagin, N. A.; Bykov, V. V. Tetrahedron 1997, 53, 14437-14450.
(10) Tanatani, A.; Mio, M. J.; Moore, J. S. J. Am. Chem. Soc. 2001,
123, 1792-1793.
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8082-8083.
J. Org. Chem, Vol. 70, No. 22, 2005 8957

Ryu et al.
SCHEME 1. Synthesis of Rod-Coil Molecules 1-4
TABLE 1. Suzuki Cross Coupling of Aryl Halides with
Aryl Boronic Acids in Aqueous Solution at Room
Temperaturea
aggregates (Figure 1). The average hydrodynamic radii
(RH) of the aggregates were observed to be approximately
4-6 nm, suggesting that the micelles consist of hydro-
phobic disklike rod bundles encapsulated by hydrophilic
poly(ethylene oxide) coils, as proposed by rod-coil theo-
ries.14 The formation of micellar aggregates was also
confirmed by transmission electron microscopy (TEM)
experiment, which shows spherical entities (see Support-
ing Information). The micrographs show the spherical
aggregates that are roughly 10-15 nm in diameter.
These values are consistent with those from dynamic
light scattering experiments.
yield (%)b
entry
X
Y
Z
rod-coil 1
rod-coil 2
1
2
3
4
5
6
7
8
9
I
NO2
H
OCH3
NO2
H
H
OCH3
H
H
OCH3
H
H
OCH3
H
99
99
99
99
99
99
72
17
15
99
97
99
30
47
34
0
I
Suzuki Coupling Reactions Dependent on Bulki-
ness of Rod Building Block. The use of each aggregate
of different rods as supramolecular reactors in aqueous
media was investigated with a Suzuki cross coupling
reaction of aryl halides and aryl boronic acids at ambient
temperature.15 As shown in Table 1, the cross coupling
reactions of iodobenzenes with 1.2 equiv of phenylboronic
acids took place in the presence of 0.5 mol % palladium
catalyst and 2 equiv of NaOH in a 2.5 × 10-3 M aqueous
solution of rod-coil molecules to give the corresponding
products with nearly quantitative conversion after 12 h,
in both 1 and 2 (Table 1, entries 1-3). Under similar
conditions, the coupling reactions of bromobenzenes
including electron-rich and electron-deficient substrates
also underwent quantitative conversion (Table 1, entries
4-6), clearly demonstrating that the cross coupling
reaction in the presence of 1 is highly effective and allows
for the room-temperature cross coupling reaction in
aqueous media.
I
Br
Br
Br
Cl
Cl
Cl
OCH3
NO2
H
0
OCH3
0
a Reaction conditions: aryl halide (0.1 mmol), aryl boronic acid
(0.12 mmol), Pd(OAc)2 (0.5 mol %), PPh3 (1.0 mol %), NaOH (0.2
mmol), rod-coil (0.025 mmol), H2O (10 mL), stirring at room
temperature for 12 h. b Percent yields are calculated on the basis
of GC analysis using xylene as the internal standard.
electron-poor aryl chlorides, which is generally unreactive
under the conditions employed to couple aryl bromides
and aryl iodides,17,18 also proceeded under similar condi-
tions to afford the corresponding biphenyl in 72% yield
(16) The difference in packing of 1 and 2 was investigated by using
the wide-angle X-ray scattering (WAXS) experiment (see Supporting
Information). The WAXS pattern of 1 shows the inter-rod distance peak
at q ) 14.7 nm-1, while that of 2 at q ) 13.5 nm-1, indicating that the
distance between rod building blocks of 2 is longer that that of 1 in
bulk. Therefore, the packing of the rod of 2 seems to be also looser
than that of 1 in solution.
(17) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-
4211.
(18) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4, 2997-3000.
In the case of 2 based on a bulkier rod segment,16
however, the coupling reaction of bromobenzenes showed
much lower conversions. The cross coupling reaction of
(14) (a) Williams, D. R. M.; Fredrickson, G. H. Macromolecules 1992,
25, 3561-3568. (b) Halperin, A. Macromolecules 1990, 23, 2724-2731.
(15) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
8958 J. Org. Chem., Vol. 70, No. 22, 2005

Aromatic Cross Suzuki Coupling Reaction at r.t.
FIGURE 2. Emission spectra of (a) 1 and (b) 2 (2 × 10-4 g/mL in H2O) by separately adding (i) nothing, (ii) phenyl boronic acid
(0.4 mg), (iii) triphenyl phosphine (0.4 mg), and (iv) 1-bromo-4-nitrobenzene (0.4 mg). Excitation wavelength, 333 and 282 nm for
1 and 2, respectively.
FIGURE 3. Schematic representation of supramolecular reactors.
in the presence of 1, but no reactions took place in the
solution of 2 (Table 1, entries 7-9). These results indicate
that the packing of bundle-like aromatic cores within the
aggregates is likely to play a key role in the room-
temperature coupling reaction in an aqueous environ-
ment. To investigate the extent of confinement of the
aromatic substrates within the aromatic bundles, entrap-
ment was confirmed with aryl halides, boronic acids, and
triphenyl phosphine, respectively, in aqueous solution of
1 and 2 by using fluorescence spectroscopy (Figure 2).
Emission spectra of the rod-coil molecules in aqueous
solution, in the absence of the aromatic substrates,
showed a strong fluorescence with a maximum at 432
and 390 nm for 1 and 2, respectively. In great contrast,
the fluorescence intensities of the aqueous rod-coil 1
solutions containing the aromatic substrates showed to
be remarkably suppressed, demonstrating that they are
effectively entrapped within the aromatic bundle of the
micelle composed of rod-coil building blocks.19 2 solu-
tions, however, showed to be much less suppressed
(Figure 2b). This implies that the packing of the rod
building block in 1 is much denser than that of 2 in
aqueous solution. As a result, self-assembly of am-
phiphilic rod-coil molecule 1 seems to give rise to a more
efficient supramolecular reactor for the aromatic coupling
reaction (Figure 3).
Suzuki Coupling Reactions with Rods of Differ-
ent Lengths and Shapes as Supramolecular Reac-
tors. To obtain more experimental details on the influ-
ence of inter-rod interactions in supramolecular reactors,
the coupling reactions in aqueous 3 and 4 solutions are
compared with those in aqueous 1 solution. Rod-coil
molecule 3 consisting of tetra-p-phenylene rod might lead
to fewer inter-rod interactions than rod-coil molecule 1
consisting of hexa-p-phenylene rod. As shown in Table
2, both iodonitrobenzene and bromonitrobenzene with
phenyl boronic acid in aqueous solutions of 1 and 3
showed very high reactivity (Table 1, entries 1 and 4, and
Table 2, entries 1 and 3). However, the coupling reaction
of chloronitrobenzene showed quiet different results.
Molecule 1 showed a good yield, 72%; however, molecule
3 based on a shorter rod than 1 showed only 23% yield
(Table 1, entry 7, and Table 2, entry 5).
The fluorescence quenching of the rod-coil molecules
by adding an aryl halide showed to be consistent with
these results. In Figure 4, the quenching of molecule 1
consisting of a longer rod is higher than that of molecule
3. This result suggests that the longer the rod length,
the higher the extent of confinement of the substrates.
Besides rod length, the extent of confinement of the
substrates can be varied by rod shape. Rod-coil molecule
(19) Zhou, Q.; Swager, T. M. J. Am. Chem. Soc. 1995, 117, 12593-
12602.
J. Org. Chem, Vol. 70, No. 22, 2005 8959

Ryu et al.
TABLE 2. Suzuki Coupling of Aryl Halide with
Phenylboronic Acid with Rods of Different Lengths and
Shapes as Supramolecular Reactorsa
TABLE 3. Suzuki Coupling at Very Low Pd Catalyst
Loadings of 4-Bromoanisole and Phenylboronic Acid in
Water at Room Temperaturea
entry
X
rod-coil yield (%)b entry
X
rod-coil yield (%)b
entry
molecule
base
solvent yield (%)b
1
2
3
I
I
Br
3
4
3
99
99
99
4
5
6
Br
Cl
Cl
4
3
4
99
23
70
1
1
1
1
1
1
1
1
1
1
1
1
1
Li2CO3
Na2CO3
K2CO3
Cs2CO3
MgCO3
CaCO3
NH4CO3
NaHCO3
NaOAc
NaOH
KF
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
THF
51
95
78
31
45
45
0
60
32
0
33
35
0
0
0
2
3
a Reaction conditions: aryl halide (0.1 mmol), aryl boronic acid
(0.12 mmol), Pd(OAc)2 (0.5 mol %), PPh3 (1.0 mol %), NaOH (0.2
mmol), rod-coil (0.025 mmol), H2O (10 mL), stirring at room
temperature for 12 h. b Percent yields are calculated on the basis
of GC analysis using xylene as the internal standard.
4
5
6
7
8
9
10
11
12
13
14
15
CsF
K2CO3
nonionic surfactantc K2CO3
1
K2CO3
a Reaction conditions: 4-bromoanisole (0.2 mmol), phenyl bo-
ronic acid (0.24 mmol), base (0.8 mmol), molecule (0.05 mol),
Pd(PPh3)4 (200 ppb), and solvent (7 mL), stirred at room temper-
ature for 24 h. b Percent yields are calculated on the basis of GC
analysis using xylene as the internal standard. c Polyethylene-
block-poly(ethylene glycol) (Mn ) 920, 50 wt % ethylene oxide).
substrates might be held in enforced proximity to each
other. As a result, this constrained environment would
lead to a highly concentrated reaction site that lowers
the energy barrier for the Suzuki aromatic coupling
reaction as described earlier. In consideration of these
facts, the use of the aggregate as a supramolecular
reactor in aqueous media at very low catalyst loading was
investigated with a Suzuki cross coupling reaction of aryl
halides and aryl boronic acids at ambient temperature.
Remarkably, the cross coupling reaction of 4-bromoani-
sole with 1.3 equiv of aryl boronic acid took place in the
presence of 4 equiv of Na2CO3 and 2 wt % of aqueous
solution of 1 with 200 ppb Pd catalyst to give the
corresponding product with nearly quantitative conver-
sion after 24 h (Table 3, entry 2). However, sodium
carbonate in the concentrations used in our experiments
included palladium with a concentration of about 50 ppb
(induced coupled plasma mass (ICP-mass) spectroscopy
result), and then instead of Na2CO3, potassium carbonate
without Pd trace was used as a base to yield 78% (Table
3, entry 3). When a variety of bases, of the group 1 metal
carbonates, were screened, only Na2CO3 and K2CO3
resulted in acceptable yields of product (Table 3, entries
2 and 3), and Li2CO3 and Cs2CO3 showed moderate yields
(Table 3, entries 1 and 4). Group 2 metal carbonates also
showed moderate yield (Table 3, entries 5 and 6), but
organic carbonate NH4CO3 showed to be inactive (Table
3, entry 7). These results suggest that the cation of the
base is important in this reaction, sodium and potassium
being particularly good. To investigate this effect more,
we performed the reaction by using other sodium- or
potassium-containing bases. In the presence of NaOH
(Table 3, entry 10), reaction did not occur, different from
the 0.5 mol % Pd-catalyzed coupling reaction in a
supramolecular reactor,11 and NaHCO3, NaOAc, and KF
showed low yields (Table 3, entries 8, 9, and 11),
indicating that anion also is critical in the reaction. In
the case of CsF, which has similar basicity, we also
FIGURE 4. Emission spectra of 3 and 1 (2 × 10-4 g/mL in
H2O) by adding (a) and (b) none and (c) and (d) 1-bromo-4-
nitrobenzene (0.4 mg), respectively. Excitation wavelength, 308
and 333 nm for 3 and 1, respectively.
4 consisting of a perylene rod that enabled strong rod-
to-rod interaction showed good yields for the coupling
reaction of chloronitrobezene as well as iodonitrobenzene
and bromonitrobenzene with phenyl boronic acid (Table
2, entries 2, 4, and 6)
Suzuki Coupling Reactions at Very Low Catalyst
Loadings. The coupling reaction with loading of low
catalytic amount has advantages not only to reduce costs
but also to minimize the effort required for the removal
of catalytic metal from the final product. Leadbeater and
Marco reported a Suzuki-type coupling of a range of aryl
halides with phenylboronic acid in water in the presence
of tetrabutylammonium bromide (TBAB) without transi-
tion-metal catalyst, by using microwave heating.20 How-
ever, their work was reassessed in their recent paper that
commercially available Na2CO3 used as a base of the
coupling reaction includes a small amount of palladium.21
This observation together with our previous result mo-
tivated us to envisage that Suzuki coupling reactions can
take place within aromatic bundles in aqueous media at
very low catalyst loading. Within the confined environ-
ment of the aromatic core of the micelle, the aromatic
(20) (a) Leadbeater, N. E.; Marco, M. Angew. Chem., Int. Ed. 2003,
42, 1407-1409. (b) Leadbeater, N. E.; Macro, M. J. Org. Chem. 2003,
68, 5660-5667.
(21) Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams, V. A.;
Granados, P.; Singer, R. D. J. Org. Chem. 2005, 70, 161-168.
8960 J. Org. Chem., Vol. 70, No. 22, 2005

Aromatic Cross Suzuki Coupling Reaction at r.t.
TABLE 4. Suzuki Coupling of Aryl Halides and Aryl
Boronic Acids at Very Low Pd Catalyst Loadings in
Water at Room Temperaturea
a para-substituent provided lower yields compared with
their bromo counterparts (Table 4, entries 10 and 12).
Aryl chlorides were not coupled with phenyl boronic acids
(Table 4, entries 13-14), which is consistent with the
results reported previously.20 These results indicate
clearly that amphiphilic rod-coil systems are well-suited
as a supramolecular reactor for aromatic coupling in an
aqueous environment at room temperature even in the
presence of only trace amounts of Pd.
Conclusion
We have demonstrated that self-assembly of am-
phiphilic rod-coil molecules in an aqueous solution can
be used as supramolecular reactors for the room-tem-
perature Suzuki coupling of a wide range of aryl halides
including even aryl chlorides with phenyl boronic acids,
giving rise to an environmentally friendly reaction sys-
tem. When extended rod segments without side groups
are used as a reaction template, the coupling reactions
can be conducted in excellent yields, indicating that the
packing of aromatic segments within aggregates is likely
to play a key role in the room-temperature coupling
reaction in an aqueous environment. Therefore, a well-
designed rod-coil molecule that enabled strong inter-rod
interactions can give rise to an efficient supramolecular
reactor. Interestingly, at very low Pd loadings coupling
reactions occur, without conventional heating or micro-
wave, at room temperature for a wide range of aryl
halides. These observations highlight the ability of su-
pramolecular rod bundles to provide confined space for
the aromatic substrates of the Suzuki cross coupling
reaction. We believe that this supramolecular approach
to a reactor in an aqueous environment will be broadly
applicable to a wide variety of catalytic chemical reac-
tions.
a Reaction conditions: aryl halide (0.2 mmol), aryl boronic acid
(0.24 mmol), K2CO3 (0.8 mmol), 1 (0.05 mmol), Pd(PPh3)4 (200
ppb), and H2O (7 mL), stirred at room temperature for 24 h.
b Percent yields are calculated on the basis of GC analysis using
xylene as the internal standard. c Reaction using 4-methoxy
benzeneboronic acid as the coupling partner.
obtained a low yield (Table 3, entry 12). These effects of
base species are well matched with the results reported
previously.20 However, no reaction took place under the
aforementioned reaction conditions without 1 (Table 3,
entry 13) or in the presence of a conventional nonionic
surfactant (Table 3, entry 14). In addition, the reaction
did not proceed with the use of tetrahydrofuran (THF)
as a solvent (Table 3, entry 15) in which 1 showed a lack
of aggregation behavior. Based on these results, it can
be concluded that the presence of a bundle-like aromatic
core of the aggregates plays a key role in the room-
temperature cross coupling reaction with very low transi-
tion-metal catalysts in an aqueous environment.
The representative results of the room-temperature
cross coupling reaction with a wide range of aryl halides
at very low palladium catalyst loading in water are
summarized in Table 4. K2CO3 with Pd free was used as
a base. The reactions of various aryl bromides including
electron-rich and electron-deficient substrates proceeded
readily and a variety of functional groups were tolerated
in the reaction (Table 4, entries 1-9). To show that the
reaction is regiospecific with respect to both the aryl
bromide and the boronic acid, we screened the reaction
of aryl bromides with 4-methoxybenzeneboronic acid and
obtained the corresponding product in good yields (Table
4, entries 2 and 4). Furthermore, sterically demanding
2-bromotoluene could be coupled with phenylboronic acid
to give moderate yield of product compared with 4-bro-
motoluene (Table 4, entry 6). The coupling reaction of
iodobenzene also proceeded under the same reaction
condition to afford the corresponding biphenyl in 81%
yield (Table 4, entry 11). Interestingly, aryl iodides with
Experimental Section
Materials. All starting materials were obtained from com-
mercial suppliers and were used without purification. All
atmosphere-sensitive reactions were done under nitrogen.
Flash column chromatography was carried out with silica gel
(230-400 mesh). Molecules 1 and 7 were synthesized according
to a previous procedure.11 Compounds were synthesized ac-
cording to the procedure described in Scheme 1 and purified
by silica gel column chromatography and then prep-HPLC
until the transition temperature and polydispersity index
remained constant.
Techniques. Molecular weight distributions (Mw/Mn) were
determined by gel permeation chromatography (GPC). Mea-
surements were made by using an UV detector, CHCl3 as a
solvent (1.0 mL min-1), and a calibration plot constructed with
polystyrene standards. The dynamic laser light scattering
experiments were performed with an aqueous solution of rod-
coil molecule (2 × 10-4 g/mL) at a scattering angle of 90°. The
transmission electron microscope (TEM) was performed at 120
kV. A drop of aqueous solution of rod-coil molecule (2 × 10-4
g/ mL) was placed onto a carbon-coated copper grid and dried
at room temperature.
Synthesis. The synthetic procedures used in the prepara-
tion of the compounds are described in Scheme 1.
Synthesis of 2. Compound 7 (4.0 g, 4.08 mmol) and 3,3′-
dimethyl-4,4′-biphenyldiboronic acid (0.50 g, 1.85 mmol) were
dissolved in degassed THF (70 mL). Degassed 2 M aqueous
Na2CO3 (70 mL) was added to the solution and then tetrakis-
(triphenylphosphine) palladium(0) (22 mg, 0.018 mmol) was
added. The mixture was heated at reflux for 48 h with vigorous
J. Org. Chem, Vol. 70, No. 22, 2005 8961

Ryu et al.
stirring under nitrogen. Cooled to room temperature, the
layers were separated, and the aqueous layer was then washed
twice with methylene chloride. The combined organic layer was
dried over anhydrous magnesium sulfate and filtered. The
solvent was removed in a rotary evaporator, and the crude
product was purified by column chromatography (silica gel)
using methlylene chloride: methanol (8:1 v/v) as eluent to yield
1.8 g (48.6%) of a waxy solid. 1H NMR (250 MHz, CDCl3,
ppm): δ 7.75-7.57 (m, 18H), 7.00 (d, 4H, J ) 8.7 Hz), 4.18 (t,
4H, J ) 4.9 Hz), 3.89-3.52 (m, 132H), 3.36 (s, 6H), 2.43 (s,
6H). 13C NMR (250 MHz, CDCl3, ppm): δ 158.5, 139.8, 139.5,
128.0, 127.4, 127.3, 115.0, 77.6, 77.1, 76.6, 71.9, 70.8, 70.6, 69.7,
67.5, 59.0, 14.6. Mn/Mw ) 1.06 (GPC). Anal. Calcd for
Hz, 4H), 3.77-3.59 (m, 132H), 3.47 (s, 6H). 13C NMR (250
MHz, CDCl3, ppm): δ 162.7, 133.7, 131.2, 123.9, 122.1, 77.6,
77.1, 76.6, 71.9, 70.8, 69.7, 67.5, 59.0. Mn/Mw ) 1.04 (GPC).
Anal. Calcd for C94H150N2O38: C, 58.92; H, 7.89; N, 1.46.
Found: C, 58.91; H, 7.90; N, 1.45.
General Procedure for Cross Coupling Reaction in
Water. Aryl halide (0.1 mmol), aryl boronic acid (0.12 mmol),
base (0.4 mmol), PPh3 (0.001 mmol, 1.0 mol %), and Pd(OAc)2
(0.0005 mmol, 0.5 mol %) were added to the solution of rod-
coil molecule (50 mg) in water (10 mL). The reaction mixture
was stirred at room temperature for 24 h. The product was
extracted with methylene chloride, washed with brine, and
dried over anhydrous magnesium sulfate. The solvent was
then removed in a rotary evaporator, and the residue was
filtered by column chromatography (silica gel) using methylene
chloride: hexane (1:1 v/v) as eluent. The yield of the reaction
was determined by GC-MASS analysis.
General Procedure for Cross Coupling Reaction in
Water at Low Pd Loadings. Aryl halide (0.2 mmol), aryl
boronic acid (0.24 mmol), base (0.8 mmol), and Pd(PPh3)4 (200
ppb) were added to the solution of 1 (0.05 mmol) in water (7
mL). The reaction mixture was stirred at room temperature
for 24 h. The product was extracted with methylene chloride,
washed with brine, and dried over anhydrous magnesium
sulfate. The solvent was then removed in a rotary evaporator,
and the residue was purified by column chromatography (silica
gel) using methylene chloride: hexane (1:1 v/v) as eluent.
GC-MS Analysis. Reference samples of the substrate,
product, byproducts, and xylene (internal standard) with
known concentrations were injected to identify the retention
time and response factor. Individual response factors [area
(product) × mg (standard)/area (standard) × mg (product)]
were determined for all products by GC analysis. Determina-
tion of the ratio of the area of each product to the area of xylene
obtained from GC run of the reaction mixture allowed calcula-
tion of the percent yields. Temperature program: 100 °C for
3 min and then 30 °C/min to 280 °C. Apart from comparing
the product and byproduct peaks to the standard (xylene)
peaks under identical conditions, their authenticity was
further confirmed by comparing their mass spectra with those
of the actual compound in the spectral library.
C108H170O36: C, 63.45; H, 8.38. Found: C, 63.44; H, 8.37.
Synthesis of 3. A mixture of compound 7 (4.0 g, 4.0 mmol),
TDAE (1.6 g, 8.0 mmol), and PdCl2(PhCN)2 (0.08 g, 0.2 mmol)
in DMF (50 mL) was heated at 50 °C for 4 h. Cooled to room
temperature, the layers were separated, and the aqueous layer
was then washed twice with methylene chloride. The combined
organic layer was dried over anhydrous magnesium sulfate
and filtered. The solvent was removed in a rotary evaporator,
and the crude product was purified by column chromatography
(silica gel) using methylene chloride: methanol (8:1 v/v) as
eluent to yield 2.1 g (54.8%) of a white solid. 1H NMR (250
MHz, CDCl3, ppm): δ 7.51-7.67 (m, 12H), 6.93-6.95 (d, 4H,
J ) 8.5 Hz), 4.12-4.14 (t, 4H, J ) 5.0 Hz), 3.53-3.75 (m,
132H), 3.36 (s, 6H). 13C NMR (250 MHz, CDCl3, ppm): δ 158.5,
139.8, 139.5, 128.0, 127.4, 127.3, 115.0, 77.6, 77.1, 76.6, 71.9,
70.8, 70.6, 69.7, 67.5, 59.0. Mn/Mw ) 1.07 (GPC). Anal. Calcd
for C94H158O36: C, 60.56; H, 8.54. Found: C, 60.56; H, 8.50.
Synthesis of 5. A solution of ROTs (4.5 g, 0.9 mmol) and
sodium azide (2.9 g, 4.5 mmol) in 50 mL of acetonitrile was
heated under reflux at 100 °C for 36 h. After cooling to room
temperature, 100 mL of water was added and the mixture was
extracted with methylene chloride. The organic layer was then
dried on MgSO4 and concentrated. A slightly yellow-brown oil
was chromatographed on silica gel column and eluted with
CH2Cl2/MeOH (10:1 v/v). Pure product was obtained as oil, 3.4
1
g (81% yield). H NMR (250 MHz, CDCl3, ppm): δ 3.77-3.59
(m, 66H), 3.40 (t, 2H, J ) 5.0 Hz), 3.37 (s, 3H).
Synthesis of 6. 5 (2.7 g, 7.4 mmol), triphenylphosphine (2.3
g, 9.0 mmol), and water (540 mg, 11 mmol) were mixed with
20 mL of THF. After the solution was stirred for 6 h at room
temperature, the solvent was eliminated under reduced pres-
sure and the residue was loaded on a silica gel column; the
product was eluted with CHCl3/CH3OH/Et3N (3:3:1). The pure
product was obtained as oil, 2 g (80% yield). 1H NMR (250
MHz, CDCl3, ppm): δ 3.77-3.59 (m, 66H), 3.40 (s, 3H), 2.82
(t, 2H, J ) 5.0 Hz).
ICP-Mass Analysis. We screened elements such as Pd, Ni,
Co, Cr, Cu, Mn, Pt, Ru, Se, and Zn. The reaction mixture was
analyzed three times and averaged.
Acknowledgment. We gratefully acknowledge the
National Creative Research Initiative Program of the
Korean Ministry of Science and Technology.
Synthesis of 4. 6 (0.7 g, 2.6 mmol) and 3,4,9,10-perylene-
tetracarboxylic anhydride (0.39 g, 1.0 mmol) were added to a
mixture of 50 mL of propan-1-ol and 25 mL of water. The
reaction mixture was stirred under argon at 100 °C for 16 h.
After the solution was chilled, a mixture of popan-1-ol and
water was removed by distillation and the crude product was
purified by column chromatography with CH2Cl2/MeOH (20:1
v/v) as an eluent and by preparative HPLC to yield 0.76 g
(76%) of a red solid. 1H NMR (250 MHz, CDCl3, ppm): δ 8.56
(d, 4H, J ) 8.1 Hz), 8.48 (d, 4H, J ) 8.1 Hz), 4.32 (t, J ) 5.7
Supporting Information Available: General method for
fluorescence measurement, TEM data, the wide-angle X-ray
scattering data, NMR data, and MALDI-TOF mass data. This
material is available free of charge via the Internet at http://
pubs.acs.org. This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
JO051398Q
8962 J. Org. Chem., Vol. 70, No. 22, 2005