A cycloalkane-based thermomorphic system for palladium-catalyzed cross-coupling reactions

Article abstract of DOI:10.1016/j.tet.2008.01.034

In this paper, we describe a practical and efficient protocol for Sonogashira, Suzuki-Miyaura, and Mizoroki-Heck cross-coupling using a CBT system. The use of substrates with cycloalkane-soluble tags facilitates separation of the desired products and the

Full text of DOI:10.1016/j.tet.2008.01.034

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2855e2863
www.elsevier.com/locate/tet
A cycloalkane-based thermomorphic system for palladium-
catalyzed cross-coupling reactions
*
Shokaku Kim, Keisuke Yamamoto, Kanako Hayashi, Kazuhiro Chiba
Laboratory of Bio-organic Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
Received 16 December 2007; received in revised form 9 January 2008; accepted 9 January 2008
Available online 13 January 2008
Abstract
In this paper, we describe a practical and efficient protocol for Sonogashira, SuzukieMiyaura, and MizorokieHeck cross-coupling using
a CBT system. The use of substrates with cycloalkane-soluble tags facilitates separation of the desired products and the homogeneous Pd catalyst
via simple liquideliquid extraction, thereby eliminating the need for a catalyst removal process.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
course of our investigations of thermomorphic systems, we
found that cycloalkanes (especially cyclohexanes) show ther-
mosensitive phase transitions with a wide variety of typical
polar organic solvents under moderate conditions (Fig. 1).5
This system, which utilizes selective separation of tagged
products from the reaction mixture into the cycloalkane phase,
is expected to be highly useful for parallel synthesis and the
construction of combinatorial libraries, and results in high re-
activity even when tagged substrates and insoluble catalysts
are used. In addition, highly selective formation of separable
phase-tagged products confers a significant advantage in terms
of monitoring the reaction progress and identification of
products.
Solution-phase tag-assisted organic synthesis is being de-
veloped as a useful alternative to the classical heterogeneous
resin-supported and combinatorial methodologies.1,2 Efforts
to design phase tags based on solid-phase extraction (SPE)
have led to investigation of the effects of high reactivity of
the soluble species and the possibility of using routine analy-
tical methods (NMR, TLC, MS, etc.) to monitor the reaction
process and directly determine the structures of products,
even when they are attached to liquid-phase tags. In particular,
hydrophobic phase-tagging strategies based on SPE using C18
silica have been recognized as useful methods which result in
effective generation of target products.3 While most proce-
dures for recovery of target molecules emphasize SPE,
liquideliquid extraction (LLE) may also have broad potential,
because suitably phase-tagged compounds in a biphasic
system often show particular affinity for one phase without
further supports.
The scope of Pd-catalyzed reactions in cycloalkane-based
thermomorphic (CBT) systems has thus far been mostly
Cycloalkanes
Cycloalkane-soluble
A recent study by Bergbreiter and co-workers opened the
door to the use of thermomorphic systems, which can be
applied in the form of a recyclable catalytic system in palla-
dium-catalyzed cross-coupling and other reactions.4 In the
heating
cooling
phase tag
Reagent, catalyst
Spatial
separation
Homogeneous
distribution
* Corresponding author. Tel.: þ81 42 367 5667; fax: þ81 42 360 7167.
E-mail address: chiba@cc.tuat.ac.jp (K. Chiba).
Figure 1. Schematic view of a CBT system.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.034

2856
S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
limited to the cycloalkane phase tag-linked aryl halides via es-
ters bond.5b In addition, synthetic application of the hydropho-
bic products has not been reported, although the CBT process
can facilitate continuous multi-step synthesis toward further
chemical modification. In this paper, we describe the applica-
tion of the CBT system in Sonogashira, MizorokieHeck, and
SuzukieMiyaura reactions as typical examples of Pd-cata-
lyzed cross-coupling reactions. Furthermore, we demonstrate
the synthetic application of a phase-tagged product containing
an internal alkyne group.
tags, were dissolved almost quantitatively in the cyclohexane
layer and obtained in highly-pure-form. In addition, the prod-
uct was monitored as a single TLC spot and identified using
1H NMR and mass spectroscopy without cleavage of the hy-
drophobic tag. In this CBT system, it was found that palladium
complex stayed mainly in the DMF section of the biphase (es-
timated from ICP-MS: less than 0.04% leaching of Pd into the
cyclohexane phase), while almost all of the tagged product
remained in the cycloalkane phase.
It is noteworthy that the CBT system employing a cycloal-
kane-soluble carrier may facilitate the construction of chemi-
cal libraries upon optimization of the reaction conditions.
Because the reaction components are homogeneously distrib-
uted in the mono-phase, hydrophobic substrates in cHex are
allowed to interact effectively with DMF-soluble alkynes, Pd
catalysts, and bases to give hydrophobic products that may
be separated into the cHex phase. It was found to be difficult
to complete these reactions under conventional monophasic
conditions, even in biphasic solutions composed of n-alkanes
and typical polar solvents. Obviously, effective mutual misci-
bility of the co-solvents plays a significant role in the reaction
of the phase-tagged substrate with the insoluble catalyst. After
completion of the reaction, the soluble tag allows spatial sep-
aration of the products from the mixture of catalyst and base.
It is generally difficult to extract low-molecular-weight com-
pounds quantitatively from DMF solution in a single run of
liquideliquid extraction because of the high solubility of polar
and even less polar compounds in DMF. It is expected that the
ability to carry out a single LLE manipulation via the CBT
process will effectively facilitate sequential reaction and puri-
fication steps, which should ensure its usefulness in the reali-
zation of continuous flow or multi-step processes.
In an attempt to further accelerate the CBT process, Sono-
gashira cross-coupling in cHex/DMF was attempted under mi-
crowave irradiation; the results are outlined in Table 2.6 Using
microwave heating at 100 W (100 ꢀC), all reactions were com-
pleted within 20 min. Combining the CBT system with micro-
wave irradiation had a positive effect in terms of acceleration
of the targeted reactions. The reaction of hydrophobic aryl
halides with terminal alkynes proceeded smoothly to give the
corresponding products in the cyclohexane phase, as occurred
under conventional heating conditions. Thus, the microwave-
assisted CBT reaction system allows for further acceleration
of Sonogashira cross-coupling reactions in monophasic solu-
tion followed by product isolation in biphase upon cooling.
Next, we attempted the synthetic application of one of the
products obtained from the CBT reaction, 2-(phenylethynyl)-
benzoate ester 5f. Treatment of 5f with iodide as an electro-
philic reagent in dichloromethane afforded the corresponding
isocoumarin derivative 6 in good yield, as shown in Scheme
3. Addition of MeOH followed by ODS-filtration allows re-
moval of the hydrophobic phase tag from the reaction mixture,
because phase tags within a certain range of molecular weight
and hydrophobicity can easily be precipitated with polar sol-
vents. Alternatively, treatment of 3f with a catalytic amount
of NaOMe in cHex/MeOH solution, followed by neutraliza-
tion with DOWEX, gave the methyl ester 7 in the MeOH
2. Results and discussion
Initially, we prepared hydrophobic aryl halides 3aed in
a cyclohexane/DMF media system. As shown in Scheme 1,
4-iodophenol was successfully attached to 3,4,5-trisoctadecyl-
oxy-benzyl bromide 1 in cHex/DMF in the presence of
K2CO3. Treatment of cycloalkane-soluble alcohol 2 with var-
ious benzoic acids using N,N0-diisopropylcarbodiimide (DIC)
as a coupling reagent in the presence of a catalytic amount
of N,N-dimethylaminopyridine (DMAP) gave the correspond-
ing product in excellent yield (Scheme 2).
OC18H37
+
OH
C18H37
C18H37
O
O
O
K2CO3
cHex
DMF
I
3a
Br
I
1
l
= 3,4,5-tris(octadecyloxy)benzy
Scheme 1. Loading of aryl halides to cycloalkane-soluble phase tag 1.
O
X
K2CO3
OH +
O
cHex
DMF
X
2
CO2H
3b;X=4-iodo, c; X=3-methyl-4-iodo
d;X=2-iodo
Scheme 2. Loading of aryl halides to cycloalkane-soluble phase tag 2.
2.1. Sonogashira reaction with hydrophobically tagged
alkene and aryl halides in a CBT system
In order to facilitate the construction of hydrophobic prod-
uct libraries in the cycloalkane phase, we examined Sonoga-
shira cross-coupling in a cHex/DMF system using substrates
3aed prepared under conventional heating conditions. The
hydrophobic aryl halides were allowed to react with terminal
alkynes in the presence of triethylamine (TEA) and 2 mol %
Pd(PPh3)2Cl2. The results are summarized in Table 1: the
cross-coupling reactions proceeded successfully to form the
corresponding products in excellent yields. Aromatic (4a and
b) and aliphatic (4cee) alkynes were successfully coupled
with electron-rich (Table 1, entries 1 and 2) and electron-defi-
cient (entries 3e5) aryl iodides. The reaction of sterically hin-
dered ortho-substituted aryl iodide 3d also proceeded
successfully. The desired products, with cyclohexane-soluble

S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
2857
Table 1
A CBT system for palladium-catalyzed Sonogashira cross-coupling reactionsa
Pd(PPh3)2Cl2
CuI, TEA
X
X
reflux, 6 h
+
R
Y
R
cHex
DMF
4a; R=Ph
3a; X=O, Y=4-I
4b; R=4-MeOPh
4c; R=(CH2)3OH
4d; R=(CH2)2OH
4e; R=TMS
5
3b; X=COO, Y=4-I
3c; X=COO, Y=4-I, 3-Me
3d; X=COO, Y=2-I
Entry
1c
Substrates
Productb
Entry
6
Substrates
Productb
O
3a/4a
3d/4a
O
O
5a (95%)
5f (98%)
OMe
OH
O
OMe
2
3
4
3a/4b
3b/4b
7
8
9
3d/4b
3d/4d
3d/4e
O
5b (98%)
O
5g (94%)
O
OMe
O
O
5c (97%)
O
5h (89%)
TMS
O
OH
3c/4c
3c/4d
O
O
O
5d (91%)
5i (98%)
O
O
OH
5
5e (99%)
a
All reactions were carried out using aryl halides 3aed, 1.5 equiv of alkyne, 3 equiv of TEA, CuI (1 mol %), and 2 mol % of Pd(PPh3)2Cl2 in cHex/DMF.
Isolated yield.
Reusability of the recovered Pd catalyst was also tested; see Section 4.
b
c
Table 2
A CBT system for palladium-catalyzed Sonogashira cross-coupling reactions
under the microwave-irradiated conditiona
phase and compound 2 in the cHex layer. In this case, com-
pound 2 was easily removed from reaction media and was
recyclable after cleavage via a simple liquideliquid extraction
process.
Entry
Product
Reaction time (min)
Yieldb (%)
1
2
3
4
5
a
5a
5b
5c
5d
5f
15
20
10
20
10
97
95
99
99
94
2.2. MizorokieHeck reaction with hydrophobically tagged
alkene and aryl halides in the CBT system
Encouraged by the excellent results described above, we
were keen to develop this methodology for use with another
palladium-mediated CeC bond-formation reaction, the Miz-
orokieHeck coupling reaction. We carried out coupling of ac-
rylate with aryl iodides in the same CBT solution. In a typical
reaction, 0.5 mmol of acrylate 8 in 3 mL of a cHex/DMF sol-
vent mixture was treated with 1.5 equiv of aryl iodide at 60 ꢀC
for 3 h under conventional heating conditions in the presence
of 3 equiv of triethylamine and 2 mol % of a palladium cata-
lyst, tris(dibenzylideneacetone)dipalladium [Pd2(dba)3]. The
results are shown in Scheme 4. The use of 4-methoxyiodobenz-
ene 9a, 4-iodoacetophenone 9b, and iodobenzene 9c gave
yields of 96, 99, and 98%, respectively. As expected, the
coupling reaction also proceeded successfully using a micro-
wave-assisted CBT system, giving the products in excellent
yields.
Reaction conditions: PdCl2(PPh3)2 (2 mol %), alkyne (1.5 equiv), TEA
(3 equiv). Microwave irradiation 100 W, 100 ꢀC.
b
Isolated yield.
I
I2
CH2Cl2
O
O
O
5f
O
6
NaOMe
cHex/MeOH
MeO
O
7
Scheme 3. The synthetic application of the separable phase-tagged product 5f
containing an internal alkyne group.

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S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
O
S
O
Pd catalyst
O
Pd catalyst
60 °C, 3 h
11
8
O
3b
MCH
DMF
I
O
cHex
DMF
R
O
13
R
10a: R=OMe (96%)
10b: R=Ac (99%)
10c: R=H (98%)
Y.=89%
9a
: R=OMe
9b: R=Ac
9c: R=H
S
3d
Scheme 4. MizorokieHeck reactions of aryl iodides 9aec in a CBT system.
O
2.3. SuzukieMiyaura cross-coupling reaction with
a cycloalkane-soluble phase-tagged boronic acid
in the CBT system
Y.=97%
O
14
Scheme 5. SuzukieMiyaura cross-coupling of both cycloalkane-soluble
phase-tagged substrates in a CBT system.
In our previous letter, we reported a general method for
microwave-promoted SuzukieMiyaura cross-coupling of aryl
halides attached to a cycloalkane-soluble tag with arylboronic
acids in a CBT system.5b We then turned our attention to de-
signing a hydrophobic tag for boronic acid to allow reaction
with aryl halides. Thus, we synthesized the boronic acid deriv-
ative 11, which was found to be an excellent coupling partner
in the reaction. The results of coupling reactions between the
hydrophobically tagged boronic acid and various aryl halides
are shown in Table 3. The target coupling reaction of the
hydrophobically tagged boronic acid 11 with aryl halides
also proceeded in excellent yield in a microwave-assisted
CBT system. These results indicated that selective tagging
onto boronic acid derivatives or aryl halides can facilitate
the construction of widely ranging cross-coupling product
libraries.
described previously. As shown in Scheme 5, the target reac-
tions between 11 and each of the cycloalkane-soluble tags
proceeded to afford double-tagged products in good yield,
although reaction with tagged substrates in the solid phase is
generally difficult. We attribute these results to the fact that
the mutual miscibility of DMF (catalyst phase) and cHex
(tag-soluble phase) and the affinity of the tagged substrates
in the CBT solution play significant roles in the coupling reac-
tion. In addition, it is expected that this reaction system will
provide a facility for constructing various useful cycloal-
kane-soluble tags.
Finally, we attempted to decrease the quantity of DMF used
in the reaction. Decreasing the volume of the lower phase (DMF
phase) was found to lead to an increase in productivity. Our ob-
jective was to determine the minimum amount of DMF required
to give the coupling products in good yield. To find this, we
carried out the reaction of aryl halide 3b and p-fluorophenyl
boronic acid in DMF/CH solvent mixtures with various ratios.
As shown in Figure 2, we found that it was possible to
reduce the amount of DMF to 5% of the solvent medium.
The quantity used can be further reduced to 1% with a signifi-
cant decrease in product yield. In the absence of DMF, the
In order to investigate the effects of interaction between
two types of cycloalkane-soluble tag in the CBT reaction sys-
tem, we prepared two hydrophobically tagged substrates and
carried out the coupling reaction under the conditions
Table 3
Microwave-promoted SuzukieMiyaura cross-couplings of aryl halides with
cycloalkane-soluble phase-tagged boronic acid 11a
O
R
B(OH)2
O
3b
+
B(OH)2
cHex
DMF
F
Pd catalyst
S
S
MCH
DMF
F
12a-e
11
100
Entry
1
Aryl halide
Product
Yieldb (%)
86
80
60
40
20
0
Br
12a: R¼CO2Me
12b: R¼NO2
MeO2C
Br
2
3
92
O2N
Br
I
12c: R¼CN
12d: R¼Ac
97
99
NC
Ac
4
0/100
1/99
5/95
10/90
cHex/DMF(v/v)
50/50
75/25
100/0
a
Reaction conditions: 0.5 mmol of boronic acid, 1.5 equiv of aryl halide,
3.0 equiv of K3PO4, and 3 mL of methylcyclohexane (MCH)/DMF (1:1).
Microwave power 150 W, 100 ꢀC, 5 min.
Figure 2. Effects of volume ratio of each phase on microwave-promoted
SuzukieMiyaura coupling of aryl bromide 3b and p-fluorophenyl boronic acid.
b
Isolated yield.

S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
2859
biaryl product was obtained in only 26% yield. The use of more
than 5% DMF resulted in quantitative yield. Similar observa-
tions were made for the reaction as carried out under conven-
tional heating conditions. To find out whether the use of
a cycloalkane in the reaction had a deleterious effect on product
yield, we monitored the conversion rate for the biaryl product
using DMF and 20% cHex/DMF, respectively, under micro-
wave conditions, and found that the conversion rates obtained
in both cases were almost the same. This result suggests that
the addition of cycloalkane to the reaction medium has no del-
eterious effect on the coupling reaction. The system is therefore
advantageous in terms of productivity (volume efficiency of the
tagged products) and also diminishes the requirement for the
cumbersome refreshment process of polar organic solvents
such as DMF, which contain catalyst, base, and other chemicals.
dimethylaminopyridine (0.2 mmol) in 3 mL of DMF were
added to the cycloalkane-soluble platform (914 mg,
1.0 mmol) dissolved in 3 mL of cyclohexane, and the reaction
mixture was stirred at 55 ꢀC for 1 h. After cooling, the cyclo-
hexane layer was separated and evaporated under vacuum.
Methanol was added to the residue, followed by filtration to
afford the compounds 3b (98%), 3c (99%), and 3d (99%).
4.2.1. 3,4,5-Tris(octadecyloxy)benzyl 4-iodobenzoate (3b)
1H NMR (400 MHz, CDCl3): d 7.80 (d, 2H, J¼8.63 Hz),
7.76 (d, 2H, J¼8.63 Hz), 6.60 (s, 2H), 5.23 (s, 2H), 3.99e
3.92 (m, 6H), 1.84e1.71 (m, 6H), 1.48e1.25 (m, 90H), 0.88
(t, 9H, J¼6.79 Hz). 13C NMR (100 MHz, CDCl3): d 165.8,
153.2, 138.2, 137.6, 131.1, 130.5, 129.5, 107.0, 73.4, 69.2,
67.4, 31.9, 30.4, 29.8, 29.7, 29.5, 29.4, 26.2, 22.8, 14.1.
TOF-MS (pos) calcd for C68H119IO5 [MþNaþ] 1165.8000,
found 1165.7965.
3. Conclusions
We have developed a practical and efficient protocol for So-
nogashira, SuzukieMiyaura, and MizorokieHeck cross-cou-
pling reactions using a CBT system. The use of substrates
with cycloalkane-soluble tags facilitates separation of the
desired products and the Pd catalyst via simple liquideliquid
extraction, thereby eliminating the need for a cumbersome
process to remove the homogeneous catalyst. In this reaction
system, there was no observable phosphorus or palladium in
the cycloalkane phase after the separation process. In addition,
the catalyst phase (DMF) can be recycled at least three times
without any significant loss of activity. It may be possible to
apply this CBT system in various Pd-catalyzed reactions,
allowing for their use in a parallel or combinatorial format.
4.2.2. 3,4,5-Tris(octadecyloxy)benzyl 4-iodo-3-
methylbenzoate (3c)
1H NMR (400 MHz, CDCl3): d 8.48 (d, 1H, J¼1.4 Hz),
7.93 (dd, 1H, J¼8.0, 1.4 Hz), 7.29 (d, 1H, J¼8.0 Hz), 6.61
(s, 2H), 5.23 (s, 2H), 3.97 (m, 6H), 2.48 (s, 3H), 1.85e1.20
(m, 96H), 0.88 (t, 9H, J¼7.0 Hz). 13C NMR (100 MHz,
CDCl3): d 165.0, 153.2, 146.9, 140.1, 138.4, 130.1, 129.5,
129.4, 129.4, 100.5, 73.5, 69.2, 68.0, 31.9, 30.3, 29.7, 29.7,
29.4, 29.4, 29.4, 29.3, 28.4, 26.1, 25.6, 22.7, 14.1. TOF-MS
(pos) calcd for C69H121IO5 [MþNaþ] 1179.8156, found
1179.8139.
4.2.3. 3,4,5-Tris(octadecyloxy)benzyl 2-iodobenzoate (3d)
1H NMR (400 MHz, CDCl3): d 7.96 (dd, 1H, J¼8.0,
1.0 Hz), 7.77 (dd, 1H, J¼8.0, 1.0 Hz), 7.37 (ddd, 1H, J¼8.0,
1.0 Hz), 7.13 (ddd, 1H, J¼8.0, 1.0 Hz), 6.63 (s, 2H), 5.25 (s,
2H), 3.93 (m, 6H), 1.88e1.07 (m, 96H), 0.88 (t, 9H,
J¼7.0 Hz). 13C NMR (100 MHz, CDCl3): d 166.6, 153.2,
142.2, 138.3, 135.2, 132.6, 131.0, 130.4, 127.9, 107.3, 94.0,
73.4, 69.2, 67.8, 31.9, 30.3, 29.7, 29.6, 29.6, 29.6, 29.4,
29.4, 29.3, 26.1, 26.1, 23.4, 22.7, 14.1. TOF-MS (pos) calcd
for C68H119IO5 [MþNaþ] 1165.8000, found 1165.7993.
4. Experimental section
4.1. Loading of aryl halides onto compound 1: 5-((4-
iodophenoxy)methyl)-1,2,3-tris(octadecyloxy)benzene (3a)
A mixture of K2CO3 (97 mg, 0.7 mmol) and 4-iodophenol
(110 mg, 0.55 mmol) in 3 mL of DMF was treated with aryl
halides attached to the cycloalkane-soluble platform 1
(488 mg, 0.5 mmol) dissolved in 3 mL of cyclohexane. The
solution was refluxed for 5 h. After cooling, the cyclohexane
layer was separated and evaporated under vacuum. Methanol
was added to the residue followed by filtration to afford the
product 3a (529 mg, 95%). 1H NMR (400 MHz, CDCl3):
d 7.56 (d, 2H, J¼8.5 Hz), 6.75 (d, 2H, J¼8.5 Hz), 6.58 (s,
2H), 4.91 (s, 2H), 3.95 (m, 6H), 1.84e1.01 (m, 96H), 0.88
(t, 9H, J¼6.6 Hz). 13C NMR (100 MHz, CDCl3): d 158.7,
153.4, 138.8, 138.1, 131.3, 117.3, 106.1, 92.5, 73.4, 70.4,
69.2, 31.9, 30.3, 29.7, 29.7, 29.6, 29.4, 29.4, 26.9, 26.1,
22.7, 14.1. TOF-MS (pos) calcd for C67H119IO4 [MþNaþ]
1137.8051, found 1137.8012.
4.3. General procedure for Sonogashira coupling reaction
A mixture of PdCl2(PPh3)2 (7.0 mg, 2 mol %), CuI (1 mg,
1 mol %), triethylamine (206 mL, 1.5 mmol), and alkynes
4aee (0.75 mmol) in 3 mL of DMF was treated with com-
pounds 3aed (0.5 mmol) dissolved in 3 mL of cyclohexane,
and the solution was refluxed for 6 h under Ar. After cooling,
the cyclohexane layer was separated and evaporated under
vacuum. Methanol was added to the residue, followed by
filtration to afford the products 5aei.
4.4. Microwave irradiation experiments
4.2. Loading of aryl halides onto compound 2
All microwave irradiation experiments were carried out in
a CEM-Discover mono-mode microwave apparatus, operating
at a frequency of 2.45 GHz with continuous irradiation power
The appropriate benzoic acid (1.5 mmol), N,N0-diisopropyl-
carbodiimide (1.5 mmol), and a catalytic amount of 4-

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S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
from 0 to 300 W. The reactions were carried out in glass tubes
sealed with a pressure lock. The pressure was controlled by
a load cell connected directly to the vessel. The reaction tem-
perature was measured using an IR sensor on the outer surface
of the process vial. Microwave irradiation of 100 W was used,
with the temperature ramped from room temperature to 100 ꢀC
in 5 min. On reaching 100 ꢀC, the reaction mixture was held at
that temperature.
(pos) calcd for C77H126O6 [MþNaþ] 1169.9452, found
1169.9458.
4.5.4. 3,4,5-Tris(octadecyloxy)benzyl 4-(5-hydroxypent-1-
ynyl)-3-methylbenzoate (5d)
1H NMR (400 MHz, CDCl3): d 8.05 (dd, 1H, J¼1.7,
0.4 Hz), 7.86 (dd, 1H, J¼8.0, 1.7 Hz), 7.29 (dd, 1H, J¼1.7,
0.4 Hz), 6.62 (s, 2H), 5.23 (s, 1H), 3.98 (t, 4H, J¼7.0 Hz),
3.95 (t, 2H, J¼6.8 Hz), 3.84 (q, 2H, J¼6.3 Hz), 2.60 (t, 2H,
J¼7.1 Hz), 2.46 (s, 3H), 1.89e1.10 (m, 98H), 0.89 (t, 9H,
J¼7.1 Hz). 13C NMR (100 MHz, CDCl3): d 165.8, 153.1,
145.3, 138.2, 133.1, 130.7, 129.3, 128.5, 127.6, 124.1,
107.1, 94.3, 79.0, 73.7, 69.2, 67.1, 61.9, 32.0, 29.7, 26.4,
22.7, 21.2, 26.3, 14.1. IR (KBr): 3400, 2912, 2850, 1716,
1587, 1468, 1376, 1226, 1118, 825 cmꢁ1. TOF-MS (pos) calcd
for C74H128O6 [MþNaþ] 1135.9609, found 1135.9638.
4.5. The reusability of the recovered Pd catalyst in the DMF
phase
Based on a coupling reaction (Table 1, entry 1), the reus-
ability of the recovered Pd catalyst in the DMF phase was
tested according to the experiment described in Ref. 4b. The
product was obtained in 99 (cycle 1), 97 (cycle 2), and 78%
(cycle 3) yields, respectively.
4.5.5. 3,4,5-Tris(octadecyloxy)benzyl 4-(4-hydroxybut-1-
ynyl)-3-methylbenzoate (5e)
4.5.1. 1,2,3-Tris(octadecyloxy)-5-((4-(phenylethynyl)-
phenoxy)methyl)benzene (5a)
1H NMR (400 MHz, CDCl3): d 8.07 (d, 1H, J¼1.7 Hz),
7.87 (dd, 1H, J¼7.8, 1.7 Hz), 7.26 (dd, 1H, J¼1.7, 0.4 Hz),
6.62 (s, 2H), 5.22 (s, 1H), 3.97 (t, 4H, J¼6.1 Hz), 3.95 (t,
2H, J¼6.5 Hz), 3.84 (q, 2H, J¼6.3 Hz), 2.74 (t, 2H,
J¼6.1 Hz), 2.46 (s, 3H), 1.89e1.14 (m, 96H), 0.88 (t, 9H,
J¼7.1 Hz). 13C NMR (100 MHz, CDCl3): d 165.9, 153.1,
145.3, 133.2, 130.9, 130.8, 129.4, 129.0, 128.0, 123.5,
107.1, 91.2, 80.4, 73.4, 69.1, 67.0, 61.1, 31.8, 30.3, 29.6,
29.6, 29.3, 29.3, 26.0, 26.0, 23.8, 22.6, 20.9, 14.0. IR (KBr):
3407, 2919, 2850, 2224, 1714, 1226, 1111 cmꢁ1. TOF-MS
(pos) calcd for C73H126O6 [MþNaþ] 1121.9452, found
1121.9450.
1H NMR (400 MHz, CDCl3): d 7.50 (d, 2H, J¼7.8 Hz),
7.47 (d, 2H, J¼8.5 Hz), 7.33 (m, 3H), 6.95 (d, 2H,
J¼8.8 Hz), 6.61 (s, 2H), 4.96 (s, 2H), 3.96 (m, 6H), 1.96e
1.10 (m, 96H), 0.87 (t, 9H, J¼6.6 Hz). 13C NMR (100 MHz,
CDCl3): d 158.5, 153.3, 133.0, 132.1, 131.4, 128.4, 128.3,
127.9, 118.0, 115.7, 114.9, 106.2, 89.3, 86.4, 73.4, 69.1,
69.1, 31.9, 30.9, 30.3, 29.7, 29.6, 29.4, 29.3, 26.1, 26.1,
22.7, 14.1. IR (KBr): 2920, 2850, 1598, 1506, 756 cmꢁ1
.
TOF-MS (pos) calcd for C75H124O4 [MþNaþ] 1111.9397,
found 1111.9401.
4.5.2. 5-((4-((4-Methoxyphenyl)ethynyl)phenoxy)methyl)-
1,2,3-tris(octadecyloxy)benzene (5b)
4.5.6. 3,4,5-Tris(octadecyloxy)benzyl 2-(phenylethynyl)-
benzoate (5f)
1H NMR (400 MHz, CDCl3): d 7.44 (d, 4H, J¼8.8 Hz),
6.93 (d, 2H, J¼8.4 Hz), 6.86 (d, 2H, J¼8.4 Hz), 6.62 (s,
2H), 4.95 (s, 2H), 3.96 (t, 4H, J¼6.2 Hz), 3.94 (t, 2H,
J¼7.3 Hz), 3.82 (s, 3H), 1.83e1.10 (m, 96H), 0.87 (t, 9H,
J¼6.6 Hz). 13C NMR (100 MHz, CDCl3): d 159.3, 158.4,
153.2, 132.8, 131.4, 125.8, 121.7, 115.9, 115.6, 114.7,
113.8, 88.0, 87.8, 73.3, 69.1, 65.6, 55.2, 31.8, 31.8, 30.2,
29.6, 29.6, 29.3, 29.3, 26.0, 26.0, 22.6, 14.0. IR (KBr):
1H NMR (400 MHz, CDCl3): d 7.97 (dd, 1H, J¼8.1,
1.2 Hz), 7.63 (d, 1H, J¼7.6, 0.7 Hz), 7.48 (d, 1H, J¼7.6,
1.5 Hz), 7.41 (m, 2H), 7.36 (d, 1H, J¼7.3, 0.7 Hz), 7.30 (m,
3H), 6.62 (s, 2H), 5.29 (s, 2H), 3.90 (t, 4H, J¼6.4 Hz), 3.85
(t, 2H, J¼6.6 Hz), 1.76e1.15 (m, 96H), 0.86 (t, 9H,
J¼6.6 Hz). 13C NMR (100 MHz, CDCl3): d 166.3, 153.2,
134.0, 131.9, 131.7, 130.7, 130.6, 128.5, 128.4, 128.3,
128.2, 127.9, 123.8, 123.2, 107.0, 94.3, 88.3, 73.5, 69.0,
67.5, 31.9, 30.3, 29.7, 29.7, 29.4, 29.4, 29.3, 26.1, 26.1,
22.7, 14.1. TOF-MS (pos) calcd for C76H124O5 [MþNaþ]
1139.9346, found 1139.9351.
2919, 2850, 1597, 1508, 1463, 1244, 1176, 1115 cmꢁ1
.
TOF-MS (pos) calcd for C76H126O5 [MþNaþ] 1141.9503,
found 1141.9523.
4.5.3. 3,4,5-Tris(octadecyloxy)benzyl 4-((4-methoxyphenyl)-
ethynyl)benzoate (5c)
4.5.7. 3,4,5-Tris(octadecyloxy)benzyl 2-((4-methoxyphenyl)-
ethynyl)benzoate (5g)
1H NMR (400 MHz, CDCl3): d 7.98 (d, 2H, J¼7.8 Hz),
7.62 (d, 2H, J¼7.8 Hz), 7.42 (d, 2H, J¼7.7 Hz), 6.93 (dd,
2H, J¼7.7 Hz), 6.65 (s, 2H), 5.36 (s, 2H), 4.00e3.86 (m,
6H), 3.97 (s, 3H), 1.84e1.73 (m, 6H), 1.47e1.25 (m, 90H),
0.88 (t, 9H, J¼6.6 Hz). 13C NMR (100 MHz, CDCl3):
d 165.8, 159.9, 153.0, 140.1, 138.0, 133.7, 133.0, 131.6,
127.6, 124.0, 115.2, 113.9, 107.0, 94.7, 92.3, 73.4, 69.2,
67.4, 55.3, 32.0, 29.9, 29.9, 29.9, 29.9, 29.8, 29.8, 29.6,
29.5, 29.5, 26.2, 22.8, 14.3. IR (KBr): 2917, 2848, 2217,
1720, 1594, 1508, 1465, 1438, 1290, 1145 cmꢁ1. TOF-MS
1H NMR (400 MHz, CDCl3): d 7.98 (d, 1H, J¼7.8 Hz),
7.62 (d, 1H, J¼7.8 Hz), 7.48 (ddd, 1H, J¼7.5, 1.2 Hz), 7.32
(ddd, 1H, J¼7.8, 1.2 Hz), 7.35 (ddd, 1H, J¼7.5, 1.2 Hz),
7.34 (d, 2H, J¼8.5 Hz), 6.83 (d, 2H, J¼8.5 Hz), 6.64 (s,
2H), 5.31 (s, 2H), 3.92 (t, 2H, J¼6.5 Hz), 3.87 (t, 4H,
J¼6.5 Hz), 3.82 (s, 3H), 1.73 (m, 6H), 1.47e1.25 (m, 90H),
0.88 (t, 9H, J¼6.6 Hz). 13C NMR (100 MHz, CDCl3):
d 165.1, 159.6, 153.0, 140.1, 138.0, 133.7, 133.0, 131.6,
130.6, 130.5, 127.6, 124.0, 115.2, 113.9, 107.0, 94.7, 92.3,

S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
2861
73.4, 69.2, 67.4, 55.3, 32.0, 29.9, 29.9, 29.9, 29.9, 29.8, 29.8,
29.6, 29.5, 29.5, 26.2, 22.8, 14.3. IR (KBr): 2917, 2848, 2217,
1720, 1594, 1508, 1465, 1438, 1290 cmꢁ1. TOF-MS (pos)
calcd for C77H126O6 [MþNaþ] 1169.9452, found 1169.9429.
(1.50 mmol), Pd2(dba)3 (9.1 mg, 2 mol %), cHex/DMF (each
3 mL), and a magnetic stirring bar. After degassing under
argon, the vessel was placed into an oil bath preheated to
60 ꢀC. The reaction mixture was kept in the oil for 3 h before
being removed, and the vessel and contents were allowed to
cool. The MCH layer was separated and evaporated under vac-
uum. Methanol was added to the residue, followed by filtration
to afford the biaryl products 9aec.
4.5.8. 3,4,5-Tris(octadecyloxy)benzyl 2-(5-hydroxypent-
1-ynyl)benzoate (5h)
1H NMR (400 MHz, CDCl3): d 7.95 (dd, 1H, J¼8.1, 1.5 Hz),
7.49(dd, 1H, J¼8.1, 0.7 Hz), 7.41(ddd, 1H, J¼8.1, 1.0 Hz), 7.29
(ddd, 1H, J¼8.1, 1.0 Hz), 6.62 (s, 2H), 5.22 (s, 2H), 3.95 (t, 4H,
J¼6.6 Hz), 3.92 (t, 2H, J¼7.0 Hz), 3.77 (q, 2H, J¼5.6 Hz), 3.47
(d, 1H, J¼5.6 Hz), 2.49 (t, 2H, J¼7.1 Hz), 2.15 (m, 2H), 1.85e
1.10 (m, 96H), 0.86 (t, 9H, J¼6.1 Hz). 13C NMR (100 MHz,
CDCl3): d 166.2, 153.3, 138.2, 134.5, 131.6, 130.8, 130.4,
127.3, 125.9, 124.5, 107.7, 95.3, 79.9, 73.5, 69.3, 67.3, 61.8,
31.9, 31.0, 30.3, 29.4, 29.3, 26.1, 22.7, 16.6, 14.1. IR (KBr):
3426, 2917, 2850, 1720 cmꢁ1. TOF-MS (pos) calcd for
C73H126O6 [MþNaþ] 1121.9452, found 1121.9498.
4.8.1. 3,4,5-Tris(octadecyloxy)benzyl acrylate (8)
1H NMR (400 MHz, CDCl3): d 6.56 (s, 2H), 6.45 (dd, 1H,
J¼17.3, 1.5 Hz), 6.17 (dd, 1H, J¼17.3, 10.3 Hz), 5.85 (dd, 1H,
J¼10.3, 1.5 Hz), 5.09 (s, 2H), 4.00e3.89 (m, 6H), 1.85e1.68
(m, 6H), 1.51e1.19 (m, 96H), 0.88 (t, 9H, J¼6.6 Hz). 13C
NMR (100 MHz, CDCl3): d 169.6, 166.1, 153.3, 153.2,
138.5, 138.3, 131.1, 130.7, 129.8, 128.4, 107.5, 107.0, 77.3,
73.5, 69.3, 69.2, 66.8, 53.8, 32.0, 30.4, 29.8, 29.7, 29.6,
29.5, 29.4, 27.8, 26.2, 26.1, 22.7, 14.1, 8.0. IR (KBr): 2918,
2848, 1728 cmꢁ1. TOF-MS (pos) calcd for C64H118O5
[MþNaþ] 989.8877, found 989.8921.
4.5.9. 3,4,5-Tris(octadecyloxy)benzyl 2-((trimethylsilyl)-
ethynyl)benzoate (5i)
1H NMR (400 MHz, CDCl3): d 7.91 (dd, 1H, J¼7.8,
1.2 Hz), 7.59 (dd, 1H, J¼7.8, 1.2 Hz), 7.4 (ddd, 1H, J¼7.8,
1.2 Hz), 7.35 (ddd, 1H, J¼7.8, 1.2 Hz), 6.62 (s, 2H), 5.27 (s,
2H), 3.95 (m, 6H), 1.96e1.20 (m, 96H), 0.88 (t, 9H,
J¼6.6 Hz), 0.22 (s, 9H). 13C NMR (100 MHz, CDCl3):
d 166.2, 153.3, 138.3, 134.9, 132.5, 131.7, 131.0, 130.5,
128.2, 123.7, 117.1, 103.4, 100.2, 73.5, 69.3, 67.2, 32.1,
30.5, 30.0, 29.9, 29.8, 29.8, 29.8, 29.6, 29.6, 29.5, 26.3,
26.3, 22.8, 14.3, 0.137. IR (KBr): 3421, 2917, 2850, 2154,
1727, 1591, 1470, 1240 cmꢁ1. TOF-MS (pos) calcd for
C73H128O5Si [MþNaþ] 1135.9429, found 1135.9427.
4.8.2. 3-(4-Methoxyphenyl)-acrylic acid 3,4,5-tris-
octadecyloxy-benzyl ester (10a)
1H NMR (600 MHz, CDCl3): d 7.68 (d, 1H, J¼16.6 Hz),
7.47 (d, 2H, J¼8.7 Hz), 6.90 (d, 2H, J¼8.7 Hz), 6.59 (s,
2H), 6.35 (d, 1H, J¼16.6 Hz), 5.12 (s, 2H), 3.99e3.93 (m,
6H), 3.84 (s, 3H), 1.82e1.71 (m, 6H), 1.49e1.44 (m, 6H),
1.33e1.25 (m, 78H), 0.88 (t, 9H, J¼6.5 Hz). 13C NMR
(150 MHz, CDCl3): d 167.2, 161.4, 153.2, 144.8, 138.2,
131.0, 129.8, 127.1, 115.4, 114.3, 107.0, 73.4, 69.1, 66.6,
55.4, 31.9, 30.3, 29.7, 29.6, 29.4, 26.1, 22.7, 14.1. TOF-MS
(pos) calcd for C71H124O6 [MþNa]þ 1095.9296, found
1095.9288.
4.6. 4-Iodo-3-phenylnaphthalen-1(2H)-one (6)
4.8.3. 3-(4-Acetyl-phenyl)-acrylic acid 3,4,5-tris-
octadecyloxy-benzyl ester (10b)
Compound 5f (447 mg, 0.4 mmol) was dissolved in dichloro-
methane and then I2 (0.45 mmol) was added. The mixture was
stirred at room temperature for 1 h. After the solution was con-
centrated under vacuum, methanol was added. The suspension
was filtrated and the residue was purified by silica gel chroma-
tography(EtOAc/hexane)to give thecompound 6 (99 mg, 71%).
1H NMR (600 MHz, CDCl3): d 7.97 (d, 2H, J¼8.7 Hz),
7.74 (d, 1H, J¼16.6 Hz), 7.60 (d, 2H, J¼8.7 Hz), 6.60 (s,
2H), 6.57 (d, 1H, J¼16.6 Hz), 5.15 (s, 2H), 3.99e3.93 (m,
6H), 2.61 (s, 3H), 1.82e1.71 (m, 6H), 1.49e1.44 (m, 6H),
1.34e1.25 (m, 78H), 0.88 (t, 9H, J¼6.5 Hz). 13C NMR
(150 MHz, CDCl3): d 197.2, 166.3, 153.3, 143.5, 138.7,
138.4, 138.1, 130.6, 128.8, 128.2, 120.5, 107.2, 73.4, 69.2,
67.0, 31.9, 30.3, 29.8, 29.7, 29.6, 29.4, 26.6, 26.1, 22.7,
14.1. TOF-MS (pos) calcd for C72H124O6 [MþNa]þ
1107.9296, found 1107.9291.
4.7. Methyl 2-(phenylethynyl)benzoate (7)
Compound 5f (447 mg, 0.4 mmol) was suspended in cHex/
MeOH (10 mL, 1:1, v/v), and sodium methoxide (11 mg,
0.2 mmol) was added. The mixture was stirred at 55 ꢀC for
3 h. After cooling and neutralized with DOWEX, cHex layer
was separated. The lower layer (MeOH) was filtrated with
ODS-filtration (methanol as eluent) followed by evaporation
to give methyl 2-(phenylethynyl)benzoate 7 (92 mg, 98%).
4.8.4. 3-Phenyl-acrylic acid 3,4,5-tris-octadecyloxy-benzyl
ester (10c)
1H NMR (600 MHz, CDCl3): d 7.72 (d, 1H, J¼16.1 Hz),
7.56e7.52 (m, 2H), 7.39e7.38 (m, 3H), 6.60 (s, 2H), 6.49
(d, 1H, J¼16.1 Hz), 5.14 (s, 2H), 3.99e3.93 (m, 6H), 1.82e
1.71 (m, 6H), 1.54e1.44 (m, 6H), 1.30e1.25 (m, 78H), 0.88
(t, 9H, J¼6.5 Hz). 13C NMR (150 MHz, CDCl3): d 166.8,
153.2, 145.1, 138.2, 134.4, 130.9, 128.9, 128.1, 107.1, 73.4,
69.2, 66.8, 31.9, 30.3, 29.8, 29.7, 29.6, 29.4, 26.1, 22.7,
4.8. General procedure for the Heck reaction in a CBT
system
In a 20-mL glass tube were placed acrylate 8 (350 mg,
0.50 mmol), aryl halides 9aec (0.75 mmol), triethylamine

2862
S. Kim et al. / Tetrahedron 64 (2008) 2855e2863
14.1. TOF-MS (pos) calcd for C70H122O5 [MþNa]þ
6H), 2.63 (s, 3H), 1.77e1.73 (m, 6H), 1.47e1.25 (m, 90H),
0.88 (t, 9H, J¼6.83 Hz). 13C NMR (100 MHz, CDCl3):
d 197.6, 153.1, 144.9, 137.7, 137.1, 135.9, 132.0, 131.7,
130.2, 128.9, 127.5, 126.8, 107.4, 73.5, 69.1, 39.4, 31.9,
30.3, 29.8, 29.7, 29.6, 29.5, 29.4, 26.6, 26.1, 22.7, 14.1.
TOF-MS (pos) calcd for C75H126O4S [MþNa]þ 1145.9274,
found 1145.9302.
1065.9190, found 1065.9213.
4.8.5. 4-Tris-octadecyloxy-benzylthiophenyl boronic acid
(11)
1H NMR (400 MHz, CDCl3): d 8.08 (d, 2H, J¼8.05 Hz),
7.39 (d, 2H, J¼8.05 Hz), 6.56 (s, 2H), 4.15 (s, 2H), 3.95e
3.89 (m, 6H), 1.80e1.71 (m, 6H), 1.46e1.25 (m, 90H), 0.88
(t, 9H, J¼7.32 Hz). 13C NMR (100 MHz, CDCl3): d 153.0,
151.4, 143.2, 137.3, 135.6, 131.3, 128.2, 107.2, 73.4, 69.1,
34.3, 31.9, 30.4, 29.8, 29.7, 29.5, 29.4, 26.2, 22.8, 14.2.
TOF-MS (pos) calcd for C67H121BO5S [MþNa]þ 1071.8925,
found 1071.8961.
4.8.10. 40-(3,4,5-Tris-octadecyloxy-benzylsulfanyl)-
biphenyl-4-carboxylic acid 3,4,5-tris-octadecyloxy ester
(13)
1H NMR (600 MHz, CDCl3): d 8.11 (d, 2H, J¼8.63 Hz),
7.61 (d, 2H, J¼8.63 Hz), 7.51 (d, 2H, J¼8.63 Hz), 7.37 (dt,
2H, J¼8.54, 1.95 Hz), 6.64 (s, 2H), 6.49 (s, 2H), 5.27 (s,
2H), 4.07 (s, 2H), 3.97e3.89 (m, 12H), 1.83e1.71 (m, 12H),
1.46e1.42 (m, 12H), 1.25 (s, 168H), 0.88 (t, 18H,
J¼6.79 Hz). 13C NMR (150 MHz, CDCl3): d 165.8, 153.2,
138.2, 137.6, 131.1, 130.5, 129.5, 107.0, 73.4, 69.2, 67.4,
31.9, 30.4, 29.8, 29.7, 29.5, 29.4, 26.2, 22.8, 14.1. TOF-MS
(pos) calcd for C136H237O8S [MþNa]þ 2042.7835, found
2042.7849.
4.8.6. 40-(3,4,5-Tris-octadecyloxy-benzylsulfanyl)-biphenyl-
4-carboxylic acid methyl ester (12a)
1H NMR (400 MHz, CDCl3): d 8.09 (d, 2H, J¼8.29 Hz),
7.62 (d, 2H, J¼8.29 Hz), 7.52 (d, 2H, J¼8.29 Hz), 7.38 (d,
2H, J¼8.29 Hz), 6.48 (s, 2H), 4.07 (s, 2H), 3.94 (s, 3H),
3.91e3.88 (m, 6H), 1.78e1.70 (m, 6H), 1.47e1.25 (m,
90H), 0.88 (t, 9H, J¼6.83 Hz). 13C NMR (100 MHz,
CDCl3): d 166.8, 152.9, 144.6, 137.8, 137.3, 136.8, 131.9,
130.1, 130.0, 128.8, 127.4, 126.6, 107.2, 73.4, 69.1, 52.2,
39.4, 31.9, 30.4, 29.8, 29.7, 29.6, 29.5, 29.4, 26.2, 26.1,
22.7, 14.2. TOF-MS (pos) calcd for C75H126O5S [MþNa]þ
1161.9224, found 1161.9253.
4.8.11. 40-(3,4,5-Tris-octadecyloxy-benzylsulfanyl)-
biphenyl-2-carboxylic acid 3,4,5-tris-octadecyloxy ester
(14)
1H NMR (600 MHz, CDCl3): d 7.80 (d, 1H, J¼7.69 Hz),
7.450 (dd, 1H, J¼8.30, 7.69 Hz), 7.39 (dd, 1H, J¼8.30,
7.69 Hz), 7.32 (d, 1H, J¼7.69 Hz), 7.26 (d, 2H, J¼8.06 Hz),
7.19 (d, 2H, J¼8.06 Hz), 6.49 (s, 2H), 6.36 (s, 2H), 4.99 (s,
2H), 4.04 (s, 2H), 3.93e3.87 (m, 12H), 1.80e1.70 (m, 12H),
1.31e1.25 (m, 180H), 0.88 (t, 18H, J¼6.96 Hz). 13C NMR
(150 MHz, CDCl3): d 168.4, 153.1, 141.7, 139.1, 138.3,
137.5, 136.0, 134.5, 132.1, 131.3, 130.9, 130.6, 130.3, 129.8,
129.1, 128.8, 128.3, 127.2, 107.4, 73.4, 69.2, 67.3, 39.4, 31.9,
30.3, 29.8, 29.7, 29.6, 29.4, 22.6, 14.1. TOF-MS (pos) calcd
for C136H237O8S [MþNa]þ 2042.7835, found 2042.7811.
4.8.7. 40-Nitro-4-(3,4,5-tris-octadecyloxy-benzylsulfanyl)-
biphenyl (12b)
1H NMR (400 MHz, CDCl3): d 8.28 (d, 2H, J¼7.69 Hz),
7.69 (d, 2H, J¼7.69 Hz), 7.51 (d, 2H, J¼7.69 Hz), 7.39 (d,
2H, J¼7.69 Hz), 6.51 (s, 2H), 4.09 (s, 2H), 3.94e3.89 (m,
6H), 1.79e1.71 (m, 6H), 1.48e1.25 (m, 90H), 0.88 (t, 9H,
J¼6.96 Hz). 13C NMR (100 MHz, CDCl3): d 153.1, 146.8,
138.4, 136.4, 134.4, 131.8, 130.7, 128.8, 127.6, 124.2,
115.8, 107.4, 73.4, 69.2, 39.4, 31.9, 30.3, 29.8, 29.7, 29.6,
29.4, 26.2, 22.7, 14.1. TOF-MS (pos) calcd for
C73H123NO5S [MþNa]þ 1148.9020, found 1148.9001.
Acknowledgements
4.8.8. 40-(3,4,5-Tris-octadecyloxy-benzylsulfanyl)-biphenyl-
4-carbonitrile (12c)
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology.
1H NMR (400 MHz, CDCl3): d 7.69 (dd, 2H, J¼8.54,
1.95 Hz), 7.62 (dd, 2H, J¼8.54, 1.95 Hz), 7.46 (dt, 2H,
J¼8.54, 1.95 Hz), 7.36 (dt, 2H, J¼8.54, 1.95 Hz), 6.48 (s,
2H), 4.06 (s, 2H), 3.92e3.85 (m, 6H), 1.77e1.67 (m, 6H),
1.47e1.25 (m, 90H), 0.86 (t, 9H, J¼6.59 Hz). 13C NMR
(100 MHz, CDCl3): d 153.2, 144.8, 137.9, 136.9, 132.6,
131.9, 129.9, 128.8, 127.5, 123.3, 118.8, 110.9, 107.4, 73.4,
69.2, 39.2, 31.9, 30.4, 29.7, 29.6, 29.5, 29.4, 29.3, 26.1,
22.7, 14.1. TOF-MS (pos) calcd for C74H123NO3S [MþNa]þ
1128.9121, found 1128.9125.
References and notes
1. (a) Reagents for High-Throughput Solid-Phase and Solution-Phase Organic
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