Synthesis of thiophene-capped [2]rotaxanes

Article abstract of DOI:10.1016/j.tet.2011.03.009

Two types of thiophene-capped [2]rotaxanes, i.e., bithienyl (2T)- and bis(3,4-ethylenedioxythiophene)-yl (BEDOT)-capped [2]rotaxanes, were synthesized. The electron-deficient cyclophane of cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺) was used as a

Full text of DOI:10.1016/j.tet.2011.03.009

Tetrahedron 67 (2011) 3046e3052
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Synthesis of thiophene-capped [2]rotaxanes
,
b
,
a,c
Taichi Ikeda a , Masayoshi Higuchi
*
a Functional Materials Chemistry Group, Organic Nanomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Japan
b Experimental Physics, Max Planck Institute for Polymer Research, Ackermannweg 10 Mainz D-55128, Germany
c International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba 305-0044, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Two types of thiophene-capped [2]rotaxanes, i.e., bithienyl (2T)- and bis(3,4-ethylenedioxythiophene)-yl
(BEDOT)-capped [2]rotaxanes, were synthesized. The electron-deficient cyclophane of cyclobis(para-
quat-p-phenylene) (CBPQT4D) was used as a macrocycle. Association constants for inclusion complex-
ation of 2T- and BEDOT-derivatives with CBPQT4D were obtained by 1H NMR titration. Due to the
donoreacceptor charge transfer absorption band, 2T- and BEDOT-capped [2]rotaxanes have red and
green colors, respectively. On the basis of electrochemical analysis, we confirmed that only BEDOT-
capped [2]rotaxane is a promising candidate for [3]rotaxane synthesis through oxidation coupling of the
thiophene unit.
Received 30 January 2011
Received in revised form 1 March 2011
Accepted 2 March 2011
Keywords:
Rotaxanes
Thiophenes
Charge transfer complex
Electrochemistry
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
CBPQT4D-based [n]rotaxanes. In this study, we synthesized two
types of thiophene-capped [2]rotaxanes (Fig.1). These [2]rotaxanes
Synthesis of [n]rotaxanes, which consists of a dumbbell-shaped
compound and [nꢀ1] macrocycles, has been developed in last two
decades.1 Now, [n]rotaxanes are attracting much attention as the
components for new materials, such as mechanically-tough gel,2
molecular machines,3 insulated molecular wires4 etc. In the fam-
ily of [n]rotaxanes, [3]rotaxane is an attractive structural motif,
because it is applicable to the linear molecular motors5 and
adaptable receptors.6 Although we can find many examples of [3]
rotaxane synthesis based on the crown ether derivatives,7 cyclo-
dextrins8 or other macrocycles,9 only a few examples of cyclobis
(paraquat-p-phenylene) (CBPQT4D)-based [3]rotaxane synthesis
have been reported so far.5,10 CBPQT4D is an electron-deficient
cyclophane and forms inclusion complex with the electron-rich
compounds.11 In the synthesis of CBPQT4D-based rotaxanes, we
have often faced difficulties due to the decomposition of CBPQT4D
under reductive conditions.12 Since CBPQT4D-based [n]rotaxanes
afford fascinating nano-electromechanical systems and electronics
devices,3a development of new synthetic pathway is quite impor-
tant. In our previous study on polythiophene polyrotaxane syn-
thesis,13 we found out that the electrochemical oxidation coupling
of the thiophene derivatives is available for the synthesis of
have electrochemically-reactive thiophene terminal at one end.
Therefore we can expect to obtain [3]rotaxane through electro-
chemical oxidation coupling of the terminal thiophene units. The
objective of this study is to clarify whether thiophene-capped [2]
rotaxane can be a precursor for [3]rotaxane synthesis.
* Corresponding author. Tel./fax: þ81 29 860 4721; e-mail address: IKEDA.
Fig. 1. Chemical structures of thiophene-capped [2]rotaxanes. (a) 2T-[2]Rx and (b)
BEDOT-[2]Rx. Labeling scheme for NMR assignment is also depicted.
Taichi@nims.go.jp (T. Ikeda).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.009

T. Ikeda, M. Higuchi / Tetrahedron 67 (2011) 3046e3052
3047
2. Results and discussion
CBPQT4D affinities to 2T- and BEDOT-dumbbells. From 1H NMR
titration experiment,18 the association constants (Ka) of CBPQT4D
inclusion complexation were determined to be 900 and 1400 Mꢀ1
for 2T-thread and BEDOT-thread, respectively (Fig. 2). Although
ethylene glycol modification of the electron-rich component often
increases the Ka value,18,19 the side chains of the bithiophene unit
contribute little to enhance affinity.
2.1. Synthesis of thiophene-capped [2]rotaxanes
Synthetic route of bithienyl-capped [2]rotaxane (2T-[2]Rx) is
shown in Scheme 1. Tosylated product 4 was synthesized according
to the literature.14 The half-dumbbell compound 9 was obtained
quantitatively bythealkylationreactionof4-bromophenol(5)with4.
3,30-Disubstituted-2,20-bithiophene was synthesized from the cor-
responding 3-substituted thiophene (6) by lithiation with n-BuLi
followed bytheoxidativecoupling with CuCl2. Afterthe stannylation
of 7, monostannylated bithiophene (8) was purified using a pre-
parative HPLC. The dumbbell-shaped compound (2T-dumbbell)
was synthesized using palladium-catalyzed Stille coupling with 8
and 9.15 2T-dumbbell was obtained in the yield of 80%. 2T-[2]Rx was
prepared through the clipping reaction of CBPQT4D on 2T-dumb-
bell in DMF under ambient condition. Pure 2T-[2]Rx was recovered
after silica gel chromatography in the yield of 6%. Free 2T-dumbbell
was recovered after the purification process (yield: 91%) and reus-
able for 2T-[2]Rx synthesis.
2.2. Characterization by 1H NMR spectroscopy
We characterized thiophene-capped [2]rotaxanes (2T-[2]Rx and
BEDOT-[2]Rx) by 1H NMR spectroscopy. Fig. 3 shows 1H NMR
spectra of 2T-dumbbell and 2T-[2]Rx. We assigned the aromatic
protons with the help of 2D ROESY spectrum (Fig. 3c). The meth-
ylene protons (h) and (i) were assignable from the cross-peaks with
the thiophene protons (b) and (c), respectively. The phenyl proton
(e) was assignable from the cross-peaks with the phenyl proton (d)
and the ethylene glycol proton. Compared to free dumbbell, the
signals of the aromatic protons (c), (d), (e) and the methylene
protons (i) in [2]rotaxane shift to higher magnetic field. These
Scheme 1. Synthesis of 2T-dumbbell and 2T-capped [2]rotaxane (2T-[2]Rx).
The synthetic route of bis(3,4-ethylenedioxythiophene)-yl-
capped [2]rotaxane (BEDOT-[2]Rx) is shown in Scheme 2. 2,20-Bis
(3,4-ethylenedioxythiophene) (BEDOT)16 and its monostannylated
product (11)17 was synthesized from 3,4-ethylenedioxythiophene
(EDOT) according to the literatures. Since monostannylated BEDOT
is unstable, the palladium-catalyzed Stille coupling was carried out
just after the purification of 11 using a preparative HPLC. BEDOT-
dumbbell was obtained in the yield of 78%. BEDOT-[2]Rx was
prepared through the clipping reaction of CBPQT4D on BEDOT-
dumbbell in DMF under ambient condition. The yield of BEDOT-[2]
Rx synthesis was 8%. Free BEDOT-dumbbell was recovered after
the purification process (yield: 85%) and reusable for BEDOT-[2]Rx
synthesis. Better yield of BEDOT-[2]Rx synthesis (8%) in compared
with 2T-[2]Rx synthesis (6%) is attributable to the difference in
protons are affected by the shielding effect of the CBPQT4D aro-
matic rings due to the encapsulation inside CBPQT4D cavity.18,19
Large chemical shift changes of the aromatic protons (c) and (d)
indicate that the CBPQT4D macrocycle preferentially stays between
the thiophene and phenyl groups in the dumbbell component. On
the contrary, the signals of the aromatic protons (a), (b) and
methylene protons (h) shift to lower magnetic field. These protons
are not encapsulated by CBPQT4D but affected by the deshielding
effect on the periphery of the CBPQT4D aromatic rings.19
Similar results were obtained for 1H NMR spectra of BEDOT-
dumbbell and BEDOT-[2]Rx. Namely, the aromatic protons en-
capsulated inside the CBPQT4D cavity, i.e., protons (d) and (e), show
large chemical shift change toward higher magnetic field, and the
terminal aromatic proton (a) shifts to lower magnetic field after
Scheme 2. Synthesis of BEDOT-dumbbell and BEDOT-capped [2]rotaxane (BEDOT-[2]Rx).

3048
T. Ikeda, M. Higuchi / Tetrahedron 67 (2011) 3046e3052
2.3. Characterization by UV/vis spectroscopy
We characterized thiophene-capped [2]rotaxanes (2T-[2]Rx and
BEDOT-[2]Rx) by UV/vis spectroscopy. The optical data are sum-
marized in Table 1. The maximum absorption wavelength of the
p
e
p
*
band for 2T-dumbbell (lThio¼314 nm, see the Supplementary
data) lies between those for the model compounds of bithiophene
(302 nm)20 and phenyl-capped bithiophene (374 nm).21 This result
is reasonable because only one end of the bithiophene unit is
capped by the phenyl group in the case of 2T-dumbbell. The same
trend was confirmed for BEDOT-dumbbell, namely, the maximum
absorption wavelength of the
pep band for BEDOT-dumbbell
*
(
lThio¼363 nm) lies between those for the model compounds of
BEDOT (320 nm)22 and phenyl-capped BEDOT (398 nm).21
Table 1
Optical data of thiophene dumbbells and thiophene-capped [2]rotaxanes in MeCN at
room temperature
a
b
c
d
e
f
Compound
lCBPQT 3CBPQT
lThio
3Thio
lCT 3CT
nm
Mꢀ1 cmꢀ1 nm
Mꢀ1 cmꢀ1 nm Mꢀ1 cmꢀ1
2T-dumbbell
BEDOT-dumbbell
2T-[2]Rx
d
d
314
363
22,000
34,000
d
d
d
d
d
d
259
263
39,000
39,000
(320)g (19,000)g 485 530
BEDOT-[2]Rx
371
27,000
625 300
Fig. 2. Chemical structures of thiophene threads (a) 2T-thread, (b) BEDOT-thread and
(c) macrocycle CBPQT4D$4PFꢀ6. (d) Chemical shift change in 1H NMR titration experi-
ments (CD3CN, room temperature). The dotted lines show the curves fitted with
calculation based on the Ka values.
a
Maximum absorption wavelength of CBPQT4D
.
b
c
d
e
f
Molar extinction coefficient at lCBPQT
Maximum absorption wavelength of phenylethiophene unit
Molar extinction coefficient at lThio
Maximum absorption wavelength of CT band.
Molar extinction coefficient at lCT
.
pep band.
*
.
.
g
Data was calculated from peak fitting to overlapped peaks.
Fig. 4 shows UV/vis spectra of thiophene-capped [2]rotaxanes.
The peak around 260 nm mainly originates from the absorption of
the CBPQT4D macrocycle.19 In the case of BEDOT-[2]Rx, we can
confirm a vibronic fine structure in the pep band due to the rigid
*
structure of the BEDOT unit.21,23 Thiophene-capped [2]rotaxane
has an additional absorption band in the visible region due to
charge transfer (CT) from the electron-rich phenylethiophene unit
to the electron-deficient bipyridinium unit in CBPQT4D 11b,18,19
The
.
maximum absorption wavelength of the CT bands (lCT) for 2T-[2]Rx
and BEDOT-[2]Rx were 485 nm and 625 nm, respectively. These
absorption bands afford red and green colors to 2T-[2]Rx and
BEDOT-[2]Rx, respectively. Compared with free dumbbell com-
pounds, we confirmed red-shift of the
pep band (lThio) for the
*
thiophene-capped [2]rotaxanes (Table 1). This result supports that
an electronic interaction exists between the phenylethiophene
unit and bipyridinium unit.18,19
Fig. 3. 1H NMR spectra of (a) 2T-dumbbell, (b) 2T-[2]Rx and partial ROESY spectrum of
2T-[2]Rx. (600 MHz, CD3CN, room temperature).
rotaxanation. We confirmed whether BEDOT-[2]Rx is rotaxane or
pseudo-rotaxane. No 1H NMR spectrum change was confirmed
when the solution of [2]rotaxane was heated at 70 ꢁC for 24 h.
Therefore, the BEDOT unit is bulky enough to interlock the
CBPQT4D macrocycle.
Fig. 4. UV/vis spectrum of (a) 2T-[2]Rx and (b) BEDOT-[2]Rx (MeCN, 1.0ꢂ10ꢀ5 M, room
temperature). Inset is photograph of solutions (a) 2T-[2]Rx and (b) BEDOT-[2]Rx.

T. Ikeda, M. Higuchi / Tetrahedron 67 (2011) 3046e3052
3049
2.4. Electrochemical characterization
result suggests that the oxidation coupling of the terminal thio-
phene unit does not take place due to the steric and electrostatic
repulsive forces between the CBPQT4D macrocycles.25 In the re-
duction part of CV (E<0), two successive two-electron reduction
peaks based on the process of CBPQT4D/CBPQT2D/CBPQT0
were observed. We confirmed small splitting of the first two-
electron reduction peak. This splitting is characteristic for
CBPQT4D-based [2]rotaxanes.25
Electrochemical properties of the thiophene dumbbells and
thiophene-capped [2]rotaxanes were analyzed using cyclic vol-
tammetry (CV) and differential pulse voltammetry (DPV).24 CV
traces and half-wave potentials (E1/2) are summarized in Fig. 5 and
Table 2, respectively.
In CV analysis of BEDOT-dumbbell, we confirmed an irrevers-
ible oxidation peak at E1/2¼þ0.61 V (Fig. 5c) corresponding to the
radical cation formation. No second oxidation peak was observable.
This result suggests that the electrochemical oxidation coupling of
BEDOT-dumbbell takes place around þ0.6 V. Compared with
BEDOT-dumbbell, the first oxidation of BEDOT-[2]Rx took place at
higher oxidation potential (E1/2¼þ0.80 V, Fig. 5d). The first oxida-
tion peak of BEDOT-[2]Rx was also irreversible and we confirmed
small new peaks in the cathodic scan (around þ0.40 and þ0.60 V).
Furthermore, we observed the spike peaks in the reduction part of
CV (E<0, Fig. 5d). These spike peaks were not observed when we
scanned the potential only in the negative region (Fig. 5e). These
results suggest the formation of [3]rotaxane through the electro-
chemical oxidation coupling of BEDOT-[2]Rx. Presumably, higher
reactivity of the bis(3,4-ethylenedioxythiophene) unit contributes
to the oxidation coupling of BEDOT-[2]Rx.26 The spike peaks in the
reduction region is attributable to the deposition of [3]rotaxane on
the electrode surface due to low solubility of reduced [3]rotaxane.
Similar spike peaks have been reported by Stoddart et al. in the CV
traces of CBPQT4D-based [3]rotaxane.5
3. Conclusion
We successfully synthesized two kinds of thiophene-capped [2]
rotaxanes. Electrochemical analysis suggested that BEDOT-[2]Rx is
a promising candidate for [3]rotaxane synthesis through the oxi-
dation coupling of the terminal thiophene unit. On the other hand,
we cannot expect [3]rotaxane synthesis from 2T-[2]Rx. This result
is also important for the design of polythiophene polyrotaxane. In
order to obtain much amount of [3]rotaxane, we have to improve
the yield in the step of rotaxanation. The improved synthesis of
thiophene-capped [2]rotaxane and [3]rotaxane synthesis through
oxidation coupling of the thiophene unit are now in progress.
Fig. 5. Cyclic voltammetry traces recorded at 200 mV sꢀ1 in argon-purged MeCN at
room temperature. Sample concentration: 1.0 mM.
Table 2
Electrochemical data of thiophene dumbbells and thiophene-capped [2]rotaxanes
Compound
Half-wave potentials versus SCE (V)
Oxidation
Reduction
2T-dumbbell
BEDOT-dumbbell
2T-[2]Rx
(þ1.07)a
d
(þ0.61)a
d
ꢀ0.24c, ꢀ0.33c, ꢀ0.85d
þ1.32b, þ1.52b
BEDOT-[2]Rx
(þ0.80)a
ꢀ0.22c, ꢀ0.30c, ꢀ0.82d
4. Experimental section
4.1. General information
a
Irreversible one-electron process.
Quasi-reversible one-electron process.
Reversible one-electron process.
Reversible two-electron process.
b
c
d
All of the reagents and solvents were purchased from the
commercial source used without further purification. Compounds
19
In CV analysis of 2T-dumbbell, we confirmed an oxidation peak
4,14 6,13 10,19 BEDOT,16 and CBPQT4$4PF6 were prepared accord-
at E1/2¼þ1.07 V (Fig. 5a). This oxidation peak corresponds to the
radical cation formation.21 No second oxidation peak attributable to
the dication formation was observable. The redox process was
irreversible, because we confirmed new peak around þ0.85 V in the
cathodic scan. This result suggests that the electrochemical oxida-
tion coupling of 2T-dumbbell takes place around þ1.1 V. Compared
with 2T-dummbell, 2T-[2]Rx showed two oxidation peaks at
higher potential (E1/2¼þ1.32 and þ1.52 V, Fig. 5b). The electro-
chemically-active unit encapsulated by the CBPQT4D macrocycle
always has higher oxidation potential, because the tetracationic
cyclophane CBPQT4D suppress the formation of additional cation
charge.25 The first and second oxidation peaks in Fig. 5b correspond
to the radical cation and dication formation. We could confirm the
reduction peak of the radical cation and dication, but the intensity
of peaks in the cathodic scan was smaller than that in the anodic
scan. We found no additional peak in the cathodic scan. Therefore,
we concluded these redox processes are quasi-reversible. This
ing to literature procedures. Thread compounds 2T-thread and
BEDOT-thread were synthesized through the same route with the
synthesis of the dumbbell-shaped components. Column chroma-
tography was carried out using BiotageÒ SNAP cartridge with
SP1TM FLASH purification system (Biotage). Some compounds
were purified by LC-9104 recycling preparative HPLC system
equipped with the linearly connected JAIGEL-1H and JAIGEL-2H
columns (Japan Analytical Industry Co.). NMR spectra were recor-
ded on a Bruker DRX600 (600 MHz and 150 MHz for 1H and 13C
nuclei, respectively) with residual solvent as the internal standard.
In 1H NMR titration, the concentration of CBPQT4D$4PFꢀ6 was
2.11 mM in both cases. The detailed procedure of 1H NMR titration
was written in our previous papers.18 High resolution electrospray
ionization (HR-ESI) mass spectra were obtained on a mass spec-
trometer equipped in the LCMS-IT-TOF system (Shimadzu, Co.).
UV/vis spectra were recorded at room temperature on a UV-2550
UV/vis spectrophotometer (Shimadzu Co.). Electrochemical

3050
T. Ikeda, M. Higuchi / Tetrahedron 67 (2011) 3046e3052
measurements were carried out at room temperature in argon-
purged MeCN, with an ALS Electrochemical Analyzer, Model 612B
(ALS Co.). Cyclic voltammetry (CV) was performed using a glassy
carbon working electrode (0.07 cm2, ALS Co.); its surface was pol-
AcOEt: 25%¼4 column) to give the compound 9 as a colorless oil.
Yield: 2.6 g (98%). 1H NMR (CDCl3, 600 MHz):
d¼1.22 (d, J¼6.9 Hz,
12H), 3.39 (m, 2H), 3.79 (s, 4H), 3.85e3.94 (m, 6H), 4.11 (t, J¼5.4 Hz,
2H), 6.80 (d, J¼9.0 Hz, 2H), 7.10 (s, 3H), 7.36 (d, J¼9.0 Hz, 2H); 13C
ished routinely with 0.05-mm alumina/water slurry on a felt surface
NMR (CDCl3, 150 MHz):
d
¼24.5, 26.6, 68.1, 70.1, 71.0, 71.4, 74.2,
before use. The counter and reference electrodes were a platinum
wire and a saturated calomel electrode (SCE), respectively (ALS Co.).
TBA$PF6 (0.1 M) was used as a supporting electrolyte. The half-
wave potential (E1/2) was calculated from the differential pulse
113.4, 116.8, 124.3, 125.0, 132.6, 142.2, 153.4, 158.3 ppm; IR (KBr):
3068, 2960, 2924, 2868, 1591, 1489, 1452, 1325, 1286, 1247, 1186,
1130, 1058, 937, 823, 796, 760, 646, 507 cmꢀ1; HRMS (ESI): found
m/z¼487.1469 [MþNa]þ; C24H33BrO4Na requires 487.1460.
voltammetry (DPV) peak top (Emax) and pulse height (
D
E) by using
2T-dumbbell: The compounds 8 (1.5 g, 2.0 mmol), 9 (0.95 g,
2.0 mmol), and Pd(PPh3)4 (50 mg, 4.3ꢂ10ꢀ5 mol) were mixed in dry
DMF (10 mL). The solution was deaerated three times. The reaction
mixture was stirred at 65 ꢁC under dark and Ar atmosphere for 14 h.
The solvent was removed in vacuo. The residue was directly sub-
jected to the column chromatography (SNAP Cartridge silica 100 g,
CH2Cl2/AcOEt: 10%¼2 column, 10%/50%¼6 column, 50%¼4 col-
umn). The recovered fraction containing the product was purified
by the preparative HPLC (Linearly connected columns of JAIGEL-1H
and JAIGEL-2H, CHCl3) to give 2T-dumbbell as a colorless oil. Yield:
the equation of E1/2¼Emax
þD DE was set to 50 mV.
E/2.24
4.2. Synthesis
Compound 7: The compound 6 (2.3 g, 10 mmol) was dissolved in
dry THF (20 mL) under Ar. The solution was cooled to ꢀ60 ꢁC using
a liquid N2/CHCl3 bath. The hexane solution of n-BuLi (4.0 mL,
10 mmol) was added dropwise with the gas-tight syringe. The re-
action mixture was stirred for 2.5 h under dark at ꢀ60 ꢁC. CuCl2
(1.5 g, 11 mmol) was added to the reaction mixture. The reaction
temperature was gradually raised to room temperature by re-
moving the liquid N2/CHCl3 bath. After 2 h, CH2Cl2 (150 mL) was
added to the reaction mixture and washed with 0.5 N HCl
(200 mLꢂ2) and 1 N NaHCO3 (200 mL) aqueous solutions. The or-
ganic layer was dried (MgSO4), filtered, and evaporated. The residue
was purified by column chromatography (SNAP Cartridge silica
100 g, hexane/AcOEt: 50%¼2 column, 50/80%¼6 column) to give
the compound 7 as a colorless oil. Yield: 1.9 g (83%). 1H NMR (CDCl3,
1.4 g (80%). 1H NMR (CD3CN, 600 MHz):
d
¼1.13 (m, 6H), 1.21 (d,
J¼6.9 Hz, 12H), 3.38e3.57 (m, 22H), 3.71 (s, 4H), 3.80 (m, 2H), 3.85
(m, 2H), 3.87 (m, 4H), 4.17 (m, 2H), 4.38 (s, 2H), 4.44 (s, 2H), 6.98 (d,
J¼8.8 Hz, 2H), 7.07e7.15 (m, 3H), 7.19 (d, J¼6.0 Hz, 1H), 7.35 (s, 1H),
7.49 (d, J¼6.0 Hz, 1H), 7.58 (d, J¼8.8 Hz); 13C NMR (CD3CN,
150 MHz):
d
¼15.6, 24.3, 26.9, 66.9, 67.1, 67.2, 68.7, 70.4, 70.5, 71.1,
71.2, 71.5, 75.0, 116.0, 125.0, 125.7, 127.4, 127.5, 127.8, 129.7, 130.2,
131.4, 139.8, 140.8, 142.9, 145.2, 154.1, 159.9 ppm; IR (KBr): 3068,
2962, 2868, 1606, 1508, 1458, 1350, 1288, 1253, 1180, 1109, 937, 829,
600 MHz):
d
¼1.20 (t, J¼7.2 Hz, 6H), 3.49e3.59 (m, 12H), 3.62 (m,
794, 760 cmꢀ1
C46H66O10S2Na requires 865.3995.
;
HRMS (ESI): found m/z¼865.3969 [MþNa]þ;
8H), 4.42 (s, 4H), 7.17 (d, J¼5.4 Hz, 2H), 7.33 (d, J¼5.4 Hz, 2H); 13C
NMR (CDCl3, 150 MHz):
d¼15.5, 67.0, 69.8, 70.2, 70.9, 71.0, 126.6,
2T-[2]Rx: 2T-dumbbell (0.42 g, 0.50 mmol),10 (1.0 g,1.4 mmol),
129.1, 131.0, 138.9 ppm; IR (KBr): 3095, 2972, 2864, 1452, 1346,
1240, 1109, 1038, 941, 881, 833, 742, 696 cmꢀ1; HRMS (ESI): found
m/z¼481.1659 [MþNa]þ; C22H34O6S2Na requires 481.1695.
and a,a
0-dibromo-p-xylene (0.37 g, 1.4 mmol) were dissolved in dry
DMF (10 mL). The mixture was stirred at room temperature under
dark and Ar atmosphere for 7 days. AcOEt was added to the solu-
tion. The solution and the precipitate were directly subjected to the
column chromatography (SiO2). 2T-dumbbell and other impurities
were eluted out by AcOEt, and then CH2Cl2/MeOH¼9:1. The prod-
uct was eluted out the mixed solvent (MeOH/2 N NH4Cl aq/
MeNO2¼6:3:1). The recovered red solution was concentrated, then
the residue was subjected to the column chromatography again
(SiO2, MeOH/2 N NH4Cl aq/MeNO2¼6:3:1). The recovered red so-
lution was concentrated to the half volume by the evaporation. An
aqueous solution of NH4PF6 was added until no further pre-
cipitation occurred. The pink-color precipitate was recovered by
filtration. The precipitate was dissolved in Me2CO and the solution
was added to the NH4PF6 aqueous solution to complete the
counter-ion exchange. The precipitate was recovered by filtration,
washed with small amount of pure water, and dissolved in Me2CO.
After the evaporation, the product 2T-[2]Rx was obtained as a red
solid. Yield: 58 mg (6%). Mp: >280 ꢁC; 1H NMR (CD3CN, 600 MHz):
Compound 8: The compound 7 (1.0 g, 2.2 mmol) was dissolved in
dry THF (10 mL) under Ar. The solution was cooled to ꢀ60 ꢁC using
a liquid N2/CHCl3 bath. The hexane solution of n-BuLi (0.85 mL,
2.2 mmol) was added dropwise with the gas-tight syringe. The
reaction mixture was stirred under dark. The reaction temperature
was gradually raised without refilling liquid N2 in the CHCl3 bath.
After 1 h, the reaction mixture was cooled to ꢀ60 ꢁC again using
a
liquid N2/CHCl3 bath. Tri-n-butyltin chloride (ClSn(n-Bu)3,
0.58 mL, 2.1 mmol) was added dropwise to the reaction mixture.
The reaction temperature was gradually raised to room tempera-
ture by removing the liquid N2/CHCl3 bath. After 1 h, CH2Cl2
(150 mL) was added to the reaction mixture and washed with 1 N
NaHCO3 (200 mL) aqueous solution. The organic layer was dried
(MgSO4), filtered, and evaporated. The residue was purified by the
preparative HPLC (Linearly connected columns of JAIGEL-1H and
JAIGEL-2H, CHCl3) to give the compound 8 as a colorless oil. Yield:
1.4 g (88%). 1H NMR (CDCl3, 600 MHz):
d
¼0.90 (t, J¼7.3 Hz, 12H),
d
¼0.88 (t, J¼7.0 Hz, 3H), 0.93 (t, 3H), 1.25 (d, J¼7.0 Hz, 12H), 3.29 (q,
1.12 (m, 6H), 1.20 (t, J¼7.0 Hz, 6H), 1.35 (m, 6H), 1.58 (m, 6H),
3.49e3.59 (m, 12H), 3.62 (m, 8H), 4.44 (d, J¼4.7 Hz, 4H), 7.17 (d,
J¼5.2 Hz, 1H), 7.19 (s, 1H), 7.31 (d, J¼5.2 Hz, 1H); 13C NMR (CDCl3,
J¼7.0 Hz, 2H), 3.35 (q, J¼7.0 Hz, 2H), 3.40 (m, 2H), 3.44 (m, 2H), 3.54
(m, 2H), 3.62 (m, 2H), 3.71 (m, 2H), 3.78e3.83 (m, 4H), 3.83e3.92
(m, 10H), 3.94e4.02 (m, 6H), 4.10 (s, 1H), 4.19 (s, 2H), 4.25 (m, 2H),
4.68 (s, 2H), 5.78 (s, 8H), 6.05 (d, J¼9.0 Hz, 2H), 7.10e7.20 (m, 3H),
7.39 (d, J¼5.2 Hz, 1H), 7.62 (br, 8H), 7.73 (d, J¼5.2 Hz, 1H), 7.87 (s,
150 MHz):
d
¼11.2, 14.0, 15.5, 27.6 29.3, 67.0, 67.1, 69.7, 70.2, 70.9,
71.0, 126.3, 129.0, 131.7, 136.9, 137.4, 138.2, 138.8, 139.5 ppm; HRMS
(ESI): found m/z¼771.2715 [MþNa]þ; C34H60O6S2SnNa requires
771.2755.
8H), 8.95 (br, 8H); 13C NMR (CD3CN, 150 MHz):
d
¼15.3, 24.4, 27.0,
65.7, 66.7, 66.8, 67.1, 69.0, 70.0, 70.1, 70.5, 70.7, 71.0, 71.1, 71.2, 71.5,
71.6, 71.7, 74.9, 115.9, 123.2, 124.3, 125.1, 125.7, 125.8, 127.8, 128.3,
130.5, 131.5, 131.7, 131.8, 138.2, 139.2, 139.5, 141.0, 142.8, 145.9, 148.7,
154.0, 160.4 ppm; IR (KBr): 3132, 3064, 2964, 2926, 2870, 1637,
Compound 9: The compounds 4 (4.6 g, 9.9 mmol), 5 (1.0 g,
5.8 mmol), and K2CO3 were mixed in dry DMF (20 mL). The reaction
mixture was stirred at 100 ꢁC under Ar atmosphere for 16 h. The
solvent was removed by evaporation. The residue was dissolved in
CH2Cl2 (200 mL) and washed with 1 N NaHCO3 (200 mL) and 1 N
NaCl (200 mL) aqueous solutions. The organic layer was dried
(MgSO4), filtered, and evaporated. The residue was purified by
column chromatography (SNAP Cartridge silica 100 g, hexane/
1560, 1508, 1448, 1348, 1298, 1257, 1107, 840, 790, 640, 557 cmꢀ1
;
HRMS (ESI): found m/z¼502.5465 [Mꢀ3PF6]3þ; C82H98F6N4O10PS2
requires 502.5455.
Compound 11: BEDOT (1.5 g, 5.3 mmol) was dissolved in dry THF
(30 mL) under Ar. The solution was cooled to ꢀ60 ꢁC using a liquid

T. Ikeda, M. Higuchi / Tetrahedron 67 (2011) 3046e3052
3051
N2/CHCl3 bath. The hexane solution of n-BuLi (2.0 mL, 5.5 mmol)
was added dropwise with the gas-tight syringe. The reaction mix-
ture was stirred under dark. The reaction temperature was gradu-
ally raised to ꢀ15 ꢁC using an ice bath. After 1 h, the reaction
mixture was cooled to ꢀ60 ꢁC again using a liquid N2/CHCl3 bath.
Tri-n-butyltin chloride (ClSn(n-Bu)3, 1.4 mL, 5.2 mmol) was added
dropwise to the reaction mixture. The reaction temperature was
gradually raised to room temperature by removing the liquid N2/
CHCl3 bath. After 1 h, CH2Cl2 (200 mL) was added to the reaction
mixture and washed with 1 N NaHCO3 (200 mL) aqueous solution.
The organic layer was dried (MgSO4), filtered, and evaporated. The
residue was purified by the preparative HPLC (Linearly connected
columns of JAIGEL-1H and JAIGEL-2H, CHCl3) to give the compound
11 as a dark green oil. Yield: 1.5 g (49%). 1H NMR (CDCl3, 600 MHz):
155.9 ppm; IR (KBr): 3128, 3064, 2964, 2929, 2872,1635,1560,1518,
1473, 1442, 1363, 1280, 1253, 1180, 1157, 1089, 1066, 945, 839, 789,
740, 640, 559, 519, 418 cmꢀ1; HRMS (ESI): found m/z¼443.8200
[Mꢀ3PF6]3þ; C72H74F6N4O8PS2 requires 443.8197.
2T-dumbbell: 1H NMR (CD3CN, 600 MHz):
d¼1.21 (t, J¼7.0 Hz,
6H), 3.51 (m, 4H), 3.54e3.61 (m, 8H), 3.61e3.67 (m,10H), 3.72e3.78
(m, 6H), 3.89 (t, J¼4.8 Hz, 2H), 4.17 (t, J¼4.8 Hz, 2H), 4.41 (s, 2H),
4.48 (s, 2H), 6.93 (d, J¼9.0 Hz, 2H), 7.18 (d, J¼4.8 Hz,1H), 7.28 (s,1H),
7.33 (d, J¼5.4 Hz, 1H), 7.51 (d, J¼9.0 Hz, 2H); 13C NMR (CD3CN,
150 MHz):
d
¼15.5, 62.1, 67.0, 67.1, 67.2, 67.8, 69.8, 70.1, 70.2, 70.7,
70.9, 71.0, 71.2, 72.8, 115.4, 124.0, 126.6, 127.3, 129.2, 131.1, 138.8,
139.7,145.1,158.9; IR (KBr): 3088, 2970, 2866,1606,1508,1458,1348,
1292, 1251, 1179, 1111, 937, 889, 827, 748, 698 cmꢀ1; HRMS (ESI):
found m/z¼705.2752 [MþNa]þ; C34H50O10S2Na requires 705.2743.
d
¼0.90 (t, J¼7.3 Hz, 9H), 1.12 (t, J¼7.8 Hz, 6H), 1.34 (m, 6H), 1.56 (m,
BEDOT-dumbbell: 1H NMR (CD3CN, 600 MHz):
d¼2.87
6H), 4.18 (m, 2H), 4.24 (m, 2H), 4.27 (m, 2H), 4.33 (m, 2H), 6.24 (s,
1H).
(t, J¼5.8 Hz, 1H), 3.52 (t, J¼5.5 Hz, 2H), 3.58e3.63 (m, 4H), 3.65 (m,
2H), 3.80 (m, 2H), 4.13 (m, 2H), 4.24 (m, 2H), 4.32e4.36 (m, 6H),
6.36 (s, 1H), 6.96 (d, J¼9.0 Hz, 2H), 7.64 (d, J¼9.0 Hz, 2H); 13C NMR
BEDOT-dumbbell: The compounds 9 (0.65 g, 1.8 mmol), 11
(0.75 g, 1.8 mmol), and Pd(PPh3)4 (30 mg, 3.5ꢂ10ꢀ5 mol) were
dissolved in dry DMF (5 mL). The solution was deaerated three
times. The reaction mixture was stirred under dark and Ar atmo-
sphere at 65 ꢁC for 16 h. The solvent was removed in vacuo. The
residue was directly subjected to the column chromatography
(SNAP Cartridge silica 50 g, CH2Cl2/AcOEt: 3%¼2 column, 3/15%¼
4 column, 15%¼4 column). The recovered fraction containing the
product was purified by the preparative HPLC (Linearly connected
columns of JAIGEL-1H and JAIGEL-2H, CHCl3) to give BEDOT-
dumbbell as a pale yellow oil. Yield: 0.68 g (78%). 1H NMR (CD3CN,
(CD3CN, 150 MHz):
d
¼61.9, 65.5, 65.7, 65.8, 66.0, 68.4, 70.2, 71.0,
71.3, 73.3, 98.5, 107.6, 110.2, 114.9, 115.8, 126.8, 127.9, 138.1, 138.2,
138.7, 142.4, 158.5; IR (KBr): 3107, 2918, 2874, 1602, 1572, 1521,
1502, 1471, 1437, 1361, 1282, 1247, 1170, 1114, 1085, 1066, 1028, 945,
904, 856, 831, 744, 675, 636, 522, 416 cmꢀ1; HRMS (ESI): found m/z
¼529.0931 [MþNa]þ; C24H26O8S2Na requires 529.0967.
Acknowledgements
This work was financially supported by Grant-in-Aid for Young
Scientists B, 22750175. The authors thank Bio-Organic Materials
Facility of Nanotechnology Innovation Center in NIMS for the NMR
measurement.
600 MHz):
d
¼1.20 (d, J¼7.2 Hz, 12H), 3.41 (m, 2H), 3.71 (m, 4H),
3.80 (m, 2H), 3.85 (m, 2H), 3.88 (m, 2H), 4.16 (m, 2H), 4.25 (m, 2H),
4.32e4.36 (m, 6H), 6.36 (s, 1H), 6.96 (d, J¼8.6 Hz, 2H), 7.08e7.16 (m,
3H), 7.63 (d, J¼8.6 Hz, 2H); 13C NMR (CD3CN, 150 MHz):
¼24.3,
d
26.9, 65.6, 65.7, 65.8, 66.0, 68.5, 70.4, 71.2, 71.5, 75.0, 98.5, 107.6,
110.3,115.0,115.8,125.0,125.6,126.8,127.9,138.1,138.2,138.7,142.5,
142.9, 154.1, 158.6 ppm; IR (KBr): 3105, 2960, 2924, 2868, 1602,
1572, 1521, 1504, 1473, 1438, 1361, 1282, 1249, 1186, 1120, 1087,
1066, 945, 904, 829, 796, 761, 713, 675, 636, 522, 418 cmꢀ1; HRMS
(ESI): found m/z¼689.2190 [MþNa]þ; C36H42O8S2Na requires
689.2219.
Supplementary data
1H and 13C NMR spectra, 2D ROESY spectra, high-resolution ESI-
MS spectra of key compounds, and UV/vis spectrum of the dumbbell-
shaped compounds are available. Supplementary data associated
with this article can be found in online version at doi:10.1016/
j.tet.2011.03.009. These data include MOL files and InChIKeys of the
most important compounds described in this article.
BEDOT-[2]Rx: BEDOT-dumbbell (0.35 g, 0.52 mmol), 10 (1.1 g,
1.6 mmol), and a,a
0-dibromo-p-xylene (0.41 g, 1.6 mmol) were dis-
solved in dry DMF (10 mL). The mixture was stirred at room tem-
perature under dark and Ar atmosphere for 7 days. AcOEt was added
to the solution. The solution and the precipitate were directly sub-
jected to the column chromatography (SiO2). BEDOT-dumbbell and
other impurities were eluted out by AcOEt, and then CH2Cl2/
MeOH¼9:1. The product was eluted out the mixed solvent (MeOH/
2 N NH4Cl aq/MeNO2¼6:3:1). The recovered green solution was
concentrated, then the residue was subjected to the column chro-
matography again (SiO2, MeOH/2 N NH4Cl aq/MeNO2¼6:3:1). The
recovered green solutionwas concentrated to the half volume by the
evaporation. An aqueous solution of NH4PF6 was added until no
further precipitation occurred. The green-color precipitate was re-
covered byfiltration. Theprecipitatewas dissolvedin Me2COand the
solution was added to the NH4PF6 aqueous solution to complete the
counter-ion exchange. The precipitate was recovered by filtration,
washed with small amount of pure water, and dissolved in Me2CO.
After the evaporation, the product BEDOT-[2]Rx was obtained as
a green solid. Yield: 74 mg (8%). Mp: >280 ꢁC; 1H NMR (CD3CN,
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