Amphiphilic viologen: Electrochemical generation of organic reductant and pd-catalyzed reductive coupling of aryl halides in water

Article abstract of DOI:10.1055/s-0032-1317857

Electroreduction of 1,1′-bis(methoxyethoxyethoxyethyl)-4,4′- bipyridinium tosylate generated amphiphilic organic reductants, which promoted the Pd-catalyzed reductive coupling of aryl bromides in water to give the corresponding biaryls. The yields and selectivity of biaryls depended on the length of ethyleneoxy groups and substituents of the aryl bromides. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317857

LETTER
▌197
lAettmer phiphilic Viologen: Electrochemical Generation of Organic Reductant and
Pd-Catalyzed Reductive Coupling of Aryl Halides in Water
Amphiphilic Viologen
Manabu Kuroboshi,* Takashi Yamamoto, Hideo Tanaka*
The Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 3-1-1, Kita-Ku, Okayama 700-8530, Japan
Fax +86(255)3424; E-mail: tanaka95@cc.okayama-u.ac.jp
Received: 10.10.2012; Accepted after revision: 16.11.2012
ter, whereas the corresponding V0 is insoluble in water.5,6
Abstract: Electroreduction of 1,1′-bis(methoxyethoxyethoxyethyl)-
We found that amphiphilic viologens V2+/quinoids V0
4,4′-bipyridinium tosylate generated amphiphilic organic reduc-
having poly(ethylene glycol) (PEG) groups dissolve in
tants, which promoted the Pd-catalyzed reductive coupling of aryl
bromides in water to give the corresponding biaryls. The yields and
water, and the quinoids V0 work as reductants in an aque-
selectivity of biaryls depended on the length of ethyleneoxy groups ous medium. In this paper, we describe that reductive cou-
and substituents of the aryl bromides.
pling of aryl bromides proceeds in water by using the
PEG-modified amphiphilic viologen 1a.
Key words: electron transfer, palladium, reduction, coupling,
arenes
PEG-modified amphiphilic viologen, 1,1′-bis(methoxy-
ethoxyethoxyethyl)-4,4′-bipyridinium tosylate (1a), was
prepared by treatment of 4,4′-bipyridyl with two molar
amount of Me(OCH2CH2)3OTs at 120 °C in 96% yield as
a brown viscous oil.7 In a similar manner, viologen 1b–e
[1b: R = MeOCH2CH2, 1c: R = Me(OCH2CH2)2, 1d: R =
Me, 1e: R = Bu] were prepared by treatment of 4,4′-bi-
pyridyl with MeOCH2CH2OTs, Me(OCH2CH2)2OTs,
MeOTs, and BuOTs, respectively.8 Viologen 1a was sol-
uble in water and MeOH, whereas 1a was insoluble in
usual organic solvents such as hexane, Et2O, toluene, and
EtOAc. A cyclic voltammogram of 1a in an aqueous
Et4NOTs (0.2 M) solution (vs. Ag/AgCl) exhibited
two sets of reversible redox peaks at –0.57 V (1a/V•+) and
–1.00 V (V•+/2a; Figure 1). Yields and redox potential val-
ues of 1b–e are summarized in Table 1.
Organic reactions in water are of current interest in organ-
ic synthesis.1 Water is a cheap, nonflammable, and non-
toxic solvent. In addition, the reactions are accelerated
and unique selectivity is observed caused by hydrophobic
effects. Water is also an ideal solvent for electroorganic
synthesis2,3 since dielectric constant of water is high
enough to pass electricity efficiently in the presence of a
small amount of supporting electrolytes.
Viologen derivatives (1,1′-dialkyl-4,4′-bipyridinium salt,
V2+) are easily prepared by N-alkylation of 4,4′-bipyridyl
and are stable in the air. Reduction of V2+ gives the corre-
sponding radical cation V•+ and quinoid V0 (Scheme 1),
both of them work as organic reductants.4
Table 1 Yields and Redox Potential Values of Compounds 1a–e
cathode
Entry Viologen
R
Yield (%)a E1/2b/V
2 p-TsO–
1a [V2+, R = Me(OCH2CH2)3]
R
N
N R
1/V•+
V•+/2
+ e–
1
2
3
4
5
1a
1b
1c
1d
1e
Me(OCH2CH2)3
MeOCH2CH2
Me(OCH2CH2)2
Me
96
87
62
82
86
–0.57 –1.00
–0.55c –0.93c
–0.57 –1.01
–0.58c –0.96c
–0.52c –0.92c
2 p-TsO–
R
N
N
N
N
R
R
V·+
+ e–
R
2a (V0)
Bu
a Isolated yield.
Ar Br
2
Ar Ar
Ar
H
+
Pd catalyst
H2O
b Viologen (10 mM), Et4NOTs (0.2 M), H2O, (GC)–(Pt)–(Ag/AgCl),
scan rate: 100 mV/s; reversible peaks. E1/2 = (Epa + Epc)/2; Epa = anod-
ic peak potential value; Epc = cathodic peak potential value.
c In MeCN–H2O (3:1).
5
3
4
Scheme 1 Electrochemical preparation and Pd-catalyzed reductive
coupling of aryl bromides
The viologen V2+/quinoid V0 redox pair is usually used in
organic–aqueous mixed solvent since V2+ dissolves in wa-
A typical procedure of electroreduction of 1a to 2a and
subsequent reductive coupling of aryl bromide 3a in water
is as follows. The electroreduction was carried out in a di-
vided cell equipped with an Mg rod anode (ø 0.6 cm) and
a Pt plate cathode (1.0 × 1.5 cm2). In the cathodic chamber
SYNLETT 2013, 24, 0197–0200
Advanced online publication: 13.12.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317857; Art ID: ST-2012-U0872-L
© Georg Thieme Verlag Stuttgart · New York

198
M. Kuroboshi et al.
LETTER
Table 2 Effects of Viologen on the Reductive Coupling of 4-Bromo-
propiophenone (3a)
Entry Viologen
R
Yield of Yield of Yield of
4a (%)a 5a (%)b 3a (%)b
1
2
3
4
5
1a
1b
1c
1d
1e
Me(OCH2CH2)3
MeOCH2CH2
Me(OCH2CH2)2
Me
90
30
59
17
31
8
12
8
0
45
19
53
49
25
6
Bu
a Isolated yield.
b Determined by 1H NMR.
Figure 1 Cyclic voltammogram of 1a. Reagents and conditions: 1a
(10 mM), aq Et4NOTs (0.2 M, 10 mL); working electrode: GC, coun-
ter electrode: Pt, reference electrode: Ag/AgCl, scan rate: 100 mV/s.
Among thus far examined catalysts, Pd(OAc)2 gave the
best result (Table 3, entry 1). PdCl2 and Pd2(dba)3 gave
4a/5a/3a in 26%, 18%, and 53% yields and 62%, 9%, and
23% yields, respectively (Table 3, entries 2 and 3). Pd/C
(10% Pd/C) gave the reduced product 5a as a major prod-
uct (26% yield, Table 3, entry 4). Palladium catalyst was
indispensable: the reductive coupling reaction did not oc-
cur in the presence of Ni catalysts in place of Pd catalysts
(Table 3, entries 5 and 6) and in the absence of catalysts
(Table 3, entry 7).
was placed an aqueous NaClO4 (0.2 M, 4 mL) solution of
1a (0.5 mmol), and in the anodic chamber was placed an
aqueous NaClO4 (0.2 M, 4 mL) solution. Electroreduction
of 1a was carried out at room temperature under constant
current conditions (30 mA) until 2 F/mol 1a of electricity
was passed to afford a dark purple solution of 2a. To a
mixture of 3a (0.25 mmol) and a catalytic amount of
Pd(OAc)2 (5 mol%) was added the catholyte by cannula-
tion, and the whole mixture was stirred at 60 °C for four
hours under argon atmosphere. After usual workup, the
desired coupling product, 4,4′-dipropanoylbiphenyl (4a)
and reduced byproduct propiophenone (5a) were obtained
in 90% and 8% yield, respectively (Table 2, entry 1).
The PEG group of 1a played an important role:9 Quinoids
2 derived from methyl viologen 1d and butyl viologen 1e
gave 4a/5a in 17% and 25% and 31% and 6% yields, re-
spectively, and half of the starting material 3a was recov-
ered unchanged (Table 2, entries 4 and 5). The length of
the PEG groups [n of Me(OCH2CH2)n] also affected on
the yields of 4a. Viologen having methoxyethyl group
(1b, n = 1) gave a similar result (4a/5a/3a = 30%, 12%,
and 45%, Table 2, entry 2) with butyl viologen 1e.
Though homocoupling of 3a with methoxyethoxyethyl-
ated viologen 1c (n = 2) gave 4a as a major product
Table 3 Effects of Catalyst
Entry
Catalyst
Yield of 4a Yield of 5a Yield of 3a
(%)a
(%)b
(%)b
1
2
3
4
5
6
7
Pd(OAc)2
PdCl2
90
8
0
53
23
56
26
18
Pd2(dba)3
10% Pd/C
Ni(OAc)2·4H2O
NiBr2(bpy)
none
62
9
9
26
n.d.c
n.d.c
n.d.c
n.d.c
n.d.c
n.d.c
a Isolated yield.
b Determined by 1H NMR.
(4a/5a/3a = 59%, 8%, and 19%, Table 2, entry 3), 1c was c Not detected.
less effective than 1a. The ethyleneoxy group in viologen
would increase the solubility of the reduced form 2 in wa-
ter. In addition, the substrate 3a and Pd catalyst would in-
teract with the ethyleneoxy group of 2a to make an
aggregate (Figure 2), and therefore, electron transfer and
oxidative addition would proceed smoothly.
The reductive coupling was carried out with several aryl
halides (Table 4).
The coupling of aryl bromides having electron-withdraw-
ing groups such as keto (3b) and cyano (3c,d) groups pro-
ceeded smoothly to give the corresponding biaryls 4b, 4c,
and 4d in good yields (Table 4, entries 1–3). Heteroaro-
matic compound, 2-acetyl-5-bromothiophene (3e), gave
dithiophene 4e in 82% yield (Table 4, entry 4). Unsubsti-
tuted bromobenzene (3f) gave biphenyl 4f in 75% yield
(Table 4, entry 5). On the other hand, aryl bromides hav-
ing electron-donating groups such as dimethylamino (3g),
methyl (3h), and hydroxyl (3i) groups gave the corre-
N
N R
e–
Ar
Br
Pd
O
OMe
O
Figure 2 A plausible aggregate of amphiphilic quinoid 2a, Pd cata-
lyst, and substrate ArBr
Synlett 2013, 24, 197–200
© Georg Thieme Verlag Stuttgart · New York

LETTER
Amphiphilic Viologen
199
ArPd(II)Br with V0 would afford [ArPd(0)]–. The subse-
quent reaction of [ArPd(0)]– with additional ArBr would
produce ArPd(II)Ar. Reductive coupling from ArPd(II)Ar
would give Ar–Ar 4 and Pd(0) species. Dissociation of
[ArPd(0)]– to Ar– and Pd(0) followed by protonation
would give ArH 5.
Pd(II)
V0
V2+
Ar-Ar
Pd(0)
Ar-Br
Ar-Pd(II)-Ar
Ar-Pd(II)-Br
V0
Substituents on the ArBr affect the reduction of Ar-
Pd(II)Br to [ArPd(0)]–: Electron-withdrawing substitu-
ents would decrease the electron density of Pd in
ArPd(II)Br to accelerate the reduction giving [ArPd(0)]–,
whereas electron-donating substituents would increase
the electron density to prevent the reduction. In the case of
ArCl, oxidative addition of ArCl on the Pd(0) and/or
[ArPd(0)]– would not occur efficiently.
In conclusion, amphiphilic organic reductant V0, electro-
chemically generated from 1,1′-bis(methoxyethoxy-
ethoxyethyl)-4,4′-bipyridinium (V2+) tosylate (1a),
promoted the Pd-catalyzed reductive coupling of aryl bro-
mides in water to give the corresponding biaryls. The
yields and selectivity of biaryls were affected by the
length of ethyleneoxy groups and substituents of the aryl
bromides.10
Br–
[Ar-Pd(0)]–
V2+
Br–
Ar-Br
Scheme 2 A plausible mechanism
sponding biaryls 4g, 4h, and 4i in moderate yields (Table
4, entries 6–8). 4-Iodobenzonitrile (3j) and 4-choropropi-
ophenone (3l) gave the corresponding biaryls in low
yields, and homocoupling of 4-chlorobenzonitrile (3k)
did not proceed at all (Table 4, entries 9–11).
Table 4 Reductive Coupling of Several Aryl Halides
Entry ArX
Temp
(°C)
Time Yield of 4
(h)
6
(%)a
1
2
3b
60
66
BuC(O)
NC
Br
Acknowledgment
This work was supported by JSPS KAKENHI Grant Number
22550102 and Shorai Foundation for Science and Technology. The
authors thank Mrs. Takamuru Atsuko, Okayama University, for ele-
mental analyses.
Br
3c 100
4
74
92
Br
S
3
3d
60
24
NC
References and Notes
MeC(O)
Br
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4
5
6
7
8
9
3e 100
4
24
24
24
22
4
82
75
45
25
34
29
H
Br
3f
60
80
60
60
Me2N
Me
HO
NC
Br
3g
3h
3i
Br
Br
I
(2) Tanaka, H.; Kuroboshi, M. Yuki Denkai Gosei no
Shintenkai; Fuchigami, T., Ed.; CMC: Tokyo, 2004, 216–
228.
3j 100
3k 100
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F.; Kubota, J.; Tanaka, H. Tetrahedron Lett. 2007, 48, 8994.
(e) Kuroboshi, M.; Yoshida, T.; Oshitani, J.; Goto, K.;
Tanaka, H. Tetrahedron 2009, 65, 7177.
NC
Cl
10
24
24
0
..
EtC(O)
Cl
11
3l
60
31
(4) (a) Endo, T.; Saotome, Y.; Okawara, M. Tetrahedron Lett.
1985, 26, 4525. (b) Park, K. K.; Lee, C. W.; Choi, S. Y. J.
Chem. Soc., Perkin Trans. 1 1992, 601. (c) Tomioka, H.;
Ueda, K.; Ohi, H.; Izawa, Y. Chem. Lett. 1986, 1359.
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Chem. Soc. 1984, 106, 6217. (e) Park, K. K.; Lee, C. W.; Oh,
S. Y. J. Chem. Soc., Perkin Trans. 1 1990, 2356.
a Isolated yield of biaryl 4.
A plausible mechanism of the reductive coupling is as fol-
lows (Scheme 2). Pd(II) species would be reduced with V0
to give Pd(0) active species. Oxidative addition of ArBr 3
on the Pd(0) would give ArPd(II)Br. Reduction of
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 197–200

200
M. Kuroboshi et al.
LETTER
1,1′-Bis(3,6-dioxaheptyl)-4,4′-bipyridinium Bis(p-
(f) Shosenji, H.; Nakano, Y.; Yamada, K. Chem. Lett. 1988,
1033. (g) Mandler, D.; Willner, I. J. Phys. Chem. 1987, 91,
3600. (h) Coche, L.; Moutet, J. C. J. Am. Chem. Soc. 1987,
109, 6887. (i) Kashiwagi, Y.; Shibayama, N.; Anzai, J.; Osa,
T. Electrochemistry 2000, 68, 42. (j) Yuan, R.; Watanabe,
S.; Kuwabata, S.; Yoneyama, H. J. Org. Chem. 1997, 62,
2494. (k) Chen, X.; Fenton, J. M.; Fisher, R. J.; Peattie, R. A.
J. Electrochem. Soc. 2004, 2, E56.
toluenesulfonate) (1c)
Colorless solids. 1H NMR (200 MHz, D2O): δ = 2.15 (s, 6
H), 3.09 (s, 6 H), 3.32–3.36 (m, 4 H), 3.44–3.49 (m, 4 H),
3.86 (t, J = 4.4 Hz, 4 H), 4.63–4.76 (m, 4 H), 7.11 (d, J = 7.7
Hz, 4 H), 7.42 (d, J = 7.7 Hz, 4 H), 8.30 (d, J = 6.2 Hz, 4 H),
8.89 (d, J = 6.2 Hz, 4 H). 13C NMR (150 MHz, CD3OD): δ =
21.3, 59.1, 62.7, 70.0, 71.2, 72.7, 126.9, 127.7, 129.9, 141.6,
143.7, 147.6, 151.2. IR (KBr): 3509, 3131, 3055, 2879,
1640, 1442, 1192, 1123, 1033, 685 cm–1.
(5) Octyl viologen bis(triflimide) and the corresponding quinoid
dissolve in organic solvent to promote the reductive
homocoupling of aryl halide. See: Kuroboshi, M.;
Kobayashi, R.; Nakagawa, T.; Tanaka, H. Synlett 2009, 85.
(6) Viologen also promotes the reductive homocoupling of aryl
halides in ionic liquid. See: Kuroboshi, M.; Kuwano, A.;
Tanaka, H. Electrochemistry 2008, 862.
1,1′-Dimethyl-4,4′-bipyridinium Bis(p-toluenesulfonate)
(1d)
Yellow solids. 1H NMR (200 MHz, D2O): δ = 2.18 (s, 6 H),
4.31 (s, 6 H), 7.13 (d, J = 8.2 Hz, 4 H), 7.45 (d, J = 8.2 Hz,
4 H), 8.25 (d, J = 6.9 Hz, 4 H), 8.81 (d, J = 6.9 Hz, 4 H). 13
NMR (150 MHz, CD3OD): δ = 21.3, 49.0, 126.8, 127.6,
130.0, 141.6, 143.7, 147.8, 150.4. IR (KBr): 3444, 3053,
C
(7) Preparation of 1a
In a round-bottomed flask were placed 4,4′-bipyridyl (3.531
g, 23 mmol) and 3,6,9-trioxadecyl p-tosylate (14.39 g, 45
mmol). The mixture was stirred at 120 °C for 24 h under
argon atmosphere to form a viscous layer. The supernatant
was decanted off, and the viscous layer was washed with
Et2O and toluene (2 × 10 mL), successively. The viscous
liquid layer was concentrated under reduced pressure to give
1,1′-bis(3,6,9-trioxadecyl)-4,4′-bipyridinium bis(p-
toluenesulfonate) (1a, 17.14 g, 22 mmol, 96%) as a brown
liquid. 1H NMR (200 MHz, CDCl3): δ = 2.28 (s, 6 H), 3.28
(s, 6 H), 3.42–3.53 (m, 16 H), 3.85 (br, 4 H), 4.93 (br, 4 H),
7.11 (d, J = 8.1 Hz, 4 H), 7.69 (d, J = 8.1 Hz, 4 H), 8.71 (d,
J = 6.8 Hz, 4 H), 9.24 (d, J = 6.8 Hz, 4 H). 13C NMR (150
MHz, CDCl3): δ = 21.04, 58.69, 61.18, 68.89, 69.91, 70.08,
70.14, 71.56, 125.66, 126.64, 128.71, 1139.42, 143.25,
146.60, 148.87; IR (neat): 3464, 3127, 3059, 2921, 2876,
1638, 1451, 1191, 1122, 822 cm–1.
3020, 2994, 1642, 1509, 1440, 1358, 1208, 1119, 818, 683
cm–1.
1,1′-Dibutyl-4,4′-bipyridinium Bis(p-toluenesulfonate)
(1e)
Colorless solids. 1H NMR (200 MHz, D2O): δ = 0.71 (t, J =
7.4 Hz, 6 H), 1.13 (sext, J = 7.4 Hz, 4 H), 1.76 (quin, J = 7.4
Hz, 4 H), 2.07 (s, 6 H), 4.40 (t, J = 7.4 Hz, 4 H), 7.01 (d, J =
8.1 Hz, 4 H), 7.32 (d, J = 8.1 Hz, 4 H), 8.16 (d, J = 6.7 Hz, 4
H), 8.77 (d, J = 6.7 Hz, 4 H). 13C NMR (150 MHz, CD3OD):
δ = 13.8, 20.4, 21.3, 34.3, 62.9, 126.9, 128.2, 129.9, 141.6,
143.7, 147.0, 151.0. IR (KBr): 3434, 3127, 3054, 2957,
2870, 1643, 1450, 1169, 1120, 1035, 818 cm–1.
(9) Viologens V2+ were easily soluble in H2O, whereas the
reduced form V0 were soluble in organic solvents.
Therefore, viologens were used in a mixed solution of H2O–
MeOH or H2O–MeCN. The amphiphilic PEG group would
increase the solubility of V2+/V0 as well as the substrates.
(10) Recycle use of aqueous viologen/Pd solution was also
examined. In the second run, the recovered aqueous solution
was placed in the cathodic chamber. The electroreduction
was carried out under constant current conditions to generate
V0. Though the reaction conditions have not been optimized
yet, 4a was obtained in 40% yield.
(8) 1,1′-Bis(2-methoxyethyl)-4,4′-bipyridinium Bis(p-
toluenesulfonate) (1b)
Colorless solids. 1H NMR (200 MHz, D2O): δ = 2.13 (s, 6
H), 3.19 (s, 6 H), 3.79 (t, J = 5.0 Hz, 4 H), 4.68 (t, J = 5.0 Hz,
4 H), 7.08 (d, J = 8.3 Hz, 4 H), 7.40 (d, J = 8.3 Hz, 4 H), 8.26
(d, J = 7.0 Hz, 4 H), 8.85 (d, J = 7.0 Hz, 4 H). 13C NMR (50
MHz, CD3OD): δ = 21.3, 59.2, 62.7, 71.3, 126.8, 127.8,
129.8, 141.6, 143.5, 147.5, 151.3. IR (KBr): 3532, 3451,
3134, 3062, 2992, 2864, 1639, 1510, 1448, 1191, 1120,
1035, 568 cm–1.
Synlett 2013, 24, 197–200
© Georg Thieme Verlag Stuttgart · New York