Viologen as catalytic organic reductant: Electro-reductive dimerization of aryl bromides in a Pd/viologen double mediatory system

Article abstract of DOI:10.1016/j.tetlet.2013.04.127

Viologen can be used as an in situ recyclable organic reductant. Pd-catalyzed electrochemical reductive coupling of aryl bromides was performed by using a catalytic amount of viologen to afford the corresponding biaryls in good to moderate yields.

Full text of DOI:10.1016/j.tetlet.2013.04.127

Tetrahedron Letters 54 (2013) 3666–3668
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Tetrahedron Letters
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Viologen as catalytic organic reductant: electro-reductive dimerization
of aryl bromides in a Pd/viologen double mediatory system
⇑
Manabu Kuroboshi, Takuya Shiba, Hideo Tanaka
The Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 3-1-1, Kita-Ku, Okayama 700-8530, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Viologen can be used as an in situ recyclable organic reductant. Pd-catalyzed electrochemical reductive
coupling of aryl bromides was performed by using a catalytic amount of viologen to afford the corre-
sponding biaryls in good to moderate yields.
Received 10 April 2013
Revised 29 April 2013
Accepted 30 April 2013
Available online 10 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Electroreduction
Viologen
Pd catalyst
Reductive coupling of aryl halide
Mediatory system
Reduction is one of the most basic organic reactions, and many
reductants such as metals, metal hydrides, and inorganic reduc-
tants have been developed. Compared to these reductants, organic
reductants have several advantages: (1) organic reductants are
soluble in organic solvents to accelerate electron transfer to the
substrates. (2) Modification of the reductants controls the redox
potential to prevent side reactions such as over-reduction. (3) A
catalytic amount of organic reductant can be used repeatedly when
the redox process of the organic reductant is reversible. 1,10-Dial-
kyl-4,40-bipyridinium (V2+) salts are potent precursors of organic
reductants. Though V2+ itself does not work as a reductant, quinoid
V0 which is generated by electroreduction of V2+ works as an
organic reductant.1 Recently, we reported that V0 promotes the
Pd-catalyzed reductive coupling of aryl halides (Ar-X) to afford
the corresponding biaryls Ar–Ar.2–4 Ar–Ar have been widely used
as functional materials such as liquid crystals and heat-resistance
compounds as well as bioactive compounds. However, (1) electro-
reduction of V2+ to V0 should be executed prior to the reductive
coupling, (2) V0 is intolerable for air-oxidation and should be trea-
ted under an inactive atmosphere, (3) an excess (more than
2 mol equiv) amount of V0 is required to complete the reductive
coupling, and (4) recovery of V2+ is not necessarily efficient be-
cause of radical–radical coupling of VÅ+. Since redox processes of
both VÅ+/V2+ and V0/VÅ+ are reversible (vide infra), V0 is expected
to play as a recyclable organic reductant. In this Letter, we describe
that the electroreductive homocoupling of Ar–Br to the
corresponding Ar–Ar was performed successfully by use of cata-
lytic amounts of viologens and Pd species (Scheme 1).
1,10-Dioctyl-4,40-bipyridinium bis(trifluimide) [OctV2+][Tf2Nꢀ]2
was prepared as follows. A mixture of 1-bromooctane (45.6 mmol)
and 4,40-bipyridyl (19.0 mmol) in DMF (20 mL) was heated to
105 °C for 18 h to give 1,10-dioctyl-4,40-bipyridinium dibromide
([OctV2+][Brꢀ]2,5 18.6 mmol, 98%) as brilliant greenish yellow sol-
ids.
A
mixture of CH2Cl2 (10 mL) solution of [OctV2+][Brꢀ]2
(5.54 mmol) and an aqueous solution (5 mL) of Li+[Tf2Nꢀ]
(13.7 mmol) was stirred vigorously at room temperature for
30 min to give [OctV2+][Tf2Nꢀ]26 (5.15 mmol, 93%) as colorless sol-
ids. Cyclic voltammogram of [OctV2+][Tf2Nꢀ]2 shows two pairs of
reversible redox peaks attributable to VÅ+/V2+ (E1/2 = ꢀ0.43 V vs
2 R
2 R
2 R
N
N
N
N
N
N
R
+ 2 e-
+ 2 e-
(V2+
)
Ar Ar
Pd cat.
R
(V+·)
R
(V0)
2 Ar
X
Scheme 1. Redox reactions of VÅ+/V2+ and V0/VÅ+ and V0/Pd-catalyzed homo-
,
coupling of aryl halides.
⇑
Corresponding author. Tel.: +81 86 251 8074.
E-mail address: mkurohos@cc.okayama-u.ac.jp (H. Tanaka).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.127

M. Kuroboshi et al. / Tetrahedron Letters 54 (2013) 3666–3668
3667
is also important9 (Table 1). Thus, in the absence of the Pd catalyst,
most of 1a (>90%) was recovered unchanged without formation of
a detectable amount of 2a (entry 2). When PdCl2 was used, 2a was
obtained in 26% yield together with 1a in 66% recovery (entry 3),
whereas Pd(OAc)2 gave mainly debrominated propiophenone 3a
(38%) without appreciable formation of 2a (entry 4). PdCl2(PhCN)2
and Pd2(dba)3 did not promote the coupling and most of 1a was
recovered (entries 5 and 6).
Among thus far examined solvents, polar aprotic solvents such
as DMF and NMP gave 2a in good yields (Table 2, entries 1 and 2).
In contrast, the yields of 2a decreased to 45%, 24%, and 19%, respec-
tively, when the reaction was carried out in DME, MeCN, and THF
(entries 3–5).9
50
0
-0.79
-0.30
-0.56
-50
-0.98
-0.8
V (vs. Ag/AgCl)
-100
-1.2
-0.4
0
To avoid undesired anodic reactions, such as re-oxidation of V0
to V2+, sacrificial anodes such as zinc, magnesium, and aluminum
were examined (Table 2).10 Among them, the coupling reaction oc-
curred only with Zn anode: neither Mg nor Al gave 2a at all, and 3a
was obtained in 11–20% yields as a by-product (entries 6 and 7).
These results indicate that electrogenerated Zn2+ from the Zn an-
ode would play a significant role for the reductive coupling of
1a.11,12
Figure 1. Cyclic voltammogram of THF solution of [OctV2+][Tf2Nꢀ]2 (25 mM) and
[Bu4N+][Tf2Nꢀ] (0.2 M). Working electrode: Pt (/ 1.5 mm), counter electrode: Ag
wire, reference electrode: Ag/AgCl. Scan rate: 100 mV/s.
Ag/AgCl) and V0/VÅ+ (E1/2 = ꢀ0.88 V7) (Fig. 1), suggesting that OctV0
is expected to play as a recyclable organic reductant.
The electroreductive coupling using a Pd/viologen double medi-
ator was applied successively to several aryl halides (Table 3) by
using 10 mol % of [OctV2+][Tf2Nꢀ]2 and 2.5 mol % of PdCl2(PPh3)2.
The coupling of aryl bromides 1b, 1c, and 1d, having electron-with-
drawing groups such as cyano, trifluoromethyl, and ethoxycar-
bonyl groups at p-position, proceeded smoothly to give the
corresponding biaryls 2b, 2c, and 2d, in good yields (entries 1–3).
Aryl bromides 1e and 1f, having the cyano group at m- and o-posi-
tions, gave the corresponding biaryls 2e and 2f in 87% and 65%
yields, respectively (entries 4 and 5). 4,40-Dialkylbiphenyls 2g
and 2h were also obtained from 4-bromotoluene 1g and 4-bro-
mo-tert-butylbenzene 1h in 90% and 68% yields, respectively (en-
tries 6 and 7). On the other hand, the homo-coupling of aryl
bromides 1i and 1j having electron-donating groups, such as meth-
oxy and dimethylamino groups, gave the corresponding biaryls 2i
and 2j in low yields (<30%) and most of the starting material was
recovered (entries 8 and 9). These results showed the different ten-
dency with the Pd-catalyzed electroreductive dimerization of aryl
halides without viologens,13 in which aryl halides having elec-
tron-donating substituents gave the corresponding products in
good yields (one-electron reduction), whereas aryl halides having
electron-withdrawing substituents gave Ar–H predominantly
(two-electron reduction). It is likely that electron-withdrawing
substituents would facilitate reduction of Ar–Pd(II)–Br 4 to [Ar–
Pd(0)]ꢀ 5, whereas electron-donating substituents would increase
the electron density on Pd of 4 to retard the reduction to 5. Since
the oxidative addition of Ar–Cl on Pd(0) species would not effi-
ciently occur, the reductive coupling of 4-chlorobromobenzene
A typical procedure of the electroreductive coupling of aryl bro-
mide 1 with catalytic amounts of [OctV2+][Tf2Nꢀ]2 and Pd species is
as follows. Into an undivided cell fitted with
a Zn anode
(1.5 ꢁ 1 cm2) and a Pt cathode (1.5 ꢁ 1 cm2) was added a DMF
(3 mL) solution of 4-bromopropiophenone (1a, 0.25 mmol),
[Bu4N+][Tf2Nꢀ]
(0.3 mmol),
[OctV2+][Tf2Nꢀ]2
(0.075 mmol,
30 mol %), and PdCl2(PPh3)2 (0.0125 mmol, 5 mol %). The whole
mixture was electrolyzed at 60 °C under constant current
(10 mA) conditions until 2 F/mol—1a of electricity was passed.
The reaction mixture was poured into 5% aq HCl and extracted
with AcOEt. Purification by column chromatography (SiO2, tolu-
ene/AcOEt = 10/1) afforded 4,40-dipropanoylbiphenyl (2a) in 94%
yield (Table 1, entry 1).
Viologen was indispensable for the coupling: since only a com-
plex mixture of unidentified products was obtained in the absence
of [OctV2+][Tf2Nꢀ]2,8 direct electroreduction of 1a would occur in
the absence of viologen. Proper choice of the palladium catalyst
Table 1
Effects of Pd catalysts
[OctV2+][Tf2N-]2 (30 mol%)
[Bu4N+][Tf2N-] (0.3 mmol)
O
Pd cat. (5 mol%)
Br
(Zn)–(Pt), Undiv. Cell
Et
DMF, 10 mA, 60 ºC, 2 F/mol-1a
1a
(0.25 mmol)
O
O
+
Table 2
2
Et
Et
Effects of solvents and anodesa
2a
3a
Entry
Solvent
Anode
Yieldb (%)
Entry
Pd cat.
Yielda (%)
2a
3a
1a
1
2
3
4
5
6
7
NMP
DMF
DME
MeCN
THF
Zn
Zn
Zn
Zn
Zn
Mg
Al
99
94
45
24
n.d.c
n.d.c
n.d.c
n.d.c
15
n.d.c
n.d.c
37
70
37
2a
3a
1a
1
2
PdCl2(PPh3)2
None
94
n.d.d
n.d.d
n.d.d
38
n.d.d
90c
66
45
91
n.d.d
26
3
PdCl2
4b
5
Pd(OAc)2
PdCl2(PhCN)2
Pd2(dba)3
n.d.d
n.d.d
n.d.d
19
NMP
NMP
n.d.c
n.d.c
11
20
54
41
n.d.d
n.d.d
6
81
a
Compound 1a (0.25 mmol), [OctV2+][Tf2Nꢀ]2 (30 mol %), PdCl2(PPh3)2 (5 mol %),
a
b
c
Isolated yield.
(anode)—(Pt), undivided cell, 60 °C, 10 mA, 2 F/mol—1a.
2.4 F/mol—1a of electricity was passed.
Determined by 1H NMR.
Not detected.
b
Determined by 1H NMR.
Not detected.
c
d

3668
M. Kuroboshi et al. / Tetrahedron Letters 54 (2013) 3666–3668
Table 3
of 4-chlorobenzonitrile 1l gave the corresponding biaryl 2b in only
3% yield (entry 11).
Electroreductive coupling of several aryl halidesa
Yieldb (%)
93
A plausible mechanism of the reductive coupling of aryl bro-
mide 1 is shown in Scheme 2. In the initial stage of the reaction,
OctV2+ would be reduced electrochemically to give quinoid OctV0,
which would reduce Pd(II) species to give ‘Pd(0)’ active species to-
gether with OctVÅ+.14 Oxidative addition of 1 on the ‘Pd(0)’ species
would give Ar–Pd(II)–Br 4. Reduction of 4 with electrogenerated
OctV0 would afford [Ar–Pd(0)]ꢀ 5. The subsequent reaction of 5
with 1 would produce Ar–Pd(II)–Ar 6, which would undergo reduc-
tive elimination to give 2. Thus generated ‘Pd(0)’ species would re-
act with 1 again to give 4 and complete the Pd(0)/Pd(II)–OctV0/
OctVÅ+ double mediatory system for the reductive coupling of 1.
Dissociation of [Ar–Pd(0)]ꢀ 5 to Arꢀ and Pd(0) followed by proton-
ation would give Ar–H 3.
Entry
Aryl halide 1
Product
1
1b
1c
1d
2b
NC
Br
Br
2
3
2c
91
84
F3C
2d
EtO2C
Br
Br
4
5
1e
1f
2e
2f
87
65
NC
In conclusion, electroreductive coupling of aryl bromides pro-
ceeded with catalytic amounts of PdCl2(PPh3)2 and viologen to af-
ford the corresponding biaryls in good to moderate yields.
Br
CN
Acknowledgments
6
1g
1h
1i
2g
2h
2i
90
68
30
n.d.d
85
3
Me
Br
Br
This work was supported by JSPS KAKENHI Grant Number
22550102 and Shorai Foundation for Science and Technology.
The authors also thank Mrs. Atsuko Takamaru, Okayama Univer-
sity, for elemental analyses.
tBu
7
8c
9
MeO
Me2N
Cl
Br
Br
References and notes
1j
2j
1. (a) Bochman, T. M.; Kochi, K. J. J. Org. Chem. 1990, 55, 4127; (b) Endo, T.;
Saotome, Y.; Okawara, M. Tetrahedron Lett. 1985, 26, 4525; (c) Park, K. K.; Lee, C.
W.; Choi, S. Y. J. Chem. Soc., Perkin Trans. 1 1992, 601; (d) Tomioka, H.; Ueda, K.;
Ohi, H.; Izawa, Y. Chem. Lett. 1986, 1359; (e) Maidan, R.; Goren, Z.; Becker, J. Y.;
Willner, I. J. Am. Chem. Soc. 1984, 106, 6217; (f) Park, K. K.; Lee, C. W.; Oh, S. Y. J.
Chem. Soc., Perkin Trans. 1 1990, 2356; (g) Shosenji, H.; Nakano, Y.; Yamada, K.
Chem. Lett. 1988, 1033; (h) Mandler, D.; Willner, I. J. Phys. Chem. 1987, 91, 3600;
(i) Coche, L.; Moutet, J. C. J. Am. Chem. Soc. 1987, 109, 6887; (j) Kashiwagi, Y.;
Shibayama, N.; Anzai, J.; Osa, T. Electrochemistry (Tokyo) 2000, 68, 42; (k) Yuan,
R.; Watanabe, S.; Kuwabata, S.; Yoneyama, H. J. Org. Chem. 1997, 62, 2494; (l)
Chen, X.; Fenton, J. M.; Fisher, R. J.; Peattie, R. A. J. Electrochem. Soc. 2004, 2, e56.
2. Kuroboshi, M.; Kobayashi, R.; Nakagawa, T.; Tanaka, H. Synlett 2009, 85.
3. Kuroboshi, M.; Yamamoto, T.; Tanaka, H. Synlett 2013, 197.
10
11
1k
1l
2k
2b
Br
Cl
NC
Compound 1 (0.5 mmol), [OctV2+][Tf2Nꢀ]2 (10 mol %), [Bu4N+][Tf2Nꢀ] (0.1 M),
PdCl2(PPh3)2 (2.5 mol %), Zn anode–Pt cathode, NMP (3 mL), 10 mA, 60 °C, 2 F/mol—1.
a
b
Isolated yield.
4 F/mol—1c of electricity was passed.
Not detected.
c
d
4. Kuroboshi, M.; Kuwano, A.; Tanaka, H. Electrochemistry 2008, 862.
5. ½OctV2þꢂ½Br2ꢀꢂ: yellow solids; 1H NMR (300 MHz, D2O) d 0.71 (t, J = 6.9 Hz, 6H),
1.07–1.29 (m, 20H), 1.89–2.02 (m, 4H), 4.59 (t, J = 7.5 Hz, 4H), 8.42 (d,
J = 6.9 Hz, 4H), 8.99 (d, J = 6.9 Hz, 4H); 13C NMR (75 MHz, CDCl3) d 13.58, 22.17,
25.40, 28.21, 28.34, 30.79, 31.14, 62.47, 127.17, 145.66, 150.18; IR (KBr) 571,
cathode
621, 1058, 1133, 1202, 1236, 1347, 2929, 2952 cmꢀ1
.
6. ½OctV2þꢂ½Tf2Nꢀꢂ2: colorless solids; 1H NMR (300 MHz, CD2Cl2) d 0.88 (t, J = 6.6
Hz, 6H), 1.12–1.50 (m, 20H), 2.00–2.15 (m, 4H), 4.63 (t, J = 7.8 Hz, 4H), 8.52 (d,
J = 6.9 Hz, 4H), 8.90 (d, J = 6.9 Hz, 4H); 13C NMR (75 MHz, CD2Cl2) d 14.02,
22.79, 26.23, 29.04, 29.11, 31.65, 31.84, 63.24, 119.98 (q, J = 320.0 Hz), 127.77,
145.71, 150.25; IR (KBr) 571, 621, 1058, 1133, 1202, 1236, 1347, 2929,
Pd(II)
2 V0
2 e-
Ar-Br
2 V·+
2952 cmꢀ1
.
2
Ar-Ar
Pd(0)
1
7. This redox potential is equivalent to ꢀ1.089 V versus SHE.
8. In the mixture, products derived from reduction of carbonyl group were
included.
9. The proper Pd catalysts depend on solvents and/or substrate: in THF, the
coupling of 4-bromobenzonitrile proceeded with PdCl2(PhCN)2, PdCl2,
Pd(OAc)2, and Pd2(dba)3 to give the corresponding biaryl quantitatively,
whereas PdCl2(PPh3)2 and Pd(PPh3)4 gave the biaryl in ca. 20% yield Ref.2.
10. Redox potentials (M/Mn+) of Zn, Mg, and Al are ꢀ0.876, ꢀ2.65, and ꢀ1.6 V
versus SHE, respectively.
cathode
Ar-H 3
Ar-Pd(II)-Ar
Ar-Pd(II)-Br
6
4
Ar-
11. In addition of direct reduction of [OctV2+][Tf2Nꢀ]2 at the cathode, a freshly
deposited Zn particle on the cathode would reduce [OctV2+][Tf2Nꢀ]2.
12. Reduction of viologen would complete direct reduction of the substrate, which
gives the reduced product 3, when Al and Mg were used as a cathode.
13. (a) Amatore, C.; Carre, E.; Jutand, A.; Tanaka, H.; Ren, Q.; Torii, S. Chem. Eur. J.
1996, 2, 957; (b) Torii, S.; Tanaka, H.; Morisaki, K. Tetrahedron Lett. 1985, 26,
1655.
2 V0
[Ar-Pd(0)]-
2 e-
1
Ar-Br
2 V·+
5
14. Though it is not clear if viologen works either one-electron or two-electron
reductant, redox potential of VÅ+/V2+ (E1/2 = ꢀ0.43 V) and V0/VÅ+ (E1/2 = ꢀ0.88 V)
were so different that V0 would work as a one-electron reductant. Catalytic use
of V2+ would decrease the concentration of VÅ+ to prevent radical–radical
coupling of VÅ+, which deactivate the reductant.
Scheme 2. A plausible mechanism for the reductive coupling by Pd/viologen
double mediatory system.
gave 4,40-dichlorobiphenyl 2k selectively (coupling as an aryl bro-
mide), and neither 4-bromo-40-chlorobiphenyl nor 4,40-dibromobi-
phenyl was obtained (entry 10). Moreover, the reductive coupling