Facile preparation of organozinc bromides using electrogenerated highly reactive zinc and its use in cross-coupling reaction

Article abstract of DOI:10.1016/j.tet.2005.09.031

Highly reactive zinc was readily prepared by electrolysis of a DMF solution containing pyrene as a mediator with a platinum cathode and a zinc anode. Preferential reduction of pyrene occurred to generate the corresponding radical anion, which reduced zinc ions generated from anodic dissolution to give zero valent zinc with high reactivity. The reactive zinc was successfully used for an efficient transformation of bromoalkanes into the corresponding organozinc bromides. Organozinc bromides obtained were further used successfully in Pd-catalyzed cross-coupling reaction with various aryl iodides and bromides.

Full text of DOI:10.1016/j.tet.2005.09.031

Tetrahedron 61 (2005) 11125–11131
Facile preparation of organozinc bromides using electrogenerated
highly reactive zinc and its use in cross-coupling reaction
*
Nobuhito Kurono, Tomio Inoue and Masao Tokuda
*
Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University, Sapporo 060 8628, Japan
Received 1 August 2005; revised 9 September 2005; accepted 12 September 2005
Available online 27 September 2005
Abstract—Highly reactive zinc was readily prepared by electrolysis of a DMF solution containing pyrene as a mediator with a platinum
cathode and a zinc anode. Preferential reduction of pyrene occurred to generate the corresponding radical anion, which reduced zinc ions
generated from anodic dissolution to give zero valent zinc with high reactivity. The reactive zinc was successfully used for an efficient
transformation of bromoalkanes into the corresponding organozinc bromides. Organozinc bromides obtained were further used successfully
in Pd-catalyzed cross-coupling reaction with various aryl iodides and bromides.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
give the corresponding organozinc iodides. Subsequent
Pd-catalyzed cross-coupling reaction with aryl halides
proceeded efficiently to give the corresponding cross-
coupled products in high yields.5 However, organozinc
bromides were only obtained in very low yields from the
corresponding organic bromides when EGZn was used in
the reaction. We have developed a new electrochemical
method to prepare zinc metal with much higher reactivity
(EGZn/Naph) than that of EGZn by using naphthalene as a
mediator (Scheme 1).6 Reaction of EGZn/Naph with ethyl
2-bromoacrylate efficiently gave the corresponding organo-
zinc bromide, which could be successfully used for
palladium-catalyzed cross-coupling reactions with various
aryl iodides to give ethyl 2-arylpropenoates.6
Organozinc compounds are very useful organometallic
compounds for carbon–carbon bond forming reactions.1
Organozinc halides can usually be prepared by direct
insertion of zinc metal into organic halides,1b but
commercially available zinc metal is generally poorly
reactive. Therefore, activation of the metal is necessary
for preparation of organozinc halides. Successful acti-
vations such as reduction of zinc salts with alkaline metal or
alkali metal naphthalenide have been reported by Rieke
2
et al. Reactive zinc was also prepared by Perichon and his
´
colleagues using electrochemical method.3 We have also
developed a different electrochemical method for prep-
aration of reactive zinc. Our simple preparation method
using a platinum cathode and a zinc anode gave an
aggregation of fine zinc particles with a large surface
area.4 The electrochemically generated reactive zinc
(EGZn) reacts with various functionalized alkyl iodides to
We carried out a detailed study on preparation of a highly
reactive zinc (EGZn/arene) using various arene compounds
as mediators and its use in a transformation of bromoalkanes
to the corresponding organozinc bromides. In this paper, we
Scheme 1.
Keywords: Electrolysis; Reactive zinc; Coupling reactions; Palladium catalyst.
*
Corresponding authors. Tel.: C81 11 706 6601; fax: C81 11 706 6598; e-mail: chrono@eng.hokudai.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.031

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N. Kurono et al. / Tetrahedron 61 (2005) 11125–11131
Scheme 2.
report those detailed results and also the results on
palladium-catalyzed cross-coupling reactions of organozinc
bromides with aryl iodides and bromide.
We have reported that there is a correlation between the
specific surface area of zinc metal and its reactivity in the
prenylation of acetophenone. EGZn having a larger specific
surface area showed higher reactivity than that having a
smaller surface area and was prepared by electrolysis at a
smaller current density.4b Accordingly, three kinds of
EGZn/pyrene were prepared by electrolysis at current
densities of 2.5, 37.5 and 60 mA/cm2. It appeared that the
reactivity of EGZn was lowered in the present case when
2. Results and discussion
2.1. Preparation and reactivity of electrochemically
generated reactive zinc
Table 1. Effects of various arene compounds on the reactivity of EGZn/
arenea
Electrogenerated zinc was readily prepared by electrolysis
of a DMF solution containing 0.1 M Bu4NClO4 in the
presence of an arene compound in a one-compartment cell
fitted with a platinum plate cathode (2!2 cm2) and a zinc
plate anode (2!2 cm2). Electrolysis was carried out at
constant current under a nitrogen atmosphere. Reactivity of
the electrogenerated zinc (EGZn/arene) was estimated in the
following manner. Ethyl 4-bromobutanoate 1a (5 mmol)
was reacted with the electrogenerated zinc (6 mmol)7 at rt
for 1 h, and unreacted 1a was determined by GC analysis
after quenching of the organozinc bromide 2a with diluted
HCl. Conversion of 1a into 2a estimated from the analysis
was regarded as a reactivity index of the electrogenerated
zinc (Scheme 2).
Entry
Arene compoundb
None
Equivc
Conversion
(%)d
1e
2e
3
4
5
—
25
52
95
93
74
63
2.0
2.0
1.0
0.5
0.25
6
7
8
9
1.0
0.5
0.25
91
77
56
10
11
12
1
0.5
0.25
86
61
72
Effects of arene mediators on the reactivity of electro-
generated zinc are summarized in Table 1. Reactivity of
EGZn obtained by electrolysis in the absence of any arene
compounds was low, and only 25% of 1a was transformed
into 2a when the EGZn was used (entry 1). Higher reactivity
was observed when EGZn/Naph generated by electrolysis at
0 8C in the presence of naphthalene mediator was used
(entry 3). When EGZn/Naph generated by using 2 or 1 equiv
of naphthalene to zinc metal was used, 1a could be
converted into 2a in 95–93% yield (entries 3 and 4).
However, a lowering of its reactivity was observed when an
electrogenerated zinc was prepared by the use of 0.5 and
0.25 equiv of naphthalene (entries 5 and 6). Similar results
were obtained when 1-methoxynaphthalene or 1-(N,N-
dimethylamino)naphthalene was used (entries 7–12). Phe-
nanthrene worked as a mediator (entries 14–16), and the
best results were obtained by the use of pyrene. The
electrogenerated reactive zinc prepared by electrolysis in
the presence of pyrene (EGZn/pyrene) converted 1a into the
corresponding organozinc bromide 2a in an almost
quantitative yield (entry 17). Furthermore, EGZn/pyrene
prepared by the use of 0.5 equiv of pyrene to zinc metal was
very reactive (entry 18), and its high reactivity was
maintained even when 0.25 equiv of pyrene was used as a
mediator (entry 20). Consequently, pyrene was found to be
the most effective mediator.
13
1.0
59
14
15
16
1.0
0.5
0.25
86
72
45
17
18
19
20
21
1.0
0.5
0.4
0.25
0.1
99
99
94
89
30
a Electrolysis was carried out at 60 mA/cm2 in 0.1 M Bu4NClO4–DMF
(10 mL) using a Pt cathode (2!2 cm2) and a Zn anode at 0 8C. An
electricity of 2 F/mol was passed. The reactive zinc (6 mmol) was reacted
with ethyl 4-bromobutanoate (5 mmol) for 1 h at rt.
b Reduction potentials were measured by cyclic voltammetry in 0.1 M
Bu4NClO4–DMF using an Ag/AgC reference electrode. Reduction peak
potentials of naphthalene, 1-methoxynaphthalene, 1-dimethyl-amino-
naphthalene, 1-cyanonaphthalene, phenanthrene and pyrene were
K3.06, !K3.20, K3.07, K2.32, K3.00 and K2.59 V versus Ag/AgC
,
respectively.
c Equivalent of arene to zinc ion (6 mmol) by dissolution from zinc anode.
d Conversions of 1a into 2a were estimated by GC of unreacted 1a.
e Electrolysis was carried out at rt.

N. Kurono et al. / Tetrahedron 61 (2005) 11125–11131
11127
Table 2. Effect of current density on the reactivity of EGZn/pyrenea
particles than that of EGZn prepared without addition of
any arene mediators (Table 2).
Entry
Current density (mA/cm2)
Conversion
(%)b
1
2
3
2.5
37.5
60.0
50
79
99
2.2. Generation pathways of EGZn/arene
Probable pathways for generation of the reactive zinc
EGZn/arene, EGZn/pyrene as one example in this case, are
shown in Figure 1. At the cathode, a one-electron reduction
of a pyrene molecule readily occurred to give pyrene radical
anions. On the other hand, at the anode, dissolution of the
zinc anode occurred to give zinc ions (Zn2C), which were
reduced by the pyrene radical anions to give zero-valence
highly reactive zinc, EGZn/pyrene (Fig. 1). These pathways
are supported by the following experimental results. First,
the current density of 60 mA/cm2 flowed constantly at 0 8C
in the presence of arene compounds, although the current
flow stopped in a few minutes in the case of electrolysis in
the absence of any arene. The formation of pyrene radical
anions indicated by a wine-red color appeared at the cathode
surface in the initial stage and the color of the electrolyte
turned black immediately due to formation of zinc particles.
a Electrolysis was carried out at 0 8C in 0.1 M Bu4NClO4–DMF (10 mL) in
the presence of 0.5 equiv of pyrene using a Pt cathode (2!2 cm2) and a
Zn anode. The reactive zinc (6 mmol) was reacted with ethyl
4-bromobutanoate (5 mmol) for 1 h at rt.
b Conversions of 1a into 2a were estimated by GC of unreacted 1a.
current density was decreased. Consequently, electrolytic
conditions using 0.5 equiv of pyrene with current density of
60 mA/cm2 at 0 8C were employed as the optimal ones in
the present study. EGZn/pyrene thus prepared was
completely dispersed in the DMF solution since the zinc
particles of EGZn/pyrene could not be collected by
filtration. Although the detailed properties and structure of
EGZn/pyrene are not clear at the present stage, it seems that
EGZn/pyrene is an aggregation of much smaller zinc
Figure 1.
Figure 2. Cathode potential in the electrolysis using a platinum cathode and a zinc anode under various conditions. (B: in the absence of any additive,
corresponding to the preparation of EGZn, &: in the presence of Zn(ClO4)2 (6 mmol), 6: in the presence of Zn(ClO4)2 (6 mmol) and pyrene (3 mmol), C: in
the presence of pyrene (6 mmol), corresponding to the preparation of EGZn/pyrene (Table 1, entry 17), ,: in the presence of pyrene (3 mmol), corresponding
to the preparation of EGZn/pyrene (Table 1, entry 18), :: in the presence of naphthalene (6 mmol), corresponding to the preparation of EGZn/Naph (Table 1,
entry 4)).

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N. Kurono et al. / Tetrahedron 61 (2005) 11125–11131
Scheme 3.
Second, a decrease in the amount of arene compound
resulted in a lower reactivity of the zinc. Zero-valent zinc
generated by direct reduction on the cathode surface showed
lower reactivity than that of EGZn/arene (Table 1, entry 1).
Third, the efficiency of reduction of pyrene was higher than
that of other arene compounds. pyrene has a more positive
reductive potential (K2.59 V vs Ag/AgC) than naphthalene
and phenanthrene, the potentials, of which are nearly
K3.0 V or more negative. Fourth, measurements of
cathodic potential during various electrolyses are shown in
Figure 2. Cathodic reaction in the presence of 1.0 or
0.5 equiv of pyrene to zinc metal (corresponding to the
results of entries 17 and 18 in Table 1) proceeded nearly at
the reductive potential of pyrene (dotted line with , and
C). Similar results were obtained in the electrolysis using
naphthalene (dotted line with :, corresponding to Table 1,
entry 4). In contrast, cathodic reaction in the absence of any
arene compounds proceeded at a much more positive
potential (dotted line with B). This potential corresponds to
a reductive potential of zinc ions, which was confirmed by
measurement of cathodic potential in the presence of zinc
ions, Zn(ClO4)2 (dotted line with &). Therefore, zinc ions
from anodic dissolution were reduced by the pyrene radical
anion in the bulk of electrolyte (Fig. 1). The reason for
preferential reduction of pyrene molecules, in spite of its
more negative reduction potential than that of zinc ions, is
probably due to the great difference between initial
concentrations of pyrene and zinc ion. The initial
concentration of zinc ions is very low since they are
generated gradually by electrolytic dissolution of the zinc
metal anode. When the electrolysis was carried out in the
presence of similar concentrations of zinc ions and pyrene,
the cathodic potential was maintained at a more positive
potential than that of pyrene (Fig. 2, dotted line with 6).
drastically improved by intermittent electrolysis. The idea
for this method comes from the preparation of Rieke zinc by
lithium naphthalenide reduction of zinc chloride using a
catalytic amount of naphthalene.2a In our case, the
electrolysis was stopped and the solution was only stirred
at constant intervals in order to completely reduce zinc ions
formed by anodic dissolution with pyrene radical anions.
Intermittent electrolysis was carried out by repeated
electrolysis (4 min) and only stirring (2 min or 6 min)
(Scheme 3).
2.3. Use of EGZn/arene in the Pd-catalyzed cross-
coupling reaction
Various alkyl bromides (1) were efficiently converted to the
corresponding organozinc compounds (2) by reaction with
EGZn/pyrene. Cross-coupling reactions of these organozinc
compounds with aryl halides in the presence of a Pd
catalyst8 were examined (Scheme 4). Results are sum-
marized in Table 3. Ethyl 4-bromobutanoate (1a), 4-bromo-
butanenitrile (1b) and ethyl 3-bromopropanonate (1c) could
readily be converted to the corresponding organozinc
compounds 2a, 2b and 2c by reaction with EGZn/pyrene.
Cross-coupling reaction of these organozinc compounds
with iodobenzene itself and iodobenzenes having electron-
donating group (3b) or electron-withdrawing group (3c)
gave the desired products (4a–i) in 77–92% yields. The
reaction of simple alkyl bromides (1d and 1e) with EGZn/
Naph and EGZn/pyrene also proceeded efficiently to give
2d and 2e, which were reacted with 3b and 3c to give the
corresponding cross-coupling products (4j–m) in 67–85%
yields. Transformation of organozinc compounds on a
larger scale was also examined. A four-times greater
amount of EGZn/pyrene was prepared and the reaction of
EGZn/pyrene with a four-times greater amount of 1a gave
the corresponding organozinc compound 2a, which was
used in the cross-coupling reaction to give the desired
Reactivity of EGZn/pyrene prepared by using 0.1 equiv of
pyrene was low (Table 1, entry 21). Its reactivity can be
Scheme 4.

N. Kurono et al. / Tetrahedron 61 (2005) 11125–11131
11129
Table 3. Cross-coupling reaction of alkyl bromides with various aryl halides using electrogenerated highly reactive zinc (EGZn/pyrene)a
Entry
1
Alkyl bromide
Aryl halide
Product
Yield (%)b
81 (79)c
1a
4a
3a
3b
2
3
83 (75)d
4b
78 (84)d
4c
4d
4e
3c
3a
4
5
83 (89)d
1b
3b
3c
89
6
88
4f
7e
3a
3b
92
86
1c
4g
8e
4h
9e
3c
77
4i
4j
10
11
3b
3c
77
85
1d
4k
4l
12
13
14
3b
3c
67
74 (76)d
1e
1a
4m
80
3d
4n
15f
77
a A DMF solution of organozinc bromide (6.4 mL, corresponding to 3 mmol of organozinc bromide) was added to a THF solution (20 mL) containing aryl
halides (2 mmol) and Pd(P(o-Tol)3)2Cl2 (0.1 mmol) and the reaction mixture was stirred at 70 8C for 3 h.
b Isolated yields.
c Organozinc compound 2a was prepared using EGZn/pyrene shown in Scheme 3.
d Yields of cross-coupling products using EGZn/Naph are shown in parantheses.
e Ethyl 3-bromopropanoate (1c) (5 mmol) was reacted at rt for 1 h with EGZn/pyrene (6 mmol).
Ethyl 4-bromobutanoate (1a) (20 mmol) was reacted at rt for 1 h with EGZn/pyrene (24 mmol). A DMF solution of organozinc bromide was added to a THF
solution containing 3d (13 mmol) and Pd(P(o-Tol)3)2Cl2 (0.72 mmol).
f

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N. Kurono et al. / Tetrahedron 61 (2005) 11125–11131
product 4n in a yield of 77% (entry 15). EGZn/Naph could
be used in the same way (Table 3, entries 2–4, 13). EGZn/
pyrene prepared by using a catalytic amount of pyrene
(Scheme 3) was also used successfully for the transform-
ation into organozinc compounds, which was shown by the
high yields of the product 4a in the following cross-coupling
reaction (Table 3, parenthesis in entry 1).
chloride (11 mL, 143 mmol) was added at 0 8C to a solution
of guaiacol (11 mL, 100 mmol) and pyridine (100 mL). The
solution was kept in a refrigerator for 10 h. The reaction
mixture was poured onto ice and extracted with Et2O. The
combined organic layers were washed with concentrated
HCl, saturated NaHCO3 aqueous solution and brine and
then dried over MgSO4. After evaporation of Et2O, the
crude product, (2-methoxyphenyl)methanesulfonate (20 g)
was obtained and used without further purification in the
next step. 1H NMR (CDCl3) d 7.33–7.24 (2H, m), 7.02–6.95
(2H, m), 3.90 (3H, s), 3.18 (3H, s).
3. Conclusion
Electrochemical preparation of highly reactive zinc (EGZn/
pyrene) could be achieved by using less than 1 equiv of
pyrene mediator with a platinum cathode and a zinc anode.
The generation mechanism of EGZn/pyrene was proposed
on the basis of experimental results: that is, preferential
reduction of pyrene occurs to give the radical anion of
pyrene, which reduces zinc ion produced by anodic
dissolution to generate zero valent zinc with high reactivity.
Organozinc compounds were readily obtained from various
alkyl bromides by their reaction with EGZn/pyrene under
mild conditions. Palladium-catalyzed cross-coupling
reaction of these organozinc compounds with aryl halides
proceeded successfully to give the corresponding cross-
coupling products in high yields.
Bromination of 2-methoxyphenyl methanesulfonate was
carried out according to the literature.9 Recrystallization of
the crude product from ethanol and CH2Cl2 gave 5-bromo-
2-methoxyphenyl methanesulfonate: IR (neat) 1331, 1160,
1
1125, 693 cmK1; H NMR (CDCl3) d 7.45 (1H, d, JZ
2.31 Hz), 7.41 (1H, dd, JZ2.31, 8.58 Hz), 6.90 (1H, d, JZ
8.58 Hz), 3.88 (3H, s), 3.20 (3H, s); 13C NMR (CDCl3) d
150.85, 138.53, 131.02, 127.53, 114.14, 112.24, 56.21,
38.46; EIMS m/z (relative intensity) 282 (26), 280 (26), 203
(66), 201 (68), 94 (100), 79 (24), 57 (21); HRMS Calcd for
C8H9SO4Br m/z 279.9404. Found m/z 279.9404.
Hydrolysis of 5-bromo-2-methoxyphenyl methanesulfonate
was carried out as described below: to 6 N NaOH aqueous
solution (50 mL), THF solution (4 mL) of the crude product
of (5-bromo-2-methoxyphenyl) methanesulfonate (1 g) was
added and reacted for 5 h under reflux. The reaction mixture
was extracted with Et2O after conversion to acidic aqueous
solution with 6 N HCl. The combined organic layers were
washed with water and brine and then dried over MgSO4.
After evaporation of Et2O, the crude product, 5-bromo-2-
methoxyphenol (0.75 g), was obtained and used without
further purification in the next step. IR (neat) 3411, 1237,
4. Experimental
4.1. General procedures
1H and 13C NMR spectra were recorded on a JEOL JNM-
EX270 FT NMR spectrometer (1H, 270 MHz; 13C,
67.8 MHz). Chemical shifts were represented as d-values
relative to the internal standard, tetramethylsilane. IR
spectra were recorded on a JASCO IR-810 infrared
spectrometer. High- and low-resolution mass spectra were
determined with a JEOL JMS-AX500 or JEOL JMS-
SX102A spectrometer. Thin-layer chromatography was
carried out on a Merck Silica gel 60 PF254. Cyclic
voltammetry was performed with BAS-50W using an Ag/
AgC reference electrode, Pt working electrode and Pt wire
counter electrode in 0.1 M Bu4NClO4–DMF solution. The
reference electrode (RE-6) was purchased from BAS, Inc.
and used after filled with 0.01 M AgNO3/0.1 M Bu4NClO4/
DMF solution. Measurement of cathode potential was
carried out using a NICHIA potentio/galvanostat G1051EH.
1
1038, 623 cmK1; H NMR (CDCl3) d 7.07 (1H, d, JZ
2.31 Hz), 6.46 (1H, dd, JZ2.31, 8.58 Hz), 6.71 (1H, d, JZ
8.58 Hz), 5.65 (1H, s), 3.87 (3H, s).
To a DMF (50 mL) solution of the crude 5-bromo-2-
methoxyphenol (0.57 g), K2CO3 (0.19 g) and benzyl
bromide (11.3 g) were added. The reaction mixture was
heated for 12 h at 80 8C (temperature of oil bath). Water
was added to dissolve residual K2CO3. The reaction mixture
was extracted with Et2O. The combined organic layers were
washed with water, 2 N NaOH aqueous solution, saturated
Na2S2O3 aqueous solution and brine and then dried over
MgSO4. After evaporation of Et2O, the crude product of
2-benzyloxy-4-bromoanisole (0.52 g) was obtained and
recrystallized from ethanol: colorless needles; mp 111–
112 8C; IR (neat) 1219, 1021, 622 cmK1; 1H NMR(CDCl3)
d 7.45–7.31 (5H, m), 7.06–7.02 (2H, m), 6.76 (1H, d, JZ
7.6 Hz), 5.11 (1H, s), 3.85 (3H, s); 13C NMR (CDCl3) d
148.98, 148.93, 136.37, 128.57, 128.36, 128.01, 127.35,
123.94, 117.23, 113.05, 112.60, 112.49, 71.16, 56.10; EIMS
m/z (relative intensity) 294(6), 292(6), 91(100), 65(7);
HRMS Calcd for C14H13O2Br m/z 292.0098. Found m/z
292.0084.
4.2. Materials
Anhydrous N,N-dimethylformamide (DMF), functionalized
alkylbromides (1a–1d), iodobenzene (3a), 4-iodoanisole
(3b) and 4-iodoacetophenone (3c) were commercially
available from Kanto Chemical, Inc. or Acros Organics,
Inc. and were used without further purification. Tetra-
butylammonium perchlorate (Bu4NClO4) was com-
mercially available and was used after recrystallization
from hexane and ethyl acetate. A zinc plate was
commercially available (NILACO, Inc.) in more than
99.9% purity, and it was washed with 2 N HCl, methanol,
and acetone and then dried before electrolysis.
4.3. Preparation of electrogenerated highly reactive zinc
(EGZn/pyrene)
4.2.1. 2-Benzyloxy-4-bromoanisole (3d). Methanesulfonyl
A one-compartment cell (26 mmol, 150 mm height)

N. Kurono et al. / Tetrahedron 61 (2005) 11125–11131
11131
equipped with a magnetic stirrer and two branched necks
References and notes
was used. The solvent and substrate were injected from a
rubber septum of one neck. EGZn/pyrene (6 mmol) was
prepared by the electrolysis of 0.1M Bu4NClO4–DMF
solution (10 mL) containing pyrene (3 mmol) in a one-
compartment cell fitted with a platinum plate cathode (2!
2 cm2) and a zinc plate anode (2!2 cm2). Two electrodes
were kept in parallel with a distance between them of about
10 mm. Electrolysis was carried out at 0 8C at a current
density of 60 mA/cm2 under nitrogen atmosphere for
80.4 min. The amount of EGZn/pyrene was estimated
from the weight of dissolved zinc anode metal. A solution
containing EGZn/pyrene was directly used for preparation
of organozinc compounds after the zinc anode had been
removed from the electrolysis cell.
1. (a) Organozinc Reagents; Knochel, P., Jones, P., Eds.; Oxford
University Press: New York, 1999. (b) Knochel, P.; Singer,
R. D. Chem. Rev. 1993, 93, 2117–2188. (c) Edrick, E.
Tetrahedron 1992, 48, 9577–9648.
2. (a) Rieke, R. D.; Hanson, M. V. Active Zinc in Organic
Synthesis. In Organozinc Reagents; Knochel, P., Jones, P., Eds.;
Oxford University Press: New York, 1999; pp 23–26. (b)
Cintas, P. Activated Metals in Organic Synthesis.; CRC: Boca
Raton, 1993; pp 45–55. (c) Zhu, L.; Wehmeyer, R. M.; Rieke,
R. D. J. Org. Chem. 1991, 56, 1445–1453. (d) Furstner, A.
Angew. Chem., Int. Ed. Engl. 1993, 32, 164. (e) Hanson, M. V.;
Brown, J. D.; Niu, Q. J.; Rieke, R. D. Tetrahedron Lett. 1994,
35, 7205–7208. (f) Hanson, M. V.; Rieke, R. D. J. Am. Chem.
Soc. 1995, 117, 10775–10776. (g) Hanson, M.; Rieke, R. D.
Synth. Commun. 1995, 25, 101–104. (h) Rieke, R. D.; Brown,
J. D.; Wu, X. Synth. Commun. 1995, 25, 3923–3930. (i)
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1999, 121, 4155–4167.
4.4. General procedure for cross-coupling reaction using
EGZn/pyrene
To a DMF solution containing EGZn/pyrene (6 mmol) was
added alkyl bromide (1) (5 mmol) and the mixture was
stirred at rt under nitrogen atmosphere. After 1 h, the DMF
solution containing organozinc bromide (6.4 mL, corre-
sponding to 3 mmol of RZnBr) was added to a THF solution
of aryl iodide (2 mmol) and Pd(P(o-Tol)3)2Cl2 (0.11 mmol),
and the reaction mixture was stirred at 70 8C for 3 h. The
resulting mixture was quenched with HCl solution and
filtrated. The filtrate was extracted with diethyl ether
(50 mL!3), and the combined organic layers were washed
with water (100 mL!3), saturated Na2S2O3 solution
(100 mL!1) and saturated NaCl solution (100 mL!1)
and then dried over MgSO4. After evaporation of diethyl
ether, the crude product was dissolved into CH2Cl2
(2–3 mL). The concentrated CH2Cl2 solution was carefully
poured into methanol (10 mL). About 70% of pyrene was
removed as a solid. After evaporation of the filtrate, the
crude product was purified by thin layer chromatography
with ethyl acetate–hexane (1/4) to give the corresponding
cross-coupling product.
´
3. (a) Perichon, J.; Gosmini, C.; Rollin, Y. Electrochemical
Generation and Reaction of Zinc Reagents. In Organozinc
Reagents; Knochel, P., Jones, P., Eds.; Oxford University Press:
New York, 1999; pp 139–156. (b) Rollin, Y.; Derien, S.;
´
Dun˜ach, E.; Gebehenne, C.; Perichon, J. Tetrahedron 1993, 49,
7723–7732. (c) Rollin, Y.; Gebehenne, C.; Derien, S.; Dun˜ach,
´
E.; Perichon, J. J. Organomet. Chem. 1993, 461, 9–13. (d)
Gosmini, C.; Rollin, Y.; Gebehenne, C.; Lojou, E.;
´
Ratovelomanana, V.; Perichon, J. Tetrahedron Lett. 1994, 35,
´ ´ ´
5637–5640. (e) Paratian, J. M.; Labbe, E.; Sibille, S.; Nedelec,
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J. Y.; Perichon, J. J. Organomet. Chem. 1995, 487, 61–64. (f)
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Gosmini, C.; Rollin, Y.; Perichon, J.; Wakselman, C.; Tordeux,
M.; Marival, L. Tetrahedron 1997, 53, 6027–6034.
4. (a) Tokuda, M.; Mimura, N.; Karasawa, T.; Fujita, T.;
Suginome, H. Tetrahedron Lett. 1993, 34, 7607–7610. (b)
Tokuda, M.; Kurono, N.; Mimura, N. Chem. Lett. 1996,
1091–1092. (c) Tokuda, M. In Novel Trends in Electroorganic
Synthesis; Torii, S., Ed.; Kodansha: Tokyo, 1995; p 241.
5. Kurono, N.; Sugita, K.; Takasugi, S.; Tokuda, M. Tetrahedron
1999, 55, 6097–6108.
Cross-coupling products (4a–m) have already been con-
firmed by spectral data in our previous report.5
6. (a) Jalil, A. A.; Kurono, N.; Tokuda, M. Synlett 2001,
1944–1945. (b) Jalil, A. A.; Kurono, N.; Tokuda, M.
Tetrahedron 2002, 58, 7477–7484. (c) Jalil, A. A.; Kurono,
N.; Tokuda, M. Synthesis 2002, 2681–2686.
4.4.1. Ethyl 4-(3-benzyloxy-4-methoxyphenyl)butanoate
(4n). Colorless oil; IR (neat) 1724, 1259, 1236, 1159,
1
1053 cmK1; H NMR(CDCl3) d 7.46–7.31 (5H, m), 6.82
7. Amount of EGZn/arene was estimated from the weight of
dissoluted zinc anode with the assumption that the zinc ions
formed from anode dissolution were completely reduced to give
reactive EGZn/arene.
(1H, d, JZ8.6 Hz), 6.73 (1H, d, JZ2.0 Hz), 6.71 (1H, d,
JZ2.0 Hz), 5.13 (2H, s), 4.12 (2H, q, JZ7.3 Hz), 3.86 (3H,
s), 2.54 (2H, t, JZ7.6 Hz), 2.25 (2H, t, JZ7.6 Hz), 1.86
(2H, quint, JZ7.6 Hz), 1.25 (3H, t, JZ7.3 Hz); 13C
NMR(CDCl3) d 173.49, 147.98 (two signals), 137.18,
133.94, 128.43 (two signals), 127.73, 127.31 (two signals),
121.01, 114.72, 111.88, 71.02, 60.18, 56.05, 34.50, 33.48,
26.58, 14.22; EIMS m/z (relative intensity) 328(22), 237(8),
191(11), 163(9), 149(9), 91(100); HRMS Calcd for
C20H24O4 m/z 328.1674. Found m/z 328.1679.
8. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. Tetrahedron
Lett. 1986, 27, 955–958.
9. Gensler, W. J.; Stouffer, J. E. J. Org. Chem. 1958, 23, 908–910.