An electrochemical tandem reaction: One-pot synthesis of homoallylic alcohols from alcohols in aqueous media

Article abstract of DOI:10.1039/c0cc01964j

A tandem electrosynthesis of homoallylic alcohols from alcohols in one-pot was realized. In virtue of this one-pot electrosynthesis, the traditional reaction substrates of allylation were broadened from carbonyl compounds to alcohols.

Full text of DOI:10.1039/c0cc01964j

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An electrochemical tandem reaction: one-pot synthesis of homoallylic
alcohols from alcohols in aqueous mediaw
Li Zhang, Zhenggen Zha,* Zhenlei Zhang, Yunfeng Li and Zhiyong Wang*
Received 19th June 2010, Accepted 5th August 2010
DOI: 10.1039/c0cc01964j
5
A tandem electrosynthesis of homoallylic alcohols from alcohols
in one-pot was realized. In virtue of this one-pot electrosynthesis,
the traditional reaction substrates of allylation were broadened
from carbonyl compounds to alcohols.
consumption wasted on the counter electrode. By this dexterously
tandem design, a variety of aromatic primary alcohols could
be converted into their corresponding homoallylic alcohols
directly with excellent yields, avoiding the tedious separation
of the intermediate aldehydes for further transformation.
Moreover, the traditional reaction substrates of allylation
were broadened from carbonyl compounds to alcohols.
Initially, different electrodes were optimized in this electro-
chemical allylation. To the best of our knowledge, smooth
platinum and graphite are good anode materials commonly
used in electrooxidation processes because they show large
overpotentials for oxygen evolution in aqueous solution, while
graphite is usually used as the cathode material in aqueous
solution because of the large overpotential for hydrogen
The development of efficient methods for the synthesis of
homoallylic alcohols is very important because of their wide
applications, especially as intermediates in organic synthesis,
and building blocks for natural products and bioactive
compounds. A number of elegant approaches to the synthesis
1
of homoallylic alcohols have been reported. Recently, the
electrochemical allylation of carbonyl compounds has also
2
been developed. For instance, electrogenerated In, Sn, Zn or
cathodic reduction has mediated the allylation to give the
corresponding homoallylic alcohols with good yields or good
chemoselectivities. However, the previous allylations involved
carbonyl compounds as the starting materials, which limited
the scope of the reactions, since some carbonyl compounds are
unstable and difficult to obtain. On the other hand, a variety of
alcohols are readily available, and most of them are stable in
storage or during reactions. Therefore, it is desirable to
synthesize homoallylic alcohols by employing alcohols as
substrates. Traditionally, the allylation of alcohols usually
involves a multi-step procedure, including the oxidation of
6
evolution. In our system, both oxygen evolution on the anode
and hydrogen evolution on the cathode were unfavorable.
Therefore, we tested different combinations of these two
electrodes (Table 1, entries 1–4). Among various electrodes
examined, it was found that platinum was more efficient for
anodic oxidation while graphite was better for cathodic
reduction, as shown in entry 1 of Table 1. In order to clarify
the differences between the electrodes, the morphology of the
Sn generated on the surface of the two electrodes was
characterized by scanning electron microscopy (SEM, Fig. S1
and S2w) and X-ray diffraction (XRD, Fig. S3w). XRD
indicated that Sn generated in situ was of b-phase, regardless
of formation from the graphite electrode or from the platinum
electrode. However, different morphological structures were
formed on the surface of different electrodes. The main
morphology of the Sn generated on the surface of graphite
was flocculent, while that on the surface of platinum was
rod-shaped. It is obvious that the flocculent morphology of Sn
had a larger surface area than that of rod-shaped Sn.
Moreover, it was also found that in situ-produced Sn
was easier to peel off from the surface of the graphite
electrode than from the platinum, which could increase the
production of metal Sn. Afterwards, different electrolytes,
3
alcohols to carbonyl compounds followed by allylation of the
2
carbonyl compounds. However, the electrosynthesis of
homoallylic alcohols from alcohols directly has not yet been
reported. Recently, on the basis of the paired electrosynthesis
of carbonyl compounds and homoallylic alcohols in a divided
4
cell, we realized the electrosynthesis of homoallylic alcohols
from alcohols directly with a tandem reaction in one pot.
As shown in Scheme 1, alcohols were oxidized to the
corresponding carbonyl compounds by losing electrons without
using any chemical oxidants on the surface of a platinum
anode, while SnCl was reduced to Sn on the graphite cathode.
2
Once the produced carbonyl compound met the Sn generated
in situ and allyl bromide in solution, the corresponding
homoallylic alcohol was produced. In this electrosynthesis
process, both the working electrode and the counter electrode
were exploited to produce useful products. Compared with the
2
,3
aforementioned electrochemical method, in which only the
working electrode was exploited, we saved 50% of the energy
Hefei National Laboratory for Physical Science at Microscale,
CAS Key Laboratory of Soft Matter Chemistry and Department of
Chemistry, University of Science and Technology of China,
96 Jinzhai Road, Hefei 230026, China. E-mail: zwang3@ustc.edu.cn;
Fax: +86 551-3603185; Tel: +86 551-3603185
w Electronic supplementary information (ESI) available: Experimental
section, characterization data and NMR spectra of all products. See
DOI: 10.1039/c0cc01964j
Scheme 1 Tandem electrosynthesis of homoallylic alcohols from
alcohols in aqueous media with an undivided cell.
7
196 Chem. Commun., 2010, 46, 7196–7198
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a
Table 1 Optimizing the transformation conditions of alcohol 1a into homoallylic alcohol 2a
b
Conditions
Yield (%)
Entry
Sn source
Electrolyte
Anode
Cathode
1a
2a
3a
1
2
3
4
5
6
7
8
9
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
2
2
2
2
2
2
2
2
2
2
2
KNO
KNO
KNO
KNO
4
Bu NBF
LiClO
3
3
3
3
0.5 M
0.5 M
0.5 M
0.5 M
0.5 M
0.5 M
1 M
2 M
3 M
5 M
Saturated
0.5 M
Saturated
0.5 M
0.5 M
0.5 M
Pt
C
C
C
Pt
C
Pt
C
C
C
C
C
C
C
C
C
C
C
C
35
62.6
5.7
6.9
33
35
45
55
51
33
45
55
50
28.6
31.8
15.7
91
2.4
0
0
0
0
0
8
8
11
13
12.5
0
17.7
3.3
19.5
0
94.3
93.1
67
65
58
37
41
56
42
32.5
50
53.7
64.9
64.8
9
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
4
4
KNO
KNO
KNO
KNO
KNO
KNO
KNO
KNO
KNO
KNO
3
3
3
3
3
3
3
3
3
3
1
1
1
1
1
1
1
0
1
2
3
4
5
6
SnSO
SnSO
4
4
c
d
e
SnCl
SnCl
SnCl
2
2
2
a
Reaction conditions: the mixture of benzyl alcohol (2 mmol), allyl bromide (3 mmol) with the corresponding Sn source (1 mmol) was electrolyzed
at a constant current of 20 mA for 4 h in an undivided cell, which was equipped with a three-electrode system at room temperature. The cell was
b
c
d
2
sealed by film in order to minimize the volatilization of the allyl bromide. GC-MS yield. The amount of SnCl was 0.5 mmol. The amount
e
of SnCl was 0.2 mmol. The reaction time was prolonged to 6 h, 2.2 F mol of current was consumed.
À1
2
such as n-Bu NBF , LiClO and KNO , were employed in this
3
p-NO substitution on the aromatic ring of benzyl alcohols
2
4
4
4
electrochemical reaction. It was found that KNO
efficient (Table 1, entries 1, 5 and 6). When the concentration
of the KNO aqueous solution was 0.5 M, the highest yield
was obtained (Table 1, entries 1, 7–11). SnSO , instead of
SnCl as the Sn source, was also examined (Table 1, entries
2 and 13). The experimental results indicate that SnCl was
more adoptable. We also tried a smaller amount of SnCl
Compared with the 0.25 equiv. and 0.1 equiv. dosage,
.5 equiv. of SnCl gave the best yield (Table 1, entries 1, 14
3
was most
resulted in a moderate yield (Table 2, entry 11). A notable
steric effect could be observed; ortho-substitution gave the
lowest yield among para, meta and ortho substitution on
phenyl, and 1-naphthyl substitution gave a medium yield
(Table 2, entries 4–6, 8, 9 and 12). Only oxidation product
and no allylation product was obtained when 1-phenylethanol
was employed as a substrate (Table 2, entry 13). A heterocyclic
substrate also gave a low yield (Table 2, entry 16). As for
aliphatic alcohols, both primary and secondary alcohols
worked well (Table 2, entries 14 and 15). Crotylation only
gave a g-product with a good yield (Table 2, entry 17).
3
4
2
1
2
2
.
0
2
and 15). It was also found that a higher reaction yield was
obtained by prolonging the reaction time to 6 h. For instance,
the allylation of benzyl alcohol gave the corresponding
In order to elucidate the reaction process, we measured the
oxidative and reductive processes of the reaction by cyclic
voltammetry (CV). As shown in Fig. 1 and Fig. 2, no oxidation
7
homoallylic alcohol with a yield of 91% (Table 1, entry 16).
Therefore the reaction conditions were chosen as below:
SnCl
2
as the Sn source, 0.5 M KNO
3
as the electrolyte,
3
or reduction waves were observed in aqueous KNO solution
platinum, graphite and saturated calomel electrodes (SCE)
as the working electrode, counter electrode and reference
electrode, respectively. All the reactions were electrolyzed at
a constant current of 20 mA for 6 h.
(trace a in Fig. 1 and Fig. 2), which indicates that blank
solutions could not be electroactive in the potential window of
interest. When the benzyl alcohol and SnCl
2
were added to the
blank solution, an oxidation wave (O ), which corresponds to
1
With the optimal reaction conditions in hand, the generality
of the reaction was investigated with a variety of alcohols. The
reaction results were summarized in Table 2. It was noted that
solid substrates with a low solubility in water incurred lower
yields compared with liquid substrates, resulting from the
the electrooxidation of benzyl alcohol, was observed, as shown
in trace b of Fig. 1. On the other hand, a couple of well-defined
reduction waves (R ) and oxidation waves (O ) were exhibited,
2
2
2
+
as shown in trace b of Fig. 2. The R
2
wave indicates that Sn
2
was reduced to Sn, while the O wave on the backward
difficulty of electron transfer between the solid electrode and
8
the solid substrates. To solve this problem, CH
potential sweep was the corresponding reverse process. In
order to investigate the reactions on both electrodes in our
system, CV of the two electrode reactions in one-pot were
measured, respectively, as shown in trace c of Fig. 1 and Fig. 2.
Compared to the CV of the single electrode reaction (trace b
in Fig. 1 and Fig. 2), similar waves of CV were observed for
the dual electrode reactions in the one-pot system (trace c in
3
CN was
added to increase the solubility of the solid substrate. The
allylation of benzyl alcohols bearing electron-donating or
electron-withdrawing substituents were carried out smoothly
to afford the corresponding aromatic homoallylic alcohols
with high yields (Table 2, entries 1–4, 7, 8 and 10). However,
This journal is c The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 7196–7198 7197

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Table 2 Scope of the electrosynthesis of homoallylic alcohols from
alcohols in aqueous media
a
1
R
2
R
3
R
Entry
Yield (%)
1
2
3
4
5
6
7
8
9
Ph
H
H
H
H
H
H
H
H
H
H
H
H
CH
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH
91
86
96
4-Me-Ph
4-MeO-Ph
4-Cl-Ph
3-Cl-Ph
2-Cl-Ph
4-F-Ph
4-Br-Ph
2-Br-Ph
4-CF
4-NO
1-Naphthyl
Ph
b
90
82
b
Fig. 2 Cyclic voltammogram curves of (a) 0.04 M KNO
.06 M SnCl , 0.04 M KNO /H O; (c) 0.17 M benzyl alcohol, 0.06 M
SnCl and 0.04 M KNO /H
3 2
/H O; (b)
b
50
85
87
70
0
2
3
2
b
b
2
3
2
O, recorded at a glassy carbon electrode
À1
b
(diameter 0.4 cm), scan rate: 100 mV s at room temperature.
10
11
12
13
14
15
16
17
3
-Ph
-Ph
88
40
b
2
then reacted with allyl bromide to afford the homoallylic
alcohol in a one-pot system.
b
62
94
c
3
In conclusion, we have reported a tandem electrosynthesis
of homoallylic alcohols directly from alcohols in one pot. In
virtue of this one-pot electrosynthesis, the traditional substrates
of allylation were broadened from carbonyl compounds to
alcohols. The results exhibit a new avenue of green synthesis,
in which conventional oxidants could be avoided and the
tedious separation of the reaction intermediates could be
circumvented. Other efficient energy-saving and environmental-
friendly reactions are under way in our laboratory.
PhCH
Cyclohexanol
2-Thienyl
Ph
2
70
80
34
H
H
d
3
82
a
Isolated yields are given. Reaction conditions: the mixture of benzyl
(1 mmol) was
alcohol (2 mmol), allyl bromide (3 mmol) with SnCl
2
electrolyzed at a constant current of 20 mA for 6 h in an undivided
cell, which was equipped with a three-electrode system at room
temperature (details in the ESI). The cell was sealed by film in order
b
to minimize the volatilization of the allyl bromide. CH
was added to increase the solubility of the solid substrate. Isolated
yields of oxidation. No corresponding allylation product was
d
observed. syn : anti = 1 : 1.
3
CN (1 mL)
c
We are grateful for financial support from the National
Science Foundation of China (no. 20772118, 20932002,
2
0972144 and 90813008).
Notes and references
1
2
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Fig. 1 Cyclic voltammogram curves of (a) 0.04 M KNO
3
/H
.17 M benzyl alcohol, 0.04 M KNO O; (c) 0.17 M benzyl alcohol,
2
.06 M SnCl and 0.04 M KNO /H O, recorded at a Pt electrode (1.0
2
O; (b)
4
8, 8994.
0
0
3
/H
2
4 L. Zhang, Z. G. Zha, Z. Y. Wang and S. Q. Fu, Tetrahedron Lett.,
2010, 51, 1426.
2
3
À1
2
5 M. M. Baizer, in Organic Electrochemistry, ed. M. M. Baizer and
H. Lund, Marcel Dekker, New York, 1991, ch. 35, pp. 1421–1430
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H. Ishida, N. Yamashita, Y. Kera, S. Kashimura, H. Masuda and
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 1.0 cm ), scan rate: 100 mV s at room temperature.
Fig. 1 and Fig. 2). This indicates that the anodic and cathodic
reactions were compatible in one pot. It is noted that the
oxidation peak in Fig. 1 is not well-defined, which can be
ascribed to the poor solubility of benzyl alcohol in aqueous
6
J. Grimshaw, Electrochemical Reactions and Mechanisms in Organic
Chemistry, Elsevier, Amsterdam, 2000.
3
media. When CH CN, instead of an aqueous medium, was
employed as a solvent to measure CV, a well-defined oxidation
peak appeared (Fig. S4w). As a result, the CV study demonstrates
that carbonyl compounds were obtained on the surface of the
platinum electrode by oxidation, while Sn was generated at the
graphite electrode by reduction. These two redox products
7 Without electrolysis, the homoallylic alcohol was not obtained and
benzyl alcohol was recovered.
8
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2
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7
198 Chem. Commun., 2010, 46, 7196–7198
This journal is c The Royal Society of Chemistry 2010