Aqueous electrosynthesis of carbonyl compounds and the corresponding homoallylic alcohols in a divided cell

Article abstract of DOI:10.1016/j.tetlet.2010.01.026

An aqueous paired electrosynthesis is studied in a divided cell. On graphite anode Br^- was oxidized to Br₂ and this generated Br₂ oxidized alcohols to the corresponding carbonyl compounds while Sn²⁺ was reduced

Full text of DOI:10.1016/j.tetlet.2010.01.026

Tetrahedron Letters 51 (2010) 1426–1429
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aqueous electrosynthesis of carbonyl compounds and the corresponding
homoallylic alcohols in a divided cell
*
*
Li Zhang, Zhenggen Zha , Zhiyong Wang , Shengquan Fu
Hefei National Laboratory for Physical Science at Microscale, Joint-Lab of Green Synthetic Chemistry and Department of Chemistry, University of Science and
Technology of China, Hefei, 230026, PR China
a r t i c l e i n f o
a b s t r a c t
An aqueous paired electrosynthesis is studied in a divided cell. On graphite anode BrÀ was oxidized to Br2
and this generated Br2 oxidized alcohols to the corresponding carbonyl compounds while Sn2+ was
reduced to Sn0 on graphite cathode. Then the produced metallic tin mediated allylation of the carbonyl
compounds with allyl bromide to generate the corresponding homoallylic alcohols. In the reaction the
mediators (Sn and Br2) were generated in situ and could be reused via the electrolysis. Both working elec-
trode and the counter electrode were utilized to generate useful products without the sacrifice of the
electrode materials.
Article history:
Received 4 November 2009
Revised 23 December 2009
Accepted 8 January 2010
Available online 13 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
In the past two decades, electrochemical synthesis has attracted
many attentions.1 Compared to the conventional organic synthesis,
electroorganic synthesis is a powerful tool for clean and safe organ-
ic synthesis. Its process is up to the standard of green chemistry.2
Electrons are inherently environment-friendly reagents and they
can substantially eliminate the waste treatment of used redox
reagents.3
Among many electrochemical-promoted reactions, the studies
of both oxidation of alcohols and the allylation of carbonyl com-
pounds are very active due to the universal intermediates of the
produced carbonyl compounds and the corresponding homoallylic
alcohols for organic synthesis or pharmaceutical design. Some pub-
lications reported the electrochemical oxidation of alcohols to
aldehydes, in which the electrogenerated hypobromine, chiral aza-
bicyclo-N-oxyls were employed as oxidizing reagents.4 In these
reaction systems, the poor conductivity of the organic solvents
led to a higher electrolysis potential and the involvement of expen-
sive mediators or catalysts. Recently the two-phase electrolysis
was developed and employed in organic synthesis. For instance,
the oxidation of benzylic alcohols in sodium bromide solution
was performed in an undivided cell.5 This method can circumvent
side reactions during electrolysis.
bination of these two reactions in a divided cell simultaneously
yet. Herein, we describe a new electrochemical synthesis method
for the formation of the carbonyl compounds and the correspond-
ing homoallylic alcohols without the sacrification of anode elec-
trode and the waste of counter electrode. And only catalytic
amount of mediator was used in the reaction.
Our design is shown in Scheme 1. We performed the oxidation
of the alcohols and the following allylation in a divided cell simul-
taneously by using paired electrolysis with a salt bridge of KNO3
under potentiostatic control. In anodic compartment, BrÀ was oxi-
dized to Br2, which oxidized alcohols to yield corresponding car-
bonyl compounds5,8 while Sn2+ was reduced to Sn0 in cathodic
compartment. Then the produced metallic tin mediated allylation
between allyl bromide and carbonyl compounds to generate
homoallylic alcohols.7,9 With the electrolysis, Sn2+ and BrÀ could
be reused for the next cycle.
Experimentally, the salt bridge of KNO3 was employed to con-
nect the two separated electrolysis cells. The two cells were
Graphite
Graphite
R= Alkyl, Aryl
Br
Sn0
On the other hand, electrochemical allylations of carbonyl com-
pounds have been reported by using different catalytic electrogen-
erated metals.6,7 Whether electrochemical oxidation or reduction,
there are still some flaws such as sacrification of the anode elec-
trode, waste of counter electrode, use of the stoichiometric amount
of mediator, byproduct incurred by over-potential and so on. To
the best of our knowledge, there have been no reports on the com-
Br -
C
A
T
RCHO
RCHO
A
N
O
D
E
salt bridge
2
H2O
+
H2O
+
KNO3
H
CH2Cl2
CH2Cl2
OH
KNO3
O
D
E
Sn2+
Br2
RCH2OH
R
1
3
aqueous phase
organic phase
aqueous phase
* Corresponding author. Tel./fax: +86 551 3603185.
E-mail address: zwang3@ustc.edu.cn (Z. Wang).
Scheme 1. The design for the divided cell.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.026

L. Zhang et al. / Tetrahedron Letters 51 (2010) 1426–1429
1427
equipped with a graphite electrode (dia. 3.0 mm) as anode, a
a
b
c
1.2
0.9
graphite electrode (dia. 3.0 mm) as cathode, saturated calomel
electrode (SCE) as reference electrode respectively. A solution of
benzyl alcohol (2 mmol) in 1 mL of CH2Cl2 was placed in anodic
compartment. To the solution, a solution of sodium bromide
(2 mmol), HBr (48%, 0.4 mL) in water (5 mL) were added as aque-
ous phase. In cathodic compartment, SnCl2 (2 mmol) in water
R1
0.6
0.3
(5 mL) was added as aqueous,
a solution of benzaldehyde
O1
0.0
(2 mmol), allyl bromide (3 mmol) in CH2Cl2 (1 mL) as organic
phase. A pair of electrode was placed in aqueous phase which
was electrolyzed at a constant potential. Subsequently, the reac-
tion conditions were optimized as follows.
-0.3
-0.6
O2
At first, different potentials were tested. When the potential
was below 0.6 V, on the cathode Sn2+ was reduced slowly and
the produced tin was coated on the electrode tightly, resulting in
the difficulty for tin to peel off from the electrode into the solution
and retarding the further electrolysis while on the anode BrÀ could
not be oxidized. When the potential was over 0.6 V, many byprod-
ucts were generated. It was found that the potential of 0.6 V was
the most efficient. Cyclic voltammograms showed us the oxidation
and reduction reactions clearly in the divided cell. According to the
curve of blank solution [Figs. 1 and 2(a)], there was no evident ano-
dic or cathodic wave, which indicated that blank solution was not
electroactive in the potential window of interest. When mediators
were added and a pair of curves were recorded, as shown in Figure
1(b), BrÀ exhibited an oxidation wave (O1) and a reduction wave
(R1). The O1 wave corresponded to the electro-oxidation of BrÀ,
which led to the formation of Br2.10 On the backward potential
sweep, the R1 wave could be ascribed to the corresponding reverse
process. In Figure 2(b), the R1 wave indicated that Sn2+ was re-
duced to Sn0.11 The O1 and O2 waves were attributed to corre-
sponding oxidation processes. After organic substrates were
added, similar waves appeared [Figs. 1 and 2(c)], which indicated
that mediator precursors (SnCl2 and NaBr) were reduced at the
cathode and oxidized at the anode, respectively. The electrogener-
ated Br2 oxidized alcohols to the carbonyl compounds while Sn0
mediated allylation reaction of the corresponding carbonyl com-
pounds to produce the corresponding homoallylic alcohols.
Afterward, the ratio of the mediator to the substrate in the reac-
tion was optimized. When the ratio of mediator to substrate (M/S)
was 1:1, the reaction was carried out smoothly. Considering that
mediators (Sn and Br2) could be regenerated by electrolysis and
be used in cycle, the ratio of M/S was reduced to 1:4 (M/S). In this
case, the reaction could be carried out very well to give the
-0.9
-0.8
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
E/V vs SCE
Figure 2. Cyclic voltammograms of the solutions in water with two glassy carbon
electrodes (3.0 mm diameter vs SCE) using KNO3 as supporting electrolyte at a scan
rate of 10 mV/s and in the presence of KNO3 salt bridge at room temperature. (a)
0.5 mmol KNO3 in water (5 mL); (b) 0.05 mmol SnCl2 and 0.5 mmol KNO3 in water
(5 mL); (c) 0.05 mmol SnCl2 and 0.5 mmol KNO3 in water (5 mL) and 1 mmol
benzaldehyde and 1.5 mmol allyl bromide in CH2Cl2 (1 mL).
corresponding homoallylic alcohols with high yields. As a result,
the mediators were converted to the catalysts to some extent. The
total reaction in divided cell could be summarized as Scheme 2.
The reaction indicated that carbonyl compounds and homoal-
lylic alcohols were synthesized in anodic and cathodic compart-
ment respectively. Both working electrode and the counter
electrode were utilized to generate synthetically useful products
in the reaction. In this case current efficiency was improved one
fold in comparison with that only using working electrode alone.
Finally, different supporting electrolytes were optimized. The
different electrolytes such as CTAB (cetyltrimethyl–ammoniumbr-
omide), Et4NBr, Bu4NI, KNO3 and LiClO4 were examined under the
conditions. It was found that the supporting quaternary ammo-
nium salt electrolyte disfavored this reaction and resulted in many
side reactions in organic phase. Eventually, KNO3 was selected as
supporting electrolyte.
Subsequently the reactions were carried out under the
optimized conditions.12 The experimental results were listed in
Table 1. From Table 1, it can be seen that halogen substituents at
the para position gave the corresponding products with higher
yields (entries 3 and 4) compared to aromatic alcohols without
substitution (entries 1 and 2). Para-NO2 and para-CH3 substituents
on the benzylic alcohol gave medium yields (entries 5 and 6).
Ortho-Br substituent on the benzylic alcohol also favored the ally-
lation (entry 7). However, ortho-NO2 substitution had a negative
effect on this allylation (entry 8). When aliphatic alcohols or sec-
ondary alcohols were employed as the reaction substrates, the
reaction could be carried out smoothly to afford the corresponding
products with moderate yields (entries 9–13). Heteroaromatic sub-
strates also worked well (entries 14 and 15). It should be noted
that rich-electron heteroaromatic substrate gave a higher yield
than poor-electron heteroaromatic substrate. In anodic compart-
ment, there was no significant effect of the substituents on the
electrochemical oxidation. Compared to the previously reported
a
b
45
c
30
15
O1
0
-15
-30
R1
-45
2Br-
Br2
+
2e-
+
Anode
-0.2 0.0
0.2
0.4
E/V vs SCE
0.6
0.8
1.0
1.2
1.4
2Br- + 2H+
PhCH OH Br
+
PhCHO
Sn
2
2
2e-
Sn2+
Figure 1. Cyclic voltammograms of the solutions in water with two glassy carbon
electrodes (3.0 mm diameter vs SCE) using KNO3 as supporting electrolyte at a scan
rate of 10 mV/s in the presence of KNO3 salt bridge and at room temperature. (a)
0.5 mmol KNO3 in water (5 mL); (b) 0.05 mmol NaBr, HBr (0.01 mL) and 0.5 mmol
KNO3 in water (5 mL); (c) 0.05 mmol NaBr, HBr (0.01 mL) and 0.5 mmol KNO3 in
water (5 mL) and 1 mmol benzylic alcohol in CH2Cl2 (1 mL).
Cathode
+
OH
+ H+
-
2+
+
+
Br
Br
+ PhCHO
Sn
+
Sn
Ph
Scheme 2. The total reaction in this electrochemical process.

1428
L. Zhang et al. / Tetrahedron Letters 51 (2010) 1426–1429
Table 1
100
cathodic product
anodic product
Paired electrochemical synthesis homoallylic alcohols from alcohols in a divided cell
Graphite anode
NaBr,HBr
H2O/CH2Cl2
(5:1)
Graphite cathode
SnCl2
H2O/CH2Cl2
80
60
40
20
0
(5:1)
KNO3
OH
O
O
KNO3
R
OH
R
R
H
R
H
Br
1a-o
2a-o
R= Alkyl, Aryl
3a-o
1k-m was secondary alcohol,
2k-m and 3k-m were the corresponding products
Entry
1
Substrate 1
Product 2
Yielda (%)
Product 3
Yielda (%)
OH
2a
95
3a
91
93
1
2
3
4
5
OH
Cycles
2
2b
85
3b
Figure 3. The reaction yields of each round for the paired electrosynthesis of
benzaldehyde and the corresponding homoallylic alcohols.
OH
OH
3
4
5
2c
2d
2e
97
97
84
3c
3d
3e
93
92
92
Cl
paired electroysnthesis to other reactions is in progress in our
laboratory.
Br
OH
OH
O2N
Acknowledgments
6
7
8
2f
85
97
45
3f
88
90
33
H3C
The authors are grateful to National Natural Science Foundation
of China (No. 20772118) for support.
OH
Br
2g
2h
3g
3h
References and notes
OH
NO2
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OH
9
2i
2j
46
82
3i
3j
76
80
OH
OH
10
5
11
12
2k
2l
99
98
3k
3l
0
OH
OH
20
13
14
2m
2n
88
85
3m
3n
87
96
OH
O
S
OH
15
2o
82
3o
71
a
Isolated yield.
oxidation in one cell,5 the yields were enhanced largely, especially
for the substrates of 4-nitrobenzyl alcohol, heptanal and diphenyl
methanol (entries 4, 10 and 11). It should be noted that the method
of paired electrosynthesis facilitated the reaction of two electrodes.
Also, we found that the amount of SnCl2 and NaBr could be reduced
to the catalytic amount and could be reused for five times without
obvious loss in catalytic activity. For example, the carbonyl com-
pound and corresponding homoallylic alcohol were obtained with
a high yield of more than 80% after the fifth round. The slight de-
crease of the reaction yield was possibly due to the loss of SnCl2
and NaBr in the extraction (Fig. 3).
In summary, the carbonyl compounds and the corresponding
homoallylic alcohols can be prepared by using a simple paired
electrosynthesis in a divided cell. The employment of these paired
electrodes makes mediators approach to catalysts without the sac-
rification of electrodes. Moreover, this electrochemical method
should be potential in organic synthesis. The application of this
12. Typical procedures: A divided cell with salt bridge of KNO3 was equipped with
a graphite electrode (dia.3.0 mm) as anode, a graphite electrode (dia.3.0 mm)
as cathode and the saturated calomel electrode at room temperature.
A
solution of benzyl alcohol (2 mmol) in 1 mL of CH2Cl2 was added in anodic
compartment. To the solution, a solution of 0.1 M sodium bromide solution
(5 mL), 48% HBr (0.1 mL) and KNO3 (0.05 M) were added as aqueous phase. In
cathodic compartment, 0.1 M SnCl2 (5 mL) and KNO3 (0.05 M) were added as
aqueous, a solution of benzaldehyde (2 mmol), allyl bromide (3 mmol) in 1 mL

L. Zhang et al. / Tetrahedron Letters 51 (2010) 1426–1429
1429
of CH2Cl2 as organic phase. The pair of electrodes were placed in the upper
layer of the aqueous phase and the upper layer was electrolyzed under
controlled potential at 0.6 V versus SCE, then stopped electrolyzing and started
stirring alternately until substrates completely transformed for about 6-7 h.
The reaction product was separated by extraction and purified with a column
chromatography. Benzaldehyde (2a) 1H NMR (CDCl3, 300 MHz, ppm): d = 10.02
(s, 1H), 7.88 (d, J = 6.9 Hz, 2 H), 7.72–7.61 (m, 1 H), 7.61-7.45 (m, 2 H); 13C NMR
(CDCl3, 75 MHz, ppm): d = 192.3, 136.5, 134.4, 129.7, 128.9; IR (liquid film,
cmÀ1): v = 3387, 3064, 2819, 2737, 1702, 1655, 1584, 1203, 827, 745, 688, 649.
Phenylbut-3-en-1-ol (3a) 1H NMR (CDCl3, 300 MHz, ppm): d = 7.39–7.21 (m,
5H), 5.90–5.69 (m, 1H), 5.21–5.10 (q, 2H), 4.78–4.60 (q, 1H), 2.42–2.62 (m, 2H),
2.00 (s,1H); 13C NMR (CDCl3, 75 MHz, ppm): d = 144.0, 134.6, 128.5, 127.6,
125.9, 118.4, 73.4, 43.9; IR (liquid film, cmÀ1): v = 3401, 3077, 3030, 2979,
2908, 1641, 1493, 1453, 1307, 1048, 1001, 916, 758, 700, 644, 609.