Organometallic reactions in aqueous media: The allylations of carbonyl compounds mediated in Zn/CdSO4 and Zn/SnCl2 bimetal systems

Article abstract of DOI:10.1016/j.tetlet.2004.05.070

Zn/CdSO₄ and Zn/SnCl₂ bimetal systems were employed in the allylations of aldehydes or ketones in distilled water to afford the corresponding homoallylic alcohols in good yields. Also, the chemoselectivity was studied under the same

Full text of DOI:10.1016/j.tetlet.2004.05.070

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5537–5540
Organometallic reactions in aqueous media: the allylations
of carbonyl compounds mediated in Zn/CdSO4 and Zn/SnCl2
bimetal systems
Cunliu Zhou, Yuqing Zhou, Jiaoyang Jiang, Zhen Xie, Zhiyong Wang,* Jiahai Zhang,
Jihui Wu and Hao Yin
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
Received 6 February 2004;revised 26 April 2004;accepted 3 May 2004
Abstract—Zn/CdSO4 and Zn/SnCl2 bimetal systems were employed in the allylations of aldehydes or ketones in distilled water to
afford the corresponding homoallylic alcohols in good yields. Also, the chemoselectivity was studied under the same condition. It
was found that good chemoselectivity of allylations could be obtained for different carbonyl compounds under the mediation of our
bimetal systems.
Ó 2004 Elsevier Ltd. All rights reserved.
Table 1. Allylation of benzaldehyde mediated by different metal
systems
A typical and popular organic reaction in aqueous
media is the allylations of carbonyl compounds.1 Up to
M/CdSO (or SnCl )
now, many metals have been used in the allylation and
different reaction conditions have been tested in order to
broaden the scope of carbonyl compounds and enhance
the reaction yield.2 However, enhancing the reaction
yield and extending the variety of carbonyl compounds
is still a challenge to chemists. Recently, we found that
Zn/CdSO4 and Zn/SnCl2 bimetal systems are quite effi-
cient for the allylations of carbonyl compounds.
4
2
Br
Ph-CHO +
PhCH(OH)CH2CH=CH2
H2O
2
3
1
Entry
Conditionsa
Yield%f /time (h)
1
Zn
CdSO4
20/24
0/24
2
b
3
Zn/CdSO4
Zn/CdSO4
85/7.0
87/7.0
23/34
0/30g
0/30
c
4
b
5
Mg/CdSO4
b
6
Fe/CdSO4
Al/CdSO4
Intrigued by the allylations of carbonyl compounds in
the bimetal systems,3 we attempted to find more efficient
bimetal systems to mediate the allylations of carbonyl
compounds. The allylation of benzaldehyde was initially
carried out in the presence of zinc in distilled water and
the corresponding homoallylic alcohol was obtained in
20% yield (Table 1, entry 1). Once 0.1 mmol of cadmium
sulfate was added to this reaction mixture, the allylation
could proceed smoothly to afford the desired product in
good yield and the reaction rate was enhanced signifi-
cantly (Table 1, entry 3). Without metal zinc, the allyl-
ation of benzaldehyde was inert in the presence of
cadmium sulfate in distilled water (Table 1, entry 2). The
experimental results demonstrated that this new bimetal
b
7
d
8
Zn/SnCl2
Zn/SnCl2
28/24
96/1.5
93/13
20/24
e
9
10
11
Sn
Cd
a Metal(0) (2.0 mmol) unless stated.
b CdSO4 (0.1 mmol).
c CdSO4 (1.0 mmol).
d SnCl2 (0.1 mmol).
e SnCl2 (1.0 mmol).
f Determined by 1H NMR.
g Polymerization occurred.
system (Zn/CdSO4) was very efficient to mediate the
allylation and there was a cooperating effect between Zn
and CdSO4 to the allylation. When the dosage of cad-
mium sulfate was increased from 0.1 to 1.0 mmol, there
was little influence on the allylation of benzaldehyde
* Corresponding author. Tel.: +86-551-3603185;fax: +86-551-36317-
60;e-mail: zwang3@ustc.edu.cn
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.070

5538
C. Zhouet al. / Tetrahedron Letters 45 (2004) 5537–5540
(Table 1, entries 3 and 4). In addition to Zn, other
metals were also employed as mediators in order to
search for more efficient bimetal systems. The allylation
of benzaldehyde gave the desired product with a low
yield in the Mg/CdSO4 system (Table 1, entry 5). In the
Fe/CdSO4 or Al/CdSO4 system, no desired product was
observed (Table 1, entries 6 and 7). Of all the examined
bimetal systems, Zn/CdSO4 turned out to be the most
efficient system for the allylation. Considering the tox-
icity of cadmium salt, however, we have attempted to
substitute CdSO4 with other Lewis acids. After many
trials, CdSO4 in the bimetal system was replaced with
SnCl2. It was found that Zn/SnCl2 bimetal system pro-
moted the allylation more effectively than Zn/CdSO4.
The difference compared with the Zn/CdSO4 system was
that the dosage of stannous chloride has an influence on
the allylation of benzaldehyde. When 0.1 mmol of
stannous chloride was added to this system, for exam-
ple, the allylation generated the corresponding product
in 28% yield after reaction for 24 h (Table 1, entry 8).
Once the dosage of stannous chloride was increased to
1.0 mmol, the allylation could proceed smoothly in 96%
yield after reaction for 1.5 h (Table 1, entry 9). In
comparison with metal Sn or Cd, Zn/SnCl2, and Zn/
CdSO4 systems for the allylation of benzaldehyde were
obviously more effective (Table 1, entries 3, 9, 10, and
11). Subsequently, allylations of a variety of aldehydes
and ketones were tested in the Zn/CdSO4 and Zn/SnCl2
systems. The results of the reactions are listed in Table 2.
entry 3). In particular, the Zn/SnCl2 system mediated
the allylations more effectively, and gave the corre-
sponding homoallylic alcohols in excellent yields. In
some cases, Zn/SnCl2-mediated allylations generated the
corresponding adducts quantitatively (Table 2, entries 2,
5, 6, 7, 8, and 10). For the allylation of p-nitrobenzal-
dehyde, as far as we know, it is difficult to get the allyl-
ation product but the reduced nitro group products
when mediated by indium or tin powder.2h;4 In the Zn/
SnCl2 system, however, the allylation of p-nitrobenzal-
dehyde gives the desired product in about 60% yield
(Table 2, entry 13). This indicates that Zn/SnCl2 could
particularly improve the allylations. The allylations of
butan-2-one, 3-hydroxy-butan-2-one, and heptanal were
also mediated by Zn/SnCl2 in distilled water and gave
the corresponding alcohols in high yields (Table 2, en-
tries 3, 4, and 10), while these allylations gave the cor-
responding adducts in the low yields of less than 50%
when mediated by tin.2h
It is interesting to note that good chemoselectivity of the
allylations can be observed in these two bimetal systems.5
The experimental results are summarized in Table 3. It
was found that allylation favored the aromatic aldehyde
(1a) in the presence of an equivalent mole of aromatic
ketone (1n) (Table 3, entry 1). When benzaldehyde (1a)
mixed with o-methoxybenzaldehyde (1o), benzaldehyde
(1a) was easier to be allylated (Table 3, entry 2). When
the methoxyl group was moved from ortho position to
para position, p-methoxy-benzaldehyde (1g) favored the
allylation more than benzaldehyde (Table 3, entry 3).
These results could be ascribed to the steric hindrance.
When aliphatic aldehyde (1d or 1p) was mixed with an
equivalent mole of aromatic aldehyde (1a), the allylation
squint toward aliphatic aldehyde (1d or 1p) (Table 3,
entries 4 and 5) under this condition. Similarly, for an
equivalent mole mixture of 1g and 1d, the allylation
favored the aliphatic aldehyde 1d (Table 3, entry 6).
However, it was found that allylation favored an aro-
matic aldehyde, 4-chloro-benzaldehyde (1e), in the
presence of an equivalent mole of heptaldehyde (1d)
possibly due to the electron-withdrawing effect of chlo-
rine atom (entry 7). Such a reactivity difference between
aldehyde and ketone or between aromatic aldehyde and
aliphatic aldehyde suggests a useful method for chemo-
selectivity in aqueous allylations that has a potential
application in synthetic strategies to construct complex
molecules. In order to study this chemoselectivity fur-
ther, some intramolecular competitive reactions were
carried out under reaction conditions A and B, (Table 3).
The compounds (1q,r) bearing both aldehyde and ketone
groups gave the absolute predominant aldehyde allyl-
ation products (3q,r) (entries 12 and 13). The compound
(1s) bearing both aromatic and aliphatic aldehyde
groups gave predominantly the aliphatic aldehyde allyl-
ation product (3s) (entry 14). In a previous report, ali-
phatic aldehyde (1d) and aromatic aldehyde (1a) could be
allylated equally in acidic aqueous media mediated by
different metals such as zinc, indium, tin, or organome-
tallic agents, respectively (entries 8, 9, 10 and 11).2d
As shown in Table 2, all the allylations proceeded
smoothly to give the corresponding products in high
yields and side reactions such as reductions and coupling
reactions were not observed. Moreover, the reaction
condition was so mild as not to affect chloro (Table 2,
entry 5), methyl (Table 2, entry 6), and methoxyl (Table
2, entry 7) groups on the aromatic ring. Even hydroxyl
group, which is unstable because of the rapid proton-
ation with an allylation reagent, gave the corresponding
allylation product under the reaction condition (Table 2,
Table 2. Allylation of various carbonyl compounds with allyl bromide
Zn/CdSO (or SnCl )
4
2
Br
PhCH(OH)CH2CH=CH2
Ph-CHO+
H2O
2
3
1
Entry
Substrate
Yield%/time (h)a;b
1
C6H5CHO (1a)
Piperonal (1b)
85/7.0 (96/1.5)
63/17 (99/2.0)
81/5.5 (90/5.0)
83/7.5 (96/3.0)
67/8.0 (99/2.0)
65/9.0 (99/2.0)
64/9.0 (99/2.0)
35/18 (99/2.0)
80/18 (50/2.5)
73/5.5 (99/2.5)
80/20 (50/4.0)
82/13 (70/3.0)
––c (60/2.0)
2
3
CH3COCH(OH)CH3 (1c)
CH3(CH2)5CHO (1d)
4-Cl–C6H4–CHO (1e)
4-CH3–C6H4–CHO (1f)
4-CH3O–C6H4–CHO (1g)
1-Naphthaldehyde (1h)
1-Furaldehyde (1i)
4
5
6
7
8
9
10
11
12
13
CH3COC2H5 (1j)
Cyclohexanone (1k)
CHO(CH2)3CHO (1l)
4-NO2–C6H4–CHO (1m)
a Isolated yield.
b Data in parenthesis are the yields in Zn/SnCl2.
c Reduction reaction was observed.
In conclusion, two novel bimetal systems were applied
to the allylations of carbonyl compounds, affording the

C. Zhouet al. / Tetrahedron Letters 45 (2004) 5537–5540
Table 3. Product distribution of allylation of different carbonyl compounds
5539
Substrate
Conditiona
Yield%b
O
CH
O
C
A
B
3a:3n >99:1
3a:3n >99:1
CH3
1
2
(1a)
(1n)
O
CH
O
CH
OCH
A
B
3a:3o >99:1
3a:3o >99:1
+
(1a)
3 (1o)
O
O
CH
CH
+
3
4
5
6
A
B
3a:3g ¼ 49:51
3a:3g ¼ 41:59
H3CO
(1g)
(1a)
O
H
+
CH3(CH2)5CHO
A
B
3a:3d ¼ 32:68
3a:3d ¼ 41:59
(1a)
(1d)
O
CH
CH3(CH2)2CHO
+
A
B
3a:3p ¼ 38:62
3a:3p ¼ 42:58
(1p)
(1a)
O
CH
CH3(CH2)5CHO
+
A
B
3g:3d ¼ 38:62
3g:3d ¼ 39:61
H3CO
(1g)
(1d)
O
CH
CH3(CH2)5CHO
+
7
A
B
3e:3d ¼ 64:36
3e:3d ¼ 84:16
Cl
(1e)
(1d)
O
CH
CH3(CH2)5CHO
+
8
Zn (0.1 N HCl)
In (0.1 N HCl)
Sn (0.1 N HCl)
3a:3d ¼ 50:50
3a:3d ¼ 50:50
3a:3d ¼ 50:50
(1a)
(1d)
O
CH
9
CH3(CH2)5CHO
+
(1a)
(1d)
O
CH
10
CH (CH ) CHO
+
3
2 5
(1a)
(1d)
O
CH
CH3(CH2)5CHO
+
11
Allylmagnesium bromide, Et2O
3a:3d ¼ 50:50
(1a)
(1d)
O
C
O
12
13
A
B
3q:4q ¼ 99:1c
3q:4q ¼ 99:1c
H3C
H3C
CH2 C H
(1q)
O
C
O
CH
A
B
3r:4r ¼ 80:20c
3r:4r ¼ 99:1c
(1r)
CHO
O
14
A
B
3s:4s ¼ 87:13c
3s:4s ¼ 81:19c
H (1s)
a Condition A: 1.0 mmol of carbonyl compound, 2.0 mmol of allyl bromide, 2.0 mmol of Zn, and 0.1 mmol of 3CdSO4Æ8H2O (based on CdSO4).
Condition B: 1.0 mmol of carbonyl compound, 2.0 mmol of allyl bromide, 2.0 mmol of Zn, and 1.0 mmol of SnCl2Æ2H2O (based on SnCl2).
b Indentified by GC–MS.
c Compounds 3q,r were the products when 1q and 1r were allylated at the aldehyde groups, and 4q,r were the products when 1q,r were allylated at the
ketone groups. Compounds 3s, 4s were the products when 1s was allylated at the aliphatic and aromatic aldehyde groups, respectively.

5540
C. Zhouet al. / Tetrahedron Letters 45 (2004) 5537–5540
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Acknowledgements
The authors are grateful to the National Nature Science
Foundation of China (No 50073021) and Science
Foundation of Anhui Province (No 01046301) for the
support.
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