SnCl2-mediated carbonyl allylation of aldehydes and ketones in ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2005.11.022

In ionic liquid [bmim]BF₄, SnCl₂·2H ₂O acts as an inexpensive and efficient metal salt for carbonyl allylation. By applying ionic liquid, some previously reported serious operational problems associated with the SnCl₂-mediated allylation reaction are avoided. Furthermore, ketones, which are less reactive than aldehydes, can also be allylated in high yields with this system.

Full text of DOI:10.1016/j.tetlet.2005.11.022

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 303–306
SnCl2-mediated carbonyl allylation of aldehydes and ketones
in ionic liquid
Long Tang, Li Ding, Wei-Xing Chang and Jing Li*
The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
Received 23 July 2005; revised 3 November 2005; accepted 4 November 2005
Abstract—In ionic liquid [bmim]BF4, SnCl2Æ2H2O acts as an inexpensive and efficient metal salt for carbonyl allylation. By applying
ionic liquid, some previously reported serious operational problems associated with the SnCl2-mediated allylation reaction are
avoided. Furthermore, ketones, which are less reactive than aldehydes, can also be allylated in high yields with this system.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The addition of allyl-metal reagents to carbonyl com-
pounds has been impressively developed in the past
few years.1 In particular, the Barbier type coupling reac-
tion between allyl halide and carbonyl compounds has
proven to be an efficient way to prepare homoallylic
alcohols by virtue of its synthetic potential and opera-
tional simplicity. Among the numerous metals that have
been applied in this reaction, tin receives more and more
attention due to its suitable activity, low cost and low
toxicity of the final inorganic tin derivatives. In the past
few years, stannous dichloride, which is even cheaper
and easier to obtain, has been considered as a new alter-
nation to mediate carbonyl allylation. It was reported
that SnCl2 mediated carbonyl allylation could be
activated by Pd(II),2 Cu(I),3 Cu(II)4 and Ti(III).5 Very
recently, Yuan and co-workers6 and Guo and co-work-
ers7 found that SnCl2 itself could mediate carbonyl allyl-
ation when ultrasonic radiation was employed or when
a strictly limited amount of water was used as the sol-
vent. However, ultrasonic radiation is not a popular
condition in organic chemistry laboratory and there is
one serious operational problem associated with Guoꢀs
reaction. As said in Guoꢀs paper, so little amount of
water was used in the process as the solvent, that the
reaction mixture might become too dense to deal with.7
On the other hand, as far as we know, there were only
two reports concerning the Barbier type SnCl2-mediated
allylation of ketones. In these two reports, copper3b or
ultrasonic radiation6 was indispensable to accomplish
the allylation.
All these previously reported examples of SnCl2 medi-
ated carbonyl allylation occur under aqueous or aque-
ous-organic biphasic conditions. The aqueous solvent
provides good solubility for SnCl2. On the other hand,
the polar environment of the aqueous solvent may be
necessary to weaken the R–X bond. The ionic liquid
[bmim]BF4 (1-n-butyl-3-methylimidazolium tetrafluoro-
borate) is known as a highly polar and hydrophilic sol-
vent, which is similar to water. By virtue of high polarity
and high hydrophilicity, when we applied ionic liquid as
the solvent in this process, the carbonyl allylations med-
iated by SnCl2 transpired as we expected. The reaction
mixture became clear and easy to deal with. The ionic
liquid could be recycled and reused in the next cycle
without any further purification. Furthermore, ketones,
which were less reactive than aldehydes, could also be
allylated in high yields with our system, which was only
mediated by SnCl2 itself without any other auxiliary
methods. Herein, we present an efficient and operation-
ally easier alternation for SnCl2-mediated carbonyl ally-
lation (Scheme 1).
The allylation of aldehydes (0.5 mmol) by allyl bromide
(0.75 mmol) was carried out with SnCl2Æ2H2O (0.6 mmol)
in [bmim]BF4 (2 mL) and H2O (0.2 mL) at room temper-
ature for 24 h.8 The experimental results are summarized
in Table 1.
OH
O
SnCl2·2H2O
+
Br
R
[bmim]BF4
H2O, rt
R
H(Me)
H(Me)
*
Corresponding author. Tel.: +86 2223 503336; fax: +86 2223
502627; e-mail: lijing@nankai.edu.cn
Scheme 1.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.022

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L. Tang et al. / Tetrahedron Letters 47 (2006) 303–306
Table 1. The application of SnCl2Æ2H2O/allyl bromide/[bmim]BF4
Table 2. The application of SnCl2Æ2H2O/allyl bromide/[bmim]BF4
system in carbonyl allylation of aldehydes
system in carbonyl allylation of ketones
Entry
1
Substrate
Product
Yield (%)a
88
Entry
1
Substrate
Product
Yield (%)a
73
OH
OH
CHO
COCH3
C
Me
OH
COCH3
COCH3
COCH3
OH
C
CHO
2
65
83
85
94
91
43
65
42
32
7b
Me
2
3
4
5
6
55
81
77
93
83
Cl
Br
Cl
Br
Cl
Cl
OH
C
OH
3
CHO
Me
H3C
OH
H3C
C
4
OH
CHO
CHO
Me
F
F
Br
Cl
OH
C
Br
Cl
F3C
COCH3
F3C
5
OH
OH
Me
OH
C
Br
COCH3
COCH3
Br
6
Cl
Cl
Me
CHO
CHO
OH
C
Cl
Cl
7
Me
H3C
O
OH
H3C
HO
F3C
F3C
7
8
95
20
8
OH
CHO
OH
O
O
a Isolated yields. Products were confirmed by 400 MHz H NMR and
1
9
100 MHz 13C NMR.
Me
OH
Me
10
It was shown that aromatic aldehydes gave moderate to
high allylation yields. Aromatic aldehydes with different
substituents could be allylated efficiently. m-Trifluoro-
methylbenzaldehyde had the highest yield due to the
strong electron-withdrawing effect. But p-nitrobenzalde-
hyde did not offer the desired product because the nitro
group could be reduced in this Barbier-type allylation
when low valence metal or its salt was used. Due to
the strong electron-donating effect, the allylation of
anisaldehyde (p-methoxybenzaldehyde) failed. n-Butyl
aldehyde exhibited a low activity because of the elec-
tron-donating effect of the aliphatic chain (entry 8).
Br
Br OH
C
COCH3
11
Me
a Isolated yields.
b 83% of the substrate was recovered.
THF instead of [bmim]BF4, no allylation occurred.
Furthermore, when H2O was employed as solvent
instead of ionic liquid, even in a strictly limited amount,
no allylation for ketones occurred.7
Ketones, due to the lower electrophilicity of the car-
bonyl carbon, are not so active in Barbier type allylation
as aldehydes. The successful examples for allylation of
ketones were much less than those for aldehydes. How-
ever, after some optimization,9 when 2.0 M equiv of
SnCl2Æ2H2O was used instead of 1.2 M equiv for alde-
hydes, the allylation yields of ketones increased signifi-
cantly. The new allylation system proved to be an
efficient and mild allylation system for ketones. The
experimental results are summarized in Table 2. Accord-
ing to Wuꢀs calculation,10 we believed that the ionic
liquid, as a high polar solvent, played an important role
in this process. The parallel experiments gave their
evidence. In parallel experiments using DCM and
As shown in Table 2, both aliphatic and aromatic
ketones could be allylated in good to excellent yields
(entries 1–10). Aromatic ketones with EWG on the
aromatic ring (entries 2–6) gave higher yields than
those with EDG (entry 7). Because of the strong elec-
tron-withdrawing effect caused by the trifluoromethyl
group, 30-trifluoromethyl acetophenone had the highest
yield in all the substrates we examined (entry 5). The
aliphatic ketone cyclohexanone gave a moderate yield
(entry 8), but the isolated yields of acyclic aliphatic
ketones were low (entries 9 and 10). The bromo group
in 20-bromoacetophenone is so large that it makes 20-
bromoacetophenone inert by steric hindrance (entry

L. Tang et al. / Tetrahedron Letters 47 (2006) 303–306
305
Table 3. Recycling and reuse of ionic liquid [bmim]BF4 in carbonyl
allylation of m-chlorobenzaldehyde
SnCl2
SnBrCl2
O
Br
Substrate
Product
Cycle
Yield (%)a
R1
R2
1
2
3
4
5
91
88
87
87
85
OH
Cl
CHO
Cl
OH
R2
SnBrCl2
R1
R2
O
R1
a Isolated yields.
Scheme 2.
11). p-Nitroacetophenone, as well as p-nitrobenzalde-
hyde, did not offer the corresponding homoallylic alco-
hol either.
Cl bonds to activate the allylic tin intermediate.12 When
we mixed SnCl2Æ2H2O (0.6 mmol), allyl bromide (0.75
mmol) in 2 mL [bmim]BF4 with 0.2 mL H2O, 1H
NMR analysis showed some new peaks at d = 2.4 and
d = 1.8, which were considered to be the signals of the
allyltin species13,7 mentioned above or its hydrolysis
product. Detailed investigation on the mechanism is still
in progress.
Effort to recycle and reuse ionic liquid was also
attempted. The recycle process was investigated starting
with fresh [bmim]BF4. After the reaction was complete,
Et2O was used to extract the products. Then the ionic
liquid was used directly in the next cycle without any
purification. Because of its high allylation yield, m-chloro-
benzaldehyde was chosen as the substrate to investigate
the recycle process (Table 3).
In conclusion, the present study demonstrated an
efficient SnCl2-mediated carbonyl allylation of allyl
bromide to aldehydes and ketones in ionic liquid. The
reaction is easy to perform and environmentally benign.
Detailed investigation on the mechanism, regio- and dia-
stereoselectivity of this allylation is in progress in our
laboratory.
As shown in Table 3, the ionic liquid could be recycled
and reused for 5 cycles without a notable reduction in
yields. This made our allylation system more environ-
mentally benign.
Detailed investigation on regio- and diastereoselectivity
is in progress in our laboratory, some primary results
showed that it was a c-addition reaction and the anti-
isomer was the major product. Those results are summa-
rized in Table 4.
Acknowledgement
This work is supported by MEC, NSFC (20372033) and
Nankai University.
A plausible mechanism is shown in Scheme 2.7,11 The
carbonyl allylation proceeded via the intermediate of
allylbromodichlorotin, which was formed by oxidative
addition of allyl bromide to SnCl2. This mechanism pro-
vided an explanation for the c-selectivity by the chair-
like transition state. In contrast to the 88% yield shown
in Table 1, entry 1, the yield of allylation of benzalde-
hyde without H2O was only 45%. The small amount
of water seemed to cause the hydrolysis of the Sn(IV)–
References and notes
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Br
3α
3γ
R
2
+
.
2H2O
SnCl2
+
OH
OH
[bmim]BF4
RCHO
8. Typical procedures for allylation of aldehydes using
SnCl2Æ2H2O/allyl bromide/[bmim]BF4 system are as
follows. The allylation of carbonyl compounds (0.5 mmol)
by allyl bromide (0.75 mmol) was carried out with
SnCl2Æ2H2O (0.6 mmol) in [bmim]BF4 (2 mL) and H2O
(0.2 mL) at room temperature for 24 h. Then the mixture
was extracted with ether (3 · 5 mL). The combined
organic layers were dried over anhydrous MgSO4, filtered
and evaporated. Purification was performed by column
chromatography over silica gel.
R
R
1
anti
syn
Entry
Substrate
Yield (%)a
3a3c (anti:syn)b
1
2
3
R = Ph
R = p-BrPh
R = p-CH3Ph
96
97
93
10:90 (78:22)
8:92 (75:25)
9:91 (69:31)
a Isolated yields.
b The ratio was determined by 400 MHz 1H NMR.

306
L. Tang et al. / Tetrahedron Letters 47 (2006) 303–306
9. The allylation of ketone (0.5 mmol) by allyl bromide
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[bmim]BF4 (2 mL) and H2O (0.2 mL) at room temperature
for 24 h.
10. Miao, W.; Chung, L. W.; Wu, Y.-D.; Chan, T. H. J. Am.
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