InCl3-Promoted Allylation of Aldehydes in Ionic Liquid: Scope and Enantioselectivity Studies

Article abstract of DOI:10.1055/s-2004-815433

Indium trichloride was successfully applied to allylation reaction of aldehydes using allytributyltin in ionic liquids. This accelerated catalytic system afforded the allylated products of various aldehydes in moderate to high yields. Preliminary studies

Full text of DOI:10.1055/s-2004-815433

534
LETTER
InCl3-Promoted Allylation of Aldehydes in Ionic Liquid: Scope and
Enantioselectivity Studies
I
nCl3-Promuoted Allyla
n
tion of
A
ldehydes
in
Ionic
L
iquid u,a Shun-Jun Ji,*a Rong Qian,a Jian-Ping Chen,a Yu Liu,a Teck-Peng Loh*a,b
a
College of Chemistry and Chemical Engineering of Suzhou University, Suzhou215006, P. R. China
E-mail: shunjun@suda.edu.cn
b
Department of Chemistry, 3 Science Drive 3, National University of Singapore, 117543 Singapore
Fax +65(677)91691; fax +86(512)65224873; E-mail: chmlohtp@nus.edu.sg
Received 10 December 2003
Table 1 InCl3-Catalyzed Allylation of Benzaldehyde in Various
Ionic Liquids
Abstract: Indium trichloride was successfully applied to allylation
reaction of aldehydes using allytributyltin in ionic liquids. This ac-
celerated catalytic system afforded the allylated products of various
aldehydes in moderate to high yields. Preliminary studies on the
enantioselectivity of this type of reaction have resulted in low to
moderate enantioselectivities.
OH
O
Ionic liquid
InCl3
+
SnBu3
H
Entry Ionic liquid
Temp Time Yield
(°C) (h) (%)
Key words: indium trichloride, allylation, aldehydes, catalyst, ion-
ic liquid
1
40
25
25
25
55
16
16
14
12
16
70
80
82
75
68
Cl -
Cl -
Cl -
N
N
Allylation reactions of various carbonyl compounds are
valuable C–C bond formation methods for the preparation
of synthetically useful homoallylic alcohols.1 Although
Lewis acids or Bronsted acids catalyzed allylation reac-
tions in aqueous media with allytributyltin have been re-
ported,2–4 more active and efficient catalytic systems are
still highly sought-after. Due to the increase in concerns
about environmental effects which therefore requires the
development of new synthetic manipulation that can min-
imize the use of hazardous chemicals. In order to achieve
this goal, many strategies have been devised and investi-
gated, especially by replacing the traditional organic sol-
vents with other non-toxic solvents such as water or
supercritical carbon dioxide. Recently, much attention has
been focused on the use ionic liquids. Ionic liquids are
considered to be excellent alternatives to traditional or-
ganic solvents, due to their favorable properties, such as
non-flammability, no measurable vapor pressure, low
toxicity, reusability, low cost, high thermal stability and
experimental simplicity. As a result, ionic liquids are con-
sidered as promising alternative solvents for organic reac-
tions.5–9 Herein, we report that InCl3-promoted allylation
reactions of aldehydes with allytributyltin in ionic liquid
to afford the corresponding allylated adducts in moderate
to high yields.
[bmin+] [Cl–]
2
3
4
5
N
N
[hmin+] [Cl–]
N
N
[omin+][Cl–]
-
BF4
N
N
[hmin+] [BF4 ]
–
Cl -
N
N
[bmmin+] [Cl–]
6
7
8
60
45
40
16
14
14
66
60
62
N
Cl -
[epy+] [Cl–]
N
Br -
First, we tested the allylation reaction of benzaldehyde (1
equiv) of allytributyltin (1.2 equiv) in hexylmethylimida-
zolium chloride ([hmin+][Cl–]) in the presence of InCl3 or
silver nitrate (0.5–2 equiv). Although silver nitrate was
found to be not effective in catalyzing the formation of the
allylation product, InCl3 could promote the allylation
reaction very effectively (Table 1, entry 2).
[bpy+] [Br–]
N
Br -
[hpy+] [Br–]
a Isolated yield.
SYNLETT 2004, No. 3, pp 0534–0536
Advanced online publication: 26.01.2004
DOI: 10.1055/s-2004-815433; Art ID: U24203ST
© Georg Thieme Verlag Stuttgart · New York
1
8.
0
2.
2
0
0
4
Next using InCl3, we investigated the effects of ionic
liquids by carrying out the reaction in a series of ionic
liquids. The results are summarized in Table 1. It can be

LETTER
InCl3-Promoted Allylation of Aldehydes in Ionic Liquid
535
seen that all these ionic liquids gave the desired allylation posed mechanism that proposed the transmetallation of tin
product with moderate to good yields (60–82% yields), with InCl3. Therefore, addition of a further 1 equivalent of
among which [hmin+][Cl–] and [omin+][Cl–] gave the best InCl3 to the recycled ionic liquid on every cycle, allowed
results (80% and 82% yields respectively).
the allylation reaction to proceed in good yields.
Next, we directed our studies to investigate the allylation
reaction with various aldehydes in the present of InCl3 in
hexylmethylimidazolium chloride ([hmin+][Cl–]). The re-
sults are shown in Table 2. In all cases, InCl3 has been
shown to be efficient promoter for both aromatic and
aliphatic aldehydes to afford the products in moderate to
high yields (Table 2).
Table 3 Recycling Study on the Allylation Reaction in [hmin+][Cl–]
Cl -
OH
O
N
N
+
5
SnBu3
H
InCl3
Cl
Cl
Entry
Aldehyde
Product
Isolated yield (%)
86
Effort to recycle and reuse the ionic liquid was also
attempted. The recycle process was investigated starting
with fresh hexylmethylimidazolium chloride ([hmin+]
[Cl–]) and 4-chlorobenzaldehyde in the presence of InCl3
(Table 3). After the reaction was complete, the ionic liq-
uid was recycled and reused in the second cycle (2nd cy-
cle) directly. Unfortunately, no desired allylated product
was obtained. This is consistent to the previously pro-
1st cycle
2f
O
H
Cl
Cl
Cl
Cl
Cl
2nd cycle
3rd cycle
4th cycle
5th cycle
2f
2f
2f
2f
0
80
76
66
O
H
O
H
Table 2 InCl3-Catalyzed Allylation Reaction with Various Alde-
hydes using [hmin+][Cl–]
Cl
O
H
N
N
OH
5
RCHO +
SnBu3
R
InCl3
1a–i
2a–i
O
H
Entry Aldehyde
Product
Time
(h)
Yield
(%)a
O
1
2
2a
8
93
HOOC
H
2b
14
88
O
O
HO
P(Tol)2
P(Tol)2
COOH
H
H
N
H
5
N
3
4
3
4
2c
2e
14
16
86
78
N
Ph
Ph
OH
H
N
Ph
Ph
H
H Ph
N
PhH2C
PhH2C
H2N
COOH
Ph
N
N
8
OH
9
OH
7
O
NH2
H
6
H
Figure 1 Chiral ligands 3–9
H3CO
5
6
2f
16
18
82
76
O
H
In the meanwhile, we investigated the asymmetric allyl-
ation reaction in ionic liquids. First we initiated our study
by using benzaldehyde and allytributyltin as substrates in
[hmin+][Cl–]. During this study, the chiral ligands 3–9
(Figure 1) have been screened, among which (S)-2-
(diphenylmethanol)-1-(2-pyridylmethyl) pyrrolidine 9
gave the best result (Table 5, entry 4). Next, using ligand
9, a series of ionic liquids were also examined. The results
are summarized in Table 4. It can be seen that all ionic liq-
uids gave the desired allylation products of 4-chlorobenz-
aldehyde with low to moderate ee (16–48%), and the
reaction carried out in [hmin+][Cl–] gave the best result.
Meanwhile we found that changing to organic solvents led
to lower selectivities (26% ee in CH2Cl2, 16% ee in THF).
Cl
2g
O
H
7
8
2h
2i
20
20
72
73
O
H
O
H
a Isolated yield of allylated product. All of the products were con-
firmed by 1H NMR and 13C NMR spectroscopy.
Synlett 2004, No. 3, 534–536 © Thieme Stuttgart · New York

536
J. Lu et al.
LETTER
Table 5 Enantioselective Allylation of Aldehyde Catalyzed by
With these results, other aldehydes were also examined in
[hmin+][Cl–] using chiral ligand 9 as chiral promoter
(Table 5). In all cases, good chemical yields were ob-
tained. The aromatic aldehydes furnished the products in
moderate selectivities (Table 5, entries 1–5) while the ali-
phatic aldehydes gave a low value (Table 5, entries 6–8).
Ligand 9 in [hmin+][Cl–]
Entry Aldehyde
Yield (%)a
88
ee (%)b
O
1
2
3
42 (R)
H
H3C
Table 4 Enantioselective Allylation of 4-Chlorobenzaldehyde in
Various Ionic Liquids using 911,
85
89
39 (R)
56 (R)
O
Entry Ionic liquid
Temp Yield ee
(°C)
H
(%)a
(%)b
H3CO
1
35
86
39
Cl -
Cl -
Cl -
O
N
N
N
N
N
N
H
2
3
25
65
88
84
48
16
O2N
4
5
88
88
46 (R)
48 (R)
O
H
O
4
5
25
40
78
82
26
21
H
-
BF4
N
N
Cl
6
7
81
79
10 (S)
12 (R)
CHO
N
N
Br -
O
6
35
80
38
H
Br -
a Isolated yield.
8
76
8 (R)
CHO
b The %ee was determined by HPLC analysis of the ester from
O-Methyl-(S)-Mandelic acid.
a Isolated yield.
b The %ee was determined by 1H NMR analysis of the ester from O-
Methyl-(S)-Mandelic acid.
c The absolute configuration was determined by comparison to
literature values of optical rotations.10
In conclusion, we have explored the InCl3-catalyzed allyl-
ation system and studied the enantioselective allylation in
ionic liquids for the first time. Although the ee’s are only
low to moderate, these results showed that we could study
the enantioselective allylation in ionic liquids. Further
work to increase the enantioselectivity by designing new
chiral ligands and other modification of the allylation
system are in progress.
(3) Marshall, J. A.; Hinkle, K. W. J. Org. Chem. 1995, 60, 1920.
(4) Loh, T. P.; Xu, J. Tetrahedron Lett. 1999, 40, 2431.
(5) Wasserscheid, P.; Keim, W. Angew. Chem. Int. Ed. 2000, 39,
3772.
(6) Zhao, D. B.; Wu, M.; Kou, Y.; Min, E. Catal. Today 2002,
74, 157.
(7) Sheldon, R. Chem. Commun. 2001, 2399.
(8) Chen, S. L.; Ji, S. J.; Loh, T. P. Tetrahedron Lett. 2003, 44,
2405.
(9) Dupont, J.; Souza, R. F.; Suarez, P. A. Z. Chem. Rev. 2002,
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Acknowledgment
We thank the National Natural Science Foundation of China for
providing the research scholarship (No. 20172039) and the National
University of Singapore and the Ministry of Education (Singapore)
for providing the research funds.
(10) Kobayashi, S.; Aoyama, N.; Manabe, K. Chirality 2003, 15,
124; and references cited therein.
(11) Typical Experimental Procedure: To a 25 mL round-
bottom flask containing an egg-shaped stirring bar were
added [hmin+][Cl–] (0.5mL) and InCl3 (53 mg, 0.24 mmol).
After stirring at 25 °C for 15 min, benzaldehyde (21.2mg,
0.2mmol) was added followed by allytributyltin (81.9 mg,
0.24 mmol). The reaction mixture was stirred at 25 °C for 16
h. Then the mixture was extracted with EtOAc (3 × 10 mL).
The combined organic extracts were washed with brine,
dried over anhyd Na2SO4, concentrated under vacuum, and
purified by silica gel column chromatography to afford 80%
of the product as a colorless oil.
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Synlett 2004, No. 3, 534–536 © Thieme Stuttgart · New York