Catalytic enantioselective allylation of aldehydes via a chiral indium(III) complex in ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2005.05.014

The ionic liquid [hmim][PF₆] has been demonstrated as an efficient and environmentally-friendly reaction medium for the enantioselective allylation of aldehydes via a chiral indium(III) complex. The allylation of a variety of aromatic, α,β-unsa

Full text of DOI:10.1016/j.tetlet.2005.05.014

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4573–4575
Catalytic enantioselective allylation of aldehydes via a
chiral indium(III) complex in ionic liquids
b
Yong-Chua Teo, Ee-Ling Goh and Teck-Peng Loh
a
a,
*
a
Division of Chemistry and Biological Chemistry, Nanyang Technological University, Singapore 637616, Singapore
b
Department of Chemistry, 3 Science Drive 3, National University of Singapore, Singapore 117543, Singapore
Received 10 March 2005; revised 27 April 2005; accepted 4 May 2005
6
Abstract—The ionic liquid [hmim][PF ] has been demonstrated as an efficient and environmentally-friendly reaction medium for the
enantioselective allylation of aldehydes via a chiral indium(III) complex. The allylation of a variety of aromatic, a,b-unsaturated and
aliphatic aldehydes resulted in moderate to good yields and enantioselectivities (upto 92% ee).
ꢀ
2005 Elsevier Ltd. All rights reserved.
7
The asymmetric allylation of the carbonyl functionality
to furnish optically active homoallylic alcohols has ac-
quired a major role in organic synthesis due to the ver-
satility of the products which are important building
blocks for the synthesis of many natural products and
allylation reactions, enantioselective epoxidations of
8
alkenes and enantioselective ring-opening of epoxides.
9
Since these solvents are immiscible with many organic
solvents, it is possible to perform the asymmetric allyla-
tion and to recover and recycle the ionic liquid layer
containing the In catalyst after simple extraction of the
product.
1
pharmaceuticals. To date, several catalysts have been
2
devised for this purpose. Recently, our group reported
an efficient protocol for the asymmetric allylation of
aldehydes using a catalytic amount of a chiral in-
3
In our initial study, we investigated the asymmetric allyl-
ation of aldehydes in a series of ionic liquids using the
following standardized protocol. The catalyst was pre-
dium(III) complex prepared from (S)-BINOL and InCl .
3
This method has proven to be practical and convenient,
furnishing a wide variety of homoallylic alcohols in
good yields and excellent enantioselectivities. In this
letter, we extended the utility of the asymmetric allylation
of aldehydes catalyzed by the chiral In(III) complex
pared by mixing (S)-BINOL and InCl in dichlorometh-
3
ane at room temperature. After 2 h of stirring, the ionic
liquid was added to the pre-formed catalyst followed by
removal of the organic solvent in vacuo. Subsequent
addition of allytributylstannane and benzaldehyde affor-
ded the corresponding homoallylic alcohol which was
isolated by a simple extraction protocol. The results
evaluating the merits of various ionic liquids are shown
in Table 1.
ꢀ
through the use of the ionic liquid [hmim]½PF6 ꢁ as an
environmentally benign reaction medium.
4
Ionic liquids (IL) are a new class of solvents which pres-
ent interesting properties such as non-volatility, high
stability and easy recyclability.
ꢀ
Among the ionic liquids investigated, [hmim]½PF6 ꢁ was
They have been found to be viable solvents for organic
synthesis and have shown promising results in the in-
vestigations of many organic reactions, notably hydro-
shown to be the best solvent system which afforded the
homoallylic alcohol in moderate yield and relatively
good enantioselectivity whereas the [Cl ]-type ionic
ꢀ
5
6
genations, Diels–Alder reactions, enantioselective
liquids did not exhibit any enantioselectivity.
Having optimized the reaction parameters, we extended
the catalytic enantioselective addition of allyltributyl-
6
Keywords: Ionic liquid; [hmim][PF ]; Chiral indium complex; Enan-
stannane to
ꢀ
a wide variety of aldehydes using
[hmim]½PF ꢁ as the solvent system. The results are
tioselective allylation.
*
Corresponding author. Tel.: +65 6790 3733; fax: +65 6316 6984;
e-mail: teckpeng@ntu.edu.sg
6
shown in Table 2.
0
040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.014

4574
Y.-C. Teo et al. / Tetrahedron Letters 46 (2005) 4573–4575
a
Table 1. Evaluation of various ionic liquids for asymmetric allylation
O
(S)-BINOL-In(III) complex
20 mol%)
OH
*
(
H
+
SnBu3
X-
N +
N
n
X = Cl, BF , PF
4
6
b
Yield (%)
c
ee (%)
Entry
Ionic liquid
ꢀ
ꢀ
1
2
3
4
5
6
[bmim]½PF6 ꢁ, n = 3
35
62
26
28
42
62
64
70
11
20
0
[hmim]½PF ꢁ, n = 5
6
ꢀ
ꢀ
[bmim]½BF ꢁ, n = 3
4
[hmim]½BF ꢁ, n = 5
4
ꢀ
ꢀ
[hmim][Cl ], n = 5
[omim][Cl ], n = 7
0
a
Unless otherwise specified, the reaction was carried out with allyltributylstannane (1.0 mmol) and the aldehyde (0.5 mmol) in the presence of the
chiral indium(III) catalyst prepared from (S)-BINOL (22 mol%) and InCl
3
(20 mol%) in 1.0 mL of ionic liquid.
b
c
Isolated yield.
Please refer to Supplementary data for enantiomeric excess determination.
Table 2. Enantioselective allylation of various aldehydes catalyzed by
a
underwent the allylation reaction affording the product
in 46% yield and 78% ee. Allylation of a representative
conjugated enone gave exclusively 1,2-allylation in good
yield and with high enantioselectivity (entry 4). Interest-
ingly, while trans-4-phenyl-3-buten-2-one underwent
allylation with 92% ee, the saturated derivative reacted
to give the homoallylic alcohol with 74% ee (entry 5).
However, the reaction of nonanal under the influence
of the chiral catalyst gave the homoallylic alcohol in
good yield but with low selectivity (entry 6).
the chiral (S)-BINOL–In(III) complex in ½hmimꢁ½PF ꢀ
ꢁ
6
(
S)-BINOL-In(III) complex
O
OH
(20 mol%)
+
SnBu3
R
H
R
PF -
+
6
N
N
n
n = 6
b
Yield (%)
c
ee (%)
Entry
1
Aldehyde
O
62
70
H
The absolute configurations of the homoallylic alcohols
were determined by comparison of the signs of their
optical rotation and HPLC results with the literature
O
1
0
2
3
4
5
6
H
42
46
60
40
72
72
78
92
74
26
values. The si-face of the aldehyde is attacked when
the (S)-catalyst is used, in agreement with the usual pre-
Cl
2
O
ference shown by BINOL-based catalysts.
H
Next, we continued our study by exploring the recycla-
bility of the chiral indium catalyst which is important
from the viewpoint of cost-effectiveness. We carried
out our study by using the reaction of benzaldehyde
O
H
ꢀ
and allytributylstannane in [hmim]½PF ꢁ as a model
O
6
study. After the reaction was completed, the reaction
mixture was extracted with ether (15 mL · 4) to give
the ionic liquid residue. Use of this residue for subse-
quent addition of the aldehyde and allyltributylstannane
resulted in no product formation even after 72 h. Inves-
tigations into this problem revealed the presence of the
BINOL ligand in the ether extracts as observed in
H
O
H
a
Unless otherwise specified, the reaction was carried out with allyl-
tributylstannane (1.0 mmol) and the aldehyde (0.5 mmol) in the
presence of the chiral indium(III) catalyst prepared from (S)-BINOL
1
the H NMR spectra. This suggests that the erosion of
the catalytic activity was most likely due to catalyst
hydration leading to deactivation of the chiral complex.
(22 mol%) and InCl
Isolated yield.
3
(20 mol%) in 1.0 mL ½hmimꢁ½PF ꢀꢁ.
6
b
c
Please refer to Supplementary data for enantiomeric excess
determination.
In conclusion, we have demonstrated an efficient cata-
lytic enantioselective allylation of aldehydes using the
ꢀ
ionic liquid [hmim]½PF ꢁ as a solvent at room tempera-
6
1
1
The allylation of benzaldehyde and 4-chlorobenzalde-
hyde under the influence of the chiral indium catalyst
furnished homoallylic alcohols with comparable enantio-
selectivites of 70% and 72%, respectively (Table 2,
entries 1 and 2). In addition, 2-naphthylaldehyde also
ture. The mild reaction and the simplicity of the reac-
tion procedure should attract interest among organic
chemists. The combinatorial synthesis of other ionic liq-
uids for this asymmetric allylation reaction to increase
conversion and enantioselectivity are in progress.

Y.-C. Teo et al. / Tetrahedron Letters 46 (2005) 4573–4575
4575
Acknowledgements
Dupoint, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev.
002, 102, 3667.
2
5
. (a) Some examples of hydrogenation using ionic liquids:
Chauvin, Y.; Mussman, L.; Olivier, H. Angew. Chem., Int.
Ed. Engl. 1995, 34, 2698; (b) Suarez, P. A. Z.; Dullins, J. E.
L.; Einloft, S.; de Souza, R. F.; Dupont, J. Polyhedron
We wish to thank the Nanyang Technological Univer-
sity and National University of Singapore for their gen-
erous financial support. Yong-Chua Teo is grateful to
the Institute of Chemical and Engineering Sciences Ltd
1
996, 15, 1217; (c) Dyson, P. J.; Ellis, D. J.; Parker, D. G.;
(
ICES) for a doctorate scholarship.
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Supplementary data
6
7
. Some examples of Diels–Alder reactions in ionic liquids:
(
1
Supplementary data associated with this article can be
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785; (b) Fischer, T.; Sethi, A.; Welton, T.; Woolf, J.
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. McCluskey, A.; Garner, J.; Young, D. J.; Caballero, S.
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11. Representative procedure for the asymmetric allylation of
aldehydes: preparation of (S)-1-phenylbut-3-en-1-ol. To
an oven dried 10 mL round-bottom flask equipped with a
(
c) Felpin, F. X.; Lebreton, J. J. Org. Chem. 2002, 67,
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9
2
2
examples of catalytic enantioselective allylation of alde-
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3
magnetic stirring bar was added InCl (22 mg, 0.1 mmol,
0.2 equiv). The solid was azeotropically dried with anhy-
drous tetrahydrofuran twice (2 mL · 2) prior to the
addition of 1.5 mL of dichloromethane. (S)-BINOL
(31 mg, 0.11 mmol, 0.22 equiv) was added to the mixture
which was stirred under nitrogen at room temperature for
2 h. Allyltributylstannane (0.093 mL, 0.3 mmol, 0.6 equiv)
was added to the resulting mixture which was then stirred
for 10 min. The solvent was removed in vacuo after
the addition of 1.0 mL of ½hmimꢁ½PF6ꢀꢁ. The pre-formed
catalyst in ionic liquid was further treated with allyltri-
butylstannane (0.22 mL, 0.7 mmol, 1.4 equiv) and stirred
for 10 min followed by benzaldehyde (53 mg in 0.5 mL
dichloromethane, 0.5 mmol, 1.0 equiv). The reaction mix-
ture was stirred for 40 h at room temperature and then
extracted with ether (5 · 10 mL). The combined organic
extracts were washed with brine, dried over anhydrous
magnesium sulfate, filtered and concentrated in vacuo.
The residual crude product was purified via silica gel
chromatography to afford the homoallylic alcohol as a
colourless oil. Colourless oil (62%). [a]D ꢀ29.5 (c 1.57,
7
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7
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1
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2 2
CH Cl ). The enantiomeric excess was determined by
3
4
HPLC analysis employing a Daicel Chiracel OD column
(hexane:i-propanol, 99:1, 1.0 mL/min: t = 9.72 min for
1
1
. For recent reviews on ionic liquids, see (a) Wassercheid,
P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3772; (b)
the R enantiomer, t
has been established that the R enantiomer elutes first.
2
= 12.78 min for the S enantiomer). It
1
0