Enantioselective allylation of aldehydes catalyzed by chiral indium(III) complexes immobilized in ionic liquids

Article abstract of DOI:10.1039/b500086f

In the presence of chiral catalytic complexes prepared from In(OTf) ₃ and chiral PYBOX ligands, allytributylstannane reacted with aldehydes in ionic liquids to afford the corresponding homoallylic alcohols in high enantioselectivities (86-94% ee) and good yields (68-89%); the chiral catalysts immobilized in ionic liquids could be reused with comparable enantioselectivities and yields. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b500086f

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Enantioselective allylation of aldehydes catalyzed by chiral indium(III)
complexes immobilized in ionic liquids{
Jun Lu,ac Shun-Jun Ji*a and Teck-Peng Loh*ab
Received (in Cambridge, UK) 6th January 2005, Accepted 18th February 2005
First published as an Advance Article on the web 15th March 2005
DOI: 10.1039/b500086f
In the presence of chiral catalytic complexes prepared from
In(OTf)3 and chiral PYBOX ligands, allytributylstannane
reacted with aldehydes in ionic liquids to afford the correspond-
ing homoallylic alcohols in high enantioselectivities (86–94% ee)
and good yields (68–89%); the chiral catalysts immobilized in
ionic liquids could be reused with comparable enantioselec-
tivities and yields.
The asymmetric allylation reaction is one of the most efficient
Scheme 1 In(III) complex-catalyzed asymmetric allylation in ionic
asymmetric C–C bond forming reactions.1 This is because
liquids.
enantiomerically enriched homoallylic alcohols are important
intermediates in organic synthesis, which can be converted to a
enantioselectivities and good yields were obtained, it is rather
wide variety of synthetically useful compounds.2 Therefore, there
inconvenient to reuse the chiral catalyst. As a result, we directed
has been intense research activity in this area in recent years,
our studies to investigate the allylation reaction in ionic liquids,
leading to the development of a large and diverse array of chiral
and the recyclability of the catalytic system, which is important
catalysts, especially concerning chiral Lewis acid-catalyzed addi-
from the industrial point of view, especially when expensive
tion of allyl transfer reagents to carbonyl functionalities.3
catalysts are used.
Furthermore, there are increasing concerns about environmental
From our previous experience, the results obtained using In(III)
effects, which require synthetic manipulation that minimize the use
complexes prepared from In(OTf)3 and chiral PYBOX ligands as
of hazardous chemicals. Aiming to achieve this goal, many
catalysts were excellent. The best results were obtained when the
strategies have been devised and investigated, especially by
reactions were carried out at 260 uC. As a result, the asymmetric
allylation reactions were performed as described below.
replacing traditional organic solvents with other non-toxic solvents
such as water or supercritical carbon dioxide. Recently, ionic
Our initial studies began with allyltributylstannane and
liquids have attracted extensive interest as excellent alternatives to
benzaldehyde in the presence of a catalytic amount of a chiral
organic solvents, due to their favourable properties, such as non-
In(III)–PYBOX complex. The chiral complex was prepared by
flammability, no measurable vapour pressure, low toxicity,
reacting In(OTf)3 (0.2 equiv.) and chiral PYBOX (2) (0.22 equiv.)
reusability, low cost and high thermal stability. In addition to
in ionic liquid at room temperature in the presence of powdered
˚
activated 4A molecular sieves. After stirring for 2 h, allyltributyl-
the polar properties of ionic liquids, they are non-coordinating,
which avoids any undesired solvent binding in pre-transition states,
and hence offer great advantages for asymmetric synthesis. As a
result, ionic liquids are considered as promising alternative solvents
for organic reactions.4 Over the past few years, these liquids have
generated a significant amount of interest. It was reported that the
allylation reaction of aldehydes with allytributystannane in ionic
liquids could afford the corresponding allylated adducts
smoothly.5
stannane (1.2 equiv.) was added followed by benzaldehyde
(1 equiv.) with TMSCl (1.2 equiv.). The homoallylic alcohol was
then obtained by aqueous work-up and column chromatography
after stirring at 260 uC for 30 h.
The initial study was performed using [hmim]PF6 at 260 uC.
Unfortunately, the reaction mixture was sticky, and the product
was obtained in low yield (10%) and low enantioselectivity
(17% ee). This is most probably due to the poor solubility of
[hmim]PF6 at 260 uC. To circumvent this problem, the reaction
was carried out in the presence of [hmim]PF6–CH2Cl2. To our
delight, the product was obtained in good yield (72%) with high
enantioselectivity (88% ee). Other solvent systems, such as
[bmim]PF6–CH2Cl2, [omim]PF6–CH2Cl2, [bmim]BF4–CH2Cl2,
[hmim]BF4–CH2Cl2, [omim]BF4–CH2Cl2, [bmim]Cl–CH2Cl2,
[hmim]Cl–CH2Cl2 and [omim]Cl–CH2Cl2 were also screened. The
products were obtained in lower yields and enantioselectivities.
Next the following six chiral PYBOX ligands (1–6) were
screened in [hmim]PF6–CH2Cl2. The results are summarized in
Table 1.
In this paper, we report asymmetric allylation reactions in ionic
liquids, which proceeded smoothly in the presence of chiral In(III)
complexes (Scheme 1).
Recently, a chiral In(III) complex-catalyzed asymmetric allyla-
tion reaction of aldehydes with allytributystannane in dichloro-
methane had been developed in our laboratory.6 Although high
{ Electronic supplementary information (ESI) available: Spectroscopic
and analytical data for all compounds and description of a representative
procedure. See http://www.rsc.org/suppdata/cc/b5/b500086f/
*shunjun@suda.edu.cn (Shun-Jun Ji)
teckpeng@ntu.edu.sg (Teck-Peng Loh)
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Table 2 In(OTf)3–PYBOX (2) catalyzed allylation of aldehydesa
Entry
1
R
Yieldb (%)
72
Eec (%)
88
2
3
88
68
91
94
4
5
81
89
92
91
From this screening, it was found that the asymmetric allylation
reaction proceeded smoothly in [hmim]PF6–CH2Cl2 at 260 uC in
the presence of chiral In(III) complexes. Of the complexes surveyed,
the tetraphenyl substituted (S)-i-PrPYBOX (2) derived complex
provided superior levels of asymmetric induction, affording the
homoallylic alcohol in 88% ee (Table 1, entry 2).
6
82
71
92
86
Having optimized the reaction conditions, we extended the
catalytic enantioselective allylation to a wide variety of aldehydes
in the presence of the tetraphenyl substituted (S)-i-PrPYBOX (2).
The results obtained are shown in Table 2.
7
a
In all cases, the homoallylic alcohols were obtained in good
yields and high enantioselectivities (up to 94% ee) not only with
aromatic aldehydes but also with a,b-unsaturated and aliphatic
aldehydes. In the reaction with a,b-unsaturated aldehydes, the 1,2-
addition reaction proceeded exclusively.
All the reactions were carried out with aldehyde (1 equiv.), TMSCl
(1.2 equiv.) and allyltributylstannane (1.2 equiv.) using In(OTf)3
(0.2 equiv.) and chiral PYBOX (2) (0.22 equiv.) in the presence of
˚
activated 4A MS in [hmim]PF6–CH2Cl2. The reaction mixture was
b
c
kept for 30 h at 260 uC. Isolated yield. Ee determined by HPLC
or 500 MHz 1H NMR spectrum of the corresponding MTPA ester.
With the success of the above reactions, we continued our
investigation by exploring the recyclability of the catalytic system.
The recycling process was studied starting with benzaldehyde and
2-naphthaldehyde as starting materials. After the reaction was
completed, CH2Cl2 was removed in vacuo. The resulting mixture
was extracted with dry hexane to give [hmim]PF6 containing the
chiral In(III) complex. The chiral catalytic system could be used
four times with comparable enantioselectivity and yield (Table 3).
In summary, chiral In(III) complex-catalyzed allylation reactions
have been successfully carried out in ionic liquids to give
enantiomerically enriched homoallylic alcohols in good yields
and excellent enantiomeric excess. Further study regarding the
recycling of the catalytic system has revealed that the chiral In(III)
complex in ionic liquid could be reused with good yields and ee
values.
Table 3 Recycling study of asymmetric allylation of aldehyde
Entry
Aldehyde
Cycle no.
Yield (%)
Ee (%)
1
2
3
4
1
2
3
4
74
76
81
78
89
87
84
78
5
6
7
8
1
2
3
4
88
86
87
84
92
89
87
80
We thank the National University of Singapore and the
National Natural Science Foundation of China (No. 20472062)
for providing the research funding. We are also grateful to
Medicinal Chemistry Program (R-143-600-600-712) for financial
support.
Table 1 Evaluation of various chiral indium(III) complexes for the
asymmetric allylation of benzaldehyde
Jun Lu,ac Shun-Jun Ji*a and Teck-Peng Loh*ab
aKey Lab. of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering of Suzhou University, Suzhou,
215006, China. E-mail: shunjun@suda.edu.cn; Fax: 86-512-65112371;
Tel: 86-512-65112853
Entry
Chiral ligand
Yield (%)
Ee (%)
1
2
3
4
5
6
1
2
3
4
5
6
81
72
78
76
85
75
70
88
55
49
74
16
bDivision of Chemistry and Biological Chemistry, Nanyang
Technological University, 637616, Singapore.
E-mail: teckpeng@ntu.edu.sg; Fax: 65-6316 6984; Tel: 65-6790 3733
cDepartment of Chemistry, National University of Singapore, 3 Science
Drive 3, Singapore, 117543. E-mail: chmlohtp@nus.edu.sg;
Fax: 65- 6779 1691; Tel: 65- 6874 7851
2346 | Chem. Commun., 2005, 2345–2347
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