Asymmetric allyltributylstannane addition to ketones catalyzed by chiral PYBOX-In(III) complex immobilized in ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2005.08.090

An indium complex of chiral PYBOX was applied in the catalytic asymmetric allylation of ketones in the ionic liquid. It was found that this chiral indium complex was strong enough to promote the reaction of ketones with allyltributylstannane smoothly. The

Full text of DOI:10.1016/j.tetlet.2005.08.090

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7435–7437
Asymmetric allyltributylstannane addition to ketones catalyzed
by chiral PYBOX–In(III) complex immobilized in ionic liquid
Jun Lu,a,c Shun-Jun Ji,a,* Yong-Chua Teoc and Teck-Peng Loha,b,
*
aKey Lab. of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical Engineering of Suzhou University,
Suzhou 215006, China
bDivision of Chemistry and Biological Chemistry, Nanyang Technological University, 637616, Singapore
cDepartment of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore
Received 2 June 2005; revised 18 August 2005; accepted 18 August 2005
Available online 13 September 2005
Abstract—An indium complex of chiral PYBOX was applied in the catalytic asymmetric allylation of ketones in the ionic liquid. It
was found that this chiral indium complex was strong enough to promote the reaction of ketones with allyltributylstannane
smoothly. The products were obtained in moderate to high enantioselectivities, and the chiral catalyst immobilized in the ionic liquid
could be reused with comparable enantioselectivities and yields.
ꢀ 2005 Elsevier Ltd. All rights reserved.
OH
*
O
Catalytic enantioselective additions of carbon-based
nucleophiles to carbonyl groups constitute an important
class of carbon–carbon bond-forming reactions that are
of great value in synthetic organic chemistry.1 The enan-
tioselective allylation of aldehydes and ketones has
attracted significant attention, for the optically active
secondary and tertiary homoallylic alcohols that are
versatile building blocks for the enantioselective synthe-
sis of many biologically active compounds. Therefore,
many methods have been developed for the enantio-
selective synthesis of this class of compounds. However,
very few catalytic enantioselective allylation of ketones
have been achieved successfully.2 To the best of our
knowledge, strong allylation reagents such as tetraallyl
stannane should be needed in these processes mainly
due to the significant difference in reactivity between
aldehydes and ketones.3
PYBOX-In(III) complex
MS 4Å
SnBu
3
+
H
/ CH Cl , TMSCl
R
R
2
2
0
-60 C, 30 hrs
up to 94% e.e
Ph
Ph
Ph
O
O
N
N
N
Ph
PYBOX
Scheme 1.
liquids.5 Further study regarding the recycle of the cat-
alytic system revealed that the chiral In(III) complex
in ionic liquid could be reused with good yields and ee
values. This observation led us to examine the possibility
of realizing the catalytic enantioselective allylation of
ketones.
Recently, we disclosed a practical catalytic enantioselec-
tive allylation of aldehydes with allyltributyl stannane in
the presence of the chiral tetraphenyl substituted (S)-i-
PrPYBOX–In(III) complex (Scheme 1).4 The products
could be obtained in good yields and excellent enantio-
meric excess when the reaction was carried out in ionic
Herein, we present the catalytic enantioselective allyl-
ation of ketones with allyltributyl stannane by the aid
of the chiral tetraphenyl substituted (S)-i-PrPYBOX–
In(III) complex in an ionic liquid (Scheme 2).
We envisioned that the indium(III) complex prepared
from indium triflate and the tetraphenyl substituted
(S)-i-PrPYBOX should work as a catalyst to promote
the allyltributyl stannane addition to ketones in ionic
liquids. A few of the reaction conditions were screened
using acetophenone as a model substrate. In the
Keywords: PYBOX; Indium; Asymmetric allylation; Ketone; Ionic
liquid.
*
Corresponding authors. Tel.: +65 67903733; fax: +65 63166984;
e-mail addresses: shunjun@suda.edu.cn; teckpeng@ntu.edu.sg
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.090

7436
J. Lu et al. / Tetrahedron Letters 46 (2005) 7435–7437
O
with allyltributylstannane smoothly. The cyclic ketone,
PYBOX-In(III) complex
OH
SnBu3
+
+
1-indanone, was an excellent substrate for our catalyst,
exhibiting an enantioselectivity of 93% with 82% yield
(entry 6). Employing a-tetralone resulted in slightly
lower enantioselectivity (81% ee, entry 8). The catalytic
allylation of aromatic ketones worked well in terms of
asymmetric induction and aliphatic ketones exhibited
less satisfactory enantioselectivity (entries 4 and 5). In
the reaction with a,b-unsaturated aldehydes, the 1,2-
addition reaction proceeded exclusively (entry 5).
R
[hmim]PF6 / CH2Cl2
*
R
0 0C, TMSCl,
MS 4Å
Ph
Ph
Ph
Ph
O
O
N
PF6
N
N
N
N
[hmim]PF6
PYBOX
Scheme 2.
In conclusion, a highly catalytic enantioselective allyl-
ation of ketones was developed to give enantiomerically
enriched homoallylic alcohols with moderate to high
enantiomeric excess in an ionic liquid. Further study
regarding the recycle of the catalytic system was
revealed that the chiral In(III) complex in the ionic
liquid could be reused with comparable yields and ee
values.
presence of 20 mol % catalyst formed in situ from the
chiral tetraphenyl substituted (S)-i-PrPYBOX and
indium triflate, the reaction worked enantioselectively
to provide the product with the best result (82% yield,
65% ee) in [hmim]PF6/CH2Cl2 at 0 ꢁC. To our delight,
the reaction mixture was extracted several times with
dry hexane to give the [hmim]PF6 containing chiral
In(III) complex, which could be reused with comparable
enantioselectivity and yield for four successive runs
(65% ee and 82% yield, 62% ee and 80% yield, 60% ee
and 81% yield, 56% ee and 79% yield).
Typical experimental procedure: To an oven dried 5 mL
round-bottomed flask equipped with a magnetic stirring
bar were added In(OTf)3 (16.9 mg, 0.03 mmol,
˚
0.2 equiv) and 4 A molecular sieve (120 mg). The solid
Under the optimized conditions, the asymmetric cata-
lytic system was examined with other ketones. The
results are presented in Table 1.
was azeotropically dried with anhydrous tetrahydrofu-
ran twice (2 mL · 2) prior to the addition of [hmim]PF6
(0.5 mL) and dichloromethane (0.5 mL). PYBOX
(20 mg, 0.033 mmol, 0.22 equiv) was added and the mix-
ture was stirred under nitrogen at room temperature for
2 h to afford a white suspension. A mixture of acetoph-
enone (18 lL, 0.15 mmol, 1 equiv) and TMSCl (23 lL,
0.18 mmol, 1.2 equiv) in dichloromethane (0.2 mL) was
added to the resulting suspension and stirred for
10 min. The mixture was then cooled to 0 ꢁC for
15 min followed by addition of allyltributyl stannane
(57 lL, 0.18 mmol, 1.2 equiv). The reaction mixture
was stirred at 0 ꢁC for 70 h, then dichloromethane was
removed in vacuo; the reaction mixture was extracted
with dry hexane (5 · 5 mL). The combined hexane was
treated with saturated sodium bicarbonate solution at
room temperature for 30 min, washed with brine, dried
over Na2SO4, filtered and concentrated in vacuo. The
residual crude product was purified via silica gel chro-
matography to afford the homoallylic alcohol as a col-
ourless oil (82% yield and 65% ee).
It was found that this chiral indium complex was strong
enough to promote all the reactions of various ketones
Table 1. Enantioselective allylations of ketones catalyzed by chiral
In(III) complex in ionic liquid
Entry
Ketone
Yielda,c (%)
82
eeb (%)
O
1
65 (R)
O
2
3
78
80
71 (R)
62 (R)
O
O
O
4
5
6
7
74
68
82
58
56 (S)
55 (S)
93 (R)
91 (R)
After the reaction mixture was washed with dry hexane
(5 · 5 mL), the catalytic system was azeotropically dried
with anhydrous tetrahydrofuran twice (2 mL · 2). A sec-
ond run was performed under identical reaction condi-
tions and resulted in the formation of the product in
83% yield and 62% ee.
O
O
(R)-2-Phenyl-4-penten-2-ol (entry 1): 1H NMR
(300 MHz, CDCl3): d 7.21–7.48 (m, 5H), 5.57–5.72 (m,
1H), 5.10–5.18 (m, 2H), 2.70 (dd, J = 13.9, 6.3 Hz,
1H), 2.51 (dd, J = 13.6, 8.0 Hz, 1H), 2.08 (s, 1H), 1.56
(s, 3H); 13C NMR (75.4 MHz, CDCl3): d 147.6, 133.6,
128.1, 126.6, 124.7, 119.4, 73.6, 48.4, 29.8; FTIR (neat):
O
8
74
81 (R)
3415, 3075, 2974, 1640, 1445, 914, 766, 700 cmÀ1
.
a Isolated yield.
b The ee values were determined on HPLC.
c All the products are characterized by 1H NMR, 13C NMR, FTIR and
mass spectrometry.
HRMS Calcd for C11H14O [MÀH2O]: 144.0939, found:
144.0934. The enantiomeric excess was determined by
HPLC analysis employing a Daicel Chiralcel OJ column

J. Lu et al. / Tetrahedron Letters 46 (2005) 7435–7437
7437
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Acknowledgements
We thank the Nanyang Technological University and
the National Natural Science Foundation of China
(No. 20472062) for providing the research funding.
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