Catalytic enantioselective allylation of aldehydes via a moisture-tolerant chiral BINOL-In(III) complex

Article abstract of DOI:10.1016/j.tetlet.2005.07.064

A moisture-tolerant chiral indium complex has been developed to effect good enantioselectivities in the addition of allyltributylstannanes to aldehydes. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic aldehydes resulted in both moderate to good yields and high enantioselectivities (up to 86% ee).

Full text of DOI:10.1016/j.tetlet.2005.07.064

Tetrahedron
Letters
Tetrahedron Letters46 (2005) 6209–6211
Catalytic enantioselective allylation of aldehydes via a
moisture-tolerant chiral BINOL–In(III) complex
a
b
b,
*
Yong-Chua Teo, Ee-Ling Goh and Teck-Peng Loh
a
Department of Chemistry, 3 Science Drive 3, National University of Singapore, Singapore 117543, Singapore
Division of Chemistry and Biological Chemistry, Nanyang Technological University, Singapore 637616, Singapore
b
Received 10 June 2005; revised 3 July 2005; accepted 14 July 2005
Abstract—A moisture-tolerant chiral indium complex has been developed to effect good enantioselectivities in the addition of allyl-
tributylstannanes to aldehydes. The allylation of a variety of aromatic, a,b-unsaturated and aliphatic aldehydes resulted in both
moderate to good yieldsand high enantio se lectivities(up to 86% ee).
ꢀ
2005 Elsevier Ltd. All rights reserved.
The asymmetric allylation of the carbonyl functionality
to furnish homoallylic alcohols has acquired a major
role in organic synthesis due to the flexibility of the
productswhich are ver sa tile building blocksfor the con-
struction of many natural products and pharmaceuti-
Previouswork from our laboratory, hasdemon ts rated
that (S)-BINOL–In(III) complexescan function aseffec-
tive chiral Lewis acid catalysts for the enantioselective
5
6
allylation of aldehydes and ketones and enantioselec-
7
tive Diels–Alder reactions. The chiral indium(III) cata-
1
cals. For this reason, there has been an intense
lyst was prepared simply by mixing (S)-BINOL with
research focus in this area in recent years, leading to
the development of a large and diverse array of chiral
catalysts, especially for the chiral Lewis acid-catalyzed
addition of an allyl transfer reagent to a carbonyl
InCl in CH Cl at room temperature for 2 h. In this
3
2
2
paper, we report the enantioselective addition of allyltri-
butylstannanes to aldehydes catalyzed by the water-tol-
erant chiral In(III) complex prepared from (S)-BINOL
and InCl3.
2
functionality.
Despite the fact that various kinds of Lewis acid pro-
moted reactionshave been developed, the es reactions
must be carried out under strictly anhydrous conditions.
The presence of even a small amount of water can stop
the progress of the reaction because most Lewis acids re-
act immediately with water. Thisleadsto the decompo-
To evaluate the (S)-BINOL–InCl catalyst for the enan-
3
tioselective allylation of aldehydes in aqueous media, the
reaction of benzaldehyde and allyltributylstannane in
the presence of 3.7 equiv of water (relative to InCl3)
wascarried out. In thisexperiment, the reaction was
executed by adding water to a stirred solution of the
pre-formed catalyst prior to the addition of the aldehyde
and allyltributylstannane. The homoallylic alcohol was
obtained in 40% yield and 80% ee. In contrast, a racemic
product wasobtained in <10% yield when water was
added prior to the formation of the active catalytic in-
dium species. This result demonstrated that the chiral
catalyst was able to maintain its reactivity in the pres-
ence of a small amount of water.
3
sition or deactivation of the catalyst.
The ability to perform enantioselective catalytic allyl-
4
ation in aqueousmedia
hasattracted coni sd erable
interest among todayÕs sy nthetic community.
Furthermore, the extension of catalytic enantioselective
transformations to aqueous media poses additional
challengesin cataly st -tolerance towardswater.
A study was initiated to explore the optimum water-tol-
erance limit of the chiral catalyst for the allylation reac-
tion. The results are shown in Table 1. Investigations into
the water-tolerance limit of the chiral indium complex re-
vealed that the addition of 37 equiv of water (relative to
Keywords: Moisture-tolerant; Catalytic; Chiral indium complex; Enan-
tioselective allylation.
*
Corresponding author. Tel.: +65 6790 3733; fax: +65 6316 6984;
e-mail: teckpeng@ntu.edu.sg
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.064

6210
Y.-C. Teo et al. / Tetrahedron Letters 46 (2005) 6209–6211
Table 1. Evaluation of the optimal water-tolerance limit for the
asymmetric allylation reaction
Table 2. Enantioselective allylation of various aldehydes catalyzed by
the chiral (S)-BINOL–In(III) complex
a
a
O
(S)-BINOL-In(III) complex
30 mol%)
OH
(S)-BINOL-In(III) complex
O
OH
(
30 mol%)
(
SnBu3
H
+
SnBu3
+
R
H
CH Cl2 / H O
R
CH Cl / H O
2
2
2
2
2
1
2
3
b
c
Entry
H
2
O (equiv relative to InCl
3
)
Yield (%)
ee (%)
b
c
Entry
R
3
Yield (%)
ee (%)
1
2
3
4
5
6
7
3.7
7.4
40
53
43
41
40
23
30
80
83
78
77
74
50
74
1
2
3
4
5
6
7
8
9
Ph
3a
3b
3c
3d
3e
3f
53
65
51
47
51
76
57
75
46
42
83
80
81
78
72
85
80
78
86
86
4-ClC
4-MeC
2-Naphthyl
1-Naphthyl
PhCHCH
6
H
4
11.1
18.5
22.2
37.0
7.4
6
H
4
d
PhCH
n-C H
17
2
CH
2
3g
3h
3i
a
Unless otherwise specified, the reaction was carried out with allyl-
tributylstannane (1.0 mmol) and aldehyde (0.5 mmol) in the presence
of the chiral indium(III) catalyst prepared from (S)-BINOL
8
BnO(CH
BnO(CH
2
)
)
2
3
1
0
2
3j
(
33 mol%) and InCl
3
(30 mol%). The reaction mixture waskept for
a
Unless otherwise specified, the reaction was carried out with allyl-
tributylstannane (1.0 mmol) and aldehyde (0.5 mmol) in the presence
of the chiral indium(III) catalyst prepared from (S)-BINOL
(33 mol%) and InCl
0 h at rt.
20 h at rt.
b
c
Isolated yield.
Refer to Supplementary data for enantiomeric excess determination.
InBr was used as the indium reagent for catalyst formation.
3
d
3
(30 mol%). The reaction mixture waskept for
2
b
c
Isolated yield.
Refer to Supplementary data for enantiomeric excess determination.
InCl ) to the pre-formed catalyst in this series gave the
3
lowest yield and enantioselectivity (Table 1, entry 6).
The optimum water-tolerance limit wasachieved at
The functionalized 3-benzyloxypropionaldehyde and 4-
benzyloxybutyroaldehyde both underwent the allylation
reaction to afford homoallylic alcoholswith 86% ee and
yieldsof 46% and 42%, re sp ectively (entries9 and 10).
7
.4 equiv of water relative to the pre-formed catalyst,
which afforded the homoallylic alcohol in 53% yield
and 83% ee (Table 1, entry 2). Although an attempt
was made to increase the chemical yield by using InBr3
for catalyst formation due to its higher Lewis acidity,
the product was isolated in a lower yield and enantiose-
lectivity (Table 1, entry 7). It isnoteworthy that the
chiral ligand, (S)-BINOL can be easily recovered by
silica gel chromatography in an almost quantitative yield
In conclusion, we have demonstrated an enantioselective
addition of the allylic moiety to aldehydesu si ng a cata-
lytic amount of a water-tolerant (S)-BINOL–In(III)
8
complex. The main featuresof thisreaction are asfol-
lows: (1) the procedure can furnish a wide variety of
homoallylic alcoholsin moderate to good yieldswith
good levels of enantioselectivities in the presence of
water; (2) the allylation can be performed exclusively
by using commercially available chemicals. The design
of new BINOL-based ligands for stronger complexation
with indium in order to function in fully aqueousmedia
is currently in progress.
(
93%).
After determination of the optimum water-tolerance
limit with retention of catalyst reactivity, we extended
the catalytic enantioselective addition of allyltributyl-
stannane to a selection of aldehydes. The results are
shown in Table 2.
Acknowledgements
Substitution of benzaldehyde with a 4-chloro group
resulted in comparable enantioselectivity and a higher
yield, with the allylation product formed in 65% yield
and 80% ee (Table 2, entry 2). A marginal electronic
influence wasal so ob se rved with 4-methylbenzaldehyde
which afforded the product with 51% yield and 81% ee
We wish to thank the Nanyang Technological Univer-
sity and National University of Singapore for their gen-
erousfinancial us pport. Yong-Chua Teo isgrateful to
the Institute of Chemical and Engineering Sciences Ltd
(
ICES) for a doctorate scholarship.
(
entry 3). In addition, the allylation of 2-naphth-
aldehyde and 1-naphthaldehyde gave the corresponding
homoallylic alcoholsin 78% and 72% ee, re ps ectively
Supplementary data
(
entries4 and 5).
Supplementary data associated with this article can be
found, in the online version at doi:10.1016/j.tetlet.2005.
The allylation of a representative conjugated enone gave
exclusively the 1,2-allylation product in high yield and
good enantioselectivity (entry 6). Interestingly, while
trans-3-phenyl-2-butenal underwent allylation with
0
7.064.
8
5% ee, the saturated derivative reacted to give the
homoallylic alcohol with 80% ee and a lower yield (entry
). Moreover, the allylation of nonanal also gave the
product in good yield but moderate ee (entry 8).
References and notes
7
1. (a) Nicolaou, K. C.; Kim, D. W.; Baati, R. Angew. Chem.,
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6211
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aldehydes: preparation of (S)-1-phenylbut-3-en-1-ol. To
an oven-dried 10 mL round-bottom flask equipped with a
2
2
examples se e (b) Aoki, S.; Mikami, K.; Terada, M.; Nakai,
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magnetic stirring bar was added InCl (33 mg, 0.15 mmol,
3
0.30 equiv). The solid was azeotropically dried with anhy-
droustetrahydrofuran twice (2 mL · 2) prior to the addi-
tion of 1.5 mL of dichloromethane. (S)-BINOL (47 mg,
0.17 mmol, 0.33 equiv) wasadded to the mixture which was
stirred under nitrogen at room temperature for 2 h.
Allyltributylstannane (0.093 mL, 0.3 mmol, 0.60 equiv)
was added to the resulting mixture and stirred for 10 min
followed by addition of
2
H O (0.02 mL, 1.11 mmol,
2.2 equiv) to afford a white suspension. The pre-formed
catalyst was further treated with allyltributylstannane
(0.22 mL, 0.7 mmol, 1.4 equiv) and stirred for 10 min
followed by addition of benzaldehyde (0.05 mL, 0.5 mmol,
1.0 equiv). The reaction mixture was tsi rred for 20 h at
room temperature and then quenched with 5 mL saturated
sodium bicarbonate. The aqueous layer was extracted with
dichloromethane (3 · 10 mL) and the combined organic
extractswa hs ed with brine, dried over anhydrousmagne-
sium sulfate, filtered and concentrated in vacuo. The
residual crude product was purified via silica gel chroma-
tography to afford the homoallylic alcohol asa colourles
8
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1
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4
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D
À44.6 (c 2.50, CH
2 2
Cl ). The enantiomeric
excess was determined by HPLC analysis employing a
Daicel Chiracel OD column (hexane–i-propanol, 99:1,
(
c) Lubineau, A. Chem. Ind. 1996, 123; (d) Organic
1.0 mL/min:
t
1
= 9.72 min for the
R
enantiomer,
Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic
and Professional: London, 1998.
t = 12.78 min for the S enantiomer). It hasbeen e ts ab-
lished that the R enantiomer elutesfir st .
2
5
,9
5
. Teo, Y.-C.; Tan, K.-T.; Loh, T.-P. Chem. Commun. 2005,
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318.