Design and synthesis of a water-tolerant chiral indium complex: Application to one-pot three-component Mannich-type reactions in water

Article abstract of DOI:10.1055/s-2007-970774

A novel chiral indium(III) camphorsulfonate complex prepared from indium trichloride, allyltributylstannane and (1S)-(+)-10-camphorsulfonic acid has been developed as a water-tolerant Lewis acid to afford high yields (up to 99%) in one-pot three-component

Full text of DOI:10.1055/s-2007-970774

LETTER
815
Design and Synthesis of a Water-Tolerant Chiral Indium Complex:
Application to One-Pot Three-Component Mannich-Type Reactions in Water
W
ater-Tol
i
erant
C
a
hiral Indiu
n
m
C
omplex Xiao, Teck-Peng Loh*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 639798, Singapore
Fax +65(6316)6984; E-mail: teckpeng@ntu.edu.sg
Received 14 December 2006
Previous studies on the synthesis of chiral BINOL–In(III)
Abstract: A novel chiral indium(III) camphorsulfonate complex
complex revealed that allylic indium species could be
obtained from transmetalation of indium trichloride with
prepared from indium trichloride, allyltributylstannane and (1S)-
(+)-10-camphorsulfonic acid has been developed as a water-toler-
allyltributylstannane. This indium species facilitate the
formation of the BINOL–In(III) complex 1c3a
(Scheme 1).
ant Lewis acid to afford high yields (up to 99%) in one-pot three-
component Mannich-type reactions in a true water environment.
Key words: chiral indium complex, one-pot three-component
Mannich-type reaction, allyltributylstannane
InCl3
+
transmetalation
SnBu3
[allylic indium species]
In recent years, organic reactions in aqueous media have
attracted a great deal of attention.1 This is because water
is a cheap, safe and environmentally benign solvent. Fur-
thermore, reactions carried out in aqueous media provide
opportunity to discover new concepts in organic synthe-
sis. In the course of our investigations to develop efficient
organic reactions in water, we have discovered that
indium complexes are water-tolerant Lewis acids which
can be used to catalyze a wide variety of organic trans-
formations in aqueous media.2
3
(S)-BINOL
O
In
O
Recently, two new chiral indium complexes, 1,1¢-bi-2-
naphthol (BINOL)–In(III) 1a–c and 2,6-bis[4¢(S)-iso-
propyloxazolin-2¢-yl]pyridine (PYBOX)–In(III) com-
plexes 2 (Figure 1) have been discovered in our group to
effect a series of reactions in high enantioselectivities.3
Scheme 1 Synthesis of BINOL–In(III) complex 1c
Based on this result, we envisaged that the resulting indi-
um species 3 can also react with more acidic (1S)-(+)-10-
camphorsulfonic acid to produce a more reactive water-
tolerant chiral indium complex. Herein, we report the syn-
thesis of this chiral water-tolerant In(III)–camphorsul-
fonate complex obtained from transmetalation of allylic
stannane with indium trihalides. Preliminary studies were
directed towards the application of this catalyst for the
one-pot three-component Mannich-type reaction in water.
Ph
Ph
O
O
O
O
Ph
Ph
N
In
X
N
N
In(OTf)3
Therefore, the reaction of one equivalent of indium
trichloride with two equivalents of allyltributylstannane
to generate allylic indium species 3, followed by the addi-
tion of (1S)-(+)-10-camphorsulfonic acid produced a new
chiral indium complex 4 (Scheme 2). The structure of this
indium complex was confirmed by X-ray crystal structure
analysis (Figure 2).5
X = Cl (a), Br (b), allyl (c)
PYBOX–In(III) complex 2
BINOL–In(III) complex 1a–c
Figure 1
However, the extension of these catalytic systems to aque-
ous media was not successful.4 Accordingly, the design of
new water-tolerant chiral indium complex poses addition-
al challenges. Therefore, in this paper we report our effort
towards the development of a new water-tolerant indium
complex which can catalyze organic transformations in
aqueous media.
To check the catalytic activity of this new indium com-
plex 4 in water, the three-component reaction of benzalde-
hyde (0.5 mmol), aniline (0.5 mmol) and l-methoxy-2-
methyl-l-trimethylsiloxypropene (1 mmol) was exam-
ined.6 To our delight, this indium complex afforded the
Mannich product in good yield even when 5 mol% of the
catalyst was used (when the catalyst loading was 20%,
10%, 5%, and 1%, the yield was 69%, 69%, 69%, and
SYNLETT 2007, No. 5, pp 0815–0817
Advanced online publication: 08.03.2007
DOI: 10.1055/s-2007-970774; Art ID: D38706ST
© Georg Thieme Verlag Stuttgart · New York
1
6.
0
3.
2
0
0
7

816
J. Xiao, T.-P. Loh
LETTER
SnBu3
+
[allylic indium species]
Table 1 Three-Component Mannich-Type Reactions Catalyzed by
Indium Complex 4 in Watera
InCl3
R2
R3
OTMS
R5
indium complex 4
NH
R3
O
R1CHO + R2NH2
+
(5 mol%)
R1
R5
R4
O
H2O, r.t.
HO3S
R4
Entry
Aldehyde (R1) Amine (R2)
Silyl ether
Yield (%)b
+
OTMS
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
2-Py
2-Py
2-Py
H
H
H
Ph
69 (54)
71 (23)
60 (30)
99 (92)
99 (90)
99c (90)
46 (30)
28 (21)
40 (35)
4-ClC6H4
4-MeOC6H4
Ph
4-ClC6H4
4-MeOC6H4
Ph
OMe
O
O
S
O
H2O
O
H O
2
–O3S
O
In Cl
H2O
H2O
4-ClC6H4
4-MeOC6H4
Scheme 2 Synthesis of indium complex 4
10
11
12
13
H
H
Ph
2-Py
Ph
99 (91)
99 (85)
71 (60)
99 (90)
OTMS
Ph
4-ClC6H4
4-ClC6H4
4-MeOC6H4
a Reaction conditions: aldehyde (1.0 equiv), amine (1.2 equiv), ketene
silyl ether (2 equiv) in H2O (5 mL) and 5% indium complex 4 stirred
for 1 d.
b Purified yield after column chromatography and the yield in paren-
thesis refers to the same reaction carried out using 20 mol% of indium
trichloride in water.
c Yield for the mixture with tertiary Mannich product.
the reaction conditions described in entry 1 of Table 1, the
catalyst could be recycled at least five times without a sig-
nificant loss in catalytic activity (1st cycle: 69%, 2nd cycle:
69%, 3rd cycle: 60%, 4th cycle: 50%, 5th cycle: 50%).9
Thus the specificity of the reaction pathway, the high
product yields, the ease and convenience of the experi-
mental procedure, in addition to the many advantages of
using water as a solvent for the reaction, make this
methodology a very attractive synthetic route for b-ami-
nocarbonyl compounds.
In summary, we have designed and synthesized a novel
chiral indium complex and found that it is an excellent
water-tolerant Lewis acid and could efficiently catalyze
the one-pot three-component Mannich-type reactions in
water using 5 mol% catalyst loading. Although control of
chirality was not possible in these aqueous reactions, this
study provides useful information on designing new
water-tolerant chiral indium catalyst. The success of this
design will open a new area of producing chiral water-tol-
erant Lewis acid catalysts. Further studies to apply this
novel indium complex to other reactions in water as well
as designing other water-stable chiral indium complexes
are in progress.
Figure 2 X-ray crystal structure of indium complex 4
24%, respectively). With these optimized conditions, the
reactions were carried out using different aldehydes,
amines and the results are shown in Table 1.7
In all cases, the reactions proceeded smoothly in water to
afford the desired products in moderate to good yields.
Furthermore, this new indium complex 4 showed higher
catalytic activity as compared with the reactions carried
out using 20 mol% of indium trichloride (yields are shown
in parenthesis).8 Unfortunately, we did not observe any
enantioselectivity with this chiral indium complex. An
important observation made from these experiments was
that no deamination or other side reactions commonly
associated with Mannich-type reactions were observed.
When 10 mol% of the indium complex was employed in
Acknowledgment
We wish to thank the Nanyang Technological University and
BMRC for their generous financial support.
Synlett 2007, No. 5, 815–817 © Thieme Stuttgart · New York

LETTER
Water-Tolerant Chiral Indium Complex
817
(6) Reactions with aliphatic aldehydes or aliphatic amines
afforded the products in low yields.
References and Notes
(1) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous
Media; John Wiley & Sons: New York, 1997. (b) Organic
Synthesis in Water; Grieco, P. A., Ed.; Blacky Academic and
Professional: London, England, 1998.
(2) Loh, T.-P.; Chua, G.-L. Chem. Commun. 2006, 2739.
(3) (a) Teo, Y.-C.; Tan, K.-T.; Loh, T.-P. Chem. Commun. 2005,
1318. (b) Teo, Y.-C.; Goh, J.-D.; Loh, T.-P. Org. Lett. 2005,
7, 2743. (c) Teo, Y.-C.; Loh, T.-P. Org. Lett. 2005, 7, 2539.
(d) Lu, J.; Ji, S.-J.; Teo, Y.-C.; Loh, T.-P. Org. Lett. 2005, 7,
159. (e) Lu, J.; Hong, M.-L.; Ji, S.-J.; Loh, T.-P. Chem.
Commun. 2005, 1010. (f) Lu, J.; Ji, S.-J.; Teo, Y.-C.; Loh,
T.-P. Tetrahedron Lett. 2005, 46, 7435.
(7) Typical Reaction Procedure: Anhydrous benzaldehyde
(0.05 mL, 0.5 mmol) and indium complex 4 (20 mg, 0.025
mmol) were mixed and stirred at r.t. in H2O (5 mL) for 10
min before the addition of anhyd aniline (0.06 mL, 0.6
mmol). The resulting mixture was stirred at r.t. for 30 min.
1-Methoxy-1-trimethylsilyloxypropene (0.2 mL, 1 mmol)
was then added. The suspension was stirred at r.t. for 1 d and
then extracted with EtOAc (3 × 25 mL). The organic layers
were combined, washed with brine (5 mL), dried over anhyd
MgSO4, and concentrated under reduced pressure. The
product was obtained in 69% yield after silica gel column
chromatography as a yellowish wet solid; Rf 0.61 (hexane–
EtOAc, 4:1). 1H NMR (CDCl3): d = 7.23–7.31 (m, 5 H),
7.03–7.10 (m, 2 H), 6.50–6.65 (m, 3 H), 4.53 (s, 1 H), 3.67
(s, 3 H), 1.30 (s, 3 H), 1.20 (s, 3 H). 13C NMR (CDCl3): d =
176.97, 146.86, 139.17, 128.95, 128.21, 127.93, 127.38,
117.22, 113.34, 64.30, 52.01, 46.95, 24.48, 20.65. FTIR
(thin film): 1715.8 cm–1. HRMS: m/z calcd for C18H21NO2:
283.1572; found: 283.1568.
(4) Teo, Y.-C.; Goh, E.-L.; Loh, T.-P. Tetrahedron Lett. 2005,
46, 6209.
(5) Crystal Data: C21H39C4InO12S2, M = 804.26, colorless prism.
Crystal dimensions: 0.20 × 0.15 × 0.04 mm, monoclinic,
space group P2(1), a = 6.9145(2) Å, b = 15.3916(6) Å, c =
15.5826 (6) Å, V = 1657.02(10) Å3, Z = 2, Dc = 1.612 Mg/
m3. Reflections collected: 34477; independent reflections:
7580 (Rint = 0.0432), final R[I > 2s(I)] = 0.0428, R (all
data) = 0.0535, Rw = 0.1327. Crystallographic data for this
crystal has been deposited with the Cambridge
(8) (a) Loh, T.-P.; Liung, S. B. K. W.; Tan, K.-L.; Wei, L.-L.
Tetrahedron 2000, 56, 3227. (b) Loh, T.-P.; Wei, L.-L.
Tetrahedron Lett. 1998, 39, 323.
Crystallographic Data Center as supplementary publication
number CCDC 624125. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road
Cambridge CB2, 1EZ, UK [fax: +44(1223)336033; e-mail:
deposit@ccdc.cam.ac.uk].
(9) The drop in reactivity by the fourth or fifth cycle may be
attributed to loss of catalyst due to organic extraction.
Synlett 2007, No. 5, 815–817 © Thieme Stuttgart · New York

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