Highly efficient synthesis of homoallylic alcohols and amines via allylation of aldehydes and imines catalyzed by ZrOCl2·8H2O in water

Article abstract of DOI:10.1016/j.tetlet.2008.04.084

The allylation of aldehydes and imines has efficiently been carried out by treatment with allyltributylstannane in the presence of a catalytic amount of ZrOCl₂·8H₂O in water to form the corresponding homoallylic alcohols and amines,

Full text of DOI:10.1016/j.tetlet.2008.04.084

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 4047–4049
Highly efficient synthesis of homoallylic alcohols and amines via
allylation of aldehydes and imines catalyzed by ZrOCl2ꢀ8H2O in water
Wei Shen, Li-Min Wang *, Jian-Jun Feng, He Tian *
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology,
130 Meilong Road, Shanghai 200237, People’s Republic of China
Received 6 January 2008; revised 9 April 2008; accepted 11 April 2008
Available online 5 May 2008
Abstract
The allylation of aldehydes and imines has efficiently been carried out by treatment with allyltributylstannane in the presence of a
catalytic amount of ZrOCl2ꢀ8H2O in water to form the corresponding homoallylic alcohols and amines, respectively, in high yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Allylation; Allyltin; ZrOCl2ꢀ8H2O; Water as solvent
1. Introduction
usually the mixture of water and organic solvent. There
has been increasing interest in the development of new cat-
alysts, which are cheap, innocuous, and effective in pure
water as solvent. Recently, ZrOCl2ꢀ8H2O has emerged as
a very effective catalyst for various organic transforma-
tions,6 and our group has been developing organic synthe-
sis in water media.7 Herein, we would like to report a
general and practical method for the synthesis of homoal-
lylic alcohols and amines using ZrOCl2ꢀ8H2O as a catalyst.
Nucleophilic additions of allyltin reagents to carbonyl
compounds1 and imines2 are important C–C bond forming
reactions to afford homoallylic alcohols3 and amines,4
which are important building blocks for the construction
of various biologically active compounds. Although a lot
of important researches in this field have been reported,
most of them use organic solvents and require strictly
anhydrous conditions. On the other hand, development
of organic reactions in aqueous media has attracted much
attention5 because of its water-tolerance, easy handling,
and the unique reactivity and selectivity attained. For the
allylation reaction using allytin reagent, water can be used
not only as solvents, but also as necessary reagents
involved in the process of intermediates hydrolysis.1i
Although several Lewis acid or Brønsted acid catalyzed
allylation reactions in aqueous media with allyltributyltin
have been reported, some of the catalysts are expen-
sive,1a,d,g some are strongly corrosive,1b,c and others are
toxic.1h,k Moreover, solvents used in those reports are
2. Results and discussion
Initially, several Lewis acids were screened for the allyl-
ation reaction of benzaldehyde (1 equiv) with allyltributyl-
tin (1.2 equiv) in pure water (Scheme 1). It could be seen
from Table 1 that even the most strong Lewis acids such
as La(OTf)3 and Yb(OTf)3 provided no product in water,
while Bi(OTf)3 gave moderate yields. When some perflu-
orooctanoates such as La(PFO)3 or Zn(PFO)2 which can
OH
Cat.
SnBu
3
PhCHO
+
1
*
R
Corresponding authors. Tel.: +86 21 64253881; fax: +86 21 64252758
H O
2
(L.-M.W.).
Scheme 1.
E-mail address: wanglimin@ecust.edu.cn (L.-M. Wang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.084

4048
W. Shen et al. / Tetrahedron Letters 49 (2008) 4047–4049
Table 1
Table 2
Synthesis of homoallylic alcohols from benzaldehyde in watera
Synthesis of different homoallylic alcohols using ZrOCl2ꢀ8H2O in watera
Entry
Lewis acid
Amount (mol %)
Conditions
Yieldb (%)
Entry
R1
Time (h)
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
a
None
La(OTf)3
Yb(OTf)3
Bi(OTf)3
La(PFO)3
Zn(PFO)2
Cd(ClO4)2
ZrOCl2ꢀ8H2O
ZrOCl2ꢀ8H2O
ZrOCl2ꢀ8H2O
ZrOCl2ꢀ8H2O
ZrOCl2ꢀ8H2O
—
10
10
10
10
10
10
10
20
30
20
20
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
30 °C, 16 h
60 °C, 5 h
60 °C, 5 h
Trace
Trace
Trace
57
28
43
Trace
71
76
1
2
3
4
5
6
7
8
9
10
11
12
13
a
C6H5
5
5
5
5
5
5
5
5
5
16
16
16
16
1a
1b
1c
1d
1e
1f
83
84
79
81
86
80
83
80
76
79
84
77
71
4-MeC6H4
4-MeOC6H4
2-HOC6H4
4-FC6H4
Me2CH
n-C7H15
CH3CH@CH
C6H5CH@CH
4-ClC6H4
4-BrC6H4
3-NO2C6H4
4-NO2C6H4
1g
1h
1i
75
83
1j
1k
1l
82, 80, 77c
1m
The reaction was conducted with 1 mmol of benzaldehyde and
1.2 mmol of allyltributylstannane in H2O (2 mL).
b
All the reaction were carried out with 20 mol % ZrOCl2ꢀ8H2O in 2 ml
Isolated yield after chromatographic purification.
Catalyst was reused three times.
H2O at 60 °C.
c
b
Isolated yield after chromatographic purification.
disperse substrates in water were used, the yield showed a
limited increase. Moreover, cadmium perchlorate, the most
effective catalyst in aqueous ethanol (H2O/EtOH =
1/9),1h,k seemed to loose catalytic activity in pure water
and afforded no product. It was surprising to discover that
reactivity was much better when adding 10 mol % ZrOCl2ꢀ
8H2O as catalyst. Further study showed that the use of just
20 mol % of ZrOCl2 ꢀ 8H2O was sufficient to provide a sat-
isfactory yield in 16 h. An increase in the amount of cata-
lyst did not improve the result to any great extent. In
order to complete the reaction in a shorter time, the tem-
perature was increased to 60 °C with the reaction finishing
in 5 h with yield as high as 83%. After the reaction, recov-
ery of the zirconium oxychloride was realized by extraction
with water (three times) after diluting the reaction mixture
with isopropyl ether. Then the catalyst can be reused after
concentrating the aqueous phase. Entry 12 describes the
yields of three consecutive runs leading to the correspond-
ing homoallylic alcohol, which showed little loss of cata-
lytic activity of zirconium oxychloride.
in good yields, even sterically hindered aldehyde such as
salicylaldehyde also underwent an easy conversion (entry
4), while solid aldehydes needed prolonged time to give sat-
isfactory results. This is a consequence of the reaction tak-
ing place at the interface of organic substrates with water.
Solid aldehydes are difficult to be dispersed in water due to
their poor solubility in water. To ensure that the reaction
proceeded successfully, vigorous stirring was required for
solid aldehydes.
Inspired by the success of allylation to aldehydes, the
synthesis of homoallylic amines by allylation to imines with
the same catalytic system was explored (Scheme 3). The
results are summarized in Table 3, which shows that both
aromatic and aliphatic aldehydes afforded the desired
products in satisfactory yields. The solid aldehydes also
need prolonged time to give improved yields, while solid
aromatic amines did not need any additives and can pro-
vide good yields.
Based on the proposed mechanism reported in the liter-
atures,1g,n,o a probable mechanistic pathway to explain the
homoallylation process is depicted in Scheme 4. The reac-
tion may proceed by initial coordination of ZrOCl2 with
the carbonyl group or imine group which facilitates X–Sn
(X = O, NR0) bond formation. Subsequent hydrolysis of
–XSnBu3 yielded the homoallylic alcohol or homoallylic
amine. ZrOCl2, used in catalytic amount, was recycled in
the reaction and can be reused for subsequent reactions.
In conclusion, ZrOCl2ꢀ8H2O has efficiently been applied
in sole water for the allylation of both aldehydes and
imines with allyltributylstannane to prepare homoallylic
alcohols and amines, respectively, in good yields. The
After optimizing the reaction conditions, the catalytic
system was applied to the allylation of various aldehydes
(Scheme 2). The results are summarized in Table 2, which
showed that liquid aldehydes gave their allylated adducts
OH
ZrOCl2·8H2O
SnBu3
R1CHO
+
R1
H2O, 60 ºC
1
Scheme 2.
3
ZrOCl2·8H2O
R
NH
2
SnBu
2
3
3
+
+
R CHO
NH
R
H O, 60 ºC
2
2
R
2
Scheme 3.

W. Shen et al. / Tetrahedron Letters 49 (2008) 4047–4049
4049
Table 3
Laboratory of Organofluorine Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of
Sciences.
Synthesis of different homoallylic amines using the ZrOCl2ꢀ8H2O in watera
Entry
R2
R3
Time (h)
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
C6H5
H
H
H
H
H
H
H
H
5
5
5
10
10
5
5
5
5
5
2a
2b
2c
2d
2e
2f
87
82
80
81
74
79
83
78
81
85
83
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
Me2CH
References and notes
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n-C7H15
2g
2h
2i
C6H5CH@CH
CH3CH@CH
C6H5
4-Cl
4-Cl
4-MeO
10
11
a
2j
2k
C6H5
5
Reaction conditions: Benzaldehyde (1 mmol); aromatic amine
(1 mmol); allyltributylstannane (1.2 mmol); ZrOCl2ꢀ8H2O (20 mol %);
water (2 mL); 60 °C.
b
Isolated yield after chromatographic purification.
XH
Bu3SnOH
+
R
H2O
XSnBu3
ZrOCl2
SnBu3
R
SnBu3
X
R
ZrOCl2
X
ZrOCl2
R
3. (a) Hoenberer, K. R.; Hamblet, C. L.; Leighton, J. L. J. Am. Chem.
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X
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(b) Bloch, R. Chem. Rev. 1998, 98, 1407.
X = O, NR'
R
Scheme 4.
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Chan, T. H. Organic Reactions in Aqueous Media; John Wiley: New
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2546.
catalyst is cheap, innocuous, environmentally friendly, and
may be reused several times without obvious loss of
activity.
Acknowledgments
6. (a) Eftekhari, S. B.; Abdollahifar, A.; Hashemi, M. M.; Zirak, M. Eur.
J. Org. Chem. 2006, 5152; (b) Reddy, C. S.; Nagaraj, A. Heterocycl.
Commun. 2007, 13, 67.
This project was financially supported by the National
Nature Science Foundation of China (20672035) and Key
7. Shen, W.; Wang, L. M.; Tian, H. J. Fluorine Chem. 2008, 129, 267.