SnCl2/PdCl2-mediated aldehyde allylation in fully aqueous media

Article abstract of DOI:10.1016/j.tetlet.2004.05.066

Catalyzed by PdCl₂, SnCl₂ can efficiently mediate the allylation of various aldehydes with allyl chloride or bromide, but not with allyl alcohol, in fully aqueous media. The yield of the reaction is very high (90-100%), and the reaction is operationally simple, environmental benign and easy to scale up.

Full text of DOI:10.1016/j.tetlet.2004.05.066

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5525–5528
SnCl /PdCl -mediated aldehyde allylation in fully aqueous media
2
2
,
Xiang-Hui Tan, Yong-Quan Hou, Bo Shen, Lei Liu* and Qing-Xiang Guo*
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
Received 12 February 2004; revised 28 April 2004; accepted 5 May 2004
2 2
Abstract—Catalyzed by PdCl , SnCl can efficiently mediate the allylation of various aldehydes with allyl chloride or bromide, but
not with allyl alcohol, in fully aqueous media. The yield of the reaction is very high (90–100%), and the reaction is operationally
simple, environmental benign and easy to scale up.
ꢀ
2004Elsevier Ltd. All rights reserved.
Carbonyl allylation is a useful approach to the homo-
allylic alcohols product, which is a versatile subunit that
can easily be converted to a number of other useful
and simpler to operate. (2) Fully aqueous allylation is
very safe and environmentally benign. Therefore, it is
ideal for large-scale industrial and laboratorial synthe-
sis.
1
functions. To achieve carbonyl allylation, traditionally
one needs to prepare a certain allylic organometallic
reagent at first and then add it to the carbonyl com-
pound in anhydrous organic solvents. Because the allylic
organometallic reagent is unstable towards air and
moisture, this synthesis approach is neither operation-
ally simple nor safe to scale up.
Our initial attempt to accomplish the fully aqueous
SnCl /Pd(II)-mediated allylation with allylic alcohols
2
was not successful. In agreement with Masuyama’s
2
work we found that the allylation reaction is not
severely quenched by the presence of a little water.
However, the reaction yields decrease dramatically when
a large amount of water is added to the reaction mixture
(see Table 1). In the fully aqueous solution, the allyl-
ation yield is only 29.5%.
An alternative approach to achieve allylation has been
2;3
developed by Masuyama and co-workers. In this ap-
proach, allylic alcohol directly reacts with the carbonyl
compound yielding the homoallylic alcohol in one pot
via an umpolung of p-palladium complexes. SnCl
2
is
Despite the low yields associated with allyl alcohol, we
found that with allyl chloride or bromide we could ob-
tain very high yields of the homoallylic alcohol products
2
þ
used as a reducing reagent and various Pd complexes
are used as catalyst. Many organic solvents such as
DMF and THF can be used as the solvent. The yields
using the SnCl
example, the reaction between allyl chloride and benz-
aldehyde in H O over 16 h at room temperature pro-
2 2
/PdCl in fully aqueous solution. For
4–6
are usually 50–80%.
2
Our recent interest in the organic reactions in aqueous
7
media prompted us to study whether we can perform
vides the allylation product almost quantitatively.
Similar results can also be achieved using THF or 1:1
Masuyama allylation reaction in fully aqueous media.
We believe that such a fully aqueous version of Masu-
yama reaction may bring about significant improve-
ments over the original procedure due to the following
reasons. (1) Fully aqueous allylation is much cheaper
THF/H
not significantly affect the yield of this SnCl /PdCl -
mediated allylation reaction with allyl chloride.
2
O media. Therefore, the addition of water does
2
2
On the basis of the above findings, we developed the
SnCl /PdCl -mediated allylation reaction to a practical
synthetic methodology (Scheme 1). We found that PdCl
2
2
2
is sufficient for the reaction. Compared to the previous
studies, this ligand-free catalysis is much less resource
demanding. A variety of carbonyl compounds were
tested. The experimental results are summarized in
Table 2.
Keywords: Allylation; SnCl
2
; Palladium; Aqueous medium.
*
Corresponding authors. E-mail addresses: leiliu@chem.columbia.
edu; qxguo@ustc.edu.cn
Present address: Department of Chemistry, Columbia University,
New York, NY 10027, USA.
0
040-4039/$ - see front matter ꢀ 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.066

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X.-H. Tan et al. / Tetrahedron Letters 45 (2004) 5525–5528
a
Table 1. Effect of water on the SnCl
2
/PdCl
2
-mediated allylation of benzaldehyde
Entry
Substrate
Solvent
THF
Yield (%)
1
2
3
Allyl alcohol
Allyl alcohol
Allyl alcohol
>99
95.0
62.0
58.8
44.8
29.5
>99
>99
>99
THF/H
THF/H
2
2
2
2
O (4:1)
O (3:2)
O (2:3)
O (1:4)
4
5
6
7
8
9
Allyl alcohol
THF/H
Allyl alcohol
Allyl alcohol
Allyl chloride
Allyl chloride
Allyl chloride
THF/H
2
H O
THF
THF/H
2
O (1:1)
2
H O
a
All the reactions were performed for 16 h at room temperature. The concentrations of all the reactants are the same for all the reactions. The yields
1
were determined using H NMR.
90–100% yields. These yields are higher than those
achieved using Masuyama’s procedure.
O
OH
SnCl /PdCl2
2
X
+
H O
2
R
H
R
X = Cl, Br
However, the attempt to allylate aliphatic ketones (entry
1
7) fails, whereas aromatic ketones (entry 18) may only
Scheme 1.
be partially allylated with more reactive allyl bromide.
Both aromatic or aliphatic aldehydes can be well allyl-
ated. For, b-unsaturated aldehydes (entry 5), allylation
only provides the 1,2-addition product. Furthermore,
when cinnamyl halides (entries 15 and 16) were used, the
According to Table 2, both allyl chloride and bromide
can be used, although allyl bromide usually provides a
higher yield. Most of the allylation reactions provide
8
;9
Table 2. Carbonyl allylation mediated by PdCl
2
/SnCl
2
in water using allyl chloride or bromide
a
Entry
Substrate
Product
X
Yield (%) /time (h)
Cl
Br
92/16
93/16
1
CHO
OH
OH
2
3
4
5
6
7
8
9
CCl
3
CHO
Cl
Br
88/16
93/16
Cl C
3
OH
CHO
Cl
Br
91/16
93/16
OH
Cl
Br
92/16
95/16
CHO
OH
CHO
Cl
Br
95/16
98/16
OH
Cl
Br
94/16
96/16
CHO
OH
CH
3
(CH
2
)
6
CHO
Cl
Br
>99/16
>99/16
OH
CHO
CHO
Cl
Br
>99/16
>99/16
OH
Cl
Cl
Cl
Br
>99/16
>99/16

X.-H. Tan et al. / Tetrahedron Letters 45 (2004) 5525–5528
5527
Table 2 (continued)
Entry Substrate
a
Product
X
Yield (%) /time (h)
OH
Cl
Cl
Cl
Br
>99/16
>99/16
1
0
1
Cl
CHO
Cl
OH
1
3
H CO
CHO
Cl
Br
95/16
97/16
H CO
3
OH
OH
OH
12
Cl
Br
>99/16
>99/16
CHO
OH
1
1
3
4
H C
CHO
Cl
Br
>99/16
>99/16
3
H C
3
OH
O N
2
O N
2
Cl
Br
51/18
93/24
CHO
OH
b
c
1
1
5
CH
3
(CH
2
)
6
CHO
Cl
Br
87/16 (83:17)
98/16 (85:15)
Cl
Br
71/16 (62:38)
83/16 (91:9)
OH
b
6
CHO
OH
O
1
1
7
8
Cl
Br
Trace/24
Trace/24
O
OH
Cl
Br
Trace/24
68/72
a
b
c
1
Based upon H NMR analyses of the products, except for entries 1, 2, 3 and 6 whose yields were calculated using the weights (i.e., isolation yields).
Reaction between aldehydes and cinnamyl halides.
Diastereoselectivity (anti:syn).
allylation reaction exhibits very high regio-selectivity as
only the a-addition products are obtained. The reaction
is also modestly diastereoselective as more anti products
are observed (entries 15 and 16).
Little product can be obtained if soley SnCl or PdCl is
2 2
used in the reaction. According to Masuyama’s stud-
2;3
2 2
ies, the SnCl /PdCl -mediated allylation may involve
3
an g -allyl-Pd complex intermediate. Allylation of
aldehydes possibly occurs with the in situ generated
allyltin compound to afford the final products.
It is noteworthy that recently a number of zero-valent
metals have also been found to be able to mediate the
10;11
carbonyl allylation reaction in water.
However,
2 2
In summary, we have demonstrated that SnCl /PdCl
because zero-valent metals are not soluble in water, it is
difficult to scale up these reactions for large-scale syn-
thesis. Irregular reactivity of the zero-valence metals due
to the surface metal-oxide is also a problem frequently
encountered in these reactions. Compared with these
reactions, SnCl and PdCl used in the present procedure
can efficiently mediate the allylation of various alde-
hydes with allyl chloride or bromide, but not with allyl
alcohol, in fully aqueous media. The reaction is opera-
tionally simple and environmentally benign. It stands
for a significantly improved procedure over Masuyama’s
SnCl /Pd(II)/allyl alcohol procedure where the yields are
2
2
2
are both very soluble in water. Therefore, the present
reaction is easy to scale up and highly reproducible.
lower and highly polar aprotic organic solvents must be
used.

5528
X.-H. Tan et al. / Tetrahedron Letters 45 (2004) 5525–5528
Acknowledgements
8. Typical procedures for the allylation are as follows: To a
mixture of carbonyl compound (4mmol) and allyl halide
(
8 mmol) in water (20 mL), PdCl
8 mmol) were added. The mixture was vigorously stirred
2 2
(0.2 mmol) and SnCl
We thank MOST, CAS and NSFC (No 20332020) for
the financial support.
(
at room temperature for several hours, before extracted
with ether (3 · 30 mL). The combined organic layers were
dried over anhydrous MgSO and evaporated. The resi-
4
due, in most cases, afforded the corresponding homoallylic
1
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2