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540
LETTER
Highly Efficient Allylation of Aldehydes Promoted by Maleic Acid in Aqueous
Media
A
G
llylation of
A
lde
u
hyde
s
Promo
i
ted by
-
Maleic
A
l
cid ong Li, Gang Zhao*
Laboratory of Modern Synthetic Organic Chemistry, Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 FengLin Lu, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: zhaog@mail.sioc.ac.cn
Received 29 July 2005
OH
Abstract: A highly efficient promoter for allylation of aldehydes in
aqueous media was developed. Under the promotion of maleic acid,
the allylation of various aldehydes can be finished in a short period
of reaction time to afford the corresponding homoallylic alcohols in
high to quantitative yields.
carboxylic acid (1 equiv)
MeCN, r.t.
SnBu3
RCHO +
R
Equation 1
Key words: aldehydes, allylation, aqueous media, allyltributyltin,
maleic acid
allyltributyltin (0.6 mmol) was promoted under various
carboxylic acids (0.5 mmol) in water (1.0 mL) at room
temperature. The results were summarized in Table 1. The
weaker carboxylic acids (pK ≥ 2.85) only gave trace
The allylation of aldehydes, as a very important method
for forming synthetically useful homoallylic alcohols, has
subjected extensive investigation. In recent years, there
has been an upsurge of interest in using water as the sol-2
vent in terms of both economical and ecological aspects.
Yamamoto et al. described that using 5 mol% of tetra-
a
amounts of allylation product of 3a (entries 2–5). Com-
1
paratively, with the decrease of pK values, the stronger
a
carboxylic acids (pK £ 2.83) provided good to high yield
a
of the desired product (entries 6–8). Among these carbox-
ylic acids, maleic acid gave the best result with a yield of
9
7
5% within a short period of reaction time (1.25 h, entry
). The further decrease of pK value of the carboxylic
allyltin or SnCl could catalyze the allylation of aldehydes
4
and ketones with allyltributyltin in aqueous HCl solution
a
3
acid, for example, using trifluoroacetic acid as a promoter
(pK = 0.23, entry 8), resulted in a lower allylation yield
and THF. Since then, there have been several examples
4
reported in this field.
a
(
89%) due to the fact that allyltributyltin was partially de-
Recently, during our studies of allylation of carbonyl
compounds, we found that carboxylic acids with appro-
priate acidity and solubility are general, practical and
highly efficient promoters for the allylation of aldehydes
composed under such a strong acidic reaction condition.
Reducing the amount of maleic acid to 0.5 equivalents
only a yield of 66% (3a) was obtained (entry 9). It is note-
worthy that compared with the fact that the tin reagent was
totally decomposed in acetonitrile within one hour in the
presence of maleic acid (monitrored by TLC); only little
amount of allyltributyltin was decomposed in deuterium
5
with allyltributyltin in acetonitrile (Equation 1). In this
allylation, p-nitrobenzoic acid gave nearly quantitative
yields, other stronger carboxylic acids were found much
faster than p-nitro benzoic acid, but lower yields were ob-
tained due to the decomposition of allyltributyltin during
the allylation. Moreover, when maleic acid was used as a
promoter, the allylation was finished within one hour in a
yield of 81%. Herein, we report that maleic acid can be
used as a highly efficient promoter for the allylation of
aldehydes with allyltributyltin in aqueous media under
mild reaction conditions.
oxide within 23 hours under the promotion of maleic acid
1
(
monitored by H NMR in deuterium oxide). And the
5
reaction in aqueous phase is slower than that in MeCN.
Next, a variety of aldehydes were examined. As shown in
Table 2, apparently, the electronic nature of the substi-
tutes of aromatic aldehydes has little effect on the high
yields (entries 1–6). Salicylaldehyde is soluble in water,
which may benefit the allylation (entry 6). As for the ali-
phatic aldehydes, the allylation promoted under maleic
acid in aqueous medium also exhibited high efficiency.
For example, the allylation of cyclohexanecarboxalde-
hyde afforded 3h in a yield of 84% within 110 minutes
We have reported originally that the allylation, which was
mediated by p-nitrobenzoic acid (insoluble in water), was
5
very sluggish in water (entry 1, Table 1). So, in order to
carry out this allylation in aqueous media, two crucial fac-
tors (the solubility and acidity of the carboxylic acids) are
taken into consideration. In the first step, several water-
soluble carboxylic acids were screened according to their
(
entry 7). Nonyl aldehyde needed a longer period of
reaction time to complete the allylation (83%, entry 8) and
this can be rationalized on the basis of its hydrophobic
pK values. The reaction of benzaldehyde (0.5 mmol) and
a
property. In the mixed solvent (THF–H O = 2:8, v/v), the
2
allylation of water-insoluble p-nitrobenzaldehyde could
proceed smoothly to produce the corresponding product
in quantitative yield (entry 9). When a reaction using
acetophenone as a substrate was performed, no reaction
SYNLETT 2005, No. 16, pp 2540–2542
Advanced online publication: 21.09.2005
DOI: 10.1055/s-2005-917088; Art ID: U26005ST
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Georg Thieme Verlag Stuttgart · New York