7720
J.-Y. Qi et al. / Tetrahedron Letters 45 (2004) 7719–7721
a
Table 1. Acetalization of aliphatic aldehydes with simple alcohols
Since water was a concomitant by-product in the acetal-
izations, it was estimated that adding a dehydration rea-
gent might increase the yield of acetal products. In this
study, the addition of anhydrous Na SO to the reaction
. 3H2O
3
OR'
OR'
0
.1% RuCl
RCHO
+
R'OH
RCH
1
0h, rt
2
4
0
b
Yield (%)
system did not show any improvement of the yield of the
acetals of aliphatic aldehydes (entries 7–10). In contrast,
the acetal products of aromatic aldehydes increase sig-
nificantly in the presence of anhydrous Na SO . For
Entry
RCHO (or ketone)
R OH
1
2
3
4
5
6
7
8
9
i-PrCHO
i-PrCHO
i-PrCHO
i-PrCHO
n-PrCHO
EtOH
n-PrOH
85
83
81
91
90
84
87
85
45
0
2
4
n-BuOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
example, the acetal yield of benzaldehyde with 1,3-pro-
panediol was only 51% in the absence of Na SO (entry
2
4
n-C
n-C
6
H
H
13CHO
17CHO
11). After adding anhydrous Na SO , the yield was in-
2 4
8
creased to 91%. The reactions of other aromatic alde-
hydes with 1,3-propanediol also gave high yields in the
presence of anhydrous Na SO (entries 14–21). In addi-
2 2
PhCH CH CHO
PhCHO
Acetone
2-Pentanone
2
4
1
1
1
1
0
1
2
3
tion, the properties of the substituent groups in the aro-
matic ring, whether electron-donating groups (p-MeO
and o-MeO) or electron-withdrawing groups (p-F, o-F,
p-Br, and p-Br), had no obvious effect on the acetaliza-
tion under the reaction conditions. Furthermore, the
acid-sensitive substrate 2-furylaldehyde was also effi-
ciently protected in excellent yield without the formation
of any by-products, which were normally encountered
under acidic conditions (entry 20). It was noteworthy
that the mono protection of aldehyde was observed
when using multifunctional 4-acetylbenzaldehyde as
substrate (entry 21). This result clearly showed that the
method is particularly useful for the chemoselectivity
protection of aldehydes in the presence of keto groups.
0
Acetophenone
Cyclohexanone
0
0
a
19
The reactions were carried out according to the typical procedure.
Isolated yields.
b
Table 2. Acetalization of aldehydes with diols
O
O
CH
CH
2
2
0
.1% RuCl
3
2
.3H O
2 n
(CH )
RCHO + HOCH
n = 0 or 1
(CH
)
n
CH
OH
RCH
2
2
2
rt
a
Yield (%)
Entry
RCHO
n
1
2
3
4
5
6
7
8
9
n-PrCHO
i-PrCHO
0
0
0
0
81
91
81
82
In summary, ruthenium(III) trichloride has been found
to be a highly efficient catalyst in the chemoselective pro-
tection of aldehydes including acid-sensitive 2-furylalde-
hyde and multifunctional 4-acetylbenzaldehyde. Various
alcohols such as methanol, ethanol, and diols such as
n-C
6
H13CHO
PhCH
CH CHO
2 2
n-PrCHO
i-PrCHO
194
195
183
185
181
181
1
n-C
n-C
8
H
17CHO
17CHO
1,2-ethanediol, 1,3-propanediol can be used as acetalat-
b
8
H
ing reagents at ambient temperature. This new protec-
tive method for aldehydes is attractive for its high
chemoselectivity, low catalyst loading, operational sim-
plicity, high yields, and mild reaction conditions.
PhCH
PhCH
2
CH
CH
2
CHO
CHO
b
10
11
12
13
14
15
16
17
18
19
20
21
2
2
PhCHO
PhCHO
51
b
1
91
p-MeO–PhCHO
p-MeO–PhCHO
o-MeO–PhCHO
p-F–PhCHO
172
182
191
193
185
186
181
190
195
b
b
Acknowledgements
b
b
o-F–PhCHO
p-Br–PhCHO
We thank the Hong Kong Polytechnic University ASD
Fund and the University Grants Committee Areas of
Excellence Scheme (AOE P/10-01) for financial support
of this study.
b
b
o-Br–PhCHO
2-Furylaldehyde
p-MeCO–PhCHO
b
b,c
a
Isolated yields.
b
The reactions were carried out in the presence of 10mmol of anhy-
drous Na SO and other conditions were according to the
typical procedure.
References and notes
2
4
19
c
1. Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999; pp 297–
Mono protection of aldehyde was observed.
2
99.
2
. (a) Ralls, J. W.; Dodson, R. M.; Riegel, B. J. Am. Chem.
Soc. 1949, 71, 3320–3325; (b) Djerassi, C.; Gorman, M.
J. Am. Chem. Soc. 1953, 75, 3704–3708.
showed the scope and generality of the acetalizations of
various aliphatic and aromatic aldehydes with these two
kinds of diols. In most cases, the reactions of aldehydes
with 1,3-propanediols gave slightly higher yields than
those with 1,2-ethanediol or methanol. For example,
the yields of isobutyraldehyde with 1,3-propanediol,
3
. (a) Yadav, V. K.; Fallis, A. G. Tetrahedron Lett. 1988, 29,
8
97–900; (b) Wilson, G. E., Jr.; Huang, M. G.; Schloman,
W. W., Jr. J. Org. Chem. 1968, 33, 2133–2134; (c) Burczyk,
B.; Kortylewicz, Z. Synthesis 1982, 831–833.
. (a) Karimi, B.; Seridj, H. Synlett 2000, 805–806; (b)
Caputo, R.; Ferreri, C.; Palumbo, G. Synthesis 1987, 386–
389.
4
1
9
,2-ethanediol, and methanol were 95%, 91%, and
1%, respectively.