Indium-mediated one-pot, three-component synthesis of homoallyl alcohol esters without catalysts and dehydrants

Article abstract of DOI:10.1016/j.tetlet.2010.01.092

Indium-mediated one-pot esterification reaction of acyl chlorides or anhydride by using in situ-prepared homoallyl alcohols from aromatic aldehydes and allyl bromide proceeded smoothly to afford the corresponding homoallyl alcohol esters in high yields within about 1 h, which provided a simple and efficient protocol for the simultaneous allylation and esterification of aldehydes without other catalysts and dehydrants.

Full text of DOI:10.1016/j.tetlet.2010.01.092

Tetrahedron Letters 51 (2010) 1745–1747
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Indium-mediated one-pot, three-component synthesis of homoallyl alcohol
esters without catalysts and dehydrants
*
Zhengyin Du , Yanchun Li, Fen Wang, Wanwei Zhou, Jin-Xian Wang
The Key Laboratory of Polymer Materials of Gansu Province & College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Indium-mediated one-pot esterification reaction of acyl chlorides or anhydride by using in situ-prepared
homoallyl alcohols from aromatic aldehydes and allyl bromide proceeded smoothly to afford the corre-
sponding homoallyl alcohol esters in high yields within about 1 h, which provided a simple and efficient
protocol for the simultaneous allylation and esterification of aldehydes without other catalysts and
dehydrants.
Received 1 December 2009
Revised 14 January 2010
Accepted 26 January 2010
Available online 1 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
The allylation reaction of carbonyl compounds is very important
due to the formation of new carbon–carbon bond between different
hybrid orbits to give synthetically useful homoallyl alcohol deriva-
tives.1 As a type of homoallyl alcohol derivatives, the synthesis of
homoallyl ethers and esters has attracted considerable attention.
Several catalysts have been used to perform this transformation.
However, most of them involve the use of corrosive, expensive,
and toxic catalysts, such as CF3COOH,2 BiBr3,3 Sc(OTf)3,4 Bi(OTf)3Áx-
H2O,5 LiBF4,6 Mn metal,7 and strictly anhydrous and inconveniently
low temperatures conditions. Furthermore, the original substrates
of these reactions are almost acetals which are not commercially
available and must be synthesized from the corresponding
aldehydes.
Recently, indium-mediated transformations have attracted the
attention of synthetic organic chemists because of certain unique
properties inherent to indium, such as low ionization potential,
high reactivity, and high stability in water, alkali aqueous and
air.8 The allylation of carbonyl compounds giving homoallyl com-
pounds,9 the synthesis of acetals and ketals,10 the Knoevenagel
condensation of aldehydes with methyl acetoacetate11 mediated
by indium metal and indium salts have been reported. The in-
dium-mediated allylation of gem-diacetates to homoallylic ace-
tates was also achieved by Yadav et al.12
in situ-prepared homoallyl alcohols from aldehydes and allyl bro-
mide mediated by indium,13 as shown in Scheme 1.
The one-pot synthesis of the homoallyl ester from p-cyanobenz-
aldehyde, propionyl chloride and allyl bromide as a model reaction
was first carried out in the presence of indium in THF at room tem-
perature. However, we found that this reaction was very sensitive
to temperature. The reaction time was shortened and high yield
(90%) was simultaneously obtained when the reaction was con-
ducted at invariable 40 °C in water bath. The molar ratios of in-
dium, p-cyanobenzaldehyde, allyl bromide and propionyl
chloride were also optimized and showed that 1.0/1.0/1.5/1.2
was ideal for this three component tandem reaction. Under these
optimized conditions, the allylation and esterification of various
aldehydes with different substituents using acyl chlorides as acyl-
ation reagents were investigated. The results are shown in Table 1.
From Table 1, it is found that all reactions of aromatic aldehydes
can proceed smoothly to yield corresponding homoallyl alcohol es-
ters and the effect of substituents of aromatic aldehydes are not
significant. When aliphatic acyl chloride was replaced by benzoyl
chloride, the allylation–esterification of aromatic aldehydes
needed more reaction times but to obtain moderate yields (Table
1, entry 9), which might be due to larger steric hindrance and elec-
tronic and resonance effect of benzoyl chloride. As for aliphatic
aldehydes and heterocyclic aromatic aldehydes with electron-rich
However, up to now, no literature is reported for the synthesis
of homoallyl alcohol esters with three component reaction of alde-
hydes, allyl bromide, and acylation reagents , which are a type of
important homoallyl alcohol derivatives with versatile functional
groups amenable to further synthetic manipulations and are med-
iated by indium.
O
O C R1
O
C Cl
R
R
R1
In
Br
O
RCHO
+
+
Herein we report a convenient and simple one-pot three-com-
ponent synthesis of homoallyl alcohol esters by esterification of
(R2CO)2O
THF
O C R2
* Corresponding author. Tel./fax: +86 931 7971989.
Scheme 1. Indium-mediated one-pot, three-component tandem synthesis of
E-mail addresses: clinton_du@126.com, zhengyin_du@nwnu.edu.cn (Z. Du).
homoallyl alcohol esters.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.092

1746
Z. Du et al. / Tetrahedron Letters 51 (2010) 1745–1747
Table 1
Table 2
Indium-mediated one-pot synthesis of homoallyl esters from aldehydes, acyl
Indium-mediated one-pot synthesis of homoallyl esters from aldehydes, acid
chlorides, and allyl bromidea
anhydrides, and allyl bromidea
O
O
O
In
In
O C R1
Br
O C R2
Br
R1 C Cl
RCHO
+
+
(R2CO)2O
RCHO
+
+
THF
THF
R
R
R1=CH3, C2H5, ph
R2=CH3, C2H5
1a-i
2a-n
Yieldb (%)
Entry
R
R1
Time (min)
Yieldb (%)
Entry
R
R2
Time (min)
1
2
3
4
5
6
7
8
9
Ph
CH3
CH3
CH3
CH3
C2H5
C2H5
C2H5
C2H5
Ph
40
50
50
45
40
35
50
50
80
1a, 87
1b, 89
1c, 87
1d, 90
1e, 90
1f, 92
1g, 91
1h, 92
1i, 51
NPc
1
2
3
4
5
6
7
8
9
3-CH3OC6H4
2-ClC6H4
4-ClC6H4
CH3
CH3
CH3
CH3
CH3
CH3
C2H5
C2H5
C2H5
C2H5
C2H5
50
50
50
50
45
50
65
40
45
50
50
2a, 94
2b, 94
2c, 93
2d, 96
2e, 92
2f, 92
2g, 91
2h, 94
2i, 92
2j, 91
2k, 93
4-ClC6H4
2-ClC6H4
4-CNC6H4
4-CH3C6H4
3-CH3OC6H4
4-CNC6H4
2-ClC6H4
2,4-Cl2C6H3
C6H11
2-CH3OC6H4
4-CNC6H4
2,4-Cl2C6H3
2,4-Cl2C6H3
2-CH3OC6H4
4-CH3C6H4
4-CNC6H4
4-BrC6H4
10
11
C2H5
Ph
120
180
10
11
C6H11
NPc
12
CH3
60
NPc
12
13
CH3
55
55
2l, 92
O
S
O
O
NPc
C2H5
2m, 93
13
Ph
100
a
14
C2H5
55
2n, 91
Reaction conditions: indium 1.0 mmol, ArCHO 1.0 mmol, allyl bromide
S
1.5 mmol, R1COCl 1.2 mmol, THF 2 ml, 40 °C water bath. The reaction was moni-
NRc
NRc
tored by TLC.
15
16
Ph
Ph
60
b
O
Isolated yield.
c
2-ClC6H4
10 h
NP: no pure product was isolated.
a
Reaction conditions: indium 1.0 mmol, ArCHO 1.0 mmol, allyl bromide
1.5 mmol, (R1CO)2O 1.2 mmol, THF 2 ml, 40 °C water bath. The reaction was mon-
itored by TLC.
systems, however, although they reacted and disappeared in long-
er time monitored by TLC, the homoallyl alcohol esters could not
be isolated because the products were very complex and included
several byproducts, such as long chain alkanes, alkyl bromide, and
homoallyl ether(Table 1, entries 10–13). The details are under
investigation.
b
Isolated yield.
NR: almost no reaction was proceeded.
c
excellent yields, short reaction times, no use of catalysts and dehy-
drants, and no separation of intermediates, which might be used in
the scale-up production of homoallyl alcohol esters in related med-
ical synthesis.
Similarly, the reactions of indium-mediated one-pot synthesis
of homoallyl esters were also conducted by using acid anhydride
as acylation reagents. The results are summarized in Table 2. As de-
picted in Table 2, aliphatic acid anhydrides, such as acetic anhy-
dride and propionic anhydride, can react well with various
aromatic aldehydes and ally bromide to form the corresponding
homoally alcohol esters in excellent yields (91–96%) within about
1 h under the above optimized conditions (Table 2, entries 1–11).
With the same to the reaction of acyl chloride, aromatic aldehydes
carrying either electron-withdrawing or electron-donating groups
could be efficiently converted into the aimed products, and differ-
ent substituents have almost no effect on the result of the reaction.
It is surprising that heterocyclic aromatic aldehydes can also be
converted into the desired products by using aliphatic anhydrides
in excellent yields (Table 2, entries 12–14). In comparison with ali-
phatic acid anhydride, benzoic anhydride almost couldn’t react
even if the reaction time was elongated to 10 h, which might be
due to large steric hindrance (Table 2, entries 15 and 16).
In summary, a new and efficient method for the synthesis of
homoallyl alcohol esters through indium-mediated one-pot three
component tandem reaction of aromatic aldehydes, acylation re-
agents, and allyl bromide in short reaction time in excellent yields
is described. The primary investigation on this reaction shows that
the allylation of aldehydes and the esterification of the aforemen-
tioned in situ-formed homoallyl alcohols are completed simulta-
neously. It is noted that aliphatic aldehydes and heterocyclic
aromatic aldehydes have a lower reactivity than aromatic alde-
hydes, and aromatic acylation reagents have larger steric hin-
drance than that of aliphatic ones. The advantages of this method
include the use of easy to handle, stable nontoxic metal indium,
Acknowledgments
Financial support by Natural Science Foundation of China (No.
20702042), Key Laboratory of Polymer Materials of Gansu Province
(No. zd-06-18) and Yong Teachers Research Foundation of NWNU
(No. NWNU-QN-06-27) is acknowledged.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.01.092.
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13. General operation for the synthesis of homoallyl alcohol ester: All reagents were
used as obtained from commercial sources except specially mentioned.
Tetrahydrofuran was dealt with sodium and benzophenone to show blue. Allyl
bromide was redistilled prior to use. The 1H and 13C NMR spectra were
recorded on a Bruker MERCURY-PLUS 400 MHz NMR spectrometer. Chemical
shifts were reported in parts per million (ppm, d). IR was measured on an Alpha
Centauri FT-IR spectrometer and MS was analyzed by a QP-1000A GC–MS with
EI sources. Typical procedures for the synthesis of 1-(4-cyanophenyl)-3-butenyl
propionate (1g): indium powder (114 mg, 1.0 mmol) was placed into a 50 ml
flask under argon, followed by the addition of THF (2 ml), p-
cyanobenzaldehyde (132 mg, 1.0 mmol), allyl bromide (181 mg, 1.5 mmol),
and propionyl chloride (111 mg, 1.2 mmol). The mixture was stirred at 40 °C
water bath for 50 min until p-cyanobenzaldehyde disappeared as detected by
TLC. The reaction was then quenched by saturated 3 ml of NH4Cl aqueous
solution. The product was extracted with ethyl acetate (3 Â 5 ml), dried with
anhydrous Mg2SO4 and concentrated under reduced pressure, then purified by
column chromatography using a mixture of petroleum ether and ethyl acetate
as the eluent, affording the pure homoallyl ester in 91% of yield, a colourless
viscous liquid. Spectra data of compound 1g: 1H NMR (400 MHz, CDCl3):
d = 7.65–7.64 (m, 2H, ArH), 7.43–7.41 (m, 2H, ArH), 5.82–5.79 (m, 1H, CH),
5.70–5.63 (m, 1H, CH), 5.08–5.03 (m, 2H, CH2), 2.63–2.52 (m, 2H, CH2), 2.41–
2.34 (m, 2H, CH2), 1.16–1.11 (t, 3H, CH3); 13C NMR (100 MHz, CDCl3): d = 9.0
(CH3), 27.6 (CH2), 40.5 (CH2), 74.0 (C–O), 118.6 (CN), 118.8, 111.6,, 127.0, 132.2,
145.5 (all unsaturated CH2 and CH), 173.4 (C@O); IR (
2924, 2853, 2230, 1740, 1643, 1177; EI-MS (m/z): 188 [M+], 129, 102, 57, 41.
m
/cmÀ1): 3079, 2982,