ReBr(CO)5-catalyzed knoevenagel condensation

Article abstract of DOI:10.1081/SCC-200028628

The Knoevenagel condensation procedure has been efficiently promoted by using a catalytic amount of ReBr(CO)₅ to afford the corresponding dehydration coupling products in high yields.

Full text of DOI:10.1081/SCC-200028628

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ReBr(CO) ‐Catalyzed
5
Knoevenagel Condensation
a
a
a
Wei‐Xiong Zuo , Ruimao Hua & Xianqing Qiu
a
Department of Chemistry , Tsinghua University,
Key Laboratory of Organic Optoelectronics &
Molecular Engineering of Ministry of Education ,
Beijing, 100084, China
Published online: 10 Jan 2011.
To cite this article: Wei‐Xiong Zuo , Ruimao Hua & Xianqing Qiu (2004)
ReBr(CO) ‐Catalyzed Knoevenagel Condensation, Synthetic Communications: An
5
International Journal for Rapid Communication of Synthetic Organic Chemistry,
34:17, 3219-3225, DOI: 10.1081/SCC-200028628
To link to this article: http://dx.doi.org/10.1081/SCC-200028628
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 17, pp. 3219–3225, 2004
ReBr(CO) -Catalyzed Knoevenagel
5
Condensation
*
Wei-Xiong Zuo, Ruimao Hua, and Xianqing Qiu
Department of Chemistry, Tsinghua University, Key Laboratory of
Organic Optoelectronics & Molecular Engineering of Ministry of
Education, Beijing, China
ABSTRACT
The Knoevenagel condensation procedure has been efficiently promoted
by using a catalytic amount of ReBr(CO)
dehydration coupling products in high yields.
5
to afford the corresponding
Key Words: Rhenium complex; Knoevenagel condensation; Transition
metal catalysis.
Knoevenagel condensations are especially important reactions for the
synthesis of alkene compounds having electron-withdrawing groups such as
*
Correspondence: Ruimao Hua, Department of Chemistry, Tsinghua University, Key
Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of
Education, Beijing 100084, China; E-mail: ruimao@mail.tsinghua.edu.cn.
3
219
DOI: 10.1081/SCC-200028628
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3
220
Zuo, Hua, and Qiu
COR, CN, COOR, and NO . The reactions, which have been long known, are
2
usually catalyzed by bases, acids, and solid catalysts, and the obtained alkenes
[
are widely used as synthetic intermediates. Recently, transition metal
1]
[
hydride ruthenium, hydride and polyhydride rhenium, and polyhydride
2]
[3]
[3b]
iridium ) complexes have been found to be the efficient catalysts for Knoe-
venagel condensation. However, the above mentioned transition metal hydride
complexes are not easy to prepare. In addition, all of them are oxygen- and
H O-sensitive, unstable compounds. Therefore, the catalytic reactions are
2
required to be carried out under an inert atmosphere and using the prepurified
reagents. In this paper, we report the development of Knoevenagel conden-
sation catalyzed by ReBr(CO) under an air atmosphere in the absence of
5
solvent.
Aromatic and aliphatic aldehydes or aromatic ketones 1 readily reacted
with active methylene compounds 2 in the presence of a catalytic amount
of ReBr(CO) to give the corresponding dehydration coupling products 3 in
5
high yields (Eq. (1). The results of the representative Knoevenagel conden-
sation are summarized in Table 1. ReBr(CO) -catalyzed Knoevenagel con-
5
densations were carried out in the absence of solvent by using equivalent
a
amounts of 1 and 2 at 1108C. In a typical experiment, a mixture of benzal-
dehyde 1a (0.53 g, 5 mmol), malononitrile 2a (0.33 g, 5 mmol), and
ReBr(CO)5 (11 mg, 0.025 mmol) was stirred at 110 C for 1.5 hr. After
cooling to room temperature, it solidified and then was treated with 5%
aqueous ethanol. The crude 2-cyano-3-phenylacrylonitrile 3a was obtained
by filtration, washed with 5% aqueous ethanol, and dried in vacuum
a
All starting materials and ReBr(CO) were analytic grade and used without further
5
purification.

ReBr(CO) -Catalyzed Knoevenagel Condensation
5
3221
a
Table 1. ReBr(CO)
5
-catalyzed Knoevenagel.
Time
(hr)
Yield
b
(%)
0
0
Entry
R
R
EWG
2a CN
2b COOEt
EWG
5
1
2
3
4
5
6
1a C
6
H
H
CN
CN
1.5
2
3a 90
3b 88
3c 61
3d 97
3e 92
3f 90
3g 45
3h 84
2c COOEt
COOEt
5
1b
H
CH3
H
2a
2b
2a
2b
2c
2
3
1c C H
6
50
70
4
5
c
7
8
1d iso-propyl
a
Reactions were carried out at 1108C by using 5.0 mmol of 1, 5.0 mmol of 2, and
0
.025 mmol of ReBr(CO) in the absence of solvent.
5
b
Isolated yields.
c
Reaction was performed at 1308C.
b
0.69 g, yield: 90%; purity: 98% by gas chromatography (GC)] (entry 1). If the
[
reaction was performed at 908C, the yield of 3a was decreased greatly (,10%).
The reaction of 1a with ethyl cyanoacetate 2b afforded selectively the
corresponding condensation product ethyl (E)-2-cyano-3-phenylpropenoate
3
b in 88% yield (entry 2). The dehydration of 1a with diethyl malonate 2c
at 1108C for 5 hr gave ethyl 2-(ethoxycarbonyl)-3-phenylpropenoate 3c in
1% yield (entry 3). Similarly, 2-furaldehyde 1b reacted with 2a and 2b to
give products 2-cyano-3-(2-furanyl)-acrylonitrile 3d and ethyl (E)-2-cyano-
-(2-furanyl)propenoate 3e in 97% and 92% yields, respectively (entries 4
6
3
and 5). Contrast to aromatic aldehydes 1a and 1b, under the same conditions,
ketone displayed low reactivity. For example, the dehydration coupling reac-
tions of phenylacetone 1c with 2a required a prolonged reaction time to
achieve the satisfactory yield of 1,1-dicyano-2-phenyl-propene 3f (50 hr,
90%, entry 6). The reaction of 1c with 2b at 1308C for 70 hr afforded the dehy-
dration products 2-cyano-3-phenyl-2-butenoate 3g in 45% yield as a mixture
of stereoisomers (E/Z ¼ 3/2). The use of an excess of amount of 1c or 2b did
not improve the yield (entry 7). In addition, ReBr(CO) also catalyzed the
5
dehydration of aliphatic aldehydes with active methylene compounds. In the
b
The solid products were further purified by recrystallization from ethanol or aqueous
enthanol, and the oil products were obtained by distillation in vaccum. All products
1
obtained are known compounds and were confirmed by H NMR and melting points
by comparison with data reported in the literature.

3
222
Zuo, Hua, and Qiu
Scheme 1. Proposed catalytic mechanism.
case of the reaction of isobutyraldehyde 1d with 2c, after heating for 4 hr, the
expected product ethyl 2-(ethoxycarbonyl)-4-methylpentenoate 3h was
obtained in 84% yield (entry 8).
Other rhenium complexes such as ReCl(CO) and Re (CO) showed
5
2
10
very low catalytic activity for the Knoevenagel condensation.
Although the detailed mechanism for ReBr(CO) -catalyzed Knoevenagel
5
condensation remains to be elucidated, a proposed mechanism for the reac-
tions of nitriles with carbonyl compounds is illustrated in Sch. 1. The reaction
initiates by the decarbonylation of ReBr(CO) to give 16-electron of inter-
5
mediate ReBr(CO)4 4, which has been reported to be generated from
[
4]
ReBr(CO)5 in refluxing toluene. The coordination of the nitrile to 4
would give complex 5, which might undergo deprotonation to give the
c
carbanion intermediate 6. The addition reaction of carbanion to C¼O bond
c
One reviewer proposed that the carbanion in the intermediate 6 might be generated by
deprotonation from 5 by a base, such as H O.
2

ReBr(CO) -Catalyzed Knoevenagel Condensation
5
3223
[3]
to give 7, which affords 8 and regenerates 5. Compound 8 undergoes dehy-
dration to afford alkene 3.
In conclusion, we have developed a new transition metal complex
ReBr(CO) -catalyzed Knoevenagel condensation to afford the dehydration
5
coupling products in good yields. Further investigations on the application
of this commercial complex on other catalytically synthetic reactions are in
progress.
ACKNOWLEDGMENTS
Financial support from Tsinghua University for scientific research is
gratefully acknowledged.
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Received in Japan March 31, 2004