Highly active gold-based catalyst for the reaction of benzaldehyde with ethyl diazoacetate

Article abstract of DOI:10.1039/b908233f

The gold complex [IPrAu(NCMe)]BF₄ catalyzes the reaction of ethyl diazoacetate with benzaldehyde to give mixtures of ethyl 3-oxo-3-phenylpropanoate and ethyl 3-hydroxy-2-phenylacrylate in the first example of a group 11 metal-based catalyst for

Full text of DOI:10.1039/b908233f

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Highly active gold-based catalyst for the reaction of benzaldehyde
with ethyl diazoacetate
Manuel R. Fructos, M. Mar Dıaz-Requejo* and Pedro J. Perez*
´
´
Received (in Cambridge, UK) 24th April 2009, Accepted 23rd June 2009
First published as an Advance Article on the web 16th July 2009
DOI: 10.1039/b908233f
The gold complex [IPrAu(NCMe)]BF
ethyl diazoacetate with benzaldehyde to give mixtures of ethyl
-oxo-3-phenylpropanoate and ethyl 3-hydroxy-2-phenyl-
4
catalyzes the reaction of
3
acrylate in the first example of a group 11 metal-based catalyst
for this transformation; the catalyst activity is improved by
a factor of 2500 compared to those of previously reported
iron-based catalysts.
The thermal reaction of ethyl diazoacetate with benzaldehyde
1
was first described in 1885 by Buchner and Curtius and
the products correctly proposed later by Dieckmann as 1,3-
2
dioxolanes (Scheme 1a). Nearly a century after the seminal
3
work, Huisgen and De March described the use of copper and
rhodium as catalysts for the reaction of diazomalonate with
benzaldehyde to give a mixture of dioxolanes (Scheme 1b).
Since then, several synthetic procedures based on the use of a
Scheme 2 Possible products of the reaction of ethyl diazoacetate
EDA) and benzaldehyde.
(
4
diazoacetate and an aryl-aldehyde, have been described
are aware of only a few systems capable of inducing such a
transformation. Iron-based catalysts developed by Hossain
9a
(
Scheme 2). Thus, acid- or base-catalyzed systems led to the
5
formation of b-ketoesters, derived from the formal insertion
of the carbene moiety into the aldehydic C–H bond (Scheme 2, i).
and co-workers provided mixtures of both ethyl 3-oxo-3-
phenylpropanoate (1) and ethyl 3-hydroxy-2-phenylacrylate
9b
(2) (eqn (1)). The use of Lewis acids as catalyst led to similar
6
A second type of transformation is an aldol-type addition,
promoted by base or by a transition metal complex, the diazo
functionality being retained in the final product (Scheme 2, ii).
The addition of the carbene group to the carbon–oxygen
double bond of the aldehyde to give oxiranes has also been
results, although the maximum 1 : 2 ratio (31 : 69) was achieved
with [CpFe(CO) (thf)]BF . Further work by Kirchner and
2
4
1
0
co-workers
3 2 4 2
using the [Fe(PNP)(CO)(CH CN) ](BF )
(PNP = diphosphine–pyridine pincer ligand) complex as the
catalyst gave a ca. 3 : 97 ratio of products, in the most selective
system reported to date for this transformation. Kanemasa
et al. also described the use of Lewis acid catalysts to give
7
observed in a few cases (Scheme 2, iii). Very often, the use of
rhodium-based catalysts has led to the formation of oxolanes
8
Scheme 2, iv), whereas in the case of iron-catalysts, 3-hydroxy-
(
1
2
2
-arylacrylic acid esters along with b-ketoesters have been
reported (Scheme 2, i, v).
mixtures of 1 and 2.
9
,10
The synthesis of the acrylic ester shown in Scheme 2 is of
1
interest since it is a precursor of naproxen or tropic acid. We
1
ð1Þ
The use of gold-based catalysts for the transfer of carbene
groups from diazo compounds is yet limited to a few
1
3
examples.
examples of gold-based catalysts of general formulae
NHC)AuCl (NHC = N-heterocyclic carbene ligand) for
Our group has recently described the first
(
2
3
such transformations, applied to sp - and sp -C–H bond
14,15
functionalization
Scheme 1
16
as well as to olefin cyclopropanation,
1
7
other examples being reported by other groups. We then
became interested in exploring the catalytic capabilities of the
complexes in the reaction of benzaldehyde with ethyl diazo-
acetate. In a series of screening tests, three complexes of type
Laboratorio de Cata´lisis Homoge´nea, Departamento de Quı´mica y
Ciencia de los Materiales, Unidad Asociada al CSIC, Universidad de
Huelva, Campus de El Carmen, 21007-Huelva, Spain.
E-mail: mmdiaz@dqcm.uhu.es, perez@dqcm.uhu.es;
1
8
(
NHC)AuCl containing the ligands IPr, IMes and SIPr were
Fax: +34 959 219942; Tel: +34 959 219956
employed as catalyst precursors in the reaction of
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Table 1 Reaction of EDA and benzaldehyde in the presence of
a
4
[IPrAu(NCMe)]BF as the catalyst
Entry
Temperature/1C
[PhCHO]/[EDA]
% 1
% 2
1
2
3
4
5
6
7
8
rt
rt
rt
rt
rt
0.5
1
2
5
10
5
45
40
35
30
30
15
33
52
55
60
65
70
70
85
67
48
b
ꢁ80
0
+80
5
5
a
Catalyst loading = 1% referred to EDA, 0.01 mmol of [Au].
b
Reaction time 10 min. Reaction time 7 h.
Scheme 3 (NHC)AuCl complexes as catalysts in the reaction of EDA
with benzaldehyde.
benzaldehyde with ethyl diazoacetate (Scheme 3). After 24 h of
stirring at room temperature, compounds 1 and 2 were
detected in the reaction mixture, although most of the ethyl
diazoacetate (EDA) remained unconsumed.
Since we have previously established that the catalytic
species when using these gold complexes are cationic in
1
4–16
nature,
derived from the removal of the halide by a
non-coordinating counterion, we decided to test the catalytic
1
9
capabilities of the complex [IPrAu(NCMe)]BF
4
, prepared by
the direct reaction of IPrAuCl and AgBF in acetonitrile as the
4
solvent.w To our delight, the use of this complex as catalyst in
the reaction of EDA with benzaldehyde afforded quite inter-
esting results (eqn (2)). Thus, when EDA (1 mmol) was added
to a methylene chloride solution of benzaldehyde (5 mmol)
Fig. 1 Effect of the [PhCHO] : [EDA] ratio on the selectivity.
containing 0.01 mmol of [IPrAu(NCMe)]BF , instantaneous
4
evolution of gas was observed, due to the release of dinitrogen
from ethyl diazoacetate. GC studies after 10 min of stirring at
room temperature demonstrated the complete consumption of
EDA, although it is very likely that the EDA was consumed
instantaneously. NMR studies of the crude reaction mixture
allowed the identification of the products formed in this
transformation as 1 and 2 in a 30 : 70 ratio, respectively. No
diethyl fumarate or maleate, the products derived from the
catalytic coupling of EDA, were observed in the NMR
detection limit, in spite of the addition of all the diazo
compound in one portion at the beginning of the reaction.
When EDA was employed in excess, unreacted EDA was
recovered at the end of the reaction. A preparative scale
in Table 1, the use of higher amounts of benzaldehyde relative
to EDA induced a slight increase in the yield of the acrylate
derivative, although the 30 : 70 mixture of 1 : 2 seems to be the
limit achievable with this catalyst (Fig. 1). Since it would be
interesting to control the selectivity of this transformation
towards the formation of 2, we wondered about the effect
of the temperature in this transformation. Therefore,
experiments at ꢁ80, 0 and +80 1C were performed, with a
clear trend extracted from them: lowering the temperature
favours the formation of the acrylate 2 whereas an increase in
temperature is accompanied by an augmentation of the relative
amounts of the ketoester. In the lower limit explored at ꢁ80 1C,
the relative ratio of products 1 : 2 was determined as 15 : 85.
To the best of our knowledge, this is the first example of the
use of a group 11 metal-based catalyst for this transformation
that leads to the formation of acrylate 2. Only copper had been
experiment carried out with
Au] : [EDA] : [PhCHO] led to the isolation of both products
in 95% isolated yield, based on initial EDA. Interestingly, only
0 min were required for all the EDA to be consumed.
a 1 : 300 : 1500 ratio of
[
1
8
5
previously reported to give either oxolanes or b-ketoesters,
and gold remained yet undiscovered for this reaction
between benzaldehyde and EDA. The selectivity of this gold
catalyst at room temperature is similar to that of Hossain’s
9
10
catalyst and far from Kirchner’s catalyst. However, it is
remarkable that the reaction rate and the turnover frequency
are higher than those for the reported iron catalysts. The
catalyst loadings for Fe-based systems were 10%, and reaction
ð2Þ
9
,10
times reached 14–16 h,
leading to TOF values, measured as
[
(mmol EDA consumed)/[(mmol catalyst) ꢂ (reaction time)],
of 0.6–0.7. Our gold-based catalyst is remarkably active,
with a TOF value of 1800, ca. 2500 times faster than the
Fe-based catalysts.
We have also investigated the effect of the benzaldehyde :
EDA ratio in the final distribution of products, 1 : 2. As shown
5
154 | Chem. Commun., 2009, 5153–5155
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Table 2 Reaction of ethyl diazoacetate (EDA) with benzaldehyde in
the presence of [PPh Au(NCMe)]BF as the catalyst
3 4
observed. After 10 min of stirring, no EDA was detected by GC.
Volatiles were removed under vacuum and the residue dissolved in
a
3
CDCl and investigated by NMR spectroscopy. The compounds were
Entry
Temperature
[PhCHO]/[EDA]
% 1
% 2
identified by comparison with pure commercial samples and/or literature
data. It is important to note that both compounds 1 and 2 display
tautomeric equilibria in solution, the resonances of the keto and enol
forms being taking into account when calculating the ratio of products.
1
2
rt
rt
2
10
57
33
43
67
a
Catalyst loading = 1% referred to EDA, 0.01 mmol of [Au].
Reaction time, 10 min.
1
E. Buchner and Th. Curtius, Ber. Dtsch. Chem. Ges., 1885, 18,
371.
W. Dieckmann, Ber. Dtsch. Chem. Ges., 1910, 43, 1024.
2
2
3
P. De March and R. Huisgen, J. Am. Chem. Soc., 1982, 104,
4
We have also explored a related catalyst that contains
952.
the phosphine PPh instead of the NHC ligand. The
4
PPh Au(NCMe)]BF complex was prepared as previously
3
4
5
M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds,
John Wiley & Sons, New York, 1998.
[
3
2
0
described and employed following the procedure identical
to that used with the NHC-containing catalyst. Two experi-
ments with two- and ten-fold excesses of benzaldehyde with
respect to EDA were carried out (Table 2). In both cases, all
the diazo compound was consumed within 10 min, also
showing a high catalytic activity. Regarding the selectivity,
the system behaves in a similar manner when using a ten-fold
excess of benzaldehyde (entry 5 Table 1 and entry 2 in
Table 2), but when lowering such excess, the phosphine-
containing catalyst provided more of the ketoester 1 than
the NHCAu catalyst (entry 3 in Table 1 and entry 1 in
Table 2). Therefore, it seems that the change from IPr to
(a) M. Liao and J. Wang, Tetrahedron Lett., 2006, 47, 8859;
(
b) C. R. Holmquist and E. J. Roskamp, J. Org. Chem., 1989,
4, 3258.
5
6 (a) B. M. Trost, S. Malhotra and B. A. Fried, J. Am. Chem. Soc.,
2009, 131, 1674; (b) M. L. Kantam, V. Balasubrahmanyam, K. B.
S. Kumar, G. T. Venkanna and F. Figueras, Adv. Synth. Catal.,
2
007, 349, 1887; (c) K. Hasegawa, S. Arai and A. Nishida,
Tetrahedron, 2006, 62, 1390; (d) W. Yao and J. Wang, Org. Lett.,
2003, 5, 1527.
M. P. Doyle, W. Hu and D. J. Timmons, Org. Lett., 2001, 3,
7
8
9
33.
M. P. Doyle, D. C. Forbes, M. N. Protopopova, S. A. Stanley,
M. M. Vasbinder and K. R. Xavier, J. Org. Chem., 1997, 62,
7210.
9
(a) S. J. Mahmood and M. M. Hossain, J. Org. Chem., 1998, 63,
3333; (b) M. E. Dudley, M. M. Morshed, C. L. Brennan,
M. S. Islam, M. S. Ahmad, M.-R. Atuu, B. Branstetter and
3
PPh in the catalyst structure does not affect the activity but
induces a certain effect on the selectivity.
In conclusion, we have discovered that the complex
M. M. Hossain, J. Org. Chem., 2004, 69, 7599.
10 D. Benito-Garagorri, J. Wiedermann, M. Pollak, K. Mereiter and
K. Kirchner, Organometallics, 2007, 26, 217.
[
IPrAu(NCMe)]BF4 catalyzes the reaction of PhCHO and
ethyl diazoacetate leading to the formation of ethyl 3-hydroxy-
-phenylacrylate and ethyl 3-oxo-3-phenylpropanoate, the
1
1 (a) S. J. Mahmood, C. Brennan and M. Hossain, Synthesis, 2002,
807; (b) M. R. Atuu, S. J. Mahmood, F. Laib and M. M. Hossain,
Tetrahedron: Asymmetry, 2004, 15, 3091.
2
1
former being the major product. The reaction rates are
extremely high, in comparison with previously reported systems.
Mechanistic studies to elucidate the nature of this transformation
are currently underway in our laboratory.
1
2 S. Kanemasa, T. Kanai, T. Araki and E. Wada, Tetrahedron Lett.,
1
999, 40, 5055.
3 M. M. Dıaz-Requejo and P. J. Pe
4 M. R. Fructos, T. R. Belderrain, P. de Fre
S. P. Nolan, M. M. Dıaz-Requejo and P. J. Pe
Int. Ed., 2005, 44, 5284.
5 M. R. Fructos, P. de Fre
and P. J. Perez, Organometallics, 2006, 25, 2237.
6 A. Prieto, M. R. Fructos, M. M. Dıaz-Requejo, P. J. Pe
P. Perez-Galan, N. Delpont and A. M. Echavarren, Tetrahedron,
009, 65, 1790.
1
1
´
´
rez, Chem. Rev., 2008, 108, 3379.
mont, N. M. Scott,
rez, Angew. Chem.,
´
We wish to thank DGI (CTQ2008-00042BQU), Junta de
´
´
´
Andalucıa (P07-FQM-02870) and Universidad de Huelva for
1
1
´
mont, S. P. Nolan, M. M. Dı
´
az-Requejo
rez,
funding.
´
´
´
´
´
Notes and references
2
w Experimental procedures. The complexes (NHC)AuCl and
17 (a) Z. Li, X. Ding and C. He, J. Org. Chem., 2006, 71, 5876;
(b) L. Ricard and F. Gagosz, Organometallics, 2007, 26, 4704;
(c) J. A. Flores and H. V. R. Dias, Inorg. Chem., 2008, 47, 4448.
18 P. de Fremont, N. M. Scott, E. D. Stevens and S. P. Nolan,
´
Organometallics, 2005, 24, 2411.
18,19
[
IPrAu(NCMe)]BF
4
were prepared according to literature
methods. EDA and benzaldehyde were purchased from Aldrich, and
employed without further purification. Solvents were dried prior to
use. NMR spectra were recorded using a Varian Mercury 400 MHz.
Catalysis procedure: in a Schlenk tube, under a dinitrogen atmosphere,
19 P. de Fre
´
mont, N. Marion and S. P. Nolan, J. Organomet. Chem.,
0.01 mmol of the catalyst was dissolved in 3 mL of CH
the desired amount of benzaldehyde. Ethyl diazoacetate was added
in one portion via microsyringe. Immediate evolution of gas was
2
Cl
2
along with
2009, 694, 551.
20 D. Michael, P. Mingos and J. Yau, J. Organomet. Chem., 1994,
479, C16–C17.
This journal is ꢀc The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5153–5155 | 5155