Novel α-ketoesters from β-diketones via a vanadium-mediated tandem transformation under an oxygen atmosphere

Article abstract of DOI:10.1016/j.catcom.2013.03.037

Novel α-ketoesters were conveniently synthesized from acetylacetone and analogs via a vanadium-mediated one-pot tandem process. These advanced α-ketoesters could be selectively prepared under additive-free, mild conditions, viz., 1 atm O₂ pressure and 50-80°C. DFT calculations were performed to provide insights into the detailed mechanism of the tandem transformation.

Full text of DOI:10.1016/j.catcom.2013.03.037

Catalysis Communications 37 (2013) 109–113
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Novel α-ketoesters from β-diketones via a vanadium-mediated tandem
transformation under an oxygen atmosphere
Yi Xiao a,b,c, Yue Xia b, Chunying Rong b, Hongmei Huang b, , Liqiu Mao a,b,c, Zaihui Fu a,b,c
,
⁎
a,b,c,⁎⁎
Ningya Yu a,b,c, Dulin Yin
a
Institute of Fine Catalysis and Synthesis, Hunan Engineering Laboratory for Petrochemical Materials, Hunan Normal University, Changsha 410081, PR China
Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, PR China
National & Local Joint Engineering Laboratory for New Petro-chemical Materials and Fine Utilization of Resources, Hunan Normal University, Changsha 410081, PR China
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel α-ketoesters were conveniently synthesized from acetylacetone and analogs via a vanadium-mediated
one-pot tandem process. These advanced α-ketoesters could be selectively prepared under additive-free,
mild conditions, viz., 1 atm O2 pressure and 50–80 °C. DFT calculations were performed to provide insights
into the detailed mechanism of the tandem transformation.
Received 24 December 2012
Received in revised form 23 February 2013
Accepted 29 March 2013
Available online 6 April 2013
© 2013 Elsevier B.V. All rights reserved.
Keywords:
Vanadium
α-Ketoester
β-Diketone
Tandem transformation
Dioxygen
1. Introduction
vanadium complexes have gained increasing attention for their catalyt-
ic potential [11–13]. To date, these complexes have been widely used as
α-Ketoesters are key intermediates for the synthesis of important sub-
stances such as optically active compounds, proteinase inhibitors and het-
erocycles [1]. Strategies for the one-pot synthesis of α-ketoesters include
the addition of Grignard reagents to oxalates or oxalyl chlorides and the
Pd-catalyzed double carbonylation of halides [2,3]. However, these meth-
odologies and related approaches often require harsh conditions [4] (e.g.,
low temperature [2], high CO pressure [3], and use of toxic SeO2 [5]) and
additives [6], which often result in relatively low atom efficiency.
Tandem reactions are powerful tools in green synthesis because of
their step economy, operational simplicity and environmental friend-
liness [7]. Furthermore, one-pot tandem protocols facilitate the prep-
aration of novel compounds that are inaccessible by conventional
step-by-step approaches [8]. Thus, many precious metals (e.g., Pd,
Ru, Rh, Ir, and Au) [8], small molecules (e.g., H2O and cinchona alka-
loid derivatives) [7,9] and enzymes [10] have been extensively ex-
plored in tandem catalysis.
catalysts in addition, condensation, cyclization, and oxidation reactions
owing to the Lewis acidity and redox capabilities of V5+ and V4+
[14,15]. The inherently multifunctional nature of vanadium makes it a
good candidate for a catalyst in tandem reaction. However, the use of
vanadium catalyst in O2-driven green tandem process remains relative-
ly unexplored probably because of reaction complexity and catalyst
compatibility issues [8]. Herein, we report the first example of the facile
synthesis of novel advanced α-ketoesters via a vanadium-catalyzed
one-pot tandem process using O2 as the terminal oxidant.
2. Experimental
2.1. General
All chemicals were commercially available and used without further
purification. FT-IR spectra of samples were measured on an Avatar-370
spectrometer. UV–Vis spectra of the oxovanadium complexes were
recorded with the Shimadzu UV-2450 UV–Vis spectrophotometer. 1H
NMR and 13C NMR spectra of the isolated products were recorded on a
Bruker 500-MHz NMR spectrometer. Gas chromatography was run on
Agilent 6890 equipped with a DB-5 (30 m × 0.25 mm × 0.25 μm) col-
umn. Mass spectra were performed on a Varian Saturn 2100T GC-MS in-
strument. Density functional theory calculations for the key species at
the B3LYP/6-31 + G(d) level have been performed on the Gaussian 03
software package.
Vanadium, which plays a vital role in chemistry and life sci-
ences, is abundant and relatively inexpensive. Since the discovery
of vanadium-dependent haloperoxidase (V-HPO) by Vilter in 1983,
⁎
Corresponding author. Tel.: +86 731 88872576; fax: +86 731 88872531.
⁎⁎ Correspondence to: D. Yin, Key Laboratory of Chemical Biology and Traditional Chinese
Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha
410081, PR China. Tel.: +86 731 88872576; fax: +86 731 88872531.
E-mail addresses: huanghongmei@hunnu.edu.cn (H. Huang), dulinyin@126.com
(D. Yin).
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.03.037

110
Y. Xiao et al. / Catalysis Communications 37 (2013) 109–113
Q2VO
2.2. Synthesis of catalysts
Oxovanadium complexes were prepared by a modified method
reported in the literature using 8-hydroxyquinoline (Q) and its
halogen-substituted derivatives as the model ligands [16]. A mixture
of 30 wt.% aq. H2O2 (10 mmol) and 10 mL tetrahydrofuran was
added into a three-necked flask containing V2O5 (5 mmol) and
10 mL water. Then a solution of 8-hydroxyquinoline (Q, 20 mmol),
5-chloro-8-hydroxy-7-iodoquinoline (Q′, 20 mmol) or 5,7-dichloro-8-
hydroxyquinoline (Q″, 20 mmol) in tetrahydrofuran (40 mL) was
added and the pH value of the solution was adjusted to 6–7 with ammo-
nia. After refluxing for 2 h, the resulting solution was filtered to give
black 8-quinolinolato vanadium complex after washing for three times
with ethanol. Bis(8-hydroxyquinolinato) oxovanadium (Q2VO), Q′2VO
and Q″2VO were obtained as black powders in 70%–79% yield.
For comparative studies, we used manganese complexes due to
their cheapness, versatility in oxidation, and potential applicability
as bifunctional redox-Lewis acid catalysts in tandem process [17].
Bis(8-hydroxyquinolinato) manganese (Q2Mn) was prepared from
5 mmol Mn(OAc)2 and 10 mmol 8-hydroxyquinoline ligand in tetra-
hydrofuran by the procedure described above. Q2Mn was obtained as
a pale yellow powder in 68% yield.
1574
1497
955
962
Q'2VO
Q''2VO
1466 1377
1566
1491
1460
1373
1574
1483
1450
1500
1369
960
3500
3000
2500
2000
1000
500
Wavenumber/ cm-1
Fig. 1. FT-IR spectra of Q2VO, Q′2VO and Q″2VO.
reaction hardly proceeded, whereas the presence of pyridine exhibited
only minor influence on the yield of 3 (entries 3, 14 and 15). It is interest-
ing to note that the reaction leading to 3 catalyzed by Q2VO can pro-
ceeded at lower temperatures (50–60 °C, entries 5 and 6), although
the conversion of acacH was slow. These results show that the vanadium
complex can efficiently serve as a multifunctional catalyst for the tandem
transformation of acacH to give 3 and has promising potential as a biomi-
metic activator of O2 at mild temperatures.
Comparison of entry 4 with entry 7 in Table 1 showed that Q greatly
improved the catalytic efficiency of vanadium compounds (per V atom).
In addition, a manganese center could also be tuned by Q to improve the
selectivity for product 3 (entries 10 and 11), which is consistent with
our recent report on the green oxidation of alcohols using a Q derivative
catalyst Q3Mn [16]. Not surprisingly, halogen-substituted ligands Q′ and
Q″ inhibited the activity of the catalyst in the tandem reaction (entries
2, 8 and 9), probably because of the electron-withdrawing effect of
the halogen substituents.
2.3. Transformation of β-diketones
A mixture of acetylacetone (58 mmol) and catalyst (0.07–0.14 mmol,
unless otherwise stated) was placed into a three-necked flask. Then the
one-pot tandem reaction was performed at 80 °C or specific temperature
for the appropriate time under 1 atm O2 supplied continuously by a com-
monly used water-seal system [18]. A small amount of mixture was taken
out using a syringe. After centrifugation, the mixture was analyzed with
an Agilent-6890 gas chromatograph. The identification of products was
done by GC-MS (Varian Saturn 2100T; injector temperature: 250 °C, col-
umn temperature from 80 °C to 200 °C for β = 7 °C/min). The resulting
product was purified by silica gel column chromatography using a mixed
solvent of n-hexane and ethyl acetate (3:1, v/v) as the eluent. The isolated
product was determined by 13C NMR (125 MHz, CDCl3), 1H NMR
(500 MHz, CDCl3), GC-MS and FT-IR analysis. Transformation of other
β-diketones was performed according to the procedure described above.
Next, we explored the scope of the tandem transformation with a
variety of β-diketones using Q2VO as the catalyst (Table 2). Interesting-
ly, the tandem reaction seemed to be substrate-selective. Fairly good
yields were obtained when using analogs bearing an acacH subunit (en-
tries 1–3), while ethyl acetoacetate, which has no acacH subunit, was
unreactive (entry 7). Other β-diketones containing α-CF3 or phenyl
3. Results and discussion
3.1. FT-IR spectra of samples
The FT-IR spectra of vanadium complexes Q2VO, Q′2VO and Q″2VO
are shown in Fig. 1. The characteristic stretching frequencies for
8-hydroxyquinoline ligands can be observed at 1566–1574 (ν(C
1483–1497 cm−1 (ν(C C)), 1450–1466 cm−1 (ν(C
C)) and 1369–
1377 cm−1 (ν(C
N)), respectively [19,20]. It is noteworthy that Q2VO,
_N)),
Table 1
a
_
_
Tandem transformation of acacH mediated by various catalysts under 1 atm of O2
.
\
Entry Catalyst (mmol) Time (h) T (°C) Conversion (%)b Selectivity (%)b
Q′2VO and Q″2VO showed strong V_O stretch around 960 cm−1
(955, 962 and 960 cm−1, respectively), indicative of mononuclear com-
plexes [21]. Complex Q2Mn also shows major bands between 1300 and
1600 cm−1, which correspond to characteristic stretching frequencies
of 8-hydroxyquinoline ligand (Fig. A. 1).
1
Q2VO (0.14)
Q2VO (0.07)
Q2VO (0.07)
Q2VO (0.07)
Q2VO (0.07)
Q2VO (0.07)
V2O5 (0.07)
Q′2VO (0.07)
Q″2VO (0.07)
Q2Mn (0.1)
Mn(OAc)2 (0.1)
Cu(OAc)2 (0.1)
FeCl3 (0.1)
8
8
8
8
8
8
8
8
8
8
8
24
24
24
8
80
80
80
70
60
50
70
80
80
80
80
80
80
80
80
47.8
20.7
14.7
16.9
3.3
78.2
76.8
76.2
76.3
72.7
72.5
68.0
53.6
49.5
66.7
34.1
b15.0
0
2
3c
4
5
6
7
8
0.4
13.5
18.6
15.7
2.1
4.4
0.8
0.6
Trace
0
3.2. Tandem transformation of β-diketones under O2
9
We began our studies by investigating the influence of different vana-
dium and manganese catalysts on the tandem reaction of acetylacetone
(acacH). The results of these studies are shown in Table 1. When cata-
lyzed by Q2VO, the transformation of acacH proceeded at 80 °C under
1 atm O2 to give a new α-ketoester, 4-oxo-2-penten-2-ylpyruvate (3),
in relatively high yield (37.4%, Table 1, entry 1). The structure of 3 was
unambiguously identified by 13C NMR, 1H NMR, GC-MS and FT-IR analy-
sis. Other metal salts studied were shown to be less effective in the tan-
dem process (entries 10–13). In the absence of catalyst or O2, the tandem
10
11
12
13
14
15d
None (0)
Q2VO (0.07)
0
0
a
AcacH (58 mmol), catalyst (0.07–0.14 mmol), O2 (1 atm), 8–24 h, 50–80 °C.
Determined by GC.
Pyridine (6 mmol) was added.
b
c
d
The reaction was performed under 1 atm of N2.

Y. Xiao et al. / Catalysis Communications 37 (2013) 109–113
111
0.5
groups (entries 4–6) were not good substrates for the tandem process,
and only decomposition products such as trifluoroacetic acid or benzoic
acid were obtained.
36h
24h
8h
4h
0h
0.4
0.3
0.2
0.1
0.0
Insight into the reaction mechanism was further explored using
acetylacetone as the model molecule. The presence of high-valent
V4+ and V5+ species in the tandem transformation of acetylacetone
was supported by UV–Vis spectroscopy, though they have not been
isolated. At different time intervals aliquot of the reaction mixture
was taken out with the help of a syringe and then analyzed. It is inter-
esting to note that intensity at ~572 nm due to the characteristic d–d
transition of V4+ gradually decreased with time, suggesting that V4+
was slowly oxidized to V5+ in the Q2VO catalytic system (Fig. 2) [22].
Color changes of the reaction solution from black to red-brown also
verified the change. However, the V2O5 catalytic system displays a
new broad band at ~582 nm after 8 h (Fig. A. 2), suggesting in situ
production of the V4+ center (blue in color) which may remain rela-
tively stable under aerobic conditions [23].
4+
5+
572
V
V
300
400
500
600
700
800
Wavelength/ nm
Radical species play a decisive role in the activation of dioxygen, as
reported in refs. [24,25]. To confirm the involvement of radical inter-
mediate in the above tandem transformation of acetylacetone, an ef-
fective free-radical inhibitor was added. The results in Fig. 3 show
that the free-radical inhibitor hydroquinone (HQ) drastically reduced
the yield of 3, indicating the importance of free radicals in the tandem
transformation.
From our results and previous studies, it can be deduced that the
vanadium-mediated tandem transformation of acetylacetone can be
readily carried out through consecutive oxidation, addition, and de-
hydrogenation under an O2 atmosphere, leading to the formation of
3 (Scheme 1).
In order to elucidate the mechanistic details of the transformation,
density functional theory (DFT) calculations for the key species I–V
(mimicking the catalytic process of Fe2+-dependent acacH dioxygenase
[24]) were performed at the B3LYP/6–31 + G(d) level of theory. The
results of these calculations indicate that concerted peroxo radicals I
and II are involved in the transformation. This is probably due to the co-
ordination of carbonyl oxygen to the metal, which is promoted by the
Lewis acidity of vanadium [14]. The optimized structure of II is also
stereochemically favorable for the conversion of II to III since the OO•
group is adjacent to the CH• group (Fig. 4A). Further calculations show
that the energy dramatically changes with the structural alterations of
critical vanadium species I–V (Fig. 4B). The highest energy barrier calcu-
lated for vanadium (30.2 kcal mol−1) is apparently lower than that of
manganese (37.1 kcal mol−1), which is consistent with the higher
product yields obtained using the vanadium complex catalysts.
Fig. 2. UV–Vis spectra of the reaction system (~0.1 μL) in 3 mL acetonitrile. Reaction
conditions: 0.14 mmol Q2VO in 58 mmol acacH, 1 atm O2, 80 °C.
It can be expected that intermediates 1 (methylglyoxal) and 2 will
be difficult to isolate and characterize experimentally in the presence
of Q2VO since the two species are reactive [26,27]. Fortunately, the
main by-product in the first step of the transformation (oxidative
cleavage), acetic acid, was detected by GC-MS, which strongly implies
the existence of 1. The addition of 1 to 2 over vanadium [14,28] or
proton [29] (H+ appears to be dispensable, see Table 1, entry 3)
and the aerobic oxidation of 2 to 3 via vanadium would proceed easily
and quickly [27]. Thus the observation of intermediate 2 is possible
using less active catalysts Q′2VO or Q″2VO. This is good evidence for
the fact that the same intermediate is formed in the reaction using
catalyst Q2VO.
4. Conclusions
In summary, we have developed a novel vanadium-mediated tan-
dem process for the transformation of acacH and its analogs into
α-ketoesters that are inaccessible by conventional step-by-step ap-
proaches. In particular, these advanced α-ketoesters can be selective-
ly prepared under additive-free, mild conditions (1 atm O2 pressure
and 50–80 °C). DFT calculations performed to provide insights into
the reaction mechanism indicate the involvement of peroxo radicals
50
no HQ
0.02 mol % HQ
Table 2
40
a
Tandem transformation of β-diketones catalyzed by Q2VO under 1 atm of O2
.
0.08 mol % HQ
30
20
10
0
Entry
R1
R2
Time (h)
T (°C)
GC yield (%)b (c)
1
2
3
Me
Et
Me
Et
i-Pr
CF3
CF3
Ph
36
72
72
72
72
72
72
80
80
80
80
65
80
80
54.9 (43.7)
51.7 (35.0)
60.5 (41.2)
Trace
Trace
0
i-Pr
Me
CF3
Me
Me
4
5d
6
7
OC2H5
0
0
4
8
12
16
20
24
a
Time / h
β-Diketone (acacH 58 mmol, others 4 mmol in 2 mL 1,2-dichloroethane), catalyst
(Q2VO 0.14 mmol for acacH, others 0.06 mmol), O2 (1 atm), 36–72 h, 65–80 °C.
b
Determined by GC.
Yield of isolated product.
Temperature was chosen based on the boiling point of substrate.
Fig. 3. Influence of HQ on the yield of 3, catalyzed by Q2VO (0.07 mmol in 58 mmol
acacH) at 80 °C under 1 atm of O2 (0.02 or 0.08 equiv HQ w.r.t acacH was added,
respectively).
c
d

112
Y. Xiao et al. / Catalysis Communications 37 (2013) 109–113
VO3+
O
O
VO2+
O
O
O
H+
VO2+
O
O
-
O
O
O2
O
I
VO2+
O
O
O
O
O
II
VO2+
O
O
III
O
O
V
O
OH
O
V5+, V4+
VO2+
V5+/ V4+
O2
O
O
O
VO2+
O
O
O
O
O
AcacH
addition
O
O
3
2
1
IV
O
O
Scheme 1. Proposed path for the tandem transformation via vanadium using acetylacetone as the model molecule.
in the tandem process, an observation supported by experimental re-
sults. Attempts to improve the transformation efficiency of this new
process are now in progress. Further investigation will be focused
on the systemic mechanism of vanadium-based biomimic activation
of dioxygen and related tandem catalysis in the green synthesis of
substituted analogs of 3.
Acknowledgments
Financial support for this research from the National Natural
Science Foundation of China (20572021, 20805014 and 20976043),
the Open Fund Project of State Key Laboratory of Chemo/Biosensing
and Chemometrics in Hunan University (201103) and the Scientific
Research Fund of Hunan Provincial Education Department (11C0809
and 12B077) are gratefully acknowledged.
A
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.catcom.2013.03.037.
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