Trisannelation of acrylates to 1,3,5-benzenetricarboxylates by a Pd(OAc)2/HPMoV/CeCl3/O2 system

Article abstract of DOI:10.1021/jo070323e

(Chemical Equation Presented) A new type of trisannelation reaction of acrylates through acetal formation was developed by Pd(OAc)₂ combined with molybdovanadophosphoric acid (HPMo₈V₄) and Lewis acid under atmospheric diox

Full text of DOI:10.1021/jo070323e

known to lead to polysubstituted benzene derivatives.6 For
instance, the Ru-catalyzed cyclotrimerization of ethyl propiolate
is reported to give a 4:1 mixture of triethyl 1,2,4- and 1,3,5-
benzenetricarboxylates, but the regioselectivity of these two
isomers is usually difficult to control by this method.7 Triethyl
1,3,5-benzenetricarboxylate8 was prepared by a stoichiometric
reaction of ethyl 3-ethoxyacrylate with benzyltrimethylammo-
nium ethoxide.9 Jacobsen et al. showed the formation of triethyl
1,3,5-benzenetricarboxylate in the course of the distillation of
the dimer of ethyl 3-ethoxyacrylate in the presence of NaHSO4
or p-TsOH.10 We have now found that a novel regioselective
trisannelation reaction of acrylates to 1,3,5-benzenetricarboxy-
lates is promoted by Pd(OAc)2 combined with molybdovana-
dophosphoric acids in the presence of a small amount of Lewis
acids in a mixed solvent of methanol and acetic acid (eq 1).
Trisannelation of Acrylates to
1,3,5-Benzenetricarboxylates by a Pd(OAc)2/
HPMoV/CeCl3/O2 System
Ken-ichi Tamaso, Yuji Hatamoto, Satoshi Sakaguchi,
Yasushi Obora, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering &
High Technology Research Center, Kansai UniVersity, Suita,
Osaka 564-8680, Japan
ishii@ipcku.kansai-u.ac.jp
ReceiVed February 16, 2007
A new type of trisannelation reaction of acrylates through
acetal formation was developed by Pd(OAc)2 combined with
molybdovanadophosphoric acid (HPMo8V4) and Lewis acid
under atmospheric dioxygen. Thus, the reaction of isobutyl
acrylate in the presence of Pd(OAc)2, HPMo8V4, and CeCl3
under O2 (1 atm) in MeOH/AcOH afforded isobutyl 1,3,5-
benzenetricarboxylate in fair yield. The reaction was found
to proceed through the palladium-catalyzed acetalization of
acrylate with methanol followed by the trisannelation reaction
of the resulting acetal promoted by CeCl3.
Table 1 shows the result of the reaction of isobutyl acrylate
(1a) by Pd(OAc)2 combined with H7PMo8V4O40‚23H2O
(HPMo8V4) and CeCl3‚7H2O under several reaction conditions.
A typical reaction was carried out as follows: To a solution
containing Pd(OAc)2 (0.10 mmol, 3.3 mol %), HPMo8V4 (0.023
mmol, 0.77 mol %), and CeCl3‚7H2O (0.20 mmol, 6.7 mol %)
in a mixed solvent of methanol (2 mL) and acetic acid (3 mL)
was added 1a (3 mmol) in acetic acid (0.3 mL) and methanol
(0.2 mL) over a period of 3.5 h under O2 (1 atm) at 70 °C, and
the mixture was stirred for an additional 18 h (entry 1). The
reaction afforded triisobutyl 1,3,5-benzenetricarboxylate (2a) in
40% yield along with unidentified polymeric products. This is
the first successful direct trisannelation reaction of acrylates to
1,3,5-trisubstituted benzene derivatives through a catalytic
process, although the product yield of 2a must be optimized. It
is noteworthy that the trisannelation of 1a was catalytically
achieved in a regioselective manner to give 2a since the
trimerization of terminal alkynes is difficult to carry out
regioselectively. When the amount of Pd(OAc)2 was increased
to 5 mol %, 2a was obtained in 56% yield (entry 2). The reaction
of 1a under these conditions for 4 h afforded 2a (15%, entry
3). The reaction of 1a in the absence of CeCl3 under these
conditions produced 2a in poor yield (6%, entry 5). The reaction
did not proceed catalytically under an argon atmosphere (entry
Dimerization of acrylates is a well-known synthetic method
to obtain bifunctional dicarboxylates, which are highly useful
compounds as polymer materials. This type of dimerization
reaction has been extensively studied by using various transition
metal complexes such as Co,1 Ni,2 Ru,3 Rh,4 and Pd.5 In contrast
to numerous studies on the dimerization of acrylates, however,
there has been little study on the trisannelation reaction of
acrylates. To the best of our knowledge, the synthesis of
benzenetricarboxylates by trisannelation of acrylates has never
been studied, although the cyclotrimerization of alkynes is
(1) (a) Kanai, H.; Okada, M. Chem. Lett. 1975, 167. (b) Kanai, H.; Ishii,
K. Bull. Chem. Soc. Jpn. 1981, 54, 1015.
(2) Wilke, G. Angew. Chem., Int. Ed. Engl. 1988, 27, 185.
(3) (a) McKinney, R. J.; Colton, M. C. Organometallics 1986, 5, 1080.
(b) McKinney, R. J. Organometallics 1986, 5, 1752. (c) Pertici, P.;
Ballantini, V.; Salvadori, P.; Bennett, M. A. Organometallics 1995, 14,
2565. (d) Yi, C. S.; Liu, N. J. Organomet. Chem. 1998, 553, 157.
(4) (a) Alderson, T.; Jenner, E. T.; Lindsey, R. V., Jr. J. Am. Chem.
Soc. 1965, 87, 5638. (b) Nugent, W. A.; McKinney, R. J. J. Mol. Catal.
1985, 29, 65. (c) Nikishin, I. P.; Klimora, T. E.; Ignatenko, A. V.; Kovalev,
I. P. Tetrahedron Lett. 1991, 32, 1077. (d) Hauptman, E.; Sabo-Etienne,
S.; White, P. S.; Brookhart, M.; Garner, J. M.; Fagan, P. J.; Calabrese, J.
C. J. Am. Chem. Soc. 1994, 116, 8038.
(6) (a) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901. (b)
Grotjahn, D. B. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, F. G. A., Wilkinson, G., Hegedus, L. S., Eds.; Pergamon: Oxford,
1995, Vol. 12; p 741. (c) Lautens, M.; Klute, W.; Tam, W. Chem. ReV.
1996, 96, 49. (d) Schore, N. E. Chem. ReV. 1988, 88, 1081. (e) Vollhard,
K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539. (f) Maitlis, P. M. J.
Organomet. Chem. 1980, 200, 161. (g) Maitlis, P. M. Acc. Chem. Res. 1976,
9, 93.
(7) Ru¨ba, E.; Schmid, R.; Kirchner, K.; Calhorda, M. J. J. Organomet.
Chem. 2003, 682, 204.
(5) (a) Barlow, M. G.; Bryant, M. J.; Haszeldine, R. N.; Mackie, A. G.
J. Organomet. Chem. 1970, 21, 215. (b) Nugent, W. A.; Hobbs, F. W., Jr.
J. Org. Chem. 1983, 48, 5364. (c) Zimmermann, J.; Tkatchenko, I.;
Wasserscheid, P. AdV. Synth. Catal. 2003, 345, 402.
(8) Baldwin, R. H. In Kirk-Othmer Encyclopedia of Chemical Technol-
ogy, 2nd ed.; Dukes, E. P., Ed.; Wiley: New York, 1968; pp 478-480.
(9) Croxall, W. J.; Van Hook, J. O. J. Am. Chem. Soc. 1950, 72, 803.
(10) Jacobsen, N.; Winckelmann, I. J. Chem. Res. 1985, 80.
10.1021/jo070323e CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/05/2007
J. Org. Chem. 2007, 72, 3603-3605
3603

TABLE 1. Trisannelation of 1a to 2a by the Pd(OAc)2/HPMo8V4/
CeCl3/O2 System under Several Reaction Conditionsa
acid in a mixed solvent of t-BuOH and acetic acid under various
reaction conditions (eq 2, Table 2).
Pd(OAc)2
(mmol)
HPMoV
(µmol)
CeCl3
(mmol)
conv
(%)
yieldb
(%)
As expected, the trisannelation of the acetal 3b was achieved
by CeCl3 in a mixed solvent of t-BuOH12 and acetic acid at 90
°C for 2 h to give triethyl 1,3,5-benzenetricarboxylate (2b) in
a considerable yield (63%, entry 1). When the reaction was
prolonged to 6 h, 2b was obtained in 78% yield (entry 2). The
reaction was induced to some extent in either acetic acid or
t-BuOH alone (entries 3 and 4), but the reaction was slow at a
temperature below 70 °C (entry 5). Among Lewis acids
examined, lanthanide metal chlorides were found to be more
efficient than normal metal chlorides. CeCl3 was the best Lewis
acid followed by GdCl3 and SmCl3 (entries 6 and 7). Use of
AlCl3 and ZrCl4 resulted in 2b in low yields (entries 8 and 9).
No trisannelation was induced by protic acids such as TsOH
and H2SO4 (entries 10 and 11).
On the basis of these results, a plausible reaction path for
the trisannelation of 1a to 2a is outlined in Scheme 1. The
reaction is initiated by the Pd(II)-catalyzed acetalization of
acrylate 1a to 3a, and the resulting acetal 3a is believed to be
converted to 3-methoxy acrylate (4a) through a Ce acetal (A)
as a transient intermediate. It seems rather difficult to presume
the subsequent reaction paths involved in the annulation.
However, we can make a proposal about the trisannelation which
seems to agree with the experimental data. The Michael-type
addition of A to 4a affords an adduct (B) on which subsequent
addition to 4a followed by annelation leads to 2a. Indeed, 4b
prepared independently was allowed to react in the presence of
CeCl3 in a mixed solvent of t-BuOH and AcOH (3:2) at 90 °C
to give 2b in 50% yield (eq 3). These results led to a conceivable
reaction sequence which involved the formation of acetal 3a
promoted by the Pd(II) catalyst followed by trisannelation of
the resulting 3a to 2a induced by CeCl3.
entry
1
0.10
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
23
23
23
30
23
23
23
23
23
0.20
0.20
0.20
0.20
0
0.20
0.20
0.20
0.20
83
97
23
97
16
40
56 (55)
15
35
2
3c
4
5d
6e
7f
8g
9h
6
no reaction
4
28
93
56
19
n.d.i (16)j
a To a solution of AcOH (3 mL) and MeOH (2 mL) containing Pd(OAc)2,
HPMo8V4, and CeCl3‚7H2O was added 1a (3 mmol) in AcOH (0.3 mL)/
MeOH (0.2 mL) at 70 °C over a period of 3.5 h and stirred for additional
18 h. b GLC yields. The number in parentheses shows isolated yield.
c Reaction time was 4 h. d Reaction was performed in the absence of
CeCl3‚7H2O. e Reaction was performed under Ar. f AcOH (5 mL) was used
without MeOH. g Water (2 mL) was used in place of MeOH. h MeOH (5
mL) was used without AcOH. i Not detected. j Yield of 3a.
6). When methanol was removed from a mixed solvent, the
conversion became very low (entry 7). However, the use of
water instead of methanol afforded 2a to some extent (19%,
entry 8). No trisannelation was induced in the reaction in
methanol alone, and isobutyl 3,3-dimethoxypropionate (3a) was
obtained in 16% yield (entry 9). These results show that a mixed
solvent of methanol and acetic acid is needed to obtain
trisannelation product 2a. The fact that the acetal 3a is formed
in the early stage of the reaction may provide powerful evidence
that 2a is formed through 3a. Previously, we have reported that
the acetalization of ethyl acrylate (1b) in ethanol is achieved
by a Pd(OAc)2/molybdovanadophosphate/hydroquinone system
under O2 to afford ethyl 3,3-diethoxypropionate (3b) in quan-
titative yield.11
TABLE 2. Trisannelation of 3b to 2b by Several Lewis Acids
under Various Conditionsa
In conclusion, we have developed a novel trisannelation
reaction of acrylates through acetals to benzenetricarboxylates
2a and 2b by using a Pd(OAc)2/HPMo8V4/CeCl3 system under
O2 in a mixed solvent of methanol and acetic acid. In addition,
acetal 3b derived from ethyl acrylate was found to undergo
trisannelation by Lewis acids to give 2b in good yield.
solvent
(mL)
yieldb
(%)
entry
Lewis acid
1c
2
3
t-BuOH/AcOH (3/2)
t-BuOH/AcOH (3/2)
AcOH (5)
t-BuOH (5)
t-BuOH (5)
t-BuOH/AcOH (3/2)
t-BuOH/AcOH (3/2)
t-BuOH/AcOH (3/2)
t-BuOH/AcOH (3/2)
t-BuOH/AcOH (3/2)
t-BuOH/AcOH (3/2)
CeCl3
CeCl3
CeCl3
CeCl3
CeCl3
GdCl3
SmCl3
AlCl3
ZrCl4
H2SO4
TsOHf
63
78 (70)
41
56
7
58
49
12
4
5d
6
Experimental Section
7
8
9
10
11
A typical reaction procedure of the reaction with 1a was carried
out as follows (Table 1, entry 2): To a solution containing Pd-
(OAc)2 (0.10 mmol, 3.3 mol %), HPMo8V4 (0.023 mmol, 0.77 mol
%), and CeCl3‚7H2O (0.20 mmol, 6.7 mol %) in a mixed solvent
of methanol (2 mL) and acetic acid (3 mL) was added 1a (3 mmol)
in methanol (0.2 mL) and acetic acid (0.5 mL) over a period of 3.5
h under O2 (1 atm) at 70 °C, and the mixture was stirred for an
additional 18 h. The conversions and the yield of products were
estimated from the peak areas based on the internal standard
technique using GLC and showed that 2a was obtained in 56%
yield. Then, the solvent was removed under reduced pressure,
neutralized with sodium bicarbonate, and extracted with ethyl
13
n.d.e
n.d.e
a 3b (3 mmol) was allowed to react in the presence of CeCl3 (0.3 mmol)
at 90 °C for 6 h. b GLC yields. The number in parentheses shows isolated
yield. c Reaction time was 2 h. d Reaction was performed at 70 °C. e Not
detected. f p-Toluenesulfonic acid.
Thus, the trisannelation of acetal 3b, available from com-
mercial source, was examined under the influence of a Lewis
(11) Yokota, T.; Fujibayashi, S.; Nishiyama, Y.; Sakaguchi, S.; Ishii,
Y. J. Mol. Catal. A.: Chem. 1996, 114, 113.
(12) t-BuOH was used to avoid the exchange reaction of 3b with primary
alcohols employed at higher temperature (90 °C).
3604 J. Org. Chem., Vol. 72, No. 9, 2007

SCHEME 1. A Plausible Reaction Path
acetate (20 mL). The product (2a) was isolated in 55% yield (207
mg) by column chromatography (230-400 mesh silica gel, n-
hexane/ethyl acetate ) 19/1).
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research on Priority Areas “Advanced
Molecular Transformations of Carbon Resources” from the
Ministry of Education, Culture, Sports, Science and Technology,
Japan, and “High-Tech Research Center” Project for Private
Universities: matching fund subsidy from the Ministry of
Education, Culture, Sports, Science and Technology, 2005-
2009.
A typical reaction procedure of the reaction with 3b was carried
out as follows (Table 2, entry 2): A mixed solvent of tert-BuOH
(3 mL) and acetic acid (2 mL) solution of 3b (3 mmol) and CeCl3‚
7H2O (0.30 mmol, 10 mol %) was placed in a round-bottomed flask,
and the mixture was stirred at 90 °C for 6 h. The yield of the product
(2b) was estimated from the peak areas based on the internal
standard technique using GLC and showed that 2b was obtained
in 78% yield. Then, the solvent was removed under reduced
pressure, neutralized with sodium bicarbonate, and extracted with
ethyl acetate (20 mL). The product (2b) was isolated in 70% yield
(205 mg) by recrystallization (H2O/MeOH/acetone ) 10/3/1).
Compounds 3b and 4b are commercially available. Products 2a,13
2b,14 and 3a15 were known compounds and have been reported
previously.
Supporting Information Available: 1H and 13C NMR spectral
data of 2a and 2b. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO070323E
(14) Becker, E.; Mereiter, K.; Puchberger, M.; Schmid, R.; Kirchner,
K.; Doppiu, A.; Salzer, A. Organometallics 2003, 22, 3164.
(15) Kishi, A.; Sakaguchi, S.; Ishii, Y. Org. Lett. 2000, 2, 523.
(13) Miles Laboratories, Inc., Patent FR1297233, 1962 (CAN 58:21337).
J. Org. Chem, Vol. 72, No. 9, 2007 3605