A simple PdCl2/O2/DMF catalytic system for highly regioselective cyclotrimerization of olefins with electron-withdrawing groups

Article abstract of DOI:10.1016/j.tetlet.2007.08.034

A highly regioselective cyclotrimerization of olefins with electron-withdrawing groups in a PdCl₂/O₂/DMF catalytic system is disclosed, and a possible mechanism has also been proposed, which reveals the PdCl₂-catalyzed cyclotrimerization of olefins with electron-withdrawing groups goes through a quite different pathway from that of alkynes.

Full text of DOI:10.1016/j.tetlet.2007.08.034

Tetrahedron Letters 48 (2007) 7542–7545
A simple PdCl2/O2/DMF catalytic system for highly regioselective
cyclotrimerization of olefins with electron-withdrawing groups
Huan-Feng Jiang,* Yan-Xia Shen and Zhao-Yang Wang
The College of Chemistry, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China
Received 22 May 2007; revised 7 August 2007; accepted 10 August 2007
Available online 15 August 2007
Abstract—A highly regioselective cyclotrimerization of olefins with electron-withdrawing groups in a PdCl2/O2/DMF catalytic sys-
tem is disclosed, and a possible mechanism has also been proposed, which reveals the PdCl2-catalyzed cyclotrimerization of olefins
with electron-withdrawing groups goes through a quite different pathway from that of alkynes.
Ó 2007 Elsevier Ltd. All rights reserved.
The synthesis of polysubstituted aromatic compounds
has long been of great interest in industrial and aca-
demic research. Traditionally these compounds have
been synthesized via aromatic electrophilic substitution
reactions or a variety of metal-mediated multistep cou-
pling reactions generally involving alkynes.1,2 Although
transition-metal-catalyzed cyclotrimerization of alkynes
has made great advances, the regioselectivity of the pro-
cess is still troublesome.3 Besides, all these methodolo-
gies suffer the challenges of available and cheap
starting materials, environmentally benign and atom
economical process.
withdrawing groups in a PdCl2/O2/DMF catalytic sys-
tem (Eq. 1), and also propose a possible mechanism.
R
PdCl2/O2
R
ð1Þ
DMF
R
R
1
2
Our initial efforts to probe the cyclotrimerization of
olefins with electron-withdrawing groups focused on
the reactivity of methyl acrylate. Table 1 shows the
results of optimization for the reaction under ranges of
reaction conditions, including dosage of catalyst, pres-
sure of molecular oxygen, temperature and reaction
time. A typical reaction was carried out with methyl
acrylate 1a (4 mmol) in 1 mL DMF, which was chosen
as the reaction solvent due to its excellent solubility of
PdCl2, compared with n-hexane, CH2Cl2, toluene and
THF.
Homogeneous catalytic systems involving PdII com-
plexes have been used as one of the most efficient oxi-
dase catalysts with the use of molecular oxygen as a
terminal oxidant.4 Molecular oxygen is an ideal oxidant
owing to its availability and subsequent production of
totally environment-safe byproducts such as water or
hydrogen peroxide.
In our previous studies, a cyclotrimerization product of
methyl acrylate has been detected in a PdCl2/O2/scCO2/
MeOH catalytic system.5 Recently, a triannelation of
acrylates to 1,3,5-benzenetricarboxylates catalyzed by a
Pd(OAc)2/HPMoV/CeCl3/O2 system was reported by
Ishii.6 Herein we disclose for the first time a highly reg-
ioselective cyclotrimerization of olefins with electron-
It is noteworthy that the cyclotrimerization of 1a was
catalytically achieved to give 2a in a regioselective man-
ner. The dosage of catalyst had an obvious effect on the
cyclotrimerization of 1a. When the amount of PdCl2 was
increased to 5 mol %, 2a was obtained in 55.8% isolated
yield (Table 1, entries 1 and 2). Further loading of PdCl2
to 7.5%, the yield decreased to 39.8% with a more seri-
ous concomitant formation of palladium black (Table
1, entry 3). The formation of 2a exhibits a sharp depen-
dence on the pressure of molecular oxygen and reaches a
maximum value of 65.4% at 0.6 MPa (Table 1, entry 6).
But further increase of the pressure of molecular oxygen
Keywords: PdCl2/O2/DMF catalytic system; Cyclotrimerization;
Regioselective; Olefins.
*
Corresponding author. Tel./fax: +86 20 8711 2906; e-mail: jianghf@
scut.edu.cn
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.08.034

H.-F. Jiang et al. / Tetrahedron Letters 48 (2007) 7542–7545
7543
Table 1. Cyclotrimerization of 1a to 2a by the catalysis of the PdCl2/O2/DMF system under ranges of reaction conditionsa
Entry
Dosage of
catalyst (mmol)
Temperature
(°C)
Pressure of
oxygen (MPa)
Time
(h)
Isolated
yield (%)
1
2
3
4b
5
6
7
8
9
10
11
12c
13d
0.1
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
50
50
50
50
50
50
50
50
50
20
70
50
50
0.5
0.5
0.5
24
24
24
24
24
24
24
24
12
24
24
24
24
42.0
55.8
39.8
9.1
36.8
65.4
42.3
28.7
32.0
Trace
35.7
Trace
60.2
Ambient air
0.1
0.6
0.7
0.9
0.6
0.6
0.6
0.6
0.6
a Reaction conditions: methyl acrylate (4 mmol), DMF (1 mL).
b Oxygen was introduced by use of a balloon.
c Pd(OAc)2 was used as catalyst.
d PdCl2(CH3CN)2 was used as catalyst.
leads to a dramatic decrease of the yield of 2a (Table 1,
entries 7 and 8). Prolongation of reaction time from 12 h
to 24 h results in a marked increase of the yield of 2a
(Table 1, entries 9 and 6). At lower temperatures of
20 °C, (Table 1, entry 10), trace of the product was
detected. Pd(OAc)2 seemed to be an inefficient catalyst
for the reaction, while PdCl2(CH3CN)2, the solvate of
PdCl2, could catalyze the reaction smoothly (Table 1,
entries 12 and 13).
To the best of our knowledge, this is the first synthesis
of these very useful compounds from simple olefins.
When 2 mmol 1a and 2 mmol 1b were mixed with
5 mol % PdCl2 under 0.5 MPa O2 in 1 mL DMF, a mix-
ture of cyclotrimerization products can be found with an
approximate ratio of 1:3:3:1 in yields (Eq. 2), which
implied that the cyclotrimerization pathway of olefins
with electron-withdrawing groups may experience a
three-step process.
Cyclotrimerization of different olefins was investigated
under optimized reaction conditions and the results
are shown in Table 2.7 It can be learned that the cyclo-
trimerization of both alkyl and aryl olefins with elec-
tron-withdrawing groups can occur smoothly in the
PdCl2/O2/DMF catalytic system. With an increasing
number of carbon atoms in the R group of alkyl acry-
lates, its reactivity decreased distinctly. Therefore both
a higher temperature and a longer time could promote
the cyclotrimerization (Table 2, entry 3). In the case of
methyl vinyl ketone, this simple catalyst system also
show a rather good activity (Table 2, entry 4). As to dif-
ferent aryl olefins, we can see from Table 2 (entries 5–7),
aspiring results can also be obtained. These correspond-
ing products are very important initiators for the synthe-
sis of well-defined star polymers, which has became an
important field in macromolecular chemistry due to
their unique spatial shapes and rheological properties.8
When the mixture of 2 mmol 1a and 2 mmol ethyl pro-
piolate was catalyzed by 5 mol % PdCl2 under 0.5 MPa
O2 in 1 mL DMF, no cross products of carbomethoxy
and ethoxy-carbonyl were detected (Eq. 3). In addition,
the cyclotrimerization of 1a gave 2a alone, while the
cyclotrimerization of ethyl propiolate gave a mixture
of 1,3,5- and 1,2,4-benzenetricarboxylates in the yields
of 47% and 46%, respectively, (based on ethyl propiolate
by GC–MS).
On the basis of the above results, several noteworthy
points can be summarized. (1) The PdCl2-catalyzed
cyclotrimerization of olefins with electron-withdrawing
groups goes through a quite different way from that of
alkynes. (2) The cyclotrimerization of olefins with elec-
tron-withdrawing groups is sensitive to the concentra-
tion of molecular oxygen in solvate, which means it
PdCl2 5%
+
COOMe
(1:1)
COOEt
O
2 5atm/ DMF
1a
1b
COOEt
COOMe
COOMe
COOMe
ð2Þ
+
+
:
+
EtOOC
COOEt
MeOOC
COOMe
MeOOC
COOEt
EtOOC
COOEt
2b
2a
1
3
:
1
:
3

7544
H.-F. Jiang et al. / Tetrahedron Letters 48 (2007) 7542–7545
PdCl2 5%
+
COOEt
COOMe
O2 5atm/ DMF
1a
COOEt
COOEt
COOEt
ð3Þ
COOMe
+
+
EtOOC
EtOOC
COOEt
MeOOC
COOMe
1b
needs an appropriate oxygen pressure. (3) Characteristic
of the a-carbonyl group of the substrates, including its
electron-withdrawing property, might be vital to the
reaction. (4) The choice of solvents is important due to
its solubility of PdCl2 and the electric property.
H–Pd–Cl þ O2 ! H–O–O–Pd–Cl
H–O–O–Pd–Cl þ HCl ! PdCl2 þ H2O2
ð4Þ
ð5Þ
Table 2. Cyclotrimerization of different olefinsa
A plausible reaction pathway for the cyclotrimerization
of 1 to 2 is outlined in Scheme 1.9 Coordination of olefin
1 to PdCl2 prefers to undergo chloropalladation and
then b-H elimination to vinylpalladium intermediate 4.
The presence of molecular oxygen converted H–Pd–Cl
to Cl–Pd–OOH, which releases H2O2 and keeps Pd(II)
oxidative state (Eqs. 4 and 5).10 Subsequent insertion
of olefins 1 to Pd–C bond and then b-H elimination–oxi-
dation afford the new chloropalladation intermediate 6,
which then cyclizes by closing the ring to generate inter-
mediate 7. The active PdCl2 species is regenerated.
Entry
R
Product
Isolated
yield (%)
COOMe
1
COOMe
65.4
53.2
38.4
58.4
25.3
59.2
48.7
MeOOC
COOMe
2a
COOEt
2
COOEt
COOnBu
COMe
EtOOC
BunOOC
MeOC
PhOC
COOEt
Why did the cyclotrimerization of olefins with electron-
withdrawing groups yield the sole regioselective product
in comparison with that of alkynes? We speculate that
the insertion of olefins to Pd–C bond might strongly
depend on electronic nature11 and different molecular
orbit states of sp-C atoms and sp2-C atoms.12
2b
COOnBu
3b
COOnBu
2c
In summary, we have developed a simple palladium
catalyst system for the highly regioselective cyclotrimer-
ization of olefins with electron-withdrawing groups to
1,3,5-trisubstituted benzene derivatives. The brand new
COMe
4
COMe
R
2d
R
R
COPh
R
2
1
5c
6c
7c
COPh
PdCl2
COPh
R
R
R
2g
COOPh
Cl
PdCl2
3
ClPd
R
R
O2
7
COOPh
β-H elimination
PhOOC
COOPh
H2O2
2e
Cl
R
R
COOCH2Ph
ClPd
ClPd
Cl
4
COOCH2Ph
β-H elimination
β-H elimination
R
+
O2
PhCH2OOC
COOCH2Ph
R
R
6
2f
R
ClPd
O2
H2O2
a Reaction conditions: acrylate (4 mmol), PdCl2 (0.2 mmol), DMF
(1 mL), Pressure of O2 (0.6 MPa), 50 °C, 24 h.
H2O2
5
Cl
R
+
b Reaction was run at the temperature of 70 °C for 36 h.
c Reaction was run at the temperature of 50 °C for 18 h.
Scheme 1.

H.-F. Jiang et al. / Tetrahedron Letters 48 (2007) 7542–7545
7545
(C@O); 1240, 1024 cmꢀ1 (C–O–C). MS (EI): m/z = 294
(M+), 266, 249, 221, 193, 73, 29. 1H NMR (400 MHz,
TMS, CDCl3): d = 1.412 (t, J = 7.2 Hz, 9H, CH3), 4.421
(q, J = 7.2 Hz, 6H, CH2), 8.830 (s, 3H, C6H3). Compound
2c. IR(neat): m = 3093 cmꢀ1 (C6H3); 2853 cmꢀ1 (CH3);
1728 cmꢀ1 (C@O); 1242, 1028 cmꢀ1 (C–O–C). MS (EI):
m/z = 378 (M+), 323, 305, 267, 249, 211, 193, 165, 120, 56,
proposed mechanism may highlight the study of cyclo-
trimerization of olefins.
Acknowledgement
1
41, 29. H NMR (400 MHz, TMS, CDCl3): d = 0.971 (t,
The authors thank the National Natural Science Founda-
tion of China (Nos. 20625205, 20572027 and 20332030)
for financial support of this work.
J = 7.2 Hz, 9 H, CH3), 1.423–1.516 (m, 6H, CH2), 1.728–
1.799 (m, 6H, CH2), 4.360 (t, J = 6.8 Hz, 6H, CH2), 8.817
(s, 3H, C6H3). Compound 2d. IR(neat): m = 3064 cmꢀ1
(C6H3); 2922, 2852 cmꢀ1 (CH3); 1688 cmꢀ1 (C@O); 1225,
1096 cmꢀ1 (C–O–C). MS (EI): m/z = 204 (M+), 189, 161,
119, 91, 75, 32,28. 1H NMR (400 MHz, TMS, CDCl3):
d = 2.694 (s, 9H, CH3), 8.684 (s, 3H, C6H3). Compound
2e. IR(neat): m = 3902, 3446, 3061, 2926, 2885, 1722, 1662,
1247, 1009, 714, 794 cmꢀ1. MS (EI): m/z = 390 (M+), 313,
285, 105, 77, 58, 44, 32. 1H NMR (400 MHz, TMS,
CDCl3): d = 8.379 (s, 3H, C6H3), 7.838–7.817 (m, 6H,
C6H5), 7.613–7.594 (m, 3H, C6H5), 7.518–7.480 (m, 6H,
C6H5). Compound 2f. IR(neat): m = 3742, 3449, 2921,
2855, 1796, 1233 cmꢀ1. MS (EI): m/z = 438 (M+), 359,
345, 317, 224, 196, 168, 139, 103, 89, 75, 65, 51, 32. 1H
NMR (400 MHz, TMS, CDCl3): d = 9.228 (s, 3H, C6H3),
7.453 (t, J = 8 Hz, 6H, C6H5), 7.320–7.246 (m, 9H, C6H5).
Compound 2g. IR(neat): m = 3433, 3088, 3034, 2956, 2854,
1721, 1224 cmꢀ1. MS (EI): m/z = 480 (M+), 389, 373, 336,
References and notes
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added into the autoclave in sequence. O2 was pumped into
the autoclave using a cooling pump to reach the desired
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