Palladium-catalyzed aerobic oxidation of terminal olefins with electron-withdrawing groups in scCO2

Article abstract of DOI:10.1016/j.tet.2007.11.013

Product control of palladium-catalyzed aerobic oxidation of terminal olefins with electron-withdrawing groups can be achieved through modifying reaction conditions. When the oxidant, such as CuCl₂/O₂, benzoquinone/O₂ or O₂, was present in scCO₂, aerobic oxidation of terminal olefins goes smoothly. With enough MeOH and sufficient oxygen, acetalization preponderated over cyclotrimerization, while with little MeOH as co-solvent in scCO₂ or no MeOH in DMF and an appropriate pressure of O₂, cyclotrimerization of terminal olefins became the dominated reaction. When oxygen is absent and triethylamine was added into the reaction system, palladium-catalyzed C-N bond formation occurs to produce β-amino acid derivatives as the sole product.

Full text of DOI:10.1016/j.tet.2007.11.013

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 508e514
www.elsevier.com/locate/tet
Palladium-catalyzed aerobic oxidation of terminal olefins with
electron-withdrawing groups in scCO2
a
a,b
Huan-Feng Jiang a, , Yan-Xia Shen , Zhao-Yang Wang
*
a College of Chemistry, South China University of Technology, Guangzhou 510640, PR China
b Department of Chemistry, South China Normal University, Guangzhou 510006, PR China
Received 5 August 2007; received in revised form 1 November 2007; accepted 2 November 2007
Available online 6 November 2007
Abstract
Product control of palladium-catalyzed aerobic oxidation of terminal olefins with electron-withdrawing groups can be achieved through mod-
ifying reaction conditions. When the oxidant, such as CuCl2/O2, benzoquinone/O2 or O2, was present in scCO2, aerobic oxidation of terminal
olefins goes smoothly. With enough MeOH and sufficient oxygen, acetalization preponderated over cyclotrimerization, while with little MeOH
as co-solvent in scCO2 or no MeOH in DMF and an appropriate pressure of O2, cyclotrimerization of terminal olefins became the dominated
reaction. When oxygen is absent and triethylamine was added into the reaction system, palladium-catalyzed CeN bond formation occurs to
produce b-amino acid derivatives as the sole product.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
oxidations have received considerable attention3 and substan-
tial developments have been achieved. These can be linked to
the discoveries of various ligands, such as DMSO,4 pyridine,5
1,2-bipyridine,6 phenanthroline,7 bathophenanthroline disulfo-
nate,8 NEt3,9 (ꢀ)-sparteine,10 N-heterocycliccarbene,11 etc.,
which stabilize the reduced palladium catalyst and enable an
efficient aerobic oxidation to be realized in the absence of
a secondary oxidant.12 At the same time, the choice of solvents
is also critical to palladium-catalyzed aerobic oxidation
because of the solubility of both palladiumeligand complexes
(Pd/L) and molecular oxygen. Various solvents were employed
according to different Pd/L systems, such as toluene,13 benz-
ene,14 CH2Cl2,15 biphasic solvents,16 ionic liquids,17 etc. How-
ever, a drawback is that in most cases excess ligand is needed
to prevent catalyst decomposition, i.e., to prevent the Pd(0)
intermediate from metal aggregation18 and unfortunately, the
excess of ligand also leads to less efficient oxidation as a
result of inhibition of either substrate binding or b-hydride
elimination.19
Since the discovery of Wacker reaction in the late 1950s,
palladium catalysis has become one of the most versatile
methodologies for the synthesis of various targeted organic
molecules.1 Palladium-catalyzed reactions include two major
classes: cross-coupling reactions initiated by Pd(0) and oxida-
tion reactions initiated by Pd(II). Although the field flourished
with palladium-catalyzed oxidation reactions, the catalytic
systems traditionally require a stoichiometric secondary oxi-
dant such as CuCl2 or benzoquinone, which leads to the com-
plexity of the reactions, reduces the atom economy, making
product isolation complicated and toilsome.
Recently, there has been an increasing demand for environ-
mentally friendly and sustainable chemical processes, aimed at
replacing stoichiometric methods by catalytic processes. Pres-
ently, the ideal ultimate stoichiometric oxidant in these reac-
tions turns to either molecular oxygen or hydrogen peroxide,
because these oxidants are environmentally friendly and give
only water as a byproduct.2 Thus, palladium-catalyzed aerobic
Pd(II)-catalyzed acetalization of terminal alkenes with
alcohols, which undergo a Wacker-type process, ranks among
the most important reactions for the functionalization of
alkene feedstocks. Many acetals, such as alkyl 3,3-dialkoxy-
propanoates, b-ketoacetals, and b-cyanoacetal, are important
* Corresponding author. Tel./fax: þ86 20 8711 2906.
E-mail address: jianghf@scut.edu.cn (H.-F. Jiang).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.013

H.-F. Jiang et al. / Tetrahedron 64 (2008) 508e514
509
intermediates in organic synthesis and have been used to syn-
thesize a variety of important compounds. In 1999, we first
reported our investigation on the Pd(II)-catalyzed aerobic ace-
talization of terminal olefins with electron-withdrawing groups
in supercritical carbon dioxide (scCO2), using CuCl2 or CuCl
as cocatalyst and a yield of 91.7% was gained (Scheme 1, A).
We also found that when the reaction solvent was replaced
with scCO2, the toxic accelerator HMPA was not necessary.20
inexpensive, inert, nontoxic, nonflammable and because its crit-
ical parameters are easily accessible (Tc¼31.0 ꢁC, Pc¼
7.38 MPa).24 It is undoubtedly much more eco-friendly to bring
together the very important green chemistry technologiesdthe
use of carbon dioxide as a solvent and the use of molecular
oxygen as the sole oxidant.
2. Results and discussion
A
PdII,CuII or CuI
MeO
MeOH/O2 in scCO2
2.1. The effect of different ligands on the PdCl2-catalyzed
acetalization
CO2Me
CO2Me
91.7%
95.5%
CO2Me
CO2Me
OMe
OMe
B
As is proved that an appropriate Pd/L system is of great
help to realize an efficient palladium-catalyzed aerobic oxida-
tion in the absence of a secondary oxidant.11 We firstly ex-
plored the effect of various ligands on the PdCl2/CH3OH/O2/
scCO2 system using methyl acrylate as substrate. In contrast,
our study of the addition of various ligands in scCO2 turned
out to be not only unnecessary but also even disadvantageous.
When the reaction was run ligand-free, a yield of 86.9% for 2
was obtained, with the formation of 1,3,5-benzenetricarboxyl-
ate as a byproduct. This was surprising because few examples
of formation of benzene derivatives from simple olefins were
reported before, and the highly regioselective manner is also
novel. Traditionally, benzene derivatives were synthesized by
aromatic electrophilic substitution reactions and a variety of
metal-mediated coupling reactions, which generally involve
multistep syntheses. Although transition-metal-catalyzed
cyclotrimerization of alkynes has been greatly advanced, the
regioselectivity of the process can still be troublesome.25
As seen in Table 1, nitrogenous ligands including pyridine,
2,20-bipyridyl, and 1,10-phenanthroline were tried out with no
good results (Table 1, entries 5e7); neither did 1,5-cycloocta-
diene nor the phosphorous ligand triphenylphosphine (Table 1,
entries 4 and 8); although moderate yield of acetalization prod-
uct 2 was obtained in the case for some oxygenous ligands (Ta-
ble 1, entries 1e3), the results were still not better than that
without ligands, though the introduction of oxygenous ligands
absolutely depressed the formation of byproduct 4. When the
aliphatic amine triethylamine was added in this reaction system,
PdII, PS-BQ
MeO
MeOH/O2 in scCO2
Scheme 1.
Our further experimental results showed that polystyrene-
supported benzoquinone (PSeBQ) was a successful substitute
for the cocatalyst CuCl2 (or CuCl) (Scheme 1, B).21 Compared
with small molecular cocatalysts, the separation of PSeBQ
from the reaction system by simple filtration obviously made
the recycling of precious palladium practical and convenient.
A systemic conclusion has been made about the selective
control and mechanistic study of Pd(II)-catalyzed aerobic ace-
talization of terminal olefins with electron-withdrawing groups
using different cocatalysts in scCO2.22 When PSeBQ was
used as cocatalyst, benzoquinone (BQ) might absorb HCl
via Michael addition in situ, and was converted to chlorohy-
droquinone (CHQ), which took part in hydrogenolysis to
give PdCl2 and products, and then regenerated BQ. Enlight-
ened by this, we further successfully explored polystyrene-
supported phenol (PSephenol) and polystyrene-supported
hydroquinone (PSeHQ) as cocatalysts for the Pd(II)-catalyzed
acetalization of terminal olefins with electron-withdrawing
groups in scCO2.23
As part of our ongoing interest in the direct utilization of mo-
lecular oxygen as the sole oxidant in the palladium-catalyzed
acetalization of terminal olefins with electron-withdrawing
groups in scCO2, we have investigated the effects of various
factors on this oxidation. Herein, we disclosed a ‘ligand-free’
palladium-catalyzed oxidative process using molecular oxygen
as the sole oxidant in scCO2 (Scheme 2). We also found that
with molecular oxygen as the sole oxidant, satisfactory results
can only be reached when using scCO2 as reaction solvent in
comparison with traditional organic solvents. It is well known
that supercritical fluids are environmentally acceptable replace-
ments for organic solvents, and as one of the most convenient of
them, scCO2 has also been widely studied because it is
Table 1
Acetalization in the presence of different ligandsa
Entry
Ligand
Dosage of
ligand/mmol
Yield of 2/
b
%
1
2
3
4
5
6
7
8
a
None
d
86.9
79.2
Ethyl acetoacetate
Acetylacetone
1,5-Cyclooctadiene
Pyridine
2,20-Bipyridyl
1,10-Phenanthroline
Triphenylphosphine
0.3
0.3
0.3
0.6
0.3
0.3
0.6
53.7
Trace
Trace
Trace
Trace
Trace
MeOOC
+
COOMe
MeO
+
MeO
PdII/O2
scCO2
Reaction was run at 50 ꢁC for 18 h with molar ratios of 4.94 and 3% of
methanol and catalyst to the substrate methyl acrylate (5 mmol), respectively,
under the pressure of O2 0.7 MPa, and the pressure of the autoclave system
14 MPa.
COOMe
MeO
COOMe
COOMe
4
COOMe
3
1
2
b
Scheme 2.
By GC.

510
H.-F. Jiang et al. / Tetrahedron 64 (2008) 508e514
acetal with a yield of about 5% was obtained as a byproduct,
with the b-N-addition product being predominant.26
pressure of carbon dioxide, temperature, and reaction time
(Table 3). The yield of 2 exhibits a sharp dependence on the
pressure of oxygen, and a higher pressure of oxygen is advan-
tageous for the reaction. When the pressure of oxygen was as
low as 0.02 MPa, the reaction cannot occur (Table 3, entry 1).
A dramatic elevation of the yield of 2 can be observed with
increasing the pressure of oxygen from 0.5 to 0.7 MPa (Table
3, entries 3 and 4) and it reaches a maximum value of 99.3% at
1 MPa (Table 3, entry 6). The conversion increases with
increasing pressure of carbon dioxide up to 14 MPa, but it
decreases thereafter probably due to the dilution effects. The
value of PCO =PO seems to influence the yield of 4 dramati-
cally and the increasing O2 concentration inhabits the forma-
tion of 4 (Table 3, entries 3e5). A reaction time of 12 h
cannot permit complete conversion of the substrate (Table 3,
entry 14), which requires another 3 h (Table 3, entry 15). Fur-
ther prolongation of the reaction time leads to no better results
(Table 3, entry 16). At lower temperatures (<40 ꢁC) (Table 3,
entries 16 and 17), the results were not good. Surprisingly, the
yield of 4 was dramatically elevated with an increase of reac-
tion temperature and reached 21.6% at 80 ꢁC (Table 3, entries
18 and 19).
2.2. Acetalization under different catalysts in scCO2
Different palladium sources were evaluated and the results
are presented in Table 2. Among various palladium salts,
PdCl2 shows the best catalytic activity for this reaction. In
the presence of 3 mol % PdCl2, the conversion of substrate
methyl acrylate reached 99.8% and product 2 was obtained
in 95.3% yield. Pd(OAc)2 and anhydrous Pd(NO3)2 also
exhibited high catalytic activity while PdBr2 and Pd/C showed
lower or no activity.
2
2
2.3. The optimization of reaction condition for aerobic
acetalization in scCO2
Using PdCl2 as catalyst, we further optimized the reaction
conditions for acetalization, including pressure of oxygen,
Table 2
Acetalization under different catalystsa
Entry
Catalyst/mmol
Conversion/%b
Yield of 2/%b
1
2
3
4
5
6
a
PdCl2
99.8
89.2
87.1
5.3
95.3
78.4
73.4
d
2.4. Aerobic acetalization in different solvents
Pd(OAc)2
Pd(NO3)2
PdBr2
Why did a ‘ligand-free’ palladium-catalyzed aerobic acetal-
ization of methyl acrylate in scCO2 occur so smoothly with
molecular oxygen as the sole oxidant? We believe that on
one hand, scCO2, which has a property of both liquid and
gas, is so excellent a solvent and dispersant of oxygen gas
that makes it more than sufficient in the reaction system and
on the other hand, scCO2 may serve appropriate as a ‘ligand’
Pd/C
None
d
d
Reaction was run at 50 ꢁC for 18 h with mole ratios of 4.94 and 3% of
methanol and catalyst to the substrate methyl acrylate (5 mmol), respectively,
under the pressure of O2 0.8 MPa, and the pressure of the autoclave system
14 MPa.
b
By GC.
Table 3
Acetalization of methyl acrylate and methanol in scCO2
a
Entry
PCo /O2/MPa
Time/h
Temperature/ꢁC
Conversion/%
Yield/%b
Selectivity for 2c
2
2
3
4
1
12/0.02
12/0.2
12/0.5
12/0.7
12/0.8
12/1.0
5/1.0
15
15
15
15
15
15
15
15
15
15
15
6
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
20
40
60
80
Trace
9.6
d
8
d
1
d
d
2
0
2.1
88.8
85.7
60.6
96.1
99.8
93.7
97.4
99.7
92.7
83.3
71.6
90.6
98.4
99.2
86.8
98.4
89.9
76.9
3
33.7
88.2
93.4
100
27.6
77.9
89.5
99.3
55.3
90.4
99.7
90.3
73.1
23.7
49.3
82.2
98.2
22.3
85.9
87.6
72.1
2.5
1.7
0.6
0.1
3.7
2.1
0.1
0.2
2.3
5.0
4.6
0.8
0.1
3.4
1.2
0.3
0.1
4
6.3
3.0
0.1
0
5
6
7
60.2
94.1
100
8
8/1.0
0.3
0.2
6.9
12.3
0.4
0.5
0.5
0.7
0
9
14/1.0
17/1.0
26/1.0
14/1.0
14/1.0
14/1.0
14/1.0
14/1.0
14/1.0
14/1.0
14/1.0
10
11
12
13
14
15
16
17
18
19
a
98.2
88.6
30.0
56.7
84.6
100
9
12
24
15
15
15
15
45.6
99.5
100
0.2
9.5
21.6
100
Reaction conditions: PdCl2 0.15 mmol, methyl acrylate 5 mmol, and the molar ratio of methanol to methyl acrylate 4.94:1.
By GC.
b
c
Selectivity¼[2/(2þ3þ4)]/100.

H.-F. Jiang et al. / Tetrahedron 64 (2008) 508e514
511
Table 4
Acetalization in different solventsa
2.5. The optimization of reaction condition for aerobic
cyclotrimerization in scCO2
Entry
Solvent
Dosage of solvent
Yield of 2/%b
Enlightened by the result presented in entry 19 of Table 3,
we further explored the cyclotrimerization of methyl acrylate
in a PdCl2/CH3OH/O2/scCO2 system at higher temperatures,
expecting an optimized condition with the benzene derivatives
4 as major product.
1
2
3
4
5
6
7c
a
scCO2
0.16 mL
2 mL
2 mL
2 mL
2 mL
2 mL
2 mL
98.2
43.4
57.8
67.5
59.6
d
Excess methanol
Toluene
CH2Cl2
n-Hexane
DMSO
DMF
As is shown in the results presented in Table 5, higher
temperature favors the cyclotrimerization of methyl acrylate.
Cyclotrimerization of methyl acrylate is sensitive to the con-
centration of molecular oxygen in scCO2, which means it
can neither be too high nor too low. There seemed to be a con-
tradiction between higher reaction conversion and good selec-
tivity to 4. It could be concluded that lower PCO =PO induced
5.6
Reaction conditions: PdCl2 0.15 mmol, methyl acrylate 5 mmol, pressure
of O2 1 MPa, 50 ꢁC, and 24 h.
b
By GC.
Trimethyl benzene-1,3,5-tricarboxylate of 56.3% was detected.
c
2
2
as such, enough to stabilize the reduced palladium species
but impuissant to inhibit either substrate binding or b-hydride
elimination. An explanation can be further supported by
the experiments in other organic solvents instead of scCO2
(Table 4).
higher reaction conversions with a relatively lower selectivity
to 4 (Table 5, entries 1e3), while higher PCO =PO favored the
2
2
formation of 4, but the reaction conversion at the same time is
moderate (Table 5, entries 6 and 7). Too high a pressure of car-
bon dioxide led to lower conversion due to its dilution effect
(Table 5, entry 8). The time required for the completion of
the reaction was 24 h and with an extended time period, no ob-
vious elevation in yield is observed (Table 5, entries 9 and 10).
In order to inhabit the formation of 2, we avoided the addi-
tion of CH3OH and resulted in a very low conversion and trace
of 4. Because of the poor solubility of PdCl2 in scCO2 without
methanol, we turned to other co-solvents, including 1,5-cyclo-
ctodiene, acetone, anhydrous ethanol, distilled water, 1,4-diox-
ane, PEG-400, and PEG-1200, but no good results were gained.
From Table 4, we can see that solvents with lower polarities
seemed to favor this reaction more than polar ones (Table 4, en-
tries 2e5). Solvents with a not so appropriate polar coordinating
property such as DMSO inhibited this reaction completely.
When using DMF as solvent, 56.3% of cyclotrimerization prod-
uct 4 was gained. This is very interesting in comparison with
that in scCO2, so we further explored the cyclotrimerization
of olefins with electron-withdrawing groups in the PdCl2/O2/
DMF catalytic system. We found that in the absence of methanol
in the PdCl2/O2/DMF system, the regioselective cyclotrimeri-
zation of both alkyl and aryl olefins with electron-withdraw-
ing groups can occur smoothly, as previously disclosed
(Scheme 3).27
2.6. Reactions of different terminal olefins under two
typical conditions in scCO2
In the evaluation of other olefin substrates, each one was
run under two conditions, conditions A and B, as is shown
in Table 6. Terminal olefins with electron-withdrawing groups
(EWG), e.g., methyl acrylate, ethyl acrylate, n-butyl acrylate,
and methyl vinyl ketone are particularly effective under both
conditions to give their acetals and 1,3,5-trisubstituted
R
PdCl2/O2
R
DMF
R
R
1
4
Scheme 3.
Table 5
Cyclotrimerization of methyl acrylate in PdCl2/O2/MeOH/scCO2 systema
Entry
PCo /O2/MPa
Time/h
Temperature/ꢁC
Conversion/%
Yield/%b
Selectivity for 4c
2
2
4
1
2
3
4
5
6
7
8
9
10
a
17/1.0
17/1.0
17/1.0
17/0.9
17/0.8
17/0.7
20/0.7
22/0.7
20/0.7
20/0.7
15
15
15
15
15
15
15
15
24
32
100
120
140
120
120
120
120
120
120
120
97.2
96.8
98.2
95.2
96.1
92.5
89.3
74.3
89.2
83.6
58.1
47.6
44.3
22.0
17.7
13.9
8.4
26.8
35.4
33.7
45.7
50.1
55.8
58.8
32.5
64.2
69.3
31.6
42.6
43.2
67.5
73.9
80.0
87.5
74.2
87.0
87.4
11.3
9.6
10.0
Reaction conditions: PdCl2 0.25 mmol, methyl acrylate 5 mmol, and the molar ratio of methanol to methyl acrylate 2.47:1.
By GC.
b
c
Selectivity¼[2/(2þ3þ4)]/100.

512
H.-F. Jiang et al. / Tetrahedron 64 (2008) 508e514
Table 6
Reactions of different olefins in PdCl2/O2/MeOH/scCO2 systema
benzene derivatives (Table 6, entries 1e4). Acetalization of
acrylonitrile also goes smoothly while acrylic acid, acrylam-
ide, and the sterically encumbered methyl methacrylate gave
no products (Table 6, entries 5e8). Although the conversion
of styrene was fair to good, the yield of 2 was low, because
most of styrene was transferred to hypnone and benzaldehyde.
When 4-chlorostyrene was explored, the reaction was even
more complicated than that of styrene and 4-chlorobenzoic
acid (56%) was obtained as the main product. The acetaliza-
tion of cyclohexene gave a mixture of its corresponding
acetal and cyclohexanone (Table 6, entries 9e11). Aryl olefin
phenyl acrylate was also explored and no corresponding
products were gained under both conditions. Transesterifica-
tion between phenyl acrylate and methanol occurred under
both conditions and yielded mainly the corresponding prod-
ucts of methyl acrylate. This is in contrast with cyclotrimeri-
zation in DMF.26
R
MeO
PdII
MeOH/scCO2
+
R
MeO
R
R
R
1
2
4
Entry Alkene
Condition Conversion/%b Yield of 2/4/%b
1
2
3
4
Methyl acrylate
A
B
100
93.6
99.7 (2a)
69.3 (4a)
Ethyl acrylate
A
B
98.0
85.2
96.4 (2b)
57.3 (4b)
n-Butyl acrylate
Methyl vinyl ketone
A
B
87.1
44.6
83.2 (2c)
32.8 (4c)
A
B
99.4
88.5
88.6 (2d)
63.4 (4d)
5
Methyl methacrylate
Acrylonitrile
Acrylic acid
Acrylamide
A
A
A
A
A
A
A
d
d
6
80.0
77.1 (2e)
d
d
7
d
d
2.7. Mechanism of palladium-catalyzed reactions of
terminal olefins with electron-withdrawing groups under
different reaction conditions
8
9
Styrene
4-Chlorostyrene
Cyclohexene
86.4
12.4 (2f)
Trace
32.4 (2g)
10
11
a
91.2
95.1
Reaction was run under two conditions, respectively, condition A: PdCl2
On the basis of the above results, three catalytic cycles are
proposed, which represent reaction pathways of the terminal
olefins with electron-withdrawing groups under different
reaction conditions.22,26,27 From Scheme 4, we can see that
product control can be achieved through modifying reaction
conditions.
0.15 mmol, substrate 5 mmol, methanol 1 mL, pressure of O2 1.0 MPa, pres-
sure of CO2 14 MPa, 50 ꢁC, and 15 h.; condition B: PdCl2 0.25 mmol, sub-
strate 5 mmol, methanol 0.5 mL, pressure of O2 0.7 MPa, pressure of CO2
20 MPa, 120 ꢁC, and 24 h.
b
By GCeMS. (Condition A for yield of 2 and Condition B for yield
of 4.)
Et
N
PdCl
Et
CO2Me
CO2Me
Et
Et
N
PdCl
CO2Me
N
PdCl
Et
Et
X=Cl or OAc
HX
HCl
Et
N
PdCl2
NEt3
NEt3
without O2
Et
CO2Me
CO2Me
MeO2C
OMe
OMe
MeO2C
PdCl2
MeOH
with O2
CO2Me
HCl
OCH3
no MeOH / little MeOH
with O2
MeO2C
CO2Me
MeO2C
ClPd
HCl
PdCl2
PdCl2
MeO2C
OCH3
Cl
ClPd
CO2Me
MeO2C
ClPd
CH3OH + PdCl2
MeO2C
CO2Me
MeO2C
O2
MeO2C
OCH3
PdCl2
β-H elimination
PdCl2
MeOH
Cl
CO2Me
PdCl2 + H2O2
O2 + HCl
Cl
MeO2C
ClPd
OCH3
β-H elimination
MeO2C
HCl
H2O2
ClPd
MeO2C
H2O2
+
O2
Scheme 4.

H.-F. Jiang et al. / Tetrahedron 64 (2008) 508e514
513
When molecular oxygen, was present in the reaction sys-
tem, aerobic oxidation of terminal olefins goes smoothly.
With enough MeOH and sufficient oxygen, acetalization pre-
ponderated over cyclotrimerization, while with no MeOH or
little MeOH (as co-solvent in scCO2) and an appropriate pres-
sure of O2, cyclotrimerization of terminal olefins became the
dominated reaction; when the oxygen is absent and triethyl-
amine was added into the reaction system, palladium-cata-
lyzed CeN bond formation occurs to produce b-amino acid
derivatives as the sole product.
CH3CO), 2.72 (d, 2H, J¼5.2 Hz, CHCH2COCH3), 3.34 (s, 6H,
OCH3), 4.77 (t, 1H, J¼5.6 Hz, CHCH2COCH3).
Compound 2e. IR (neat, cmꢀ1): n¼2936, 2845 (CH3, CH2,
CH), 2255 (C^N), 1455, 1417 (CH3, CH2), 1075, 1122
1
(CeOeC). MS (EI): m/z¼114 (Mþ), 84, 75, 56. H NMR
(400 MHz, TMS, CDCl3): d¼2.65 (d, 2H, J¼5.6 Hz, CH2CH),
3.39 (s, 6H, OCH3), 4.66 (t, 1H, J¼5.6 Hz, CH2CH ).
4-Chlorobenzoic acid. IR (neat, cmꢀ1): n¼3179 (OeH),
1683 (C]O), 1592, 1423, 1399 (C6H4), 759 (CeCl). MS (EI):
1
m/z¼156 (Mþ), 139, 111, 75, 50, 38. H NMR (400 MHz,
TMS, DMSO-d6): d¼7.9295 (d, 2H, J¼8.2 Hz, C2, C6),
7.5615 (d, 2H, J¼8.2 Hz, C3, C5).
3. Experimental section for aerobic reaction of terminal
olefins with electron-withdrawing groups in scCO2
3.2. Typical experimental procedure for the synthesis of
polysubstituted aromatic compounds
3.1. Typical experimental procedure for the synthesis of
acetals
Catalyst PdCl2 (0.15 mmol, 3 mol %), MeOH (0.5 mL,
12.35 mmol), and methyl acrylate (5 mmol) were added into
a 25 mL autoclave in sequence. O2 was pumped into the auto-
clave using a cooling pump to reach the desired pressure. Then
the autoclave was put into an oil bath under magnetic stirring
for the desired reaction time. After the reaction, the autoclave
was allowed to cool to ꢀ30 ꢁC. The surplus O2 was then
vented and the residue was extracted with n-hexane. The ex-
tract was filtrated and condensed under reduced pressure.
The product was analyzed using GC (quantitative) and GCe
Catalyst PdCl2 (0.15 mmol, 3 mol %), MeOH (1 mL,
24.7 mmol) and methyl acrylate (5 mmol) were added into
a 25 mL autoclave in sequence. O2 and CO2 were pumped
into the autoclave using a cooling pump to reach the desired
pressure. Then the autoclave was put into an oil bath under
magnetic stirring for the desired reaction time. After the reac-
tion, the autoclave was allowed to cool to ꢀ30 ꢁC. CO2 and
the surplus O2 were then vented and the residue was extracted
with n-hexane. The extract was filtrated and condensed under
reduced pressure. The product was analyzed using GC (quan-
1
MS, H NMR, and IR analyses (identification of products:
the benzene derivatives were purified by preparative TLC on
silica gel using light petroleum ether/ethyl acetate as eluent
1
titative) and GCeMS, H NMR, and IR analyses (identifica-
tion of products: some acetals were purified by preparative
TLC on silica gel using light petroleum ether/ethyl acetate
1
before H NMR and IR analyses).
1
as eluent before H NMR and IR analyses).
Compound 4a. IR (neat, cmꢀ1): n¼3091, 3007 (C6H3),
Compound 2a. IR (neat, cmꢀ1): n¼2948, 2840 (CH3, CH2,
CH), 1740 (COO), 1378, 1444 (CH3O), 1069, 1122, 1176
(CeOeC). MS (EI): m/z¼147 (Mþ), 133, 117, 101, 85, 75,
2956, 2847 (CH3), 1731 (C]O), 1254 (CeOeC). MS (EI):
1
m/z¼252 (Mþ), 221, 193, 147, 75, 29. H NMR (400 MHz,
TMS, CDCl3): d¼3.953 (s, 9H, CH3), 8.835 (s, 3H, C6H3).
Compound 4b. IR (neat, cmꢀ1): n¼3095 (C6H3), 2993
(CH3), 1722 (C]O), 1240, 1024 (CeOeC). MS (EI):
m/z¼294 (Mþ), 266, 249, 221, 193, 73, 29. 1H NMR
(400 MHz, TMS, CDCl3): d¼1.412 (t, 9H, J¼7.2 Hz, CH3),
4.421 (q, 6H, J¼7.2 Hz, CH2), 8.830 (s, 3H, C6H3).
1
59, 47, 31. H NMR (400 MHz, TMS, CDCl3): d¼2.62 (d,
2H, J¼2.0 Hz, CH2), 3.33 (s, 6H, OCH3), 3.65 (s, 3H,
OCH3), 4.80 (s, 1H, CH).
Compound 2b. IR (neat, cmꢀ1): n¼2985, 2944, 2837 (CH3,
CH2, CH); 1738 (COO), 1378, 1455 cmꢀ1 (CH3, CH2), 1069,
1123, 1176 cmꢀ1 (CeOeC). MS (EI): m/z¼161 (Mþ), 147,
131, 117, 103, 89, 75, 61, 43, 29; 1H NMR (400 MHz,
TMS, CDCl3): d¼1.25(t, 3H, J¼3.2 Hz, OCH2CH3), 2.63 (d,
2H, J¼6.0 Hz, CH2CH), 3.35 (s, 6H, OCH3), 4.15 (q, 2H,
J¼3.6 Hz, OCH2CH3), 4.82 (t, 1H, J¼6.0 Hz, CH2CH ).
Compound 2c. IR (neat, cmꢀ1): n¼2961, 2876, 2838 (CH3,
CH2, CH), 1737 (COO), 1461, 1402 (CH3, CH2), 1070, 1122,
1192 (CeOeC), 740 (CH2CH2CH2). MS (EI): m/z¼189
Compound 4c. IR (neat, cmꢀ1): n¼3093 (C6H3), 2853
(CH3), 1728 (C]O), 1242, 1028 (CeOeC). MS (EI):
m/z¼378 (Mþ), 323, 305, 267, 249, 211, 193, 165, 120, 56, 41,
1
29. H NMR (400 MHz, TMS, CDCl3): d¼0.971 (t, 9H, J¼
7.2 Hz, CH3), 1.423e1.516 (m, 6H, CH2), 1.728e1.799 (m,
6H, CH2), 4.360 (t, 6H, J¼6.8 Hz, CH2), 8.817 (s, 3H, C6H3).
Compound 4d. IR (neat, cmꢀ1): n¼3064 (C6H3), 2922,
2852 (CH3), 1688 (C]O), 1225, 1096 (CeOeC). MS (EI):
m/z¼204 (Mþ), 189, 161, 119, 91, 75, 32, 28. 1H NMR
(400 MHz, TMS, CDCl3): d¼2.694 (s, 9H, CH3), 8.684 (s,
3H, C6H3).
1
(Mþ), 159, 117, 103, 85, 75, 57, 41, 29. H NMR (400 MHz,
TMS, CDCl3): d¼0.92 (t, 3H, J¼2.4 Hz, OCH2CH2CH2CH3),
1.34e1.38 (m, 2H, OCH2CH2CH2CH3), 1.57e1.64 (m, 2H,
OCH2CH2CH2CH3), 2.63 (d, 2H, J¼6.0 Hz, CH2CH), 3.34
(6H, s, OCH3), 4.09 (t, 2H, J¼3.2 Hz, OCH2CH2CH2CH3),
4.82 (t, 1H, J¼6.0 Hz, CH2CH ).
4. Conclusions
Compound 2d. IR (neat, cmꢀ1): n¼2937, 2839 (CH3, CH2,
CH), 1718 (C¼O), 1446 (CH3O), 1362 (CH3CO), 1080, 1122,
1167, 1192 (CeOeC). MS (EI): m/z¼132 (Mþ), 117, 101, 85,
75, 59, 31. 1H NMR (400 MHz, TMS, CDCl3): d¼2.16 (s, 3H,
In summary, on the basis of our group’s work on the aerobic
acetalization of terminal olefins with electron-withdrawing
groups in scCO2 using CuCl2 and PS-BQ as a mediated sec-
oxidants, we for the first time, to our knowledge, disclose

514
H.-F. Jiang et al. / Tetrahedron 64 (2008) 508e514
8. Brink, G. J. T.; Arends, I. W. C. E.; Papadogianakis, G.; Sheldon, R. A.
Chem. Commun. 1998, 2359.
a palladium-catalyzed acetalization of terminal alkenes in
scCO2 using molecular oxygen as the sole oxidant. We also
found that product control of palladium-catalyzed aerobic
oxidation of terminal olefins with electron-withdrawing groups
can be achieved through modifying reaction conditions
and to yield acetals and benzene derivatives differently.
When the oxygen is absent and triethylamine was added
into the reaction system, palladium-catalyzed CeN bond for-
mation occurs to produce b-amino acid derivatives as the sole
product.
9. (a) Schultz, M. J.; Park, C. C.; Sigman, M. S. Chem. Commun. 2002,
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The authors thank National Natural Science Foundation of
China (Nos. 20332030, 20572027, 20625205 and 20772034)
and Young Foundation of SCUT for the financial support of
this work.
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