Protonolysis of the carbon-palladium bond in palladium(II)-catalyzed enyne cyclization in imidazolium-type ionic liquids

Article abstract of DOI:10.1016/j.tet.2008.01.079

The Pd-catalyzed cyclizations of 1,6-enynes are efficient reactions for the synthesis of α-methylene-γ-butyrolactones and lactams. The effects of solvent, proton source, chloride concentration, and temperature on the protonolysis of the carbon-Pd bond wer

Full text of DOI:10.1016/j.tet.2008.01.079

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2930e2937
www.elsevier.com/locate/tet
Protonolysis of the carbonepalladium bond in palladium(II)-
catalyzed enyne cyclization in imidazolium-
type ionic liquids
b
a
a
a
Shao-Rong Yang a, Huan-Feng Jiang a, , Yi-Qun Li , Huo-Ji Chen , Wei Luo , Yan-Bin Xu
*
a College of Chemistry, Analytical and Testing Centre, South China University of Technology, Guangzhou 510640, PR China
b Department of Chemistry, Jinan University, Guangzhou 510630, PR China
Received 11 November 2007; received in revised form 14 January 2008; accepted 18 January 2008
Available online 25 January 2008
Abstract
The Pd-catalyzed cyclizations of 1,6-enynes are efficient reactions for the synthesis of a-methylene-g-butyrolactones and lactams. The
effects of solvent, proton source, chloride concentration, and temperature on the protonolysis of the carbonePd bond were investigated and
the optimal reaction conditions were identified. We showed that imidazolium-type ionic liquids played an important role in the reaction both
as a ligand for the palladium catalyst and as a solvent. The crystal structure of the Pd complex was obtained and the reaction mechanisms
were discussed.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
sp3-CePd bond adjacent to an electron-withdrawing group.11
For example, the protonolysis of carbonepalladium bond in
the cyclization of 1,6-enynes could be successfully carried
out when the olefin bears an electron-withdrawing group
(Scheme 1).9 To our knowledge, few examples of protonolysis
of sp3-CePd bond adjacent to electron-rich groups have been
reported.12 For theoretical study and practical uses, it is impor-
tant to have an effective method to carry out the protonolysis
of sp3-CePd bond. Therefore, we investigated various factors
affected the protonolysis of the carbonepalladium bond in the
palladium(II)-catalyzed cyclization of 20-alkenyl 2-alkynoates
and N-20-alkenyl 2-alkynamides. Herein, we report the find-
ings of our investigation.
Transition metal-catalyzed enyne cyclization1 is a powerful
reaction for the assembly of cyclic structures, which are im-
portant scaffolds in some bioactive compounds.2 Up to date,
a series of palladium-catalyzed enyne cyclization reactions
have been developed.3 In these processes, specific conditions
are generally required to break the carbonepalladium bond
and to regenerate the activated palladium species. Some of
these reactions are b-H elimination,4 b-heteroatom elimina-
tion,5 reductive elimination,6 oxidative cleavage,7 reductive
cleavage,8 and protonolysis.9
As one of the fundamental reactions in organopalladium
chemistry, protonolysis generally involves the reactions of
Pdearyl bond (sp2-CePd bond), Pdealkenyl bond (sp2-Ce
Pd bond), and Pdealkyl bond (sp3-CePd bond). The sources
of proton include an ammonium salt, CF3CO2H, HOAc,
EtOH, and HCl.10 Protonolysis is usually restricted to the
R1
R1
COR2
COR2
X
Pd(II)
HOAc
Y
Z
Z
Y
R1 = alkyl; R2 = H, alkyl;
X = Cl, OAc; Y = H2, O; Z = O, NTs, CH2
* Corresponding author. Tel./fax: þ8620 8711 2906.
E-mail address: jianghf@scut.edu.cn (H.-F. Jiang).
Scheme 1. Schematic presentation of palladium(II)-catalyzed cyclization.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.079

S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
2931
2. Results and discussion
to 3a or 4a depending upon the concentration of HCl (Table 1,
entries 7 and 8). Higher concentration of HCl favored the
hydrochlorination of alkyne with HCl, and lower concentra-
tion of HCl favored the procedures of enyne cyclization and
CeCl bond formation. On the basis of the above results, it
appeared that the efficient protonolysis of sp3-CePd bond
was accomplished only in ILs.
2.1. Palladium-catalyzed reaction of allyl 2-butynoate under
acidic conditions
Recently, we successfully performed the palladium(II)-
catalyzed enyne cyclization of 20-alkenyl 2-alkynoates in
imidazolium-type ionic liquids (ILs) and in the presence of cu-
pric chloride.13 a-Chloroethylidene-b-chloromethyl-g-butyro-
lactone 4a was obtained in good yield. Accidentally we found
that when cupric chloride was absent, the reaction proceeded
through a protonolysis process to afford a-chloroethylidene-
b-methyl-g-butyrolactone 2a as one of the main products.
This finding encouraged us to explore new methods for the
protonolysis of the sp3-CePd bond in the final step of the
cyclization reaction of 20-alkenyl 2-alkynoates.14
Allyl 2-butynoate 1a was used to optimize the reaction con-
ditions. Under the atmosphere of dry hydrogen chloride,15 the
effects of several solvents on the reaction yield and product
distribution were first investigated. The results are summarized
in Table 1. With 6 mol % PdCl2 as the catalyst in two different
anion imidazolium-type ILs,16 1-butyl-3-methylimidazolium
chloride ([bmim]Cl) and 1-butyl-3-methylimidazolium tetra-
fluoroborate ([bmim][BF4]), reaction of allyl 2-butynoate 1a
afforded protonolysis product 2a predominantly, although
the yields and the selectivity were not ideal (Table 1, entries
1 and 2). However, with the conventional solvents such as
CH3CN, CH2Cl2, and 1,4-dioxane, only traces of hydrochlori-
nation product 3a and oxidative cleavage product 4a were de-
tected after 12 h and there was no product 2a detected (Table
1, entries 4e6). The oxidant of the oxidative cleavage reaction
was oxygen in the air. Compound 1a in HOAc was converted
2.2. Effects of the proton source
During the early investigation of palladium-catalyzed
cyclization in [bmim][BF4], we found that the reaction was
sensitive to water. The protonolysis of CePd bond in the
cyclization of allyl 2-butynoate could proceed even in the
presence of moisture absorbed by LiCl (Table 2, entry 1).
However, the reaction was inconsistent in its conversion rate
and selectivity. Later, we found that LiCl promoted the hydro-
lysis of BFꢀ4 anion in the presence of H2O and produced HCl
in the [bmim][BF4]eLiCleH2O system. It was the proton pro-
vided by HCl that led to the protonolysis of CePd bond.17 It
was apparent that the amount of water affected the concentra-
tions of produced HCl and chloride ions in the reaction
system, which resulted in the inconsistent conversion rate
and selectivity. To further investigate the effect of H2O on
protonolysis, dry MgSO4 was added to the reaction mixture
(Table 2, entry 2). As expected, the conversion rate decreased
remarkably compared with that of the reaction without
MgSO4 (Table 2, entry 1). In order to keep the reaction to
proceed under defined acidic condition, dry HCl gas was
introduced to the reaction mixture containing dry MgSO4.
The expected conversion rate and yield were obtained (Table
2, entry 3). In the previous report,9 HOAc was used as the
proton source. However, in this work, the reaction did not
occur when HCl was replaced with HOAc in [bmim]Cl (Table
2, entry 5), indicating that strong acid is required for the
protonolysis and regeneration of active Pd(II) species.
Table 1
Solvent effects of the cyclization of allyl 2-butynoate under acidic conditionsa
Cl
Cl
+
Cl
Cl
PdCl2
+
Table 2
The effects of different proton sourcesa
O
O
3a
O
O
Solvent, LiCl
O
O
2a
O
O
1a
4a
Cl
Cl
PdCl2
Entry
Solvent
Time (h)
GC yield (%)
+
O
O
3a
Ionic liquid
O
O
2a
O
O
2a
3a
4a
1a
1
[bmim][BF4]
[bmim]Cl
HOAc
12
72
24
12
12
12
12
12
73
74
0
4
25
0
2
0
Entry Ionic liquid LiCl
(equiv)
HA
Time Conversion GC yield (%)
(%)
3b,c
4b
5b
6d
7
Trace
Trace
Trace
Trace
87
Trace
Trace
Trace
Trace
0
(h)
2a (Z/E) 3a
CH3CN
CH2Cl2
0
0
1
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim]Cl
6
H2Ob
H2Ob
HCld
H2Ob
12
12
12
96
100
27
62 (93:7)
56 (93:7)
1
4
1,4-Dioxane
HOAc
HOAc
0
2c
3c
4
6
6
6
0
0
100
No reaction
No reaction
73 (94:6) 0.4
8e
a
0
6
65
5
[bmim]Cl
HOAce 96
Reaction conditions: 1a (1 mmol), PdCl2 (0.056 mmol), and LiCl
(6 mmol) were stirred in solvent (2 mL) under the atmosphere of 0.4 mmol/
mL HCl at rt.
a
Reaction conditions: 1a (1 mmol), PdCl2 (0.056 mmol), and LiCl were
stirred in ionic liquid (2 mL) at rt.
b
b
The starting material was recovered.
In the absence of HCl.
The water was formed from the moisture absorbed by LiCl.
Dry MgSO4 was added to the reaction system.
c
c
d
d
The starting material was consumed.
The reaction proceeded under the atmosphere of 0.05 mmol/mL HCl.
The reaction proceeded under the atmosphere of 0.4 mmol/mL HCl.
HOAc of 0.5 mL was added to the reaction system.
e
e

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S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
2.3. Effects of chloride ion concentration and reaction
temperature
2.4. Cyclization with recycled catalyst and solvent
One of the most attractive features of using ionic liquids as
the solvent for transition metal-catalyzed reactions is to recy-
cle the catalysteionic liquid solution.16 To confirm this possi-
bility, we carried out cyclization reaction with the recovered
catalysteionic liquid solution.
In bivalent palladium catalysis, the concentration of chlo-
ride ions plays an important role in the regioselectivity and
stereoselectivity of the reaction.3b When [bmim][BF4] is
used as the solvent, the selectivity of the reaction can be con-
trolled by the amount of LiCl. However, [bmim]Cl could play
the roles of both as the solvent and as the source of chloride
ion. When added different amounts of [bmim]Cl as the chlo-
ride source to the [bmim][BF4] solution, experimental results
showed that the Z/E ratio of product 2a increased with the
increase of the amount of [bmim]Cl (Table 3, entries 1e4).
When [bmim]Cl was employed as the sole solvent (Table 3,
entry 5), which provided a high concentration of chloride
ion, the Z/E ratio of product 2a was higher than 98:2. But
the hydrochlorination product 3a was also increased to 25%
(Table 3, entry 5). Unexpectedly, the Z/E ratio changed from
>98:2 to 13:87 when the temperature was raised from room
temperature to 100 ꢁC (Table 3, entries 5e7). When allyl
2-butynoate 1a and HCl were mixed in [bmim]Cl without
palladium catalyst at 70 ꢁC for 2 days, the hydrochlorination
product 3a was obtained as the sole product (Table 3, entry
8), which confirmed that the competitive hydrochlorination
reaction occurred in the system.
Allyl 2-butynoate 1a was added to the reaction system
composed of [bmim]Cl and PdCl2 under the atmosphere of
dry HCl. After complete reaction of 1a, the ionic liquid reac-
tion solution was extracted with ethyl acetate and then dried in
vacuo for 1 h at 80 ꢁC. To the recovered catalysteionic liquid
solution was added substrate 1a again and the reaction was
allowed to proceed under the same reaction conditions. The
experimental results are listed in Table 3 (entries 10 and 11).
As shown, the cyclization reaction with recycled catalyst
and solvent afforded the product in a little bit lower yield
than that with fresh catalyst and solvent, indicating that the
catalysteionic liquid solution could be reused to obtain satis-
factory yields and stereoselectivity.
2.5. Cyclization of various 20-alkenyl 2-alkynoates and
N-alkenyl 2-alkyamides
Under the optimized reaction conditions, a variety of
substituted 20-alkenyl 2-alkynoates and N-20-alkenyl 2-alkyna-
mides were tested. As shown in Table 4, when substrates 1be
1e were employed as the substrates, protonolysis products
2be2e were afforded with high Z-stereoselectivity in 60e
88% isolated yields. It is interesting that no oxidative cleavage
products 4 or b-H elimination products4 were detected for sub-
strates 1d and 1e (Table 4, entries 3 and 4). The reaction of 1f
yielded both the E and Z forms of cyclization product 2f and
hydrochlorination product 3f, which was likely due to steric
and electronic properties of the phenyl group (Table 4, entry
Finally, the optimal reaction conditions were determined as
following: (A) substrate 1 (1 mmol) and PdCl2 (0.178 mmol)
were stirred in [bmim]Cl (2 mL) at room temperature under
the atmosphere of 0.4 mmol/mL HCl (Table 3, entry 4); (B)
substrate
1 (1 mmol), [bmim]Cl (6 mmol), and PdCl2
(0.056 mmol) were stirred in [bmim][BF4] (2 mL) at room
temperature under the atmosphere of 0.4 mmol/mL HCl (Table
3, entry 4). When the protonolysis was carried out in these two
conditions, the expected product 2a was obtained in satisfac-
tory yields with Z/E ratio ꢂ98:2.
Table 3
Optimization of the reaction conditions of allyl 2-butynoatea
Cl
+
Cl
PdCl2, HCl
Ionic liquid
O
O
3a
O
O
2a
O
O
1a
Entry
Ionic liquid
[bmim]Cl (equiv)
Pd catalyst (equiv)
T
Time (h)
GC yield (%)
2a (Z/E)
3a
1
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim]Cl
0
2
4
6
[bmim]4[Pd3Cl10] (0.056)
PdCl2 (0.056)
PdCl2 (0.056)
PdCl2 (0.056)
PdCl2 (0.056)
PdCl2 (0.056)
PdCl2 (0.056)
0
rt
rt
rt
rt
rt
24
48
48
48
72
9
65 (83:17)
91 (92:8)
94 (95:5)
92 (98:2)
74 (>98:2)
78 (87:13)
76 (13:87)
0
8
9
6
8
2
3
4
5
25
22
4
6
[bmim]Cl
[bmim]Cl
70 ꢁC
100 ꢁC
70 ꢁC
rt
7
24
48
72
72
72
8
[bmim]Cl
[bmim]Cl
100
7
9
PdCl2 (0.178)
Second run
Third run
93 (>98:2)
90 (>98:2)
88 (>98:2)
10b
11c
a
Second run
Third run
rt
7
rt
8
Reaction conditions: 1a (1 mmol) and PdCl2 (0.056 mmol) were stirred in ionic liquid (2 mL) under the atmosphere of 0.4 mmol/mL HCl.
The catalyst and ionic liquid mixture in entry 9 was reused in entry 10 after extracted with ethyl acetate.
The catalyst and ionic liquid mixture in entry 10 was reused in entry 11 after extracted with ethyl acetate.
b
c

S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
2933
Table 4
Cyclization of different substrates in ILs
R1
O
R2
R1
R2
R1
O
R2
Cl
Cl
PdCl2, HCl
Ionic liquid
+
X
3
X
2
O
X
1
Entry
1
Substrates
Conditionsa
Productsb
Isolated yield (%)
72
C5H11
C5H11
1b
A
2b
Cl
O
O
O
O
Ph
Ph
2
3
1c
A
A
Cl
Cl
2c
60
80
O
O
O
O
O
1d
2d
O
O
O
C5H11
C5H11
A
B
85
88
4
1e
1f
Cl
Cl
2e
2f
O
O
O
O
O
Ph
Ph
O
Ph
Z-2f:40
E-2f:5
3f:5
5
6
A
A
3f
Cl
O
O
O
O
Ph
Ph
Ph
Ph
1g
3g
10
Cl
O
O
O
O
Cl
Cl
Z-2h:68
E-2h:17
7
1h
1i
A
2h
2i
O
N
O
N
Ph
Ph
Ph
C5H11
C5H11
A
B
87
83
8
O
N
O
N
Ph
a
Condition A: 1 (1 mmol) and PdCl2 (0.178 mmol) were stirred in [bmim]Cl (2 mL) under the atmosphere of 0.4 mmol/mL HCl. Condition B: 1 (1 mmol),
[bmim]Cl (6 mmol), and PdCl2 (0.056 mmol) were stirred in [bmim][BF4] (2 mL) under the atmosphere of 0.4 mmol/mL HCl.
b
Only Z-isomers of products 2 were purified and identified by 1H NMR, 13C NMR, IR, MS, and HRMS.
5). Another example of the effects of the phenyl group was the
reaction of 1g (Table 4, entry 6), which yielded only the
hydrochlorination product of 3f.
N-20-Alkenyl 2-alkynamides were also smoothly cyclized
under the given reaction conditions, and the protonolysis prod-
ucts were obtained in excellent isolated yields (Table 4, entries
7 and 8).
and identified the optimal reaction conditions, we then carried
out experiments to solve the structure of palladium complex
and studied the role of imidazolium-type ionic liquids.
Dupont’s group reported that a Pd complex 5 was formed
through the reaction of PdCl2 with [bmim]Cl (Scheme 2).18
We postulated that 5 or a Pd complex similar to 5 might be
n-Bu
n-Bu
Me
Cl
Cl Pd Cl
Cl
N
N
PdCl2
Cl-
2.6. The structure of the Pd catalyst and proposed reaction
mechanisms
H
2
H
N
N
N
Me
Me
n-Bu
5
After investigated the effects of proton sources, chloride ion
concentration, and temperature on the protonolysis reaction
Scheme 2. The proposed Pd complex.

2934
S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
formed in situ in our reaction systems, even in the
[bmim][BF4]eLiClePdCl2 system. To prove our hypothesis,
the complex was prepared by mixing PdCl2 (1 mmol) and
LiCl (2 mmol) in [bmim][BF4] (2 mmol) for 12 h at room tem-
perature. A red-black crystal was obtained. The structure of
observation suggested that imidazolium-type ionic liquids
might serve as the stabilizer for the Pd complex in the reaction
and enhance the protonolysis process. When the Pd complex 6
was dissolved in other solvents, PdCl2 was released immedi-
ately and participated in the reaction as PdCl2.
The reaction mechanisms of the palladium-catalyzed cycli-
zation of enynes in ionic liquids are proposed (Scheme 3). Pd
complex 6 is formed in situ in ILs, and chloropalladation of
substrate 12b could generate the Pdealkenyl intermediate 7.
Then, intermediate 7 could undergo intramolecular insertion
to generate a Pdealkyl intermediate 8, which could complex
with IL ligand efficiently to inhibit both b-hydride elimination
and oxidative cleavage of CePdeCl bond. Through the proto-
nolysis of the CePd bond of 8 promoted by HCl, product 2 is
therefore produced and active Pd(II) species could be
regenerated.
1
the complex (6) was fully characterized by IR, H, and 13C
NMR and its crystal structure was also determined by X-ray
diffraction analysis (Figs. 1 and 2). The result showed that
the structure of 6 was [bmim]4[Pd3Cl10] and [bmim]Cl served
as one of the ligands of palladium atom.
We examined the catalytic activity of Pd complex 6 in the
reaction of 1a in [bmim][BF4] and some of the conventional
solvents (Eq. 1). In [bmim][BF4], the reaction gave the proto-
nolysis product 2a in 65% yield. However, in the conventional
solvents including HOAc, CH3CN, 1,4-dioxiane, and CH2Cl2,
the reaction yielded the same product just as with PdCl2. This
Figure 1. ORTEP plot with atom labeling scheme of the structure of Pd complex 6.
(a)
0
(c)
(b)
Figure 2. Crystal packing of Pd complex 6.

S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
2935
R1
R2
in conventional solvents
Cl
Cl
PdCl2
solvolysis
ILs
O
4
O
R1
R2
oxidative cleavage
in conventional solvents
or CuCl2 in ILs
PdLnCl2
L= [bmim]Cl
6
O
O
1
chloropalladation
protonolysis
in ionic liquids
HCl
R2
R1
R2
R1
R2
R1
R2
[Pd]
Cl
R1
Cl
Cl
[Pd]
Cl
O
O
7
O
O
8
O
O
O
O
3
2
alkene insertion
[Pd] = PdLn
protonolysis
Scheme 3. Proposed mechanistic cycle.
After chloropalladation of the triple bond, [bmim]Cl, as the
ligand for the palladium, could enable 7 to undergo olefin in-
sertion by activating the alkene. However, in HOAc, without
the aid of [bmim]Cl ligand, the Pdealkenyl bond could be eas-
ily protonolyzed to give product 3. Alternatively, product 3
could also be formed by the direct reaction of 1 with HCl in
[bmim]Cl in the absence of palladium catalyst. When catalyst
6 was used in a conventional solvent, it might be solvolyzed to
PdCl2 and the reaction might proceed through the normal pro-
cess to form product 4. Product 4 could also be formed
through the oxidative cleavage of PdeC bond of Pdealkyl
intermediate 8 in HOAc under low concentration of HCl or
in the presence of CuCl2.
20-Alkenyl 2-alkynoates,7a N-alkenyl 2-alkyamides,7c and
ionic liquids19 were synthesized according to the reported pro-
cedures. All other reagents were used directly as obtained
commercially. TLC was performed using commercially pre-
pared 100e400 mesh silica gel plates (HF254) and visualized
at 254 nm.
2.7.2. Synthesis of [bmim]4[Pd3Cl10] 6
A mixture of PdCl2 (1 mmol), LiCl (2 mmol), and
[bmim][BF4] (2 mmol) was stirred at room temperature for
12 h. A white precipitant was filtered after 5 mL of CH2Cl2
was added to the mixture. The dichloromethane was removed,
and a red-black solid was obtained in 81% yield. Crystals suit-
able for X-ray diffraction study were obtained by slow volatil-
ization of the dichloromethane solution of the compound at
Cl
Cl
PdCl2, HCl
Ionic liquid
Cl
1
PdCl2, HCl
HOAc
room temperature. H NMR (400 MHz, CDCl3): d 9.33 (s,
O
O
4a
O
O
2a
O
O
1a
1H), 7.77e7.84 (m, 2H), 4.47 (t, 2H, J¼7.4 Hz), 4.14 (s,
3H), 1.97e2.01 (m, 2H), 1.44 (q, 2H, J¼7.4 Hz), 0.96 (t,
3H, J¼7.4 Hz); 13C NMR (100 MHz, CDCl3): d 136.9,
124.2, 122.8, 49.7, 36.3, 32.1, 19.3, 13.0; IR (cmꢀ1) 3140,
3103, 3076, 2951, 2863, 1619, 1565, 1457, 1162, 850, 757.
2.7. Experimental section for the synthesis of
[bmim]4[Pd3Cl10] and for the palladium-catalyzed
cyclization and protonolysis of 20-alkenyl 2-alkynoates in
ionic liquids
2.7.3. General procedure for the palladium-catalyzed
cyclization and protonolysis of 20-alkenyl 2-alkynoates in
ionic liquids
2.7.1. General methods
1H NMR (400 MHz) and 13C NMR (100.6 MHz) spectra
were recorded on BRUKER DRX-400 spectrometer using
CDCl3 as the solvent and TMS as the internal standard. GC
analyses were performed on a GC-930 chromatography instru-
ment (Shanghai Haixian Chromatography Instrument Ltd.
Co.) with a flame ionization detector equipped with an
OV-101 capillary column (internal diameter¼0.25 mm,
length¼30 m). Mass spectra were recorded on a Shimadzu
GCMS-QP5050A at an ionization voltage of 70 eV equipped
with a DB-WAX capillary column (internal diameter¼
0.25 mm, length¼30 m). IR spectra were recorded on Analect
RFX-65A spectrometer.
To a mixture of PdCl2 (10 mg, 0.056 mmol), [bmim]Cl
(1044 mg, 6 mmol), and ionic liquids (2 mL) was added 1a
(1 mmol). The reaction was stirred at room temperature under
the atmosphere of 0.4 mmol/mL HCl and monitored by TLC
with 10:3 petroleum ether and ethyl acetate as eluents. After
the reaction was complete, the mixture was extracted with
ethyl acetate (5ꢃ8 mL). The combined organic layers were
washed with water (3ꢃ8 mL), dried over MgSO4, and concen-
trated in vacuo. Purification of the residue on a preparative
TLC afforded the pure product. The ionic liquid solution
was dried in vacuo for 1 h at 80 ꢁC and was ready for reuse
in a repeated reaction.

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S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
2.7.3.1. (Z)-a-(10-Chloroethylidene)-b-methyl-g-butyrolactone
(Z-2a). 1H NMR (400 MHz, CDCl3): d 4.27 (dd, 1H, J¼9.0,
7.2 Hz), 3.91 (dd, 1H, J¼9.0, 1.7 Hz), 3.22e3.25 (m, 1H),
2.30 (d, 3H, J¼0.92 Hz), 1.23 (d, 3H, J¼7.2 Hz); 13C NMR
(100 MHz, CDCl3): d 167.0, 140.8, 126.3, 71.0, 35.5, 25.7,
19.5; IR (cmꢀ1) 1759, 1651, 1442, 1376, 1224, 1139, 790,
674; MS (m/z): 162 (Mþ (37Cl), 16), 160 (Mþ (35Cl), 50),
145, 117, 102, 81, 67 (100); HRMS calcd for C7H9O2Cl:
160.0286. Found: 160.0286.
2.7.3.7. (Z)-a-(10-Chlorobenzylidene)-b-ethyl-g-butyrolactone
(Z-2f). 1H NMR (400 MHz, CDCl3): d 7.42 (s, 5H), 4.29
(dd, 1H, J¼9.0, 7.1 Hz), 4.04 (dd, 1H, J¼9.0, 2.5 Hz),
3.20e3.21 (m, 1H), 1.31e1.35 (m, 2H), 0.72 (t, 3H,
J¼7.6 Hz); 13C NMR (100 MHz, CDCl3): d 167.6, 141.1,
138.2, 129.8, 128.7, 127.6, 126.7, 68.6, 41.9, 26.2, 10.2; IR
(cmꢀ1) 1746, 1633, 1450, 1377, 1208, 1130, 758, 696; MS
(m/z): 238 (Mþ (37Cl), 18), 236 (Mþ (35Cl), 55), 207, 179,
115 (100); HRMS calcd for C13H13O2Cl: 236.0599. Found:
236.0595.
2.7.3.2. (E)-a-(10-Chloroethylidene)-b-methyl-g-butyrolactone
(E-2a). 1H NMR (400 MHz, CDCl3): d 4.33 (dd, 1H, J¼9.0,
7.2 Hz), 3.95 (dd, 1H, J¼9.0, 1.7 Hz), 3.32 (m, 1H), 2.61 (d,
3H, J¼0.92 Hz), 1.40 (d, 3H, J¼7.2 Hz); MS (m/z): 162 (Mþ
(37Cl), 16), 160 (Mþ (35Cl), 50), 145, 117, 102, 81, 67 (100).
2.7.3.8. (E)-a-(10-Chlorobenzylidene)-b-ethyl-g-butyrolactone
(E-2f). 1H NMR (400 MHz, CDCl3): d 7.35e7.45 (m, 5H),
4.37 (dd, 1H, J¼9.0, 7.1 Hz), 4.17 (dd, 1H, J¼9.0, 2.5 Hz),
3.34e3.36 (m, 1H), 1.79e1.88 (m, 2H), 1.01 (t, 3H,
J¼7.6 Hz); MS (m/z): 238 (Mþ (37Cl), 18), 236 (Mþ (35Cl),
55), 207, 179, 115 (100).
2.7.3.3. (Z)-a-(10-Chlorohexylidene)-b-methyl-g-butyrolactone
(Z-2b). 1H NMR (400 MHz, CDCl3): d 4.27 (dd, 1H, J¼9.0,
6.9 Hz), 3.92 (dd, 1H, J¼9.0, 1.5 Hz), 3.22e3.26 (m, 1H),
2.45 (t, 2H, J¼6.9 Hz), 1.62e1.71 (m, 2H), 1.32e136 (m,
4H), 1.24 (d, 3H, J¼7.1 Hz), 0.88e0.91 (m, 3H); 13C NMR
(100 MHz, CDCl3): d 166.5, 145.1, 125.2, 70.3, 37.5, 34.7,
30.4, 26.4, 21.7, 19.5, 13.1; IR (cmꢀ1) 2960, 2865, 1760,
1644, 1456, 1374, 1222, 1135, 784, 675; MS (m/z): 218
(Mþ (37Cl), 3), 216 (Mþ (35Cl), 10), 181 (100); HRMS calcd
for C11H17O2Cl: 216.0912. Found: 216.0902.
2.7.3.9.
N-Benzyl-(Z)-a-(10-chloroethylidene)-b-methyl-g-
butyrolactam (Z-2h). 1H NMR (400 MHz, CDCl3): d 7.26e
7.32 (m, 5H), 4.64 (d, 1H, J¼14.9 Hz), 4.40 (d, 1H,
J¼14.9 Hz), 3.35e3.40 (m, 1H), 3.01e3.04 (m, 1H), 2.75
(d, 1H, J¼9.8 Hz), 2.23 (s, 3H), 1.12 (d, 3H, J¼7.1 Hz); 13C
NMR (100 MHz, CDCl3): d 165.1, 136.3, 133.5, 131.4,
128.6, 128.2, 127.5, 50.5, 46.9, 31.8, 24.9, 20.5; IR (cmꢀ1
)
1683, 1628, 1427, 1362, 1281, 1171, 739, 701; MS (m/z):
251 (Mþ (37Cl), 23), 249 (Mþ (35Cl), 74), 234, 214, 91
(100); HRMS calcd for C14H16ONCl: 249.0915. Found:
249.0917.
2.7.3.4. (Z)-a-(10-Chlorobenzylidene)-b-methyl-g-butyrolac-
tone (Z-2c). 1H NMR (400 MHz, CDCl3): d 7.42 (s, 5H),
4.33 (dd, 1H, J¼9.0, 7.1 Hz), 3.88 (dd, 1H, J¼9.0, 2.9 Hz),
3.28e3.33 (m, 1H), 0.98 (d, 3H, J¼7.1 Hz); 13C NMR
(100 MHz, CDCl3): d 167.5, 141.1, 137.9, 129.9, 128.7,
127.9, 127.6, 71.2, 35.9, 19.1; IR (cmꢀ1) 1746, 1640, 1446,
1371, 1210, 1091, 761, 693; MS (m/z): 224 (Mþ (37Cl), 6),
222 (Mþ (35Cl), 20), 207, 187, 177, 163, 141 (100); HRMS
calcd for C12H11O2Cl: 222.0442. Found: 222.0458.
2.7.3.10.
N-Benzyl-(E)-a-(10-chloroethylidene)-b-methyl-g-
butyrolactam (E-2h). 1H NMR (400 MHz, CDCl3): d 7.23e
7.35 (m, 5H), 4.59 (d, 1H, J¼14.7 Hz), 4.40 (d, 1H,
J¼14.7 Hz), 3.38e3.42 (m, 1H), 3.09e3.13 (m, 1H), 2.76
(d, 1H, J¼9.8 Hz), 2.68 (s, 3H), 1.17 (d, 3H, J¼7.3 Hz); 13C
NMR (100 MHz, CDCl3): d 165.8, 140.3, 136.2, 132.9,
128.7, 128.1, 127.6, 50.9, 46.9, 32.3, 29.6, 22.1; MS (m/z):
251 (Mþ (37Cl), 23), 249 (Mþ (35Cl), 74), 234, 214, 91 (100).
2.7.3.5. (Z)-a-(10-Chloroethylidene)-b-ethyl-g-butyrolactone
(Z-2d). 1H NMR (400 MHz, CDCl3): d 4.26 (dd, 1H, J¼9.0,
7.2 Hz), 4.11 (dd, 1H, J¼9.0, 1.5 Hz), 3.11e3.13 (m, 1H),
2.33 (d, 3H, J¼0.73 Hz), 1.59e1.67 (m, 2H), 0.98 (t, 3H,
J¼7.2 Hz); 13C NMR (100 MHz, CDCl3): d 167.4, 140.8,
125.4, 68.8, 42.2, 27.0, 26.1, 10.8; IR (cmꢀ1) 1761, 1651,
1460, 1375, 1220, 1133, 775, 688; MS (m/z): 176 (Mþ
(37Cl), 12), 174 (Mþ (35Cl), 36), 145, 117 (100); HRMS calcd
for C8H11O2Cl: 174.0442. Found: 174.0445.
2.7.3.11.
N-Benzyl-(Z)-a-(10-chlorohexylidene)-b-methyl-g-
butyrolactam (Z-2i). 1H NMR (400 MHz, CDCl3): d 7.23e
7.32 (m, 5H), 4.64 (d, 1H, J¼14.7 Hz), 4.32 (d, 1H, J¼
14.7 Hz), 3.35 (dd, 1H, J¼10.0, 7.3 Hz), 2.99e3.03 (m, 1H),
2.71 (d, 1H, J¼9.6 Hz), 1.58e1.68 (m, 4H), 1.31e1.32 (m,
4H), 1.10 (d, 3H, J¼7.1 Hz), 0.87e0.90 (m, 3H); 13C NMR
(100 MHz, CDCl3): d 165.4, 138.8, 136.5, 131.1, 128.7,
128.3, 127.6, 50.8, 47.0, 37.5, 32.0, 31.2, 27.2, 22.4, 21.2,
13.9; IR (cmꢀ1) 2928, 2867, 1693, 1646, 1423, 1358, 1281,
1168, 748, 701; MS (m/z): 307 (Mþ (37Cl), 13), 305 (Mþ
(35Cl), 41), 290, 270, 262, 91 (100); HRMS calcd for
C18H24ONCl: 305.1541. Found: 305.1539.
2.7.3.6. (Z)-a-(10-Chlorohexylidene)-b-ethyl-g-butyrolactone
(Z-2e). 1H NMR (400 MHz, CDCl3): d 4.19 (dd, 1H, J¼9.0,
7.1 Hz), 4.06 (dd, 1H, J¼9.0, 1.5 Hz), 3.06e3.07 (m, 1H),
2.41e2.45 (m, 2H), 1.55e1.59 (m, 4H), 1.28e1.33 (m, 4H),
0.93 (t, 3H, J¼7.6 Hz), 0.88 (t, 3H, J¼6.8 Hz); 13C NMR
(100 MHz, CDCl3): d 167.4, 145.8, 124.9, 68.5, 41.9, 38.3,
31.1, 27.3, 27.0, 22.3, 13.8, 10.5; IR (cmꢀ1) 2961, 1760,
1642, 1460, 1374, 1220, 1134, 792, 687; MS (m/z): 232
(Mþ (37Cl), 6), 230 (Mþ (35Cl), 20), 195 (100); HRMS calcd
for C12H19O2Cl: 230.1068. Found: 230.1060.
2.7.3.12.
N-Benzyl-(E)-a-(10-chlorohexylidene)-b-methyl-g-
1
butyrolactam (E-2i). H NMR (400 MHz, CDCl3): d 7.20e7.31
(m, 5H), 4.54 (d, 1H, J¼14.7 Hz), 4.41 (d, 1H, J¼14.7 Hz),
3.37 (dd, 1H, J¼10.0, 7.6 Hz), 3.08e3.15 (m, 1H), 2.73 (d,
1H, J¼9.5 Hz), 1.56e1.62 (m, 4H), 1.31e1.34 (m, 4H),

S.-R. Yang et al. / Tetrahedron 64 (2008) 2930e2937
2937
1.10 (d, 3H, J¼7.1 Hz), 0.87e0.90 (m, 3H); MS (m/z): 307
Young Foundation of SCUT for the financial support of this
work.
(Mþ (37Cl), 13), 305 (Mþ (35Cl), 41), 290, 270, 262, 91 (100).
2.7.3.13. 20-Propenyl (Z)-2-chloro-2-butenoate (Z-3a). 1H
NMR (400 MHz, CDCl3): d 6.04 (d, 1H, J¼1.2 Hz), 5.89e
5.96 (m, 1H), 5.32 (dm, 1H, J¼17.1 Hz), 5.22 (dm, 1H,
J¼10.8 Hz), 4.63 (dm, 2H, J¼5.6 Hz), 2.25 (d, 3H,
J¼1.2 Hz); 13C NMR (100 MHz, CDCl3): d 163.4, 146.5,
132.0, 118.2, 116.5, 64.9, 28.1; MS (m/z): 162 (Mþ (37Cl),
0), 160 (Mþ (35Cl), 0), 125, 103 (100).
References and notes
1. For reviews, see: (a) Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev.
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Zhang, Z.; Zhu, G.; Tong, X.; Wang, F.; Xie, X.; Wang, J.; Jiang, L.
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Appl. Chem. 1997, 69, 553.
2.7.3.14. (E)-20-Butenyl (Z)-2-chloro-2-phenyl-2-propenoate
(E,Z-3f). 1H NMR (400 MHz, CDCl3): d 7.36e7.67 (m,
5H), 6.54 (d, 1H, J¼1.2 Hz), 5.82e5.87 (m, 1H), 5.62e5.66
(m, 1H), 4.62 (dm, 2H, J¼7.2 Hz), 1.73 (d, 3H, J¼1.2 Hz);
13C NMR (100 MHz, CDCl3): d 164.0, 146.5, 137.3, 131.9,
130.7, 128.6, 127.2, 124.9, 116.2, 65.4, 17.8; MS (m/z): 238
(Mþ (37Cl), 1), 236 (Mþ (35Cl), 4), 201, 181, 165 (100).
3. (a) Trost, B. M. Acc. Chem. Res. 1990, 23, 34; (b) Lu, X.; Ma, S. New Age
of Divalent Palladium Catalysts. In Transition Metal Catalyzed Reaction;
Murahashi, S.-I., Davies, S. G., Eds.; Blackwell Science: Oxford, UK,
1999; Chapter 6, p 133.
4. (a) Lu, X. Top. Catal. 2005, 35, 73; (b) Han, X.; Liu, G.; Lu, X. Chin. J.
Org. Chem. 2005, 25, 1182; (c) Wilkinsion, G. Science 1974, 185, 109.
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2005, 70, 1712; (b) Zhang, Q.; Xu, W.; Lu, X. J. Org. Chem. 2005, 70,
1505.
2.7.3.15. (E)-30-Phenyl-20-propenyl (Z)-2-chloro-2-butenoate
(E,Z-3g). 1H NMR (400 MHz, CDCl3): d 7.25e7.38 (m,
5H), 6.56 (d, 1H, J¼16.0 Hz), 6.27e6.30 (dm, 1H,
J¼16.0 Hz), 6.05 (d, 1H, J¼1.2 Hz), 4.79 (m, 2H), 2.25 (d,
3H, J¼1.2 Hz); 13C NMR (100 MHz, CDCl3): d 163.7,
146.8, 136.4, 134.5, 128.7, 128.2, 126.8, 123.2, 116.7, 65.0,
28.4; MS (m/z): 238 (Mþ (37Cl), 1), 236 (Mþ (35Cl), 3),
133, 115, 103 (100).
6. (a) Tong, X.; Beller, M.; Tse, M. K. J. Am. Chem. Soc. 2007, 129, 4906;
(b) Hartwig, J. F. Inorg. Chem. 2007, 46, 1936.
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¨
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2.7.3.16. (Z)-a-(10-Chloroethylidene)-b-chloromethyl-g-butyro-
lactone (Z-4a).7a 1H NMR (400 MHz, CDCl3): d 4.24e4.34
(m, 2H), 3.49e3.57 (m, 3H), 3.23 (m, 1H), 2.35 (s, 3H); MS
(m/z): 198 (Mþ (237Cl), 1), 196 (Mþ (37Cl, 35Cl), 6), 194
(Mþ (235Cl), 11), 159, 145 (100).
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3. Conclusions
In summary, we have developed an efficient method for the
protonolysis of carbonepalladium bond in the palladium-cat-
alyzed cyclization reaction of 1,6-enynes in imidazolium-type
ionic liquid, which plays an important role in the reaction both
as a ligand for the palladium catalyst and as a solvent. The
process can be easily carried out with high conversion rate,
yield, and stereoselectivity. Moreover, the catalysteionic
liquid can be recycled several times without obvious loss of
catalytic activity. This process provides a new methodology
for constructing five-membered rings from 1,6-enynes. The
compounds obtained from these reactions may have potential
uses in pharmaceutical and natural product chemistry.
11. (a) Lu, X.; Lin, S. J. Org. Chem. 2005, 70, 9651; (b) Shen, Z.; Lu, X.
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Acknowledgements
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The authors thank National Natural Science Foundation of
China (Nos. 20332030, 20572027, 20625205, and 20772034),
Guangdong Natural Science Foundation (No. 07118070), and
19. Hemeon, I.; Singer, R. D. J. Mol. Catal. A: Chem. 2004, 214, 33.