Intramolecular Pauson-Khand reaction catalyzed by oxime-derived palladacycles

Article abstract of DOI:10.1016/j.tetlet.2011.11.106

Oxime-derived palladacycles were successfully applied as a novel class of catalysts in the intramolecular Pauson-Khand reactions. Allylpropargyl ethers and allylpropargyl amines can be efficiently converted to the cyclopentenone products with good to exce

Full text of DOI:10.1016/j.tetlet.2011.11.106

Tetrahedron Letters 53 (2012) 589–592
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Intramolecular Pauson–Khand reaction catalyzed by oxime-derived
palladacycles
Xue-Rui Wang a, Fu-Hua Lu a, Yang Song a, Zhong-Lin Lu a,b,
⇑
a The College of Chemistry, Beijing Normal University, Xinjiekouwai Street 19, Beijing 100875, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Oxime-derived palladacycles were successfully applied as a novel class of catalysts in the intramolecular
Pauson–Khand reactions. Allylpropargyl ethers and allylpropargyl amines can be efficiently converted to
the cyclopentenone products with good to excellent yields.
Received 12 September 2011
Revised 29 October 2011
Accepted 22 November 2011
Available online 26 November 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Pauson-Khand reactions
Oxime-palladacycles
Enynes
Catalysis
The construction of complex polycyclic systems using transition
metal-catalyzed annulation reactions provides an effective method
for the synthesis of many complex molecules. A very attractive
example is the Pauson–Khand reaction (PKR),1,2 a formal [2+2+1]
cycloaddition of an alkene, an alkyne, and carbon monoxide leading
to cyclopentenones which are useful synthetic intermediates in nat-
ural product synthesis.3 Catalytic and catalytic asymmetric PKR
using Co,4 Ti,5 Ni,6 Ru,7 Rh,8 Ir9, and Pd10 complexes have been re-
ported in the past two decades. As a class of intensively investigated
organometallic compounds of great importance, palladacycles have
been successfully exploited in catalytic reactions ranging from clas-
sical hydrogenation to asymmetric aldol-type condensations.11 Due
to their important contributions in the catalytic cross-coupling reac-
tions with palladacycle compounds, Heck, Suzuki, and Negishi have
been awarded the 2010 Nobel Prize in chemistry. Furthermore, the
structures of palladacycles can be easily modified for their high cat-
alyticactivity and selectivity. However, to the best of our knowledge,
palladacycles have not been used in catalytic PKR. Thus, exploring
the application of palladacycles to PKR will be of great value.
At the same time, we have realized that palladium(II)–thiourea
complexes were successfully applied in PKR by the Yang group.10
Also some palladacycles were used for the carbonylation reac-
tions.12 Based on the above considerations and our experience in
palladacycle chemistry,13 we investigated the possibility of using
palladacycles as a new type of catalysts in the PKR. We report here-
in the preliminary results from our work.
Oxime-derived palladacycles are described as being very stable
and showing high efficiency in catalytic processes.14 So we first
checked the possibility of using oxime palladacycles 2 (shown in
Scheme 1) in PKR. The syntheses of these palladacycles began from
oxime-derived chloro-bridged dimer 1, which was prepared fol-
lowing the literature method reported by Baleizao and Corma.15
Addition of pyridine or its derivatives to dimer 1 in benzene at
room temperature afforded palladacycles 2a–d. Counter ions
exchange by treating 2a with silver nitrate or silver triflate resulted
in palladacycles 2e and 2f, respectively. The characterization of
these palladacycles has been deposited in Supplementary data.
pyridines
R
N
Pd
Cl
N
Pd
N
Cl
benzene
OH
OH
2
1
R = H, 2a; CN, 2b;
CF3, 2c; N(CH3)2, 2d
AgX
CH2Cl2
N
Pd
N
OH
X
X = CF3SO3 , 2e; NO3-, 2f
-
⇑
Corresponding author.
E-mail address: luzl@bnu.edu.cn (Z.-L. Lu).
Scheme 1. Synthesis of palladacycles 2a–f.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.106

590
X.-R. Wang et al. / Tetrahedron Letters 53 (2012) 589–592
Enyne 3a was selected as a substrate for the optimization of
Ph
Ph
other reaction conditions (Scheme 2). The reactions were carried
out in parallel in ampules sealed under carbon monoxide. The ef-
fects of solvents, temperature, pressure of CO, and reaction time
were screened, results from which are summarized in Table 1.
The obtained results demonstrate that reaction temperature is
an important factor, as the yields of the desired product increase
as the reaction temperature was raised (entries 1–4). Among the
solvents used, DME seems to lead to the best results (entries 7
and 8). THF is also a good solvent but its lower boiling point trans-
lates into a longer reaction time for achieving higher yields. The
higher boiling point of toluene is beneficial for reducing reaction
time. However the limited solubility of the catalysts in this solvent
compromises the outcome of the reaction. The results also demon-
strate that higher pressure of CO resulted in higher yields. Thus,
extending reaction time improves the yields of product, although
the efficiency of a reaction is also dependent on other factors such
as solvent, temperature, and pressure of CO.
2a (10% mol)
solvent, CO
O
O
O
3b
Scheme 2. The intramolecular Pauson–Khand reaction with catalyst 2a.
3a
Table 1
Optimization of reaction conditions in the palladacycle 2a catalyzed Pauson–Khand
reaction of 3aa
Entry Solvent
Temp (°C) (oil bath) pCOb (atm) Time (h) Yieldc (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
THF
THF
THF
THF
60
100
120
110
110
130
130
130
130
130
1
1
1
2
2
2
2
2
2
2
2
2
2
48
24
24
24
12
4
10
14
10
10
2.5
4
32
50
56
55
75
64
94
85
69d
59e
54
66
69
THF
DME
DME
DME
DME
DME
As a short summary, an optimal conversion to the desired cycli-
zation product 3b was achieved with a yield of 94% in the presence
of 10 mol % palladacycle 2a in DME at 130 °C (oil bath) and 2 atm
of carbon monoxide for 10 h.
Toluene 130
Toluene 130
Toluene 130
A series of analogous palladacycles 2b–h and a pincer pallada-
cycle 2i (Scheme 3), along with the effects of the additives were
then tested in the PKR of 3a. The results are summarized in Table
2. To make a clear comparison of catalytic activities in the presence
of different palladacycles and additives, THF, in which substrate 3a
was converted into 3b in moderate yields was used as solvent for
the PK reactions. The results suggested that the structures of the
palladacycles played very important roles in catalytic perfor-
mances. Regarding the effect of coligand, palladacycles containing
weakly coordinating co-ligands including 4-cyanopyridine (2b)
and 4-trifluoromethylpyridine (2c) gave good to excellent conver-
sion with the yields of 91% and 77%, respectively, (entries 2 and 3
in Table 2). Meanwhile palladacycle containing strongly coordinat-
ing 4-N,N-dimethylaminopyridine (2d) showed a very poor cata-
lytic efficiency with a yield of only 30% (entry 4 in Table 2). The
observed effect of co-ligand on the catalytic activity is consistent
with their catalytic performance in the transesterification of neu-
tral thiophosphates.13a At the same time, the readily available
oxime-derived palladacycles 2g and 2h also showed good catalytic
activities (entrries 5 and 6 in Table 2). However, the pincer pallada-
cycle 2i showed no catalytic activity for the same reaction (entry 7
in Table 2).
10
a
b
c
Reagents and conditions: enyne 3a (0.5 mmol) in 10 mL of solvent.
CO pressure in the reaction vessel at room temperature.
Yield of isolated product.
d
e
In the presence of 7 mol % 2a.
In the presence of 5 mol % 2a.
Cl
Cl
HO
O
O
N
Pd
N
N Pd N
Cl
N Pd N
Cl
2g
OH
OH
Br
2i
2h
Scheme 3. Palladacycles 2g–i.
Table 2
Changing counter ions from chloride to weakly coordinating tri-
flate (2e) or nitrate (2f) resulted in poor catalytic efficacy, and the
Palladacycles 2a–i catalyzed Pauson–Khand reactions of 3aa
Entry
Palladacycles
Additives
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
2a
2b
2c
2d
2g
2h
2i
2e
2e
2f
2f
2a
2a
2a
2a
2a
1
—
—
—
—
—
—
—
—
75
91
77
30
74
72
N.R.
11
57
Traces
32
48
42
37
19
Trace
41
Table 3
Palladacycles catalyzed intramolecular PKRa,b
No.
Sub.
Prd.
Yieldc (%)
2a
1
2
3
4
5
6
7
8
9
3a
4a
5a
6a
7a
8a
9a
10a
11a
12a
3b
4b
5b
6b
7b
8b
9b
10b
11b
12b
94 (75)
97
86
51
85
92
51
31
50
LiCl (1.0)
—
LiCl (1.0)
LiCl (0.5)
LiCl (1.0)
LiCl(5.0)
LiCl (10)
PPh3 (1)
—
10
41
a
Conditions: DME, 10 h, 130 °C (oil bath), 2 atom CO pressure in the reaction
1
Pyridine
70
vessel at room temperature, 10 mol % palladacycle.
a
b
Reagent and conditions: THF, 12 h, 110 °C, 2 atom of CO pressure in the reaction
For the yield in the parenthesis the condition is the same as ‘a’ except that: THF,
vessel at room temperature, 10 mol % palladacycle 2a was applied.
12 h, 110 °C (oil bath).
b
c
Yield of isolated product after column chromatography (silica gel, petroleum/
Yield of isolated product after column chromatography (silica gel, petroleum/
EtOAc, 10:1–2:1).
EtOAc, 10:1–2:1).

X.-R. Wang et al. / Tetrahedron Letters 53 (2012) 589–592
591
Pd species are usually needed.10b Furthermore, the obtained results
showed that the presence of both a weakly coordinated co-ligand
and chloride in the palladacycles plays a critical role for the catalysis
of PKR. The role of chloride is consistent with the study by Yang et al.
in which a halometalation of the alkyne is involved in their cataly-
sis.10b Thus a Pd(II)–Pd(IV) catalytic cycle would be more reasonable
for the present catalysis. Further work is needed to prove the actual
reactive species for the oxime-palladacycle catalyzed PKRs.
In summary, we have shown that oxime-derived palladacycles
with pyridine co-ligand are a novel class of catalysts for the PKR.
Good to excellent conversions for allylpropargyl ethers and allyl-
propargylamines have been achieved. Considering the wide appli-
cations of oxime palladacycles in the cross-coupling reactions, this
work has provided an avenue for developing new catalysts for PKR
to cascade other catalytic reactions. Further study to examine the
reactive species in the catalytic cycle and the application of palla-
dacycles in the cascade PKR is currently undergoing in our
laboratory.
R
R
Palladacycle
solvent, CO
X
R'
X
O
R'
Xb
X
4
5
6
7
8
9
Xa
R = 4-ClC6H4, R' = H:
R = 4-EtOC6H4, R' = H:
R = C6H5, R' = Me:
X = O
R = C6H5, R' = H:
X = NTs
R = 4-ClC6H4, R' = H:
R = 4-MeOC6H4, R' = H:
R = C6H5, R' = H:
10
R = H, R' = H:
11
X = C(COOEt)2
R = 4-ClC6H4, R' = H: 12
Scheme 4. The intramolecular Pauson–Khand reactions of various substrates with
palladacycle 2a.
yield dropped to 11% or even 0 (entries 8 and 10 in Table 2). The
observed behavior is quite different from that of the catalysis in
the degradation of neutral thiophosphates, where palladacycles
containing triflate counter anion showed better reactivity.13a In
contract to the observation made on Pd(II)–tetramethylurea com-
plex catalyzed PKR,10a adding LiCl did not facilitate the reaction,
but instead reduced the yield of the product (see entries 12–15
in Table 2). Addition of the strongly coordinating PPh3 poisoned
the catalyst (entry 16 in Table 2). However, the presence of chlo-
ride in a palladacycle is essential for maintaining the catalytic
activity as addition of LiCl to the palladacycles with nitrate or tri-
flate counter ions greatly improved the reaction yields (entries 9
and 11 in Table 2). Palladacycle dimer 1 can also catalyzed PKR.
Addition of pyridine to the reaction mixture clearly improved the
catalytic activity (entries 17 and 18 in Table 2).
Acknowledgments
The authors gratefully acknowledge the financial assistances
from the Fundamental Research Funds for the Central Universi-
ties (2009SC-1), Beijing Municipal Commission of Education; Spe-
cialized Research Fund for the Doctoral Program of Higher
Education (273911); Program for New Century Excellent Talents
at Universities (15770703), the Ministry of Education, China and
Nature Science Foundation of China (202028). The authors also
thank Professor Bing Gong and Dr. Rui-Bing Wang for their english
improving and helpful discussion.
Supplementary data
To explore the scope of the palladacycle catalyzed PKR, a broad
range of substrates were tested in the presence of 2a. Along this
line, allylpropargyl-ethers 4a–6a (entries 2–4 in Table 3), allyl-
propargyl-amines 7a–9a (entries 5–7 in Table 3), and allylpropar-
gyl-malonates 10a–12a (entries 8–10 in Table 3) were prepared
and examined in different solvents (Scheme 4). The results includ-
ing that of 3a at the optimized conditions are listed in Table 3.
At first, three allylpropargyl ethers 4a–6a were investigated.
Interestingly, the enyne with electron-withdrawing substituent
(chloro-) 4a gave a higher yield while the enyne with electrondonat-
ing substituent(ethoxy-) 5a afforded a relativelylower yield (entries
3 and 4 in Table 3). The additional methyl group attached to the C@C
bond of 6a reduced the reactivity significantly in comparison to the
analogous substrate 3a, thus only low yields were obtained with the
palladacycles tested (entry 4 in Table 3). Such results are consistent
with the reported PKR catalyzed by other catalysts.9d,16 Among allyl-
propargylamines 7a–9a, compounds 8a, with an alkyne moiety
bearing electron-withdrawing group (4-chloro, entry 6 in Table 3),
gave an excellent yield (92%), while 9a, with an alkyne moiety bear-
ing an electron-rich group (4-methoxyl, entry 7 in Table 3), afforded
a lower yield (51%). Whereas with allylpropargyl malonates 10a–
12a, it was found that these substrates were not as reactive, for
which only lower yields (31–50%) were obtained.
Supplementary data (experimental procedures and NMR spectra
of the substrates and products) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2011.11.106.
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