Magnetically separable Pd catalyst for carbonylative sonogashira coupling reactions for the synthesis of α,β-alkynyl ketones

Article abstract of DOI:10.1021/ol801478y

(Chemical Equation Presented) A magnetically separable palladium catalyst was simply synthesized through a wet impregnation incorporating palladium nanoparticles and superparamagnetic Fe₃O₄ nanoparticles in KBH₄ solution,

Full text of DOI:10.1021/ol801478y

ORGANIC
LETTERS
2008
Vol. 10, No. 18
3933-3936
Magnetically Separable Pd Catalyst for
Carbonylative Sonogashira Coupling
Reactions for the Synthesis of
r,ꢀ-Alkynyl Ketones
Jianming Liu,†,‡ Xingao Peng,†,‡ Wei Sun,*,† Yongwei Zhao,† and Chungu Xia*,†
State Key Laboratory for Oxo Synthesis and SelectiVe Oxidation, Lanzhou Institute of
Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, P. R. China, and
Graduate School of the Chinese Academy of Sciences, Beijing, 100039, P. R. China
wsun@lzb.ac.cn; cgxia@lzb.ac.cn
Received May 5, 2008
ABSTRACT
A magnetically separable palladium catalyst was simply synthesized through a wet impregnation incorporating palladium nanoparticles and
superparamagnetic Fe3O4 nanoparticles in KBH4 solution, which is a highly efficient catalyst for the carbonylative Sonogashira coupling
reaction of aryl iodides with terminal alkynes under phosphine-free conditions. This catalyst is completely magnetically recoverable due to the
super paramagnetic behavior of Fe3O4 and can be reused with sustained selectivity and activity.
Transition-metal-catalyzed carbonylation reactions have be-
come a straightforward and powerful method in organic
synthesis. This protocol has been repeatedly modified and
improved to prepare aromatic carbonyl compounds which
cannot be easily or efficiently formed using classical
transformations, including esters, acids, R-keto amide, and
R,ꢀ-alkynyl ketones.1,2 Of particular interest among these
important carbonyl intermediates are the R,ꢀ-alkynyl ketones
because they appear in many biologically active molecules
and also play crucial roles as intermediates in the synthesis
of natural products. A direct method to prepare R,ꢀ-alkynyl
ketones involves the alkynyl organometallic reagent with acid
chlorides.3,4 An alternative route for these compounds is the
Pd-catalyzed carbonylative coupling reaction of terminal
alkynes or the metalated derivatives with aryl idodes in the
presence of carbon monoxide under mild conditions.5a
After the early reports on the carbonylative Sonogashira
coupling reaction, a variety of modifications were reported
for this reaction.5 But the most restricting aspect of these
(3) (a) Kalinin, V. N.; Shostakovsky, M. V.; Ponamaryov, A. B.
Tetrahedron Lett. 1990, 31, 4073. (b) Ciattini, P. G.; Morera, E.; Ortar, G.;
Rossi, S. S. Tetrahedron 1991, 47, 6449. (c) Torri, S.; Okumoto, H.; Xu,
L.-H.; Sadakane, M.; Shostakovsky, M. V.; Ponomaryov, A. B.; Kalinin,
V. N. Tetrahedron 1993, 49, 6773. (d) Bernard, D.; Daniel, C.; Robert, L.
Tetrahedron Lett. 1996, 37, 1019. (e) Dodero, V. I.; Koll, L. C.; Faraoni,
M. B.; Mitchell, T. N.; Podesta, J. C. J. Org. Chem. 2003, 68, 10087. (f)
Marco-Contelles, J.; de Opazo, E. J. Org. Chem. 2002, 67, 3705. (g) Vong,
B. G.; Kim, S. H.; Abraham, S.; Theodorakis, E. A. Angew. Chem., Int.
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(b) Trost, B. M.; Schmidt, T. J. Am. Chem. Soc. 1988, 110, 2301. (c) Matsuo,
K.; Sakaguchi, Y. Heterocycles 1996, 43, 2553. (d) Jeevandandam, A.;
Narkunan, K.; Cartwright, C.; Ling, Y.-C. Tetrahedron Lett. 1999, 40, 4841.
(e) Cabarrocas, G. Tetrahedron: Asymmetry 2000, 11, 2483. (f) Kel’in,
A. V.; Sromek, A. W.; Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 2074.
(g) Chang, K.-T.; Choi, S.-H.; Kim, S.-H.; Yoon, Y.-J.; Lee, W. S. J. Chem.
Soc., Perkin Trans. I 2002, 207. (h) Kel’in, A. V.; Gevorgyan, V. J. Org.
Chem. 2002, 67, 95.
(5) (a) Ahmed, M. S. M.; Mori, A. Org. Lett. 2003, 5, 3057. (b) Liang,
B.; Huang, M. W.; You, Z. J.; Xiong, Z. C.; Lu, K.; Fathi, R.; Chen, J. H.;
Yang, Z. J. Org. Chem. 2005, 70, 6097. (c) Fukuyama, T.; Yamaura, R.;
Ryu, I. Can. J. Chem. 2005, 83, 71. (d) Sans, V.; Trzeciak, A. M.; Luis, S.;
Ził´kowski, J. J. Catal. Lett. 2006, 109, 37. (e) Liu, J. H.; Chen, J.; Xia,
C. G. J. Catal. 2008, 258, 50. (f) Rahman, M. T.; Fukuyama, T.; Kamata,
N.; Sato, M.; Ryu, I. Chem. Commun. 2006, 2236. (g) Tambade, P. J.; Patil,
Y. P.; Nandurkar, N. S.; Bhanage, B. M. Synlett 2008, 886.
† Lanzhou Institute of Chemical Physics.
‡ Graduate School.
(1) (a) Tafesh, A. M.; Weiguny, J. Chem. ReV. 1996, 96, 2035. (b) Tietze,
L. F.; IIa, H.; Bell, H. P. Chem. ReV. 2004, 104, 3453. (c) Gabriele, B.;
Salerno, G.; Costa, M.; Chiusoli, G. P. Curr. Org. Chem. 2004, 8, 919. (d)
Morimoto, T.; Kakiuchi, K. Angew. Chem., Int. Ed. 2004, 43, 5580
(2) Chowdhury, C.; Kundu, N. G. Tetrahedron 1999, 55, 7011
.
.
10.1021/ol801478y CCC: $40.75
Published on Web 08/23/2008
2008 American Chemical Society

studies is that they were focused on homogeneous catalytic
systems together with phosphine ligands, wherein the
expensive palladium catalysts are difficult to be separated
and reused. This transformation was accomplished to over-
come several significant limitations: (a) higher activity
palladium-based catalyst, (b) copper-free and phosphine-free
routes eliminated the noncarbonylative product, (c) the
reusability of the Pd catalyst. In this regard, the development
of an easily recoverable and recyclable heterogeneous catalyst
is still in high demand, although a large number of supported
Pd catalysts for C-C coupling reactions, in particular the
Heck reaction, have been reported.6 To overcome these
limitations, magnetically nanosized catalysts are a better
choice because their magnetic separation is an alternative to
filtration or centrifugation as it prevents loss of catalyst and
increases the reusability. Magnetically nanosized catalysts
of palladium had been widely used in a variety of organic
reactions, such as hydrogenation processes,7 epoxide hydro-
genolysis reactions,8 and Suzuki, Heck, and Sonogashira
cross-coupling reactions.9,10 In most cases, palladium was
immobilized onto the modified surface of the magnetic
nanoparticles (MNP). Very recently, Ru(OH)x/Fe3O4, ruthe-
nium hydroxide was directly supported on the surface of
Fe3O4 and showed excellent catalytic activities in both
oxidation and reduction.11
Figure 1
Pd/Fe3O4.
. (a) TEM image of Pd/Fe3O4 catalyst. (b) XPS spectra of
In our initial screens, more reaction parameters, such as
temperature and CO pressure, were investigated. The results
are summarized in Table 1. The desired product, 1,3-
Table 1. Carbonylative Sonogashria Coupling Reaction of
Iodobenzene under Different Conditionsa
In this paper, we demonstrate that the Pd/Fe3O4 catalyst,
which could be easily prepared with a modified method
according to Mizuno’s procedure,11 could act as an efficient
catalyst in the Sonogashira carbonylative coupling reaction.
To the best of our knowledge, this is the first report for the
use of Pd/Fe3O4 for Sonogashira carbonylative coupling
reactions with high efficiency. The catalyst could be easily
separated from the reactant with the simple application of
an external magnetic field, and its catalytic efficiency remains
unaltered even after recycling seven times.
The catalyst was characterized by transmission electron
microscopy (TEM). In the TEM images, iron oxide nano-
particles of 25-50 nm in diameter and palladium nanopar-
ticles of 5 nm entrapped in iron oxide are observed (Figure
1a). Figure 1b shows that the Pd spectra contain two peaks
with 335.8 and 341.1 eV. These two peaks are assigned to
electron transitions of 3d5/2 and 3d3/2 of Pd0, which indicates
that the Pd2+ can be reduced to metallic Pd0.12
entry
solvent
toluene
toluene
toluene
toluene
toluene
DME
base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
DABCO
K3PO4
Cs2CO3
temp (°C)
yield (%)b
1
2
3
130
110
120
130
130
130
130
130
130
130
130
130
98 (92c)
79
94
68
93
49
63
51
64
4d
5e
6
7
8
9
10
11
12
THF
1,4-dioxane
CH3CN
toluene
toluene
toluene
79
6.5
5.7
a Reactions were carried out in 5.0 mL of solvent under 2.0 MPa pressure
of CO at 130 °C for 4 h with 2.5 mmol iodobenzene, 3.0 mmol
phenylacetylene, 7.2 mmol Et3N, and Pd/Fe3O4 catalyst (Pd, 1.04 wt %),
50 mg (Pd/substrate ) 1/511). b Determined by GC. c Isolated yield. d 1.0
MPa of CO. e 1.5 MPa of CO.
(6) For reviews, see: (a) Astruc, D.; Lu, F.; Aranzaes, J. R. Angew.
Chem., Int. Ed. 2005, 44, 7852. (b) de Vries, J. G. Dalton Trans. 2006,
421. (c) Ko¨hler, K.; Kleist, W.; Pro¨ckl, S. Inorg. Chem. 2007, 46, 1876.
(d) Astruc, D. Inorg. Chem. 2007, 46, 1884.
diphenylprop-2-yn-1-one, was formed in a 92% isolated
yield, when toluene was selected as solvent under 2.0 MPa
pressure of CO at 130 °C, in the presence of 50 mg of Pd/
Fe3O4. Low reaction temperature resulted in low yield in
forming the carbonylative Sonogashira coupling product
(Table 1, entries 1-3). We also investigated the effect of
the pressure of CO: 2.0 MPa of CO led to a nearly quantitive
transformation. Several solvents were also screened, and
toluene proved to be the best choice for the carbonylative
Sonogashira coupling reaction. Next, an evaluation of a
variety of bases in the carbonylative Sonogashira coupling
confirmed that Et3N exhibited superior selectivity and activity
than other tested bases (Table 1, entry 1). DABCO gave a
(7) (a) Guin, D.; Baruwati, B.; Manorama, S. V. Org. Lett. 2007, 9,
1419. (b) Hu, A.; Yee, G. T.; Lin, W. J. Am. Chem. Soc. 2005, 127, 12486.
(c) Yi, K. D.; Lee, S. S.; Ying, Y. J. Chem. Mater. 2006, 18, 2459. (d)
Abu-Reziq, R.; Wang, S.; Post, M.; Alper, H. Chem. Mater. 2008, 20, 2544.
(8) Kwon, M. S.; Park, I. S.; Jang, J. S.; Lee, J. S.; Park, J. Org. Lett.
2007, 9, 3417.
(9) (a) Stevens, P. D.; Fan, J.; Gardimalla, H. M. R.; Yen, M.; Gao, Y.
Org. Lett. 2005, 7, 2085. (b) Stevens, P. D.; Li, G.; Fan, J.; Yen, M.; Gao,
Y. Chem. Commun. 2005, 4435. (c) Baruwati, B.; Guin, D.; Manorama,
S. V. Org. Lett. 2007, 9, 5377
.
(10) Zhu, Y.; Peng, S. C.; Emi, A.; Su, Z.; Monalisa; Kempd, R. A.
AdV. Synth. Catal. 2007, 349, 1917
.
(11) Kotani, M.; Koike, T.; Yamaguchi, K.; Mizuno, N. Green Chem.
2006, 8, 735.
(12) The X-ray diffraction spectrum of Pd/Fe3O4 shows only a broad
peak at 2θ ) 40.45° between Fe3O4 and Pd/Fe3O4 that is characteristic of
amorphous Pd (see Supporting Information).
3934
Org. Lett., Vol. 10, No. 18, 2008

moderate yield. Poor selectivity and activity were observed,
when inorganic bases such as K3PO4 and Cs2CO3 were
applied (Table 1, entries 11 and 12). The nanocatalyst
displays a high turnover number (TON) for iodobenzene and
phenylacetylene (Table 1, entry 1, TON is about 501), a great
increase when compared to the results obtained with the
homogeneous palladium catalysts.5 The turnover frequencies
(TOF) reached 125 mol/mol/h.
Table 2. Sonogashira Carbonylative Coupling of Alkynes and
Aryl Iodidesa
To explore the generality and scope of the carbonylative
Sonogashira coupling reaction, the reaction of various aryl
iodides and terminal alkynes was carried out under the above
conditions, and the results are summarized in Table 2. Aryl
iodides bearing an electron-withdrawing group or an electron-
donating group in the para, meta, and ortho positions afforded
the corresponding substituted R,ꢀ-alkynyl ketones in good
yields. When 2-methoxy-1-iodobenzene, 3-methoxy-1-iodo-
benzene, and 4-methoxy-1-iodobenzene were employed in
the reaction with phenylacetylene (2a), the desired products
were isolated in high yields (Table 2, entries 5-7). The
reaction of 4-iodo-1-chlorobenzene and phenylacetylene (2a)
also afforded the corresponding product in satisfactory yield
(Table 2, entry 8). We also investigated the reactions of
several phenylacetylenes containing different groups on the
aromatic ring. All substituted phenylacetylenes were coupled
with iodobenzene to afford the R,ꢀ-alkynyl ketones in good
to excellent yields (Table 2, entries 10 and 12-14). The
reaction of 1-hexyne with iodobenzene only proceeded to
yield 50% of the carbonylative coupling product. The
carbonylative Sonogashira coupling reaction of aryl bromides
or chlorides with phenylacetylene using Pd/Fe3O4 under the
optimal conditions was also investigated, and no correspond-
ing R,ꢀ-alkynyl ketones were observed. Indeed, aryl bro-
mides or chlorides may served as substrates in the Sono-
gashira coupling reaction.13,14 Until now, these compounds
could not be successfully applied to the carbonylative
Sonogashira coupling reaction.5
Finally, catalyst cycles were run to investigate the stability
of the catalytic activity and recycling. In each cycle, the
catalyst was separated by magnetic separation. The separated
catalyst was then washed several times with ethanol and dried
under vacuum to remove the residual solvent (Figure 2, (b)
reactants containing Pd/Fe3O4 catalyst, (c) recycled Pd/Fe3O4
catalyst in ethanol). As shown in Figure 2a, the catalyst could
be reused seven times only with a slight loss of activity for
the carbonylative Sonogashira coupling of iodobenzene and
phenylacetylene. For the carbonylative Sonogashira coupling
reaction catalyzed by the Pd/Fe3O4 catalyst, the mechanism
is quasi-homogeneous. In the catalytic process, the actual
active species is a small palladium species in solution.6 The
a Reactions were carried out in 5.0 mL of toluene under 2.0 MPa pressure
of CO at 130 °C for 4 h with 2.5 mmol aryl iodides, 3.0 mmol
phenylacetylene alkynes, 7.2 mmol Et3N, and Pd/Fe3O4 catalyst (Pd, 1.04
wt %), 50 mg (Pd/substrate ) 1/511). b Isolated yield.
(13) (a) Choudary, B. M.; Madhi, S.; Chowdari, N. S.; Kantam, M. L.;
Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127. (b) Lipshutz, B. H.;
Chung, D. W.; Rich, B. Org. Lett. 2008, DOI: 10.1021/ol801589p.
(14) For recent reviews, see: (a) Chinchilla, R.; Na´jera, C. Chem. ReV.
2007, 107, 874. (b) Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007,
46, 834.
results also show that the active Pd catalyst is dissolved from
the Pd/Fe3O4 catalyst during the reaction and partially or
completely reprecipitated onto the support at the end of the
reaction.6,15,16
In summary, we have developed a highly efficient Pd(0)
catalyst immobilized on Fe3O4 nanoparticles highly suitable
(15) Diallo, A. K.; Ornelas, C.; Salmon, L.; Aranzaes, J. R.; Astruc, D.
Angew. Chem., Int. Ed. 2007, 46, 8644.
(16) After the first catalytic run, about 0.03 mg of Pd was determined
in the reaction solution by atomic absorption spectroscopy. After the
seventh catalytic run, about 0.01 mg of Pd was determined in the reaction
solution.
Org. Lett., Vol. 10, No. 18, 2008
3935

palladium is redeposited onto the support. As a result, the
catalyst is recoverable and could be reused seven times
without significant loss in catalytic activity and selectivity.
The Pd/Fe3O4 catalyst not only solves the basic problems of
catalyst separation and recovery but also avoids the use of
phosphine ligands in comparison with the homogeneous Pd
catalyst system.
Acknowledgment. We are grateful for financial support
from the Chinese Academy of Sciences and National Natural
Science Foundation of China (20625308).
Figure 2. Recycle of the Pd/Fe3O4 catalyst.
Supporting Information Available: Experimental sec-
tion, XPS, XRD, and NMR spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
for a carbonylative Sonogashira coupling reaction of aryl
iodides. During the reaction, the palladium is leached and
served as the active catalyst, and at the end of the reaction,
OL801478Y
3936
Org. Lett., Vol. 10, No. 18, 2008