Recyclable and reusable Pd(OAc)2/DABCO/PEG-400 system for Suzuki-Miyaura cross-coupling reaction

Article abstract of DOI:10.1021/jo050353m

A stable and efficient Pd(OAc)₂TDABCO (triethylenediamine) catalytic system for Suzuki-Miyaura cross-coupling reaction has been developed. In the presence of Pd(OAc)₂ and DABCO, coupling of aryl halides with arylboronic acids was carried out smoothly to afford good to excellent yields and high turnover numbers (TONs) (the maximal TONs were up to 960 000 for the reaction of 1-iodo-4-nitrobenzene with phenylboronic acid) using PEG-400 as the solvent. Moreover, the Pd(OAc)₂/DABCO/PEG-400 system could be recycled and reused five times without any loss of catalytic activity for aryl iodides and bromides.

Full text of DOI:10.1021/jo050353m

Recyclable and Reusable Pd(OAc) /DABCO/PEG-400 System for
2
Suzuki-Miyaura Cross-Coupling Reaction
Jin-Heng Li,* Wen-Jie Liu, and Ye-Xiang Xie
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research, College of Chemistry and
Chemical Engineering, Hunan Normal University, Changsha 410081, China
jhli@hunnu.edu.cn
Received February 24, 2005
A stable and efficient Pd(OAc)
cross-coupling reaction has been developed. In the presence of Pd(OAc)
2
/DABCO (triethylenediamine) catalytic system for Suzuki-Miyaura
and DABCO, coupling of
2
aryl halides with arylboronic acids was carried out smoothly to afford good to excellent yields and
high turnover numbers (TONs) (the maximal TONs were up to 960 000 for the reaction of 1-iodo-
2
4-nitrobenzene with phenylboronic acid) using PEG-400 as the solvent. Moreover, the Pd(OAc) /
DABCO/PEG-400 system could be recycled and reused five times without any loss of catalytic activity
for aryl iodides and bromides.
Introduction
fore, the development of phosphine-free recycling cata-
lytic systems to overcome these difficulties is considered
The biaryl nucleus is found in many natural and
synthetic products that display a wide range of biological
to be one of the most challenging fields in organic
chemistry.5
u,14
There are also significant economical and
1
activity. Consequently, considerable effort has been
directed to the development of efficient and selective
2-14
methods for the synthesis of biaryls.
Besides the
(5) For recently selected papers on phosphine-palladium catalysts,
see: (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
Ullmann coupling reaction,2 the palladium-catalyzed
,3
1998, 120, 9722. (b) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald,
Suzuki-Miyaura cross-coupling reaction has become one
S. L. J. Am. Chem. Soc. 1999, 121, 9550. (c) Littke, A. F.; Dai, C.; Fu,
G. C. J. Am. Chem. Soc. 2000, 122, 4020. (d) Bedford, R. B.; Cazin, C.
S. J.; Hazelwood, S. L. Angew. Chem., Int. Ed. 2002, 41, 4120. (e)
Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Synlett 2002, 1807.
(f) Mori, K.; Yamaguchi, K.; Hara, T.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. J. Am. Chem. Soc. 2002, 124, 11572. (g) Yin, J.; Rainka,
M. P.; Zhang, X.-X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
of the most widely useful tools for the synthesis of biaryls
in organic chemistry.2
c,4-14
Generally, the phosphine
ligands are used to complex the palladium species,
resulting in excellent results for the palladium-catalyzed
2c,4,5
Suzuki-Miyaura cross-coupling reaction.
However,
1
162. (h) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002,
124, 6343. (i) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41,
176. (j) Kwong, F. Y.; Lam, W. H.; Yeung, C. H.; Chan, K. S.; Chan,
many phosphines are sensitive to air and moisture with
conversion to, for example, phosphine oxide species. In
such cases, reuse of these catalysts is difficult.15 There-
4
A. S. C. Chem. Commun. 2004, 1922. (k) Kwong, F. Y.; Chan, K. S.;
Yeung, C. H.; Chan, A. S. C. Chem. Commun. 2004, 2336. (l)
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2004, 69, 7635. (m) Baillie, C.; Zhang, L.; Xiao, J. J. Org. Chem. 2004,
69, 7779. (n) DeVasher, R. B.; Moore, L. R.; Shaughnessy, K. H. J.
Org. Chem. 2004, 69, 7919. (o) Mukherjee, A.; Sarkar, A. Tetrahedron
Lett. 2004, 45, 9525. (p) Zhang, W.; Shi, M. Tetrahedron Lett. 2004,
45, 8921. (q) Peyroux, E.; Berthiol, F.; Doucet, H. Santelli, M. Eur. J.
Org. Chem. 2004, 1075. (r) Willis, M. C.; Powell, L. H.; Claverie, C. K.
Angew. Chem., Int. Ed. 2004, 43, 1249. (s) Wang, A.-E.; Zhang, J.; Xie,
J.-H.; Li, K.; Zhou, Q.-L. Adv. Synth. Catal. 2004, 346, 595. (t) Berthiol,
F.; Kondolff, I.; Doucet, H.; Santelli, M. J. Organomet. Chem. 2004,
689, 2786. (u) Okamoto, K.; Akiyama, R.; Kobayashi, S. Org. Lett. 2004,
6, 1987. (v) Barder, T. E.; Buchwald, S. L. Org. Lett. 2004, 6, 2649. (w)
Colacot, T. J.; Shea, H. A. Org. Lett. 2004, 6, 3731. (x) Walker, S. D.;
Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2004, 43, 1871. (y) Barder, T. E.; Walker, S. D.; Martinelli, J. R.;
Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685.
(1) Bringmann, G.; Gunther, C.; Ochse, M.; Schupp, O.; Tasler, S.
In Progress in the Chemistry of Organic Natural Products; Herz, W.,
Falk, H., Kirby, G. W., Moore, R. E., Eds.; Springer: New York, 2001;
Vol. 82, pp 1-293.
(2) (a) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 977. (b) Hegedus, L. S. In Organometallics in
Synthesis; Schlosser, M., Ed.; J. Wiley & Sons: Chichester, 2002;
p1123. (c) Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York, 2002.
(3) For selected Ullmann coupling reactions, see: (a) Zhang, S.;
Zhang, D.; Liebeskind, L. S. J. Org. Chem. 1997, 62, 2312. (b) Li, J.-
H.; Xie, Y.-X.; Yin, D.-L. J. Org. Chem. 2003, 68, 9867 and reference
cited therein.
(
4) For reviews, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995,
9
5, 2457. (b) Diederich, F.; Stang, P. J. Metal-Catalyzed Cross-coupling
Reactions, Wiley-VCH: Weinheim, 1998. (c) Miyaura, N. Cross-
Coupling Reaction, Springer: Berlin, 2002. (d) Bellina, F.; Carpita,
A.; Rossi, R. Synthesis 2004, 2419. (e) Nakamura, I.; Yamamoto, Y.
Chem. Rev. 2004, 104, 2127.
(6) For recent reviews on N-heterocyclic carbene-palladium cata-
lysts, see: (a) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(b) Yong, B. S.; Nolan, S. P. Chemtracts: Org. Chem. 2003, 205.
1
0.1021/jo050353m CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/02/2005
J. Org. Chem. 2005, 70, 5409-5412
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Li et al.
environmental reasons for developing recyclable catalytic
reactions from both academic and industrial perspectives.
To satisfy both recyclability and environmental concerns,
a more facile method is to immobilize the catalyst in a
liquid phase by dissolving it into a nonvolatile and
nonmixing liquid, such as PEG.16 Recently, we found that
DABCO was a highly efficient ligand for the palladium-
catalyzed Suzuki-Miyaura cross-coupling reaction, pro-
viding high turnover numbers (TONs) (up to 950 000
TONs for the reaction of PhI and p-chlorophenylboronic
TABLE 1. Efficient Suzuki-Miyaura Cross-Coupling
Reaction of Aryl Iodides and Bromides with Arylboronic
Acids in PEG-400a
12c
acid) (eq 1). Thus, we expected to employ the palladium
complex to effect the Suzuki-Miyaura cross-coupling
reaction on a recyclable basis. Here, we report that Pd-
(
2
OAc) /DABCO, in combination with PEG-400 as the
solvent, is an extremely effective and reusable system
for the coupling of aryl halides with arylboronic acids.
Results and Discussion
As shown in Table 1, the catalytic activity of Pd(OAc)
2
/
DABCO for the Suzuki-Miyaura reaction between 1-iodo-
(
7) For a representative paper on thiourea-palladium catalyst,
see: Dai, M.; Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org. Lett. 2004,
, 221.
8) For a representative paper on C,N-based 2-aryl-2-oxazolines-
palladium catalyst, see: Tao, B.; Boykin, D. W. Tetrahedron Lett. 2002,
3, 4955.
9) For selected representative papers on aryloximes-palladium
6
(
4
(
catalyst, see: (a) Alonso, D. A.; N a´ jera, C.; Pacheco, M. C. Org. Lett.
2
000, 2, 1823. (b) Botella, L.; N a´ jera, C. Angew. Chem., Int. Ed. 2002,
4
1, 179.
(10) For a paper on arylimines-palladium catalyst, see: Bedford,
R. B.; Cazin, C. S. Chem. Commun. 2001, 1540.
11) For recent representative papers on diazabutadiene-palladium
catalysts, see: (a) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett.
001, 3, 1077. (b) Palencia, H.; Garcia-Jimenez, F.; Takacs, J. M.
Tetrahedron Lett. 2004, 45, 3849.
(
a
Unless otherwise indicated, the reaction conditions were as
2
follows: 1 (0.5 mmol), 2 (0.7 mmol), Pd(OAc)2/DABCO (1:2), and
K2CO3 (3 equiv) in PEG-400 (2 g) at 110 °C. Isolated yield. c 1j
(0.25 mmol).
b
(12) For the representative papers on amine-palladium catalysts,
see: (a) Tao, B.; Boykin, D. W. Tetrahedron Lett. 2003, 44, 7993. (b)
Tao, B.; Boykin, D. W. J. Org. Chem. 2004, 69, 4330. (c) Li, J.-H.; Liu,
W.-J. Org. Lett. 2004, 6, 2809.
4
-nitrobenzene (1a) and phenylboronic acid (2a) was first
evaluated. The results indicated that Pd(OAc) /DABCO
(13) For recent representative papers on other phosphine-free
2
palladium catalysts, see: (a) Alonso, D. A.; N a´ jera, C.; Pacheco, M. C.
J. Org. Chem. 2002, 67, 5588 and reference cited therein. (b) de Vries,
A. H. M. Mulders, J. M. C. A.; Mommers, J. H. M.; Henderickx, H. J.
W.; de Vries, J. G. Org. Lett. 2003, 5, 3285 and references therein.
as the catalytic systems is highly efficiently, proving high
TONs up to 910 000 for the reaction. In the presence of
0.1 mol % of Pd, 96% yield of the desired product 3 was
obtained for 6 h (entry 1). A high yield of 3 was still
isolated after prolonged heating when the loadings of Pd
were decreased to 0.0001 mol % (entry 2). Treatment of
(
14) For selected papers on recyclable palladium catalysts for
Suzuki-Miyaura cross-coupling reaction: (a) Kaneda, K.; Terasawa,
M.; Imanaka, T.; Teranishi, S. Fundam. Res. Homogeneous Catal. 1973,
3
, 671. (b) Terasawa, M.; Kaneda, K.; Imanaka, T.; Teranishi, S. J.
Organomet. Chem. 1978, 162, 403. (c) Andersson, C.-M.; K. Karabelas,
A. Hallberg, J. Org. Chem. 1985, 50, 3891. (d) Zhang, Z. Y.; Hu, H.
W.; Kao, T. Y. React. Polym. Ion. Exch. Sorbents 1988, 9, 249. (e) Zhang,
Z. Y.; Pan, Y.; Hu, H. W.; Kao, T. Y. Synth. Commun. 1990, 20, 3563.
1
b and 1c bearing an electron-withdrawing group with
2a, respectively, also afforded high yields in the presence
of 0.0001 mol % of Pd (entries 3 and 4). For coupling of
aryl iodides bearing electron-neutral groups and electron-
(
f) Jang, S. B. Tetrahedron Lett. 1997, 38, 4421. (g) Bergbreiter, D. E.;
L.Osburn, P.; Liu, Y. S. J. Am. Chem. Soc. 1999, 121, 9531. (h) Chechik,
V.; Crooks, R. M. J. Am. Chem. Soc. 2000, 122, 1243. (i) Akiyama, R.;
Kobayashi, S. Angew. Chem., Int. Ed. 2001, 40, 3469. (j) an der Heiden,
M.; Plenio, H. Chem. Eur. J. 2004, 10, 1789. (k) Kim, N.; Kwon, M. S.;
Park, C. M.; Park, J. Tetrahedron Lett. 2004, 45, 7057. (l) Phan, N. T.
S.; Brown, D. H.; Styring, P. Tetrahedron Lett. 2004, 45, 7915.
2
donating groups, the Pd(OAc) /DABCO catalytic system
is still highly efficient. For example, 1-iodo-4-methoxy-
benzene (1e) was treated with 2a and 0.001% Pd afforded
a 98% yield of the corresponding product 9 for 15 h (entry
(15) (a) Pignolet, L. H., Ed.; Homogeneous Catalysis with Metal
1
0). The results showed that the reactions of iodobenzene
Phosphine Complexes; Plenum: New York, 1983. (b) Parshall, G. W.;
Ittel, S. Homogeneous Catalysis; Wiley and Sons: New York, 1992. (c)
Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles
and Applications of Organotransition Metal Chemistry; University
Science: Mill Vallley, CA. 1987.
(16) For a selected representative paper on PEG as the media for
the other cross-coupling reactions, see: Chandrasehar, S.; Narsihmulu,
C.; Sultana, S. S.; Reddy, N. R. Org. Lett. 2002, 4, 4399.
5410 J. Org. Chem., Vol. 70, No. 14, 2005

2
Recyclable and Reusable Pd(OAc) /DABCO/PEG-400
TABLE 2. TBAB-Promoted Suzuki-Miyaura
Cross-Coupling Reaction of Aryl Chlorides with
Arylboronic Acids in PEG-400a
the presence of 3 mol % of Pd(OAc)
2
, 6 mol % of DABCO,
and 3 equiv of K CO , whereas 91% yield was obtained
2
3
when 0.1 equiv of TBAB was added (entries 1 and 2).
For coupling of aryl chlorides 1m-o, however, the
efficiency of the catalytic system was decreased to some
extent (entries 5-10). For example, treatment of chlo-
robenzene (1m) with 2a and 2e, respectively, afforded
the corresponding coupled products 10 and 9 in moderate
yields (entries 5 and 6). For coupling of deactivated aryl
chloride 1o, only 41% yield of 9 was isolated even in the
presence of 1 equiv of TBAB (entry 10).
2
We were gratified to observe that the Pd(OAc) /DABCO/
PEG-400 system could be recycled and reused five times
without any loss of activity for the coupling reactions of
1
e, 1f, and 1g with 2a or 2e, respectively (entries 1 and
-5 in Table 3). Furthermore, the reaction was also
3
successful using lower catalyst loadings. To check the
reusability of the solvent as well as the catalyst, the
coupling reaction of 1-iodo-4-methoxybenzene (1e) with
2
a was first examined in the presence of 0.1 mol % of
Pd. After initial experimentation, the reaction mixture
was extracted with dry diethyl ether, and the PEG and
2
Pd(OAc) /DABCO were solidified and subjected to a
second run of the Suzuki-Miyaura reaction by charging
with the same substrates (1-iodo-4-methoxybenzene,
2 3
phenylboronic acid, and K CO ). The results of five runs
showed that they were almost consistent in yields and
rates (93%, 91%, 94%, 95%, and 97%, respectively, for 4
h; entry 1). For the reaction of aryl bromide (1f) with 2a
even in the presence of 3 mol % Pd, however, the activity
of the system was decreased sharply in the second run
due to the generation of palladium black. It is noteworthy
that the presence of TBAB can rule out the generation
of palladium black to make the catalytic system stably.
The system for the reaction of aryl bromide (1f) with 2a
could be recycled and reused five times without any loss
of activity even in the presence of 0.01 mol % loading of
Pd when 0.1 equiv of TBAB was added (entries 3 and 4).
The suitable Pd loading for the recoverable and reusable
coupling of bromobenzene (1g), respectively, were 3 mol
a
Unless otherwise indicated, the reaction conditions were as
follows: 1 (0.5 mmol), 2 (0.7 mmol), Pd(OAc)2 (3 mol %), DABCO
(
6 mol %), TBAB (0.1 equiv), and K2CO3 (3 equiv) in PEG-400 (2
g) at 110 °C. Isolated yield. Without TBAB. d TBAB (1.0 equiv).
b
c
e
KOH (3 equiv) instead of K2CO3.
(
1d) with a number of arylboronic acid 2a-e, respec-
tively, gave excellent results in the presence of 0.1 mol
of Pd (entries 5-9). However, the efficiency of Pd-
OAc) /DABCO was decreased to some extent for the
coupling of aryl bromides with arylboronic acids (entries
1-19). The results demonstrated that aryl bromides
%
(
%
(entries 5-7). Although the Pd loadings could be
2
decreased to 0.1 mol %, only moderate yields were
obtained from the second through fourth runs. Unfortu-
nately, the catalyst system could not be reused for the
reaction of aryl chloride (1l) with 2a (entry 8).
1
were suitable substrates at the loadings of from 3 to 0.01
mol % Pd. It is noteworthy that the catalytic activity of
2
Pd(OAc) /DABCO in PEG-400 is more active than those
1
2c
of the previous report in MeCN. For example, in the
Conclusion
presence of 0.1 mol %, coupling of 1i with 2a afforded
1
00% yield of 9 for 20 h in PEG-400 (entry 18), whereas
In summary, a highly efficient and reusable Pd(OAc)2/
DABCO/PEG system for the Suzuki-Miyaura cross-
coupling reaction has been developed. In the presence of
12c
only 42% yield was isolated after 48 h in MeCN.
12c
Compared with our previous results in MeCN, the
scope of the Pd(OAc) /DABCO catalytic system in PEG
2
Pd(OAc) and DABCO, a number of aryl halides, includ-
2
could be further extended to the coupling reactions of aryl
chlorides 1k-o with arylboronic acids, and the results
are summarized in Table 2. The results showed that
TBAB was required to improve the Suzuki-Miyaura
cross-coupling reaction of aryl chlorides. Without TBAB,
only a 54% yield of 10 was isolated after 15 h from the
reaction of 1-(4-chlorophenyl)ethanone (1k) with 2a in
ing aryl iodides, bromides, and chlorides, were coupled
with arylboronic acids smoothly and efficiently to produce
good to excellent yields and high TONs (maximal TONs
1
7
17
up to 960 000). As in the earlier reports, TBAB was
required to improve the Suzuki-Miyaura cross-coupling
reaction. Furthermore, the Pd(OAc) /DABCO/PEG-400
2
system could be recycled and reused five times without
any loss of catalytic activity for aryl iodides and bromides.
Currently, further efforts to extend the application of the
system in other palladium-catalyzed transformations are
underway in our laboratory.
(
17) For the representative papers on TBAB-promoted the cross-
coupling reactions, see: (a) Selvakumar, K.; Zapf, A.; Beller, M. Org.
Lett. 2002 4, 3031. (b) Yang, D.; Chen, Y.-C.; Zhu, N.-Y. Org. Lett. 2004,
6
, 1557 and references therein.
J. Org. Chem, Vol. 70, No. 14, 2005 5411

Li et al.
TABLE 3. Recovery and Reuse of the System for the Suzuki-Miyaura Cross-Coupling Reactiona
a
Unless otherwise indicated, the reaction conditions were as follows: 1 (0.5 mmol), 2 (0.7 mmol), Pd(OAc)2/DABCO (1:2), TBAB (0.1
b
equiv), and K2CO3 (3 equiv) in PEG-400 (2 g) at 110 °C. Without TBAB.
Experimental Section
rated under vacuo) and subjected to a second run of the
Suzuki-Miyaura cross-coupling reaction by charging with the
Typical Experimental Procedure for the Palladium-
Catalyzed Suzuki-Miyaura Cross-Coupling Reaction in
PEG-400. A mixture of aryl halide 1 (0.5 mmol), arylboronic
2 3
same substrates (aryl halide 1, arylboronic acid 2, and K CO ).
Acknowledgment. We thank the National Natural
Science Foundation of China (No. 20202002) for finan-
cial support.
acid 2 (0.7 mmol), Pd(OAc)
2
/DABCO (1:2; the identical amount
3
(3 equiv), and PEG-400 (2 g) was
in Tables 1 and 2), K CO
2
added to a sealed tube and stirred at 110 °C for the desired
time until complete consumption of the starting material as
judged by TLC. After the mixture was extracted with dry
diethyl ether (3 × 10 mL) and evaporated, the residue was
purified by flash column chromatography (hexane or hexane/
ethyl acetate) to afford the desired coupled products 3-14.
Supporting Information Available: Analytical data and
1
13
spectra ( H and C NMR) for all the products 3-14. This
material is available free of charge via the Internet at
http://pubs.acs.org.
After extracting with diethyl ether, the mixture of Pd(OAc)
DABCO, and PEG-400 was solidified (cooled and then evapo-
2
,
JO050353M
5412 J. Org. Chem., Vol. 70, No. 14, 2005