Highly efficient suzuki cross-coupling catalyzed by palladium/phosphine- imidazolium carbene system

Article abstract of DOI:10.1002/adsc.200404015

Novel phosphine-imidazolium salts 2 have been synthesized and successfully used in palladium-catalyzed Suzuki cross-coupling. A combination of 0.05 mol % of [Pd(η-C₃H₅)Cl]₂ and 0.1 mol % of 2b in the presence of 2 equivs. of K₃PO₄ as base provided coupling products in excellent yields in the reaction of aryl bromides and chlorides with aryl boronic acids.

Full text of DOI:10.1002/adsc.200404015

COMMUNICATIONS
Highly Efficient Suzuki Cross-Coupling Catalyzed by
Palladium/Phosphine-Imidazolium Carbene System
Ai-E Wang, Jun Zhong, Jian-Hua Xie, Kai Li, Qi-Lin Zhou*
Sate Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, P. R. China
Fax: (þ86)-22-2350-6177, e-mail: qlzhou@nankai.edu.cn
Received: January 16, 2004; Accepted: April 10, 2004
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
[
9,10]
Abstract: Novel phosphine-imidazolium salts 2 have
been synthesized and successfully used in palladium-
catalyzed Suzuki cross-coupling. A combination of
a pendant group.
Phosphine-functionalized NHC×s
[
11]
were rather rare, with only one successful application
[
11c]
in the Heck reaction reported by Nolan.
We describe
0
.05 mol % of [Pd(h-C H )Cl] and 0.1 mol % of 2b
herein the synthesis of novel phosphine-functionalized
imidazolium salts and their application in palladium-
catalyzed Suzuki couplings of aryl bromides and activat-
ed chlorides.
3
5
2
in the presence of 2 equivs. of K PO as base provid-
3
4
ed coupling products in excellent yields in the reac-
tion of aryl bromides and chlorides with aryl boronic
acids.
Starting with benzaldehyde, o-(diphenylphosphino)-
benzyl chloride (1) was prepared according to the re-
[
12]
Keywords: carbene ligands; functionalized phos-
phane ligands; imidazolium salts; N-heterocyclic car-
benes; palladium; Suzuki cross-coupling
ported method, and reacted with various 1-substitut-
ed imidazoles in refluxing ethanol, giving the bidentate
phosphine-imidazolium salts 2. Using K CO as the
2
3
base, the tridentate phosphine-imidazolium salt 3 was
obtained from1 H-imidazole and 1 (Scheme 1).
Preliminary studies with 4-bromotoluene and phenyl-
boronic acid as the coupling partners revealed that the
Since the first isolation and X-ray characterization of a palladiumcomplexes generated from[Pd( h-C H )Cl]
3
5
2
[
1]
stable imidazol-2-ylidene in 1991, nucleophilic N-het- (0.25 mol %) and phosphine-imidazolium salts
2
erocyclic carbenes (NHC×s) and their transition metal (0.5 mol %) in the presence of Cs CO were efficient cat-
2
3
[
2]
complexes have attracted much attention. With the alysts in Suzuki coupling (Table 1, entries 1±3). The best
pronounced s-donating but very weak p-accepting result was obtained with 2b, while the reaction with tri-
[3]
properties, NHC×s resemble conventional phosphine dentate phosphine-imidazolium 3 required a longer
[4]
ligands. Owing to the high stability of the metal com- time for completion. A control experiment without the
plexes of NHC×s toward heat, moisture and oxygen, sig- imidazolium salt was carried out in order to confirm
nificant improvements have been achieved by replacing whether a nucleophilic carbene generated in situ oper-
phosphine ligands with nucleophilic carbenes in various ates as a ligand in the reaction. As expected, a remarka-
[
5]
catalytic reactions, such as amination of aryl chlorides,
olefin metathesis, and hydrogenations.
ble decrease in activity was observed (entry 5) and pre-
cipitation of palladiumblack occurred within a few
[
6]
[7]
The palladium-mediated cross-coupling of arylboron- hours. This result indicated that the addition of the imi-
ic acid with aryl halides, the Suzuki reaction, is a versa- dazoliumsalt is necessary in the reaction and that a nu-
tile and highly useful method for the synthesis of biar- cleophilic carbene formed from 2 or 3 plays an impor-
[
8]
yl-containing molecules. With the renaissance and tant role as a ligand to afford the product in good yield.
flourishing of the nucleophilic carbenes, a number of A range of palladiumcompounds was screened for use
palladium/N-heterocyclic carbene systems have been
[
9]
employed in this process with great success. Most of
them used pre-prepared palladium-imidazol-2-ylidene
complexes as catalysts. There were only a few examples
using in situ formed palladium-NHC species from imi-
dazoliumsalts and palladiumsources in the presence
[9c,e, f,k, l]
of bases,
and the carbenes used were usually mon-
odentate NHC×s with bulky groups at the imidazole ring.
In addition, most reported functionalized NHC×s had a
nitrogen-donor such as pyridine, imine or oxazoline as Scheme 1.
Adv. Synth. Catal. 2004, 346, 595±598
DOI: 10.1002/adsc.200404015
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
595

COMMUNICATIONS
Ai-E Wang et al.
as catalyst precursor and the best result was obtained Table 2. Effect of base on the Pd/2b-catalyzed Suzuki cou-
[a]
pling reaction.
with [Pd(h-C H )Cl] . The Suzuki coupling reaction
3
5
2
was prevented when the ratio of imidazolium salt to pal-
ladium( 2b/Pd) was increased from1:1 to 2:1 (entry 9),
which revealed, fromone side, that the phosphine-imi-
dazoliums 2 are bidentate ligands. Two ligands 2 occu-
pied all of four coordination sites of palladiumto form
a stable complex, which was inert in the oxidative-addi-
tion step.
Entry
Base
Time
[h]
Conversion
[%]
Yield
[%]
[
b]
[c]
1
2
3
4
5
6
7
8
9
Cs CO
10
24
6
24
24
4
4
4
24
24
99
99
99
51
4
100
99
100
2
97
95
94
31
±
100
94
95
±
2
3
Investigations into the optimal base showed that the
rate of reaction and the activity of catalyst were signifi-
cantly influenced by the base used (Table 2). A number
of inorganic bases, such as Cs CO , K CO , KOH,
K CO
2
3
KF
KOBu-t
KOAc
2
3
2
3
NaOH, KF and K PO , could provide cross-coupling
K
PO
3
4
3
4
KOH
NaOH
NEt3
products in excellent yield. But when organic bases
such as triethylamine and diisopropylethylamine were
used, the reactions ceased within minutes and palladium
black was observed. Considering its high activity, K PO
10
EtN(i-Pr)2
6
±
3
4
[
[
[
a]
was ultimately chosen as the base for the system. Various
solvents were tested in the coupling reaction with K PO
Performed at 0.5 mol % Pd/L (1: 1) and 0.33 M.
Determined by GC.
GC yield.
b]
c]
3
4
as the base (Table 3). Dioxane proved to be a suitable
solvent, giving the fastest reaction. An attempt to con-
duct the reaction at a lower temperature led to a dramat-
ic decrease in the conversion of aryl bromide (508C/ chlorides can also couple with phenylboronic acid effi-
4 h, 61% conversion). Using 0.05 mol % [Pd(h-C H ) ciently under the same conditions in high yields (Table 4,
2
3
5
Cl] and 0.1 mol % 2b also gave the coupling product entries 16±21).
2
in 100% yield after 12 h (entry 2).
A variety of arylboronic acid (with electron-donating
Under the optimized reaction conditions, a wide array and electron-withdrawing substituents) reacted
of aryl bromides can react with phenylboronic acid smoothly with 4-bromotoluene and the cross-coupling
providing cross-coupling products in excellent yields products were obtained in excellent yields (Table 5).
(
Table 4). The palladium/phosphine-imidazolium car-
In summary, we have developed a highly efficient,
convenient to handle palladium/phosphine imidazolium
bene systemwas indeed very efficient toward Suzuki
coupling and displayed remarkable tolerance towards salt systemfor the cross-coupling reaction of arylboron-
both ™deactivating∫ electron-donating substituents and ic acids and aryl bromides and activated chlorides to
sterically encumbering otho-substituents on the aryl produce biaryl compounds in excellent yields. The phos-
bromide. We were delighted to find that activated aryl phine-functionalized heterocyclic carbenes generated in
Table 1. Effect of imidazolium salts and palladium resource on the Suzuki coupling of 4-bromotoluene and phenylboronic
[a]
acid.
[
b]
Entry
Pd complex
Ligand
Time [h]
Conversion [%]
Yield [%]
1
2
3
4
5
6
7
8
[Pd(h-C H )Cl]
2a
2b
2c
14
10
13
24
24
17
18
12
24
99
99
100
93
23
97
99
99
5
92
97
89
82
±
90
99
96
±
3
5
2
2
2
2
2
[Pd(h-C H )Cl]
3
5
[Pd(h-C H )Cl]
3
5
[Pd(h-C H )Cl]
3
3
5
[Pd(h-C H )Cl]
none
2b
2b
2b
2b
3
5
Pd(dba)2
Pd (dba) CHCl
2
3
3
Pd(OAc)2
[Pd(h-C H )Cl]
[
c]
9
3
5
2
[
[
[
a]
b]
c]
Performed at 0.5 mol % Pd/L (1: 1) and 0.33 M.
GC yield.
Pd/L¼1: 2.
596
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 595±598

Highly Efficient Suzuki Cross-Coupling
COMMUNICATIONS
[a]
Table 3. Effect of solvent.
Table 5. Suzuki cross-coupling of 4-bromotoluene with var-
ious arylboronic acids.
[a]
Entry Solvent
Time [h] Conversion [%] Yield [%]
[
b]
Entry
R
Conversion [%]
Yield [%]
1
2
3
4
5
6
7
8
9
0
Dioxane
Dioxane 12
THF
Toluene
EtOH
DMF
DMAc
DME
4
100
100
100
99
100
100
97
94
93
89
83
38
43
54
[
b]
1
2
3
4
5
6
H
100
100
100
100
98
100
99
97
100
93
96
6
6
6
6
6
6
4
4
m-OCH3
p-OCH3
p-CH3
o-CH3
p-COCH3
100
93
87
60
61
99
[
[
a]
b]
DMSO
Performed at 0.1 mol% Pd/L (1: 1) and 0.33 M.
Average of isolated yields based on two runs.
1
CH CN
70
3
[
[
a]
Performed at 0.5 mol % Pd/L (1: 1) and 0.33 M.
b]
Using 0.05 mol % [Pd(h-C H )Cl] .
Experimental Section
3
5
2
situ from imidazolium salt were for the first time intro- Cross-Coupling Reactions of Aryl Halides with
duced to the palladiumcatalyzed Suzuki coupling. Ap-
plications involving this new family of phosphine imida-
zoliumsalts in other metal-promoted reactions are cur-
rently under investigation.
Arylboronic Acids; General Procedure
Under an atmosphere of argon, 3.0 mL dioxane were injected
to Schlenk tube charged with [Pd(h-C H )Cl]
2
a
3
5
(
(
0.0025 mmol), imidazolium salt (0.005 mmol), and K PO4
2.0 mmol) (performed at 0.5 mol % cat.), or 3.0 mL dioxane
3
[a]
Table 4. Suzuki cross-coupling of bromides and activated chlorides with phenylboronic acid.
[
b]
Entry
X
R
Time [h]
Conversion [%]
Yield [%]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
p-CH3
o-CH3
m-CH3
12
12
12
12
12
12
6
6
6
6
6
6
6
6
12
6
12
12
24
12
36
100
100
100
100
100
100
100
100
100
100
100
100
100
96
100
98
100
100
100
100
100
100
100
98
m-OCH3
p-OCH3
3,5-diCH3
p-CN
m-COCH3
p-COCH3
p-CF3
3,5-diCF3
m-CHO
p-NO2
1
1
1
1
1
1
1
1
1
1
2
2
93
97
100
93
100
100
92
99
85
80
97
H
1-Br-2-Me-Naph
p-NO2
p-COCH3
p-CN
o-CHO
p-CHO
o-NO2
100
100
96
99
97
89
98
[
c]
[
[
[
a]
Performed at 0.1 mol % Pd/L (1: 1) and 0.33 M.
Average of isolated yields based at two runs.
Using 0.5 mol % Pd.
b]
c]
Adv. Synth. Catal. 2004, 346, 595±598
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
597

COMMUNICATIONS
Ai-E Wang et al.
solution of [Pd(h-C H )Cl] (0.0005 mmol) and imidazolium
well, D.-R. Hou, J. H. Reibenspies, K. Burgess, J. Am.
Chem. Soc. 2003, 125, 113; d) M. T. Powell, D.-R. Hou,
M. C. Perry, X. Cui, K. Burgess, J. Am. Chem. Soc.
3
5
2
salt (0.001 mmol) was injected to a Schlenk tube charged
with K PO (2.0 mmol) (performed at 0.1 mol % cat.). The
3
4
mixture was stirred for 30 min at room temperature. Then
2
001, 123, 8878.
8] a) S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron 2002,
8, 9633; b) S. R. Chemler, D. Trauner, S. J. Danishefsky,
Angew. Chem. 2001, 113, 4676; Angew. Chem. Int. Ed.
1
0
.0 mmol of aryl halide, 1.5 mmol of arylboronic acid (and
.5 mmol of tridecane as internal standard, if the yield was de-
[
[
5
termined by GC) were added. The reaction mixture was placed
in a 808C oil bath and the course of the reaction was monitored
by GC. After the reaction was complete, the mixture was load-
ed on a small plug of silica gel and washed with a copious
2
001, 40, 4544; c) A. Suzuki, J. Organomet. Chem. 1999,
5
76, 147; d) S. P. Stanforth, Tetrahedron 1998, 54, 263;
e) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.
9] a) W. A. Herrmann, C.-P. Reisinger, M. Spiegler, J. Orga-
nomet. Chem. 1998, 557, 93; b) V. P. W. Bˆhm, C. W. K.
Gstˆttmayr, T. Weskamp, W. A. Herrmann, J. Organo-
met. Chem. 2000, 595, 186; c) C. Zhang, J. Huang, M. L.
Trudell, S. P. Nolan, J. Org. Chem. 1999, 64, 3804;
d) C. W. K. Gstˆttmayr, V. P. W. Bˆhm, E. Herdtweck,
M. Grosche, W. A. Herrmann, Angew. Chem. 2002,
amount of Et O. The washings were concentrated and purified
2
by flash chromatography on silica gel column and the products
1
were identified by H NMR.
Acknowledgements
We thank the National Natural Science Foundation of China,
the Major Basic Research Development Program (Grant
G2000077506),and the Ministry of Education of China for fi-
nancial support.
1
14, 1421; Angew. Chem. Int. Ed. 2002, 41, 1363; e) C.
Zhang, M. L. Trudell, Tetrahedron Lett. 2000, 41, 595;
f) A. F¸rstner, A. Leitner, Synlett 2001, 290; g) A. C.
Hillier, G. A. Grasa, M. S. Viciu, H. M. Lee, C. Yang,
S. P. Nolan, J. Organomet. Chem. 2002, 653, 69;
h) A. M. Magill, D. S. McGuinness, K. J. Cavell, G. J. P.
Britovsek, V. C. Gibson, A. J. P. White, D. J. Williams,
A. H. White, B. W. Skelton, J. Organomet. Chem. 2001,
References
[1] A. J. Arduengo III, R. L.Harlow, M. Kline, J. Am. Chem.
Soc. 1991, 113, 361.
6
17, 546; i) W. A. Herrmann, V. P. W. Bˆhm, C. W. K.
Gstˆttmayr, M. Grosche, C.-P. Reisinger, T. Weskamp,
J. Organomet. Chem. 2001, 617, 616; j) T. Weskamp,
V. P. W. Bˆhm, W. A. Herrmann, J. Organomet. Chem.
[
2] a) W. A. Herrmann, Angew. Chem. 2002, 114, 1342; An-
gew. Chem. Int. Ed. 2002, 41, 1290; b) W. A. Herrmann,
T. Weskamp, V. P. W. Bˆhm, Adv. Organomet. Chem.
1
999, 585, 348; k) G. A. Grasa, M. S. Viciu, J. Huang, C.
Zhang, M. L. Trudell, S. P. Nolan, Organometallics
002, 21, 2866; l) Y. Zhao, Y. Zhou, D. Ma, J. Liu, L.
Li, T. Y. Zhang, H. Zhang, Org. Biomol. Chem. 2003,
, 1643; m) G. Altenhoff, R. Goddard, C. W. Lehmann,
2
002, 48, 1; c) L. Jafarpour, S. P. Nolan, Adv. Organomet.
Chem. 2001, 46, 181; d) D. Bourissou, O. Guerret, F. P.
GabbaÔ, G. Bertrand, Chem. Rev. 2000, 100, 39;
e) W. A. Herrmann, C. Kˆcher, Angew. Chem. 1997,
2
1
1
09, 2256; Angew. Chem. Int. Ed. 1997, 36, 2162.
F. Glorius, Angew. Chem. 2003, 115, 3818; Angew.
Chem. Int. Ed. 2003, 42, 3690.
[
[
3] A. J. Arduengo III, H. V. Rasika, R. L. Harlow, M. Kline,
J. Am. Chem. Soc. 1992, 114, 5530.
4] a) J. P. Collman, L. S. Hegedus, J. R. Norton, R. G. Finke,
Principles and Applications of Organotransition Metal
Chemistry; University Science Books: Mill Valley, CA,
[
10] a) D. S. McGuinness, K. J. Cavell, Organometallics 2000,
9, 741; b) P. L. Arnold, A. C. Scarisbrick, A. J. Blake, C.
1
Wilson, Chem. Commun. 2001, 2340; c) A. A. Danopou-
los, S. Winston, W. B. Motherwell, Chem. Commun. 2002,
1
987; b) G. W. Parshall, S. Ittel, Homogeneous Catalysis;
1
376; d) S. Grundemamm, M. Albrecht, J. A. Loch, J. W.
J. Wiley and Sons, New York, 1992; c) L. H. Pignolet,
Homogeneous Catalysis with Metal Phosphine Com-
plexes; Plenum: New York, 1983.
Faller, R. H. Crabtree, Organometallics 2001, 20, 5485;
e) J. A. Loch, M. Albrecht, E. Peris, J. Mata, J. W. Faller,
R. H. Crabtree, Organometallics 2002, 21, 700.
[5] a) J. Huang, G. Grasa, S. P. Nolan, Org. Lett. 1999, 1,
[
11] a) A. A. Danopoulos, S. Winston, T. Gelbrich, M. B.
Hursthouse, R. P. Tooze, Chem. Commun. 2002, 482;
b) W. A. Herrmann, C. Kˆcher, L. J. Goo˚en, G. R. J.
Artus, Chem. Eur. J. 1996, 2, 1627; c) C. Yang, H. M.
Lee, S. P. Nolan, Org. Lett. 2001, 3, 1511; d) H. Seo, H.
Park, B. Y. Kim, J. H. Lee, S. U. Son, Y. K. Chung, Orga-
nometallics 2003, 22, 618.
12] a) S. Bhattacharyya, J. Org. Chem. 1995, 60, 4928;
b) T. B. Rauchfuss, F. T. Patino, D. M. Roundhill, Inorg.
Chem. 1975, 14, 652; c) J. Herrmann, P. S. Pregosin, R.
Salzmann, A. Albinati Organometallics 1995, 14, 3311.
1
307; b) S. R. Stauffer, S. Lee, J. P. Stambuli, S. I. Hauck,
J. F. Hartwig, Org. Lett. 2000, 2, 1423.
[6] a) C. W. Bielawski, R. H. Grubbs, Angew. Chem. 2000,
1
12, 3025; Angew. Chem. Int. Ed. 2000, 39, 2903; b) J. P.
Morgan, R. H. Grubbs, Org. Lett. 2000, 2, 3153; c) J. J.
van Veldhuizen, S. B. Garber, J. S. Kingsbury, A. H. Hov-
eyda, J. Am. Chem. Soc. 2002, 124, 4954; d) J. C. Conrad,
G. P. A. Yap, D. E. Fogg, Organometallics 2003, 22, 1986.
7] a) H. M. Lee, T. Jiang, E. D. Stevens, S. P. Nolan, Orga-
nometallics 2001, 20, 1255; b) M. Albrecht, J. R. Mieczni-
kowski, A. Samuel, J. W. Faller, R. H. Crabtree, Organo-
metallics 2002, 21, 3596; c) M. C. Perry, X. Cui, M. T. Po-
[
[
598
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 595±598