Highly active palladium catalyst for the sonogashira coupling reaction of unreactive aryl chlorides

Article abstract of DOI:10.1002/adsc.201100747

This communication reports on the β-diketiminatophosphane palladium-catalyzed copper-free Sonogashira coupling of aryl chlorides with alkynes. A catalyst loading of 0.5 mol% is sufficient to achieve high performance under relatively mild reaction conditio

Full text of DOI:10.1002/adsc.201100747

COMMUNICATIONS
DOI: 10.1002/adsc.201100747
Highly Active Palladium Catalyst for the Sonogashira Coupling
Reaction of Unreactive Aryl Chlorides
Dong-Hwan Lee,a Young-Jun Kwon,a and Myung-Jong Jina,*
a
Department of Chemical Engineering, Inha University, Incheon 402-751, South Korea
Fax :ACHTUNGTRENNUNG(+82)-32-872-0939; e-mail: mjjin@inha.ac.kr
Received: September 26, 2011; Published online: November 16, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100747.
Abstract: This communication reports on the b-di-
ketiminatophosphane palladium-catalyzed copper-
free Sonogashira coupling of aryl chlorides with al-
kynes. A catalyst loading of 0.5 mol% is sufficient
to achieve high performance under relatively mild
reaction conditions. Furthermore, dialkynylben-
zenes are efficiently prepared by one-pot double
Sonogashira couplings of aryl dichlorides.
dides as the useful coupling substrates. From an in-
dustrial point of view, however, aryl chlorides are
much more attractive due to their low cost and wide
availability. However, deactivated aryl chlorides are
most reluctant to undergo catalytic oxidative addition
[6]
À
due to the strong C Cl bond. Only a few reports
can be found on the successful coupling of aryl chlor-
ides.[7] Most of these examples, however, suffer from
disadvantages such as harsh reaction conditions, high
reaction temperatures, high catalyst loadings, and
long reaction times. Hence, there is a need to develop
highly active catalysts for the mild couplings of deac-
tivated aryl chlorides. We have recently discovered b-
diketiminatophosphane palladium catalysts for the
Suzuki reaction of aryl chlorides.[8] In continuation of
our exploration on their applications, we herein de-
Keywords: aryl chlorides; cross-coupling; homoge-
neous catalysts; palladium; phosphane ligands; So-
nogashira reaction
Over the last decades, palladium-catalyzed cross-cou- scribe the Sonogashira coupling reaction of unreactive
pling reactions have become fundamental methodolo- aryl chlorides in the presence of catalytic amounts of
gies in organic synthesis.[1] Among them, the Sonoga- Pd catalysts 2.
shira reaction of aryl and vinyl halides with terminal
The synthetic route for b-diketiminatophosphane
alkynes is the most valuable method for the synthesis palladium complexes 2 is shown in Scheme 1.
of arylalkynes and conjugated enynes, which are po-
tential precursors to natural products, pharmaceuti-
b-Diketimines 1 were readily produced from acetyl-
AHCTUNGTREGUNaNN cetone and primary amines under microwave heat-
cals and other materials.[2] A variety of palladium cat- ing. The deprotonation of 1 with EtOTl followed by
alysts has been developed to enhance the efficiency treatment with Pd2ACHTUNGTRNE(UGN m-Cl)2Me2L2 (L=PPh3, PEt3) af-
and generality of this reaction.[3] In particular, cyclo- forded the Pd complexes 2 with air and moisture sta-
palladated phosphanes[4] and N-heterocyclic car- bility.
benes[5] have attracted considerable attention. The re-
To evaluate the catalytic activity of 2 in the Sonoga-
action seems to be limited to aryl bromides and io- shira coupling, the reaction between deactivated 4-
Scheme 1. b-Diketiminatophosphane Pd catalysts 2.
3090
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3090 – 3094

Highly Active Palladium Catalyst for the Sonogashira Coupling Reaction of Unreactive Aryl Chlorides
Table 1. Sonogashira coupling of 4-chloroanisole with phenylacetylene.[a]
Entry
1 (mol%)
Solvent
Base
Time [h]
Yield [%][b]
1
2
2a (0.5)
2a (0.1)
2a (0.02)
2a (2.0)
2a (0.5)
2a (0.5)
2a (0.5)
2a (0.5)
2a (0.5)
2a (0.5)
2a (0.5)
2a (0.5)
2a (0.5)
2b (0.5)
2c (0.5)
DMF-H2O
DMF-H2O
DMF-H2O
DMF-H2O
DMSO-H2O
DMA-H2O
NMP-H2O
EtOH-H2O
DMF-H2O
DMF-H2O
DMF-H2O
DMF-H2O
DMF-H2O
DMF-H2O
DMF-H2O
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
pyrrolidine
Et3N
5
8
24
24
5
5
5
5
5
5
5
5
5
5
5
91
82
68
72
88
74
69
46
82
53
71
62
67
62
79
3[c]
4[d]
5
6
7
8
9
10
11
12
13
14
15
A
Cs2CO3
KO-t-Bu
piperidine
piperidine
[a]
4-Chloroanisole (1.0 mmol), phenylacetylene (1.2 mmol), 2 (0.5 mol%), base (2.0 mmol), TBAB (0.5 mmol), DMF-H2O
(2 mL, 1:3), and 508C.
Yields determined by GC/MS.
At 708C.
[b]
[c]
[d]
At room temperature.
chloroanisole and phenylacetylene was carried out in steric effects in increasing the reactivity of this cou-
our initial studies (Table 1). With a catalyst loading of pling. Although the structure of the catalytically
0.5 mol% in the presence of piperidine and active Pd species remains unclear, the diketiminate
tetrabutyl
ACHTUNGTRENNUNGammonium bromide (TBAB), the reaction and the phosphane both are unlikely to remain coor-
worked effectively in aqueous DMF at 508C and gave dinated in the active species.
the coupled product in 91% yield (Table 1, entry 1).
Various aryl chlorides reacted with terminal alkynes
The palladium loading could be reduced to 0.1 mol% in the presence of 0.5 mol% of 2a at 508C (Table 2).
with a slight drop in reaction rate, but a further de- As expected, the coupling of activated aryl chlorides
crease to 0.02 mol% gave incomplete conversion or chlorobenzene occurred to completion within short
(Table 1, entries 2 and 3). It was possible to achieve reaction times and formed the desired products in ex-
the coupling even at room temperature, although a cellent yields (Table 2, entries 1–4). Remarkably, the
long reaction time was needed (Table 1, entry 4). catalyst still displayed high activity in the reactions of
After a brief optimization of the reaction conditions, deactivated electron-rich aryl chlorides such as 4-
the use of other solvents like aqueous DMSO, DMA, chloroanisole, 2-chloroanisole, and 2-chlorotoluene
NMP, and EtOH was also tested. However, none of under these conditions (Table 2, entries 5–8). Chloro-
them gave better results (Table 1, entries 5–8). We naphthalenes also reacted efficiently with 4-ethynyl-
found that aqueous DMF was preferred as solvent
ACHTUNGTRENaNGNU nisole (Table 2, entries 9 and 10). Hindered 2-chloro-
with catalyst 2a. The choice of the base was also deci- 1,3-dimethylbenzene smoothly underwent the cou-
sive for the success of this coupling. Piperidine pro- pling at 708C to produce the desired products in good
vided better efficiency than pyrrolidine, Et3N, (i- yields, although a higher temperature and longer time
Pr)2EtN, Cs2CO3 and KO-t-Bu (Table 1, entries 9–13). were required (Table 2, entries 11–13). The scope of
It was noted that catalysts 2b and 2c gave inferior re- this coupling was extended to other alkynes such as
sults under the same conditions (Table 1, entries 14 propargyl alcohol, 5-hexyn-1-ol, ethynylcyclopentane,
and 15). The higher activity of precatalyst 2a is as- 1-hexyne, 1-octyne, (triisopropylsilyl)acetylene, and 3-
cribed to the combination of methyl groups on the allyloxyprop-1-yne (Table 2, entries 14–22). All of the
phenyl rings and triethylphosphane. Strong s-donat- reactions afforded the corresponding products in high
ing triethylphosphane seems to be very effective at yields. Regardless of the substituents, most of the re-
À
the oxidative addition to Ar Cl bonds or the forma- actions were very clean and highly efficient under
tion of the active Pd species. It is also plausible that mild conditions. To the best of our knowledge, cata-
the methyl groups have favourable electronic and
Adv. Synth. Catal. 2011, 353, 3090 – 3094
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3091

Dong-Hwan Lee et al.
COMMUNICATIONS
Table 2. Sonogashira coupling of aryl chlorides with alkynes.[a]
Entry Aryl chloride Product
Time Yield Entry Aryl chloride Product
[h]
Time Yield
[h]
[%][b]
[%][b]
1
2
94
12[c]
12
83
2
3
2.5
2.5
91
94
13[c]
14
12
5
76
93
4
5
6
7
5
5
6
6
93
91
92
90
15
16
17
18
6
6
4
8
89
84
88
87
8
6
86
19
8
83
9
6
6
85
89
20
21
8
8
86
89
10
11[c]
10
85
22
6
84
[a]
4-Chlorotoluene (1.0 mmol), phenylacetylene (1.2 mmol), 2a (0.5 mol%), piperidine (2.0 mmol), TBAB (0.5 mmol),
DMF-H2O (2 mL, 1:3), and 508C.
Isolated yield.
At 708C.
[b]
[c]
lyst 2a shows the highest known catalytic activity to- as promising charge transport materials in organic
wards deactivated aryl chlorides.
electronic devices.[9] 6,13-Bis(phenylethynyl)penta-
Encouraged by the above success, we extended our cene could be synthesized through the reaction of
work to a double Sonogashira coupling reaction of 6,13-dichloropentacene with phenylacetylene
aryl dichlorides (Table 3). From the view point of effi- (Table 3, entry 6). This is the first attempt to date at
ciency, one-pot double couplings of inexpensive aryl the challenging double Sonogashira coupling of aryl
dichlorides would be highly desirable. However, no dichlorides. We anticipate that this work can make a
successful examples have been reported. It is note- significant contribution to the advancement of the So-
worthy that the catalyst 2a showed excellent perfor- nogashira reaction.
mance in the reactions of 1,2-dichlorobenzene with
phenylacetylene, 1-ethynyl-2-methylbenzene, and (2- diketAHCTUNTGRENNUNG
In summary, we have demonstrated that the b-
iminatophosphane Pd complex acts as a highly
ethynylphenyl)methanol (Table 3, entries 1–4). More- active and general catalyst for the Sonogashira cou-
over, 1,2-dichlorobenzene reacted efficiently with 1- pling of less reactive aryl chlorides with terminal al-
octyne (Table 3, entry 5). Especially, 6,13-disubstitut- kynes. Structurally and electronically diverse aryl
ed pentacenes have recently attracted much attention chlorides were coupled with a variety of alkynes at
3092
asc.wiley-vch.de
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3090 – 3094

Highly Active Palladium Catalyst for the Sonogashira Coupling Reaction of Unreactive Aryl Chlorides
Table 3. One-pot double Sonogashira coupling of aryl dichlorides.[a]
Entry
1
Aryl chloride
Product
Time [h]
6
Yield [%][b]
84
2
3
8
8
88
89
4
5
8
8
8
91
81
84
6
[a]
Aryl chloride (1.0 mmol), alkyne (2.4 mmol), 2a (1.0 mol%), piperidine (4.0 mmol), TBAB (1.0 mmol), DMF-H2O (3 mL,
1:3), and 708C.
Isolated yield.
[b]
low catalyst loadings under mild conditions. Notably,
a one-pot double Sonogashira coupling of aryl di-
chlorides was successfully accomplished.
bined organic layers was washed with H2O and brine, dried
over anhydrous MgSO4, filtered, and concentrated under
vacuum. The residue was purified by column chromatogra-
phy with a gradient eluent of 0–25% ethyl acetate in hex-
anes to give the coupled product.
Experimental Section
General Procedure for Sonogashira Coupling
Reactions
General Procedure for One-Pot Double Sonogashira
Coupling Reactions
Aryl chloride (1.0 mmol), alkyne (1.2 mmol), piperidine
(170 mg, 2.0 mmol), TBAB (161 mg, 0.5 mmol) and catalyst
2a (2.5 mg, 0.5 mol%) were mixed in DMF-H2O (2.0 mL,
1:3). The mixture was stirred at 508C in an air atmosphere
and monitored by GC/GC-MS. Water was then added and
the mixture was extracted with Et2O three times. The com-
Aryl chloride (1.0 mmol), alkyne (2.4 mmol), piperidine
(340 mg, 4.0 mmol), TBAB (322 mg, 1.0 mmol) and catalyst
2a (5 mg, 1.0 mol%) were mixed in DMF-H2O (3 mL, 1:3).
The mixture was stirred at 708C for 8 h in an air atmosphere
and monitored by GC/GC-MS. The reaction mixture was
treated in the same work-up manner as described above.
Adv. Synth. Catal. 2011, 353, 3090 – 3094
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3093

Dong-Hwan Lee et al.
COMMUNICATIONS
Acknowledgements
Ulven, J. Org. Chem. 2010, 75, 1301; j) R. Severin, J.
Reimer, S. Doye, J. Org. Chem. 2010, 75, 3518.
[4] a) R. B. Bedford, Chem. Commun. 2003, 1787; b) D. A.
Alonso, C. Naꢁjera, M. C. Pacheco, Adv. Synth. Catal.
2003, 345, 1146; c) C. S. Consorti, F. R. Flores, F. Ro-
minger, J. Dupont, Adv. Synth. Catal. 2006, 348, 133;
d) F. Yang, Y. Wu, Eur. J. Org. Chem. 2007, 3476; e) B.-
S. Zhang, C. Wang, J.-F. Gong, M.-P. Song, J. Organo-
met. Chem. 2009, 694, 2555; f) J. L. Bolliger, C. M.
French, Adv. Synth. Catal. 2009, 351, 891.
[5] a) R. A. Batey, M. Shen, A. J. Lough, Org. Lett. 2002, 4,
1411; b) M. Eckhanlt, G. C. Fu, J. Am. Chem. Soc. 2003,
125, 13642; c) Y. Ma, C. Song, W. Jiang, Q. Wu, Y.
Wang, X. Liu, M. B. Andrus, Org. Lett. 2003, 5, 3317;
d) E. Peris, R. H. Crabtree, Coord. Chem. Rev. 2004,
248, 2239; e) L. Ray, S. Barman, M. M. Shaikh, P.
Ghosh, Chem. Eur. J. 2008, 14, 6646; f) A. John, M. M.
Shaikh, P. Ghosh, Dalton Trans. 2009, 10581; g) S. Gu,
W. Chen, Organometallics 2009, 28, 909; h) A. Zanardi,
J. A. Mata, E. Peris, Organometallics 2009, 28, 4335; i) S.
Roy, H. Plenio, Adv. Synth. Catal. 2010, 352, 1014.
[6] A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350;
Angew. Chem. Int. Ed. 2002, 41, 4176.
[7] a) A. Kçllhofer, T. Pullmann, H. Plenio, Angew. Chem.
2003, 115, 1086; Angew. Chem. Int. Ed. 2003, 42, 1056;
b) D. Gelman, S. L. Buchwald, Angew. Chem. 2003, 115,
6175; Angew. Chem. Int. Ed. 2003, 42, 5993; c) K. W.
Anderson, S. L. Buchwald, Angew. Chem. 2005, 117,
6329; Angew. Chem. Int. Ed. 2005, 44, 6173; d) M.
Heiden, H. Plenio, Chem. Commun. 2007, 972; e) C. Yi,
R. Hua, H. Zeng, Q. Huang, Adv. Synth. Catal. 2007,
349, 1738; f) C. A. Fleckenstein, H. Plenio, Organome-
tallics 2007, 26, 2758; g) A. Komꢁromi, Z. Novꢁk, Chem.
Commun. 2008, 4968; h) H. Huang, H. Liu, Hu. Jiang,
K. Chen, J. Org. Chem. 2008, 73, 6037; i) M.-J. Jin, D.-H.
Lee, Angew. Chem. 2010, 122, 1137; Angew. Chem. Int.
Ed. 2010, 49, 1119.
This work was supported by a National Research Foundation
of Korea Grant funded by the Korean Government (2011-
0003169) and an Inha University Research Grant.
References
[1] For reviews, see; a) A. deMeijere, F. Diederich, (Eds.),
Metal-Catalyzed Cross-Coupling Reactions, Vol. 2,
Wiley-VCH, Weinheim, 2004; b) T. N. Mitchell, Metal-
Catalyzed Cross-Coupling Reactions, Wiley-VCH, Wein-
heim, 2004.
[2] a) J. Lam, H. Bretler, T. Arnason, L. Hansen, (Eds.),
Chemistry and Biology of Naturally Occurring Acety-
lenes and Related Compounds, Elsevier, Amsterdam,
1988; b) U. H. F. Bunz, Y. Rubin, Y. Tobe, Chem. Soc.
Rev. 1999, 28, 107; c) E. Negishi, L. Anastasia, Chem.
Rev. 2003, 103, 1979; d) Z. NovNk, A. Kotschy, Org.
Lett. 2003, 5, 3495; e) M. J. Piao, K. Chajara, S. J. Yoon,
H. M. Kim, S.-J. Jeon, T.-H. Kim, K. Song, I. Assel-
berghs, A. Persoons, K. Clays, B. R. Cho, J. Mater.
Chem. 2006, 16, 2273; f) C. Nꢁjera, R. Chinchilla, Chem.
Rev. 2007, 107, 874; g) H. Doucet, J.-C. Hierso, Angew.
Chem. 2007, 119, 850; Angew. Chem. Int. Ed. 2007, 46,
834; h) R. Chinchilla, C. Nꢁjera, Chem. Soc. Rev. 2011,
40, 5084.
[3] a) G. Adjabeng, T. Brenstrum, C. S. Frampton, A. J.
Robertson, J. Hillhous, J. McNulty, A. Capretta, J. Org.
Chem. 2004, 69, 5082; b) J.-C. Hierso, A. Fihri, R. Amar-
deil, P. Meunier, Org. Lett. 2004, 6, 3473; c) C. A. Fleck-
enstein, H. Plenio, Chem. Eur. J. 2007, 13, 2701; d) J. V.
Seregin, V. Ryabova, V. Gevorgyan, J. Am. Chem. Soc.
2007, 129, 7742; e) C. Torborg, A. Zapf, M. Beller,
ChemSusChem 2008, 1, 91; f) V. P. Mehta, A. Sharma, E.
Van der Eycken, Org. Lett. 2008, 10, 1147; g) D.-H. Lee,
H. Qiu, M.-H. Cho, I.-M. Lee, M.-J. Jin, Synlett 2008,
1657; h) D.-H. Lee, Y. H. Lee, J. M. Harrowfield, I.-M.
Lee, H. I. Lee, W. T. Lim, Y. Kim, M.-J. Jin, Tetrahedron
2009, 65, 1630; i) E. Christiansen, M. E. Due-Hansen, T.
[8] D.-H. Lee, M.-J. Jin, Org. Lett. 2011, 13, 252.
[9] C. Kim, P.-Y. Huang, J.-W. Jhuang, M.-C. Chen, J.-C.
Ho, T.-S. Hu, J.- Y. Yan, L.-H. Chen, G.-H. Lee, A. Fac-
chetti, T. J. Marks, Org. Electron. 2010, 11, 1363.
3094
asc.wiley-vch.de
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3090 – 3094