Suzuki-Miyaura cross-couplings of arenediazonium tetrafluoroborate salts with arylboronic acids catalyzed by aluminium hydroxide-supported palladium nanoparticles

Article abstract of DOI:10.1039/c1ob06752d

Suzuki-Miyaura cross-couplings of arenediazonium salts with arylboronic acids catalyzed by highly active aluminium hydroxide-supported palladium nanoparticles catalyst have been investigated for the first time. The reactions are performed at 25 °C in MeOH without any base and ligand to afford biaryls in good to excellent yields under non-anhydrous and non-degassed conditions.

Full text of DOI:10.1039/c1ob06752d

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Suzuki–Miyaura cross-couplings of arenediazonium tetrafluoroborate salts
with arylboronic acids catalyzed by aluminium hydroxide-supported palladium
nanoparticles†
Xing Li,* Xu-Ying Yan, Hong-Hong Chang,* Li-Chao Wang, Yan Zhang, Wen-Wen Chen, Yan-Wei Li and
Wen-Long Wei
Received 19th October 2011, Accepted 27th October 2011
DOI: 10.1039/c1ob06752d
Suzuki–Miyaura cross-couplings of arenediazonium salts
with arylboronic acids catalyzed by highly active aluminium
hydroxide-supported palladium nanoparticles catalyst have
been investigated for the first time. The reactions are per-
formed at 25 ◦C in MeOH without any base and ligand
to afford biaryls in good to excellent yields under non-
anhydrous and non-degassed conditions.
considerable challenges and are highly desirable. Herein, we wish
to disclose in this paper an efficient, and highly active Suzuki
cross-coupling reaction of aryldiazonium salts with arylboronic
acids catalyzed by heterogeneous palladium nanoparticles catalyst
which was prepared by a simple one-pot three-component method
with as low as 0.3 mol% Pd under base-free, non-anhydrous and
non-degassed conditions in methanol at 25 ◦C.
We initiated our optimization studies by selecting benzenediazo-
nium tetrafluoroborate and phenylboronic acid as partners for the
Suzuki–Miyaura cross-coupling in the presence of the aluminium
hydroxide-supported palladium catalyst 1 which was prepared
and purified according to Min Serk Kwon’s reported procedure
(Scheme 1).9 In the course of the preparation of this catalyst 1,
110 ◦C was used as the reaction temperature instead of 120 ◦C
(in the literature).10 Firstly, the catalytic activity of the catalyst 1
was tested, and the results are summarized in Table 4 (see ESI†).
High yields were observed for the coupling reaction when using
the catalyst 1 for 4 h, whereas in the presence of the catalyst 2,
26% yield was obtained after 24 h. Only 31% yield of biphenyl
was isolated after 32 h if Pd (PPh3)4 was used as the catalyst. The
catalyst 1 proved to be exceptionally active for Suzuki Miyaura
reaction.
The palladium-catalyzed Suzuki–Miyaura cross-coupling reac-
tions have evolved as a reliable method1 to synthesize biaryls,
which are widely present in numerous classes of organic com-
pounds, such as advanced materials, ligands and molecules of
medicinal interest.2 A great number of studies have been devoted to
this cross-coupling reaction since the pioneering work from Suzuki
and Miyaura3, the vast majority of which involve the use of halo-
genated or sulfonated electrophiles.4 Recently, some attention has
been focused on the reaction that incorporates arenediazonium
tetrafluoroborate salts as aryl electrophilic components because
they can be easily synthesized from the corresponding amine
with high yield5 and are more reactive than the corresponding
aryl halides in the palladium-catalyzed Suzuki–Miyaura reaction.6
In addition, numerous kinds of palladium catalysts have been
extensively investigated and some new catalysts are gradually
being developed which have enabled this transformation to be
applied with a broad substrate scope, a wide functional group
tolerance, and low catalyst loadings.6b,7,8 Among these palladium
catalysts, nanoparticles catalysts are more promising, efficient
and practical because of their advantages and have made some
progress, showing enhanced reactivity with low catalyst loading
under mild conditions. At the same time, tremendous attention
and efforts have been devoted to the potential applications of them
in various coupling reactions. Despite these creative efforts and
significant progress, the design and synthesis of new nanoparticles
palladium catalysts that are cheaper and more efficient and the
development of new methods that are more effective remain
Scheme 1
Subsequently, the effectofcatalyst loadingonthe cross-coupling
reaction was investigated under air atmosphere at room tempera-
ture and the results are shown in Table 1. The yields were improved
apparently and gradually with the increase of the catalyst (Table 1,
entries 1–3). 92% of yield was obtained when as low as 0.3 mol%
Pd was utilized (Table 1, entry 3). Unfortunately, 0.4 mol% gave a
moderate 72% yield (Table 1, entry 4). The investigation of some
solvents usually used in Suzuki–Miyaura cross-coupling, such as
MeOH, EtOH, i-PrOH, H2O, THF, and so on, revealed that the
yields were significantly influenced by the sorts of the solvents and
the results clearly highlighted the beneficial effect of MeOH as
the best solvent (Table 1, entry 3).11 In sharp contrast, EtOH and
i-PrOH gave no product (Table 1, entries 5 and 6). The impact
Department of Chemistry and Chemical Engineering, Taiyuan University of
Technology, 79 West Yingze Street, Taiyuan, 030024, People’s Republic of
China. E-mail: lixing@tyut.edu.cn; Fax: +86-351-6111165; Tel: +86-351-
6111165
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1ob06752d
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Table 1 Optimization of the cross-coupling reaction with catalyst 1a
Table 2 Cross-couplings of arenediazonium tetrafluoroborate salts and
arylboronic acids catalyzed by palladium nanoparticles catalyst 1a
Equiv. of
phenyl-
Pd
Solvent
Yield
Entry R1
R2
H
t (h)
Product
Yield (%)b
92
Entry (mol%) Solvent dose (mL) T/◦C boronic acid t (h) (%)b
1
2
H
4
1
2
3
4
5
6
7
8
0.1
0.2
0.3
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
MeOH 1.8
MeOH 1.8
MeOH 1.8
MeOH 1.8
25
25
25
25
25
25
25
25
25
25
13
35
25
25
25
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.1
1.3
1.2
5.5 56
4
4
4
4
4
4
4
4
4
10
1
69
92
72
ND
ND
ND
trace
70
75
85
2-NO2
H
H
11
3
94c
92
EtOH
1.8
3
3-NO2
i-PrOH 1.8
H2O
THF
1.8
1.8
97c
73
45
9
MeOH 1.5
MeOH
4
5
6
4-NO2
4-Br
H
H
H
6
10
11
12
13
14
15c
2
MeOH 1.8
MeOH 1.8
MeOH 1.8
MeOH 1.8
MeOH 1.8
3.5
3.5
62
2.2 55
2.2 75
3-CH3
4
trace
a Unless otherwise specified, all reactions were performed on a 0.3 mmol
scale of benzenediazonium tetrafluoroborate. b Isolated yield. c Reaction
was performed without benzenediazonium.
7
4-CH3
H
H
20 (7)d
4
73 (72)d
69
8f
2-CH3
9f
H
3-CH3
4
88
of the solvent dosage on the yield was also studied. From that
work, we noticed that the reaction was best conducted with a
solvent dosage of 1.8 mL (Table 1, entry 3).12 The yield dropped
drastically to 70% and 75% when the solvent dosages were 1.5 mL
and 2 mL, respectively (Table 1, entries 9 and 10). Temperature
obviously influenced the reaction yield too. 25 ◦C was found to be
suitable temperature (Table 1, entry 3). Decreasing or elevating the
reaction temperature failed to increase the yield and an unwanted
by-product formed at higher temperature (Table 1, entries 11–
12). The amount of phenylboronic acid apparently affected the
reaction yield. It was preferable to use 1.2 equiv. of phenylboronic
acid with the yield of 92% (Table 1, entry 3). Lowering and
increasing its quantity to 1.1 equiv. and 1.3 equiv. could sharply
decrease the yields to 55% and 75%, respectively (Table 1, entries
13 and 14). After all these extensive experiments, it was discovered
that the optimal conditions employed 0.3 mol%◦Pd and 1.2 equiv.
of phenylboronic acid in 1.8 mL MeOH at 25 C for 4 h, which
provided biphenyl in 92% isolated yield. Note that biphenyl that
may come from homocoupling of phenylboronic acid has been
eliminated as supported by the fact that no biphenyl product
is observed under the same experimental conditions except for
the absence of benzenediazonium tetrafluoroborate. (Table 1,
entry 15).
Next, a variety of arenediazonium tetrafluoroborate salts and
arylboronic acids were examined for the cross-coupling reactions
using the optimized reaction conditions. As shown in Table 2,
whatever the electronic and steric nature of the cross-coupling
partners, most of the reactions gave biaryl products in good to
excellent yields under mild conditions with as low as 0.3 mol%
Pd. With regard to a series of salts, phenylboronic acid supplied
better results than 4-Me-phenylboronic acid (Table 2, entries 1–5, 7
vs. 10, 17–21). As for phenylboronic acid and 4-Me-phenylboronic
acid, the nitro-based diazonium salts gave good to excellent yields,
better than the methyl-based diazonium salts (Table 2, entries 2–4
and 17–19 vs. 7, 21). Using a variety of arylboronic acids, benzene-
10
H
H
4-CH3
4
4
74
97
11f
2-OCH3
12
H
H
3-OCH3
3-Cl
4
4
67
80
13f
14
15
16f
H
H
H
4-Cl
4
4
4
85
78
92
4-Br
3,5-(CH3)2
17
18
2-NO2 4-CH3
3-NO2 4-CH3
4-NO2 4-CH3
4.5
20
79
82e
19
20
21
12
4
73e
78c
70
4-Br
4-CH3
4-CH3 4-CH3
10
a Reaction conditions: arenediazonium tetrafluoroborate (0.3 mmol),
arylboronic acid (1.2 equiv, 0.36 mmol), catalyst (0.3 mol% Pd, 11.2 m◦g),
MeOH (1.8 mL), 25 ◦C. b Isolated yield. c Reaction was conducted at 20 C
(See ref. 13). d 0.5 mol% Pd catalyst was used. e Reaction was conducted at
0 ◦C. f 0.4 mol% Pd catalyst and 2 mL MeOH were used.
496 | Org. Biomol. Chem., 2012, 10, 495–497
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Table 3 Recycling and reuse of the catalyst 1
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Littke, C. Dai and G. C. Fu, J. Am. Chem. Soc., 2000, 122, 4020; (f) M.
Feuerstein, D. Laurenti, C. Bougeant, H. Doucet and M. Santelli,
Chem. Commun., 2001, 325; (g) F. Bellina, A. Carpita and R. Rossi,
Synthesis, 2004, 2419; (h) N. T. S. Phan, M. V. D. Sluys and C. W.
Jones, Adv. Synth. Catal., 2006, 348, 609; (i) N. Marion, O. Navarro,
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1875.
Diazonium
salts
(mmol)
Recovery of the
t (h) Yielda(%) catalyst 1 (%)
Entry Catalyst
1
2
3
Fresh
First Reuse 0.86
Second
Reuse
1.20
6
22
28
97
81
80
105b
78
58
0.30
a Isolated yield. b Ref. 15.
diazonium tetrafluoroborate afforded the corresponding products
with good yields (Table 2, entries 8–16). To our delight, the cross-
coupling reactions of 2-nitrobenzenediazonium salt proceeded
smoothly and showed good yields (Table 2, entries 2 and 17).
It is also important to point out that good chemoselectivity was
achieved in the coupling reactions using 4-bromophenyldiazonium
tetrafluoroborate (Table 2, entries 5 and 20), suggesting potential
utility in additional synthetic chemistry.
6 (a) K. Selvakumar, A. Zapf, A. Spannenberg and M. Beller, Chem.–
Eur. J., 2002, 8, 3901; (b) M. B. Andrus and C. Song, Org. Lett., 2001,
3, 3761.
7 (a) S. Darses, T. Jeffery, J. P. Geneˆt, J. L. Brayer and J. P. Demoute,
Tetrahedron Lett., 1996, 37, 3857; (b) S. Sengupta and S. Bhattacharyya,
J. Org. Chem., 1997, 62, 3405; (c) S. Darses, J. P. Geneˆt, J. L. Brayer
and J. P. Demoute, Tetrahedron Lett., 1997, 38, 4393; (d) S. Darses, G.
Michaud and J. P. Geneˆt, Eur. J. Org. Chem., 1999, 1875; (e) D. M.
Willis and R. M. Strongin, Tetrahedron Lett., 2000, 41, 6271; (f) K.
Selvakumar, A. Zapf, A. Spannenberg and M. Beller, Chem.–Eur. J.,
2002, 8, 3901; (g) M. J. Dai, B. Liang, C. H. Wang, J. H. Chen and Z.
Yang, Org. Lett., 2004, 6, 221; (h) F. X. Felpin, J. Org. Chem., 2005,
70, 8575; (i) V. Gallo, P. Mastrorilli, C. F. Nobile, R. Paolillo and N.
Taccardi, Eur. J. Inorg. Chem., 2005, 582; (j) Y. C. Qin, W. Wei and
M. M. Luo, Synlett., 2007, 2410; (k) R. H. Taylor and F. X. Felpin,
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Chem.–Asian J., 2007, 2, 1020; (m) J. T. Kuethe and K. G. Childers,
Adv. Synth. Catal., 2008, 350, 1577; (n) F. X. Felpin and E. Fouque,
Adv. Synth. Catal., 2008, 350, 863; (o) F. X. Felpin, E. Fouquet and C.
Zakri, Adv. Synth. Catal., 2009, 351, 649.
We further explored the catalyst recycling through the Suzuki–
Miyaura cross-coupling of 3-nitrobenzenediazonium tetrafluo-
roborate and phenylboronic acid (Table 3).14 The catalyst could
be recovered and reused after separation, washing with CH2Cl2,
and drying under vacuum under the same reaction conditions.
Although it could be recycled and reused three times without a
significant reduction in the yield, the catalyst activity obviously
decreased after the first, second and third consecutive cycles,
respectively. The significant decrease of the catalytic activity was
probably due to some loss of the nanocomposite catalysts during
the recovery process which was caused by the decrease of the
recovery percent of this catalyst.
In summary, we have investigated for the first time the Suzuki–
Miyaura cross-couplings of arenediazonium tetrafluoroborate
salts and arylboronic acids catalyzed by this very highly active
and easily synthesized palladium catalyst entrapped in aluminium
hydroxide with as low as 0.3 mol% Pd. It is a practical, efficient
and general protocol for cross-coupling with the advantages of
good substrate generality, ease of experimental operation and
mild conditions without inert-gas protection and any additional
additives (base and ligand). More importantly, this palladium
catalyst shows good to excellent yields towards a series of
arenediazonium tetrafluoroborate salts.
8 For a recent review on diazonium salts as substrates in palladium-
catalyzed cross-coupling reactions, see: A. Roglans, A. Pla-Quintana
and M. Moreno-Man˜as, Chem. Rev., 2006, 106, 4622.
9 M. S. Kwon, N. Kim, C. M. Park, J. S. Lee, K. Y. Kang and J. Park,
Org. Lett., 2005, 7, 1077.
10 The boiling point of 1-butanol is 116 ◦C–118 ◦C. The reaction
temperature could only reach 110 ◦C at the reflux under the local
atmospheric pressure.
11 Among the solvents investigated, alcoholic solvents were the best.
Especially, methanol was the most efficient in terms of yield and
rate for the cross-coupling, which might be related to the solubility
of arenediazonium tetrafluoroborate salts. Because EtOH and i-
PrOH provided the worst solubility, EtOH could only provide the
product with 61% yield and i-PrOH could still give no product after
28 h.
12 The amount of MeOH was related to the solubility of arenediazonium
tetrafluoroborate salts. Although it was best that arenediazonium
tetrafluoroborate salts were dissolved fully, which facilitated the
proceeding of the reaction, too much MeOH would play a negative
effect on the yield.
13 Side reactions would occur and the yields of the corresponding products
decreased obviously when these reactions were performed at 25 ◦C,
although the reaction time were shortened. The corresponding yields
at 25 ◦C were 71%, 61%, 54%, respectively. For more details, see Table
5 in the Supporting Information†.
14 For more details of a typical recycling procedure, see Supporting
Information†.
15 It was confirmed that the results of the subsequent recovery experiments
were best if the first recovery of the catalyst 1 was well beyond 100%
and the solvent was used as little as possible when the catalyst 1 was
recovered.
Notes and references
1 For recent reviews, see: (a) N. Miyaura, Top. Curr. Chem., 2002, 219,
11; (b) N. Miyaura, J. Organomet. Chem., 2002, 653, 54; (c) A. Suzuki,
Chem. Commun., 2005, 4759.
2 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457>; (b) P.
Lloyd-Williams and E. Giralt, Chem. Soc. Rev., 2001, 3, 145; (c) J.
Hassan, M. Se´vignon, C. Gozzi, E. Schulz and M. Lemaire, Chem. Rev.,
2002, 102, 1359; (d) S. Kohta, K. Lahiri and D. Kashinath, Tetrahedron,
2002, 58, 9633; (e) A. Suzuki, J. Organomet. Chem., 2002, 653, 83; (f) B.
S. Yong and S. P. Nolan, Chemtracts: Org. Chem., 2003, 205; (g) L. X.
Yin and L. Ju¨rgen, Chem. Rev., 2007, 107, 133; (h) X. Q. Shen, G. O.
Jones, D. A. Watson, B. Bhayana and S. L. Buchwald, J. Am. Chem.
Soc., 2010, 132, 11278.
3 For recent reviews and examples, see: (a) N. Miyaura and A. Suzuki,
Chem. Rev., 1995, 95, 2457; (b) D. W. Old, J. P. Wolfe and S. L.
This journal is
The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 495–497 | 497
©