Pd(OAc)2 catalyzed homocoupling of arenediazonium salts in ionic liquids: Synthesis of symmetrical biaryls

Article abstract of DOI:10.1016/j.tetlet.2015.12.108

A facile, high yielding, and simple method for the synthesis of a library of symmetrical biaryls by homocoupling of arenediazonium salts is reported, employing catalytic amounts of Pd(OAc)₂ and the readily available imidazolium ionic liquids (ILs), without oxidants, ligands, additives, or volatile solvents. Simple product isolation and recycling/reuse of the IL represent additional advantages of this method.

Full text of DOI:10.1016/j.tetlet.2015.12.108

Accepted Manuscript
Pd(OAc)2 Catalyzed Homocoupling of Arenediazonium Salts in Ionic Liquids:
Synthesis of Symmetrical Biaryls
Hemantkumar M. Savanur, Rajesh G. Kalkhambkar, Kenneth K. Laali
PII:
S0040-4039(15)30523-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.12.108
TETL 47155
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
25 November 2015
23 December 2015
26 December 2015
Please cite this article as: Savanur, H.M., Kalkhambkar, R.G., Laali, K.K., Pd(OAc)2 Catalyzed Homocoupling of
Arenediazonium Salts in Ionic Liquids: Synthesis of Symmetrical Biaryls, Tetrahedron Letters (2015), doi: http://
dx.doi.org/10.1016/j.tetlet.2015.12.108
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Revised
Pd(OAc)2 Catalyzed Homocoupling of Arenediazonium Salts in Ionic
Liquids: Synthesis of Symmetrical Biaryls
Hemantkumar M. Savanur,a Rajesh G. Kalkhambkar,*a Kenneth K. Laali*b
a)
Department of Chemistry, Karnatak University’s Karnatak Science College,
Dharwad Karnatak 580001, India
b)
Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville,
Florida 32224, USA
ABSTRACT
A facile, high yielding, and simple method for the synthesis of a library of
symmetrical biaryls by homocoupling of arenediazonium salts is reported, employing
catalytic amounts of Pd(OAc)2 and the readily available imidazolium ionic liquids
(ILs), without oxidants, ligands, additives, or volatile solvents. Simple product
isolation and recycling/reuse of the IL represent additional advantages of this method.
TOC graphic
Keywords: symmetrical biaryls; imidazolium-IL; arenediazonium salts; Pd(OAc)2
homocoupling
*Corresponding Author: Tel: 904-620-1503, Fax: 904-620-3535. E-mail:
kenneth.laali@UNF.edu (Kenneth K. Laali); rgkalkhambkar@gmail.com (RGK)
1

The biaryl moiety is an important structural motif and building block that is
widely present in natural products, pharmaceuticals, advanced materials, conducting
polymers and liquid crystals.1 Consequently, a plethora of synthetic methods for aryl-
aryl bond formation have been developed over the years.1a Among various metal-
mediated protocols for the synthesis of biaryls, the palladium-catalyzed Suzuki
coupling utilizing aryl halides, sulfonates, or triflates, and aryl-boronic acids have been
widely employed.1
The discovery of aryl-diazonium salts as highly efficient coupling partners in
Pd-catalyzed reactions,2 opened up a new chapter in diazonium ion chemistry, and
prompted the development of improved methods for arylation via Suzuki-Miyaura,3-7
Sonogashira,8-10 and Heck reactions.11-12
Imidazolium ILs represent ideal media for metal-mediated coupling reactions
+
with arenediazonium salts because both ArN2 salts and Pd(OAc)2 can be dissolved in
the ionic liquid. The method also offers the added advantage to recycle and reuse the
IL.
We previously reported on Heck-Matsuda coupling reactions with [ArN2][X] in
IL solvents to synthesis a wide range of olefins,13 and on the synthesis of novel SF5-
bearing alkenes, alkynes, and biaryls via Heck, Sonogashira, and Suzuki couplings by
employing the pentafluorosulfanyl-diazonium salt [SF5-PhN2][BF4] as coupling
partner.14
Here we report our study of Pd(OAc)2-catalyzed homocoupling of
benzenediazonium terafluoroborates in readily available imidazolium ILs, exploring
the scope of the reaction to access to a library of symmetrical biaryls (Scheme 1).
Scheme 1. Synthesis of symmetrical biaryls by homocoupling of [ArN2][BF4] in IL
2

To our knowledge previous studies on the synthesis of symmetrical biaryls via
Pd-catalyzed homocoupling of arenediazonium salts have not been extensive,15 and use
of methanol as solvent for this reaction in an earlier study resulted in competing
formation of ArH due to hydro-dediazoniation.
RESULT AND DISCUSSION
At the onset feasibility studies were performed for metal-catalyzed
homocoupling of parent benzenediazonium-BF4 to form biphenyl in (bmim)BF4 and
(bmim)PF6 as solvents, and optimization of the reaction conditions namely type of
catalyst, the IL, reaction time, and temperature were carried out (Table 1).
Table 1. Catalyst optimization study for the synthesis of symmetrical biphenyl in ILa
Catalyst
N2BF4
IL
1a
1
Entry Catalystb
IL
Time (h) Tempc (oC) Yieldd (%)
1
2
PdCl2
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
3
4
50
50
55
55
60
60
60
58
50
50
55
55
60
60
60
60
36
41
NI
NI
NI
NI
40
38
38
34
39
40
NI
NI
NI
NI
PdCl2
3
Pd2(dba)3
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(dppf)
PdCl2(dppf)
Pd/C (10%)
Pd/C (10%)
PdI2
4
4
4
5
5
6
5
7
5
8
4
9
5
10
11
12
13
14
15
16
4
4
4
4
PdI2
3
Pd(acac)2
Pd(acac)2
3.5
4
3

17
18
19
20
21
22
Pd(OAc)2
Pd(OAc)2
Fe(acac)3
Fe(acac)3
Cu(OAc)2
RhCl(PPh3)3
(bmim)PF6
(bmim)BF4
(bmim)PF6
(bmim)BF4
(bmim)BF4
(bmim)PF6
1.2
1
45
50
50
55
60
50
89
94
5
NR
NR
NR
NR
5
4
4
a Reactions were carried out by using compound 1 (1.0 mmol) with catalyst (10 mol%)
in 3 mL of the IL solvent
b 10 mol% of catalyst was used.
c Oil-bath temperature
d Isolated yield of pure product
NI – not isolated (low conversion); NR – no reaction
Optimizations were initially performed in (bmim)PF6 with 10 mol % of PdCl2 at
50 °C for 3 h under air, leading to a 36% yield of biphenyl (entry 1), and with a slight
improvement in conversion (41%) when the reaction was carried out in (bmim)BF4 at
50 °C for 4 h (entry 2). Poor conversions were noted (TLC monitoring) when Pd2(dba)3
or Pd(PPh3)4 were used as catalysts in (bmim)PF6 or in (bmim)BF4 as solvent (entries 3-
6; therefore not isolated). Slight improvement was observed by employing Pd-catalysts
along with phosphine ligands (entries 7−10), and by using 10% Pd/C (entries 11-12).
No significant improvement in the homocoupling yields was achieved in the Pd-I2
catalyzed reaction (entries 13-14), and by using Pd(acac)2 (entries 15-16). Interestingly,
the desired biphenyl was obtained within 1.2 h in 89% yield from the Pd(OAc)2-
catalyzed reaction in (bmim)PF6 (entry 17), and in 94% yield when the reaction was
carried out at 50 °C in (bmim)BF4 for 1 h (entry 18). Several other metal catalysts were
also tested but proved ineffective (entries 19-22).
After optimizing the type of catalyst, the catalyst loading was varied to reach
optimal conversion (Table 2). Initially the reaction was carried out with 5 mol% of
Pd(OAc)2 at room temperature, and the progress of the reaction was monitored by TLC.
After 2h, only 39% yield was reached (entry 1). By increasing the temperature to 45oC,
a 58% yield was achieved after 1h (entry 2), and 62% yield was obtained at 60 oC (entry
3). By increasing the catalyst loading to 8-10% optimal conversions (88-90%) were
reached (entries 4 and 5), and further increase in catalyst loading did not result in
notable improvement (entry 6 and 7).
4

Table 2. Optimization of catalyst loadinga
Catalyst
IL
N2BF4
1a
1
Entry
1
IL
Pd(OAc)2 (mol %) Time (h) Tempb (oC) Yieldc (%)
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)PF6
(bmim)BF4
(bmim)BF4
(bmim)BF4
(bmim)Cl
5
5
2
1
28
45
60
45
45
45
50
50
50
45
50
52
60
60
60
39
58
2
3
5
3
62
4
8
0.45
1
88
5
10
12
15
8
90
6
1
90
7
1.2
1
93
8
86d
81 e
91
9
8
1
10
11
12
13
14
15
8
1
8
1
87d
79e
NR
44
8
1.2
1
5
(bmim)Cl
10
15
2
(bmim)Cl
3
48
a Reaction carried out using compound 1 (1.0 mmol) and Pd(OAc)2 (5-15 mol%) in 3
mL of the IL solvent
b Oil-bath temperature
c Isolated yield of pure product.
d Reaction performed in used IL (2nd cycle)
e Reaction performed in used IL (3rd cycle)
NR – No Reaction
5

In control experiments using (bmim)Cl, no reaction occurred with 5 mol%
o
catalyst at 60 C, (Table 2, entry 13), and with 10-15 mol% catalyst only moderate
yields (44-48%) could be reached after 3h (Table 2, entries 14 and 15).
Based on the yield data in Table 2, the prospect of recycling and reuse of the
imidazolium IL solvent in these reactions appear reasonable, given the conversions
obtained in entries 8 and 9 (for bmim-PF6), and in 11 and 12 (with bmim-BF4) in which
recycled IL had been employed (see Table 2 and footnotes).
With the optimization data at hand a survey study of the scope of symmetrical
biaryl synthesis via the Pd(OAc)2-catalyzed homocoupling reaction of arenediazonium
salts in (bmim)PF6 and (bmim)BF4 as solvent was undertaken and the results are
summarized in Table 3.16,17
Table 3. Scope of the Pd(OAc)2 catalyzed homocoupling of arenediazonium salts in
imidazolium-ILs
Entry
Substrate
Product
Time
(h)
Ionic liquid
Isolated
yield* (%)
N2BF4
1
0.45
(bmim)PF6
88a
N2BF4
2
3
1
1
(bmim)BF4
(bmim)PF6
94a
82b
N2BF4
O
O
O
N2BF4
F
F
4
5
0.50
0.30
(bmim)PF6
(bmim)BF4
80b
78b
F
N2BF4
Cl
Cl
Cl
6

N2BF4
Br
Br
6
7
1
1.2
1
(bmim)BF4
(bmim)BF4
(bmim)PF6
75c
90a
90a
Br
N2BF4
NO2
N2BF4
NC
CN
8
9
CN
N2BF4
0.45
1
(bmim)PF6
(bmim)PF6
87b
90a
O
N2BF4
10
O
O
Cl
N2BF4
11
12
1
(bmim)PF6
(bmim)PF6
71b
68c
Cl
Cl
NO2
N2BF4
1.5
O2N
O2N
N2BF4
13
14
1.2
(bmim)BF4
80a
O
N2BF4
1.3
1.5
(bmim)BF4
(bmim)BF4
85b
90a
O
O
NO2
N2BF4
15
16
NO2
N2BF4
O2N
Cl
1.2
(bmim)PF6
78a
Cl
Cl
7

77b
70a
Br
17
18
1.5
1.2
(bmim)PF6
(bmim)PF6
N2BF4
Br
Br
N2BF4
Br
Br
F
Br
84a
F
19
2
(bmim)BF4
N2BF4
F
*employing 10 mol% Pd(OAc)2
a Fresh IL was used
b 2nd cycle
c 3rd cycle
Isolated yields were in 94% to 68% range, depending on the nature and position
of the substituents. The relatively lower yields observed for the ortho-Br (entry 18) and
ortho-Cl (entry 11) analogs likely stems from steric effect. With the less bulky ortho-
OMe (entry 10) and ortho-methyl (entry 9) the yields were in optimal range. The lowest
conversion was observed with the ortho-NO2 (entry 12).
In summary, we have developed a simple, mild, and high yielding method for
the synthesis of a symmetrical biaryls by homocoupling of arenediazonium salts in
readily available imidazolium ILs, in the presence of catalytic amounts of Pd(OAc)2.
Solubility of diazonium salts and Pd-catalyst in imidazolium ILs allows the reactions
to be carried out under homogeneous conditions, and the prospect of recycling and
reuse of the IL provides an added advantage.
Supporting Information
1
Full experimental details, H, 13C NMR, GC-MS, and IR spectra of various
biaryls. This material is available free of charge via the Internet at supporting
information content.
Acknowledgements
The authors at Karnatak University thank the University Sophisticated
Instrument Center, KUD for IR, GC, and GC-MS, and the NMR Research Centre at
1
13
Indian Institute of Science Bangalore for H NMR and C NMR Spectral Data, and
8

Prof. M V. Kulkarni for useful discussions. Financial assistance to authors at Karnatak
University form Department of Science and Technology, Science and Engineering
Research Board New Delhi (DST-SERB) Project No SB/FT/CS-175/2013 is gratefully
acknowledged. KL thanks UNF for the award of Presidential Professorship.
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9

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Typical procedure for the synthesis of symmetrical biaryls by homocoupling
of arenediazonium salts. The desired arenediazonium tetrafluoroborate (1
mmol) was introduced at rt into an oven-dried Schlenk tube charged with
[bmim][PF6] or [bmim][BF4] ionic liquid (~3 mL) under a nitrogen
atmosphere. After efficient magnetic stirring (for 10–20 min), Pd(OAc)2 (8-10
mol %) was introduced under nitrogen and the reaction mixture was stirred at
o
45–60 C. The progress of the reaction was monitored by TLC until the
diazonium salt was fully consumed (this was determined based on
disappearance of the reddish-purple color upon treatment with an alkaline
solution of H-acid (4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid). The
brownish-colored reaction mass was cooled to r.t., and the products were
extracted with dry diethyl ether (4 times). Removal of solvent under vacuum
furnished the crude products which were chromatographed with hexane/ethyl
acetate or DCM/MeOH mixtures to afford the pure products which were
characterized by GC–MS and NMR. The brown-colored IL was dried
overnight under vacuum at 60oC and reused in the next 2–3 run, after which it
was set aside for recovery and recycling as outlined below.
17.
Procedure for recycling of ionic liquid: The combined brown-colored ionic
liquids recovered from several set of experiments were dissolved in MeCN,
and filtered through celite to remove insoluble black particles. After removal of
solvent from the filtrate under vacuum, the recycled IL was dried overnight
under vacuum at 60 oC and reused in subsequent runs.
10