Coupling of boronic acids with amines in the presence of a supported copper catalyst

Article abstract of DOI:10.1007/s10562-014-1301-x

An efficient heterogeneous catalytic method was developed for Chan-Lam reaction, coupling of amines and boronic acid. Copper on 4 A molecular sieve provided yields comparable to the methods published. The method provides the main advantages of a heterogeneous catalytic procedure, the preparation of the catalyst is easy, the workup of the reaction mixture is simple. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-014-1301-x

Catal Lett (2014) 144:1547–1551
DOI 10.1007/s10562-014-1301-x
Coupling of Boronic Acids with Amines in the Presence
of a Supported Copper Catalyst
N o´ ra Debreczeni
•
Anna Fodor
Zolt a´ n Hell
•
Received: 15 April 2014 / Accepted: 12 June 2014 / Published online: 4 July 2014
Ó Springer Science+Business Media New York 2014
Abstract An efficient heterogeneous catalytic method
was developed for Chan-Lam reaction, coupling of amines
˚
and boronic acid. Copper on 4 A molecular sieve provided
having NH or OH groups. Among the substrates amines,
amides, imides, phenols, carbamides and sulfonamides
have been described. The reaction was catalyzed by cop-
per(II)-acetate, and generally pyridine or triethylamine
were used as base [11, 12] (Fig. 1).
yields comparable to the methods published. The method
provides the main advantages of a heterogeneous catalytic
procedure, the preparation of the catalyst is easy, the
workup of the reaction mixture is simple.
Numerous modifications of this method has been pub-
lished. Thus e.g. aromatic amines were coupled with
methylboronic acid in the presence of copper(II)-acetate
and pyridine [13]. Vinyl boronates and allylalcohols in the
presence of copper(II)-acetate gave allyl vinyl ethers [14].
Instead of boronic acids organotrifluoroborate salts were
also used for the preparation of aryl, alkenyl or diaryl
ethers [15] as well as aryl and diaryl amines [16]. Different
catalysts were also tested, thus copper(I) oxide in boiling
methanol [17], or copper-exchanged fluorapatite in meth-
anol at room temperature [18] gave also good results. A
detailed review has been published recently presenting the
scope and limitation of the method, the published reagents,
as well as descriptions about the mechanism [19]. Some
interesting variations were also presented, thus e.g. the
arylation of tetrazoles in the presence of copper(I) oxide,
oxidative atmosphere and DMSO as solvent. The authors
established that copper(I) will oxidize to copper(II), which
then forms a complex with both tetrazole and DMSO. A
disproportionation of copper(II) yields copper(I) and cop-
per(III) and this copper(III) is the responsible for the cat-
alytic effect [20, 21]. A Ni-catalyzed method was also
Keywords Chan-Lam reaction Á Copper Á Molecular
sieve Á Heterogeneous catalysis
1
Introduction
The metal catalyzed cross-coupling reactions gave valuable
synthetic tools in the preparative organic chemistry.
Among the methods developed the palladium catalyzed
C–C(aryl) bond formation has an outstanding role [1, 2].
However, there are fewer examples for the formation of
C(aryl)-heteroatom bond. The traditional Ullmann reaction
[
3] requires hard reaction conditions, produces large
amount of harmful waste and gives variable yields.
Recently an efficient method was developed by Buchwald
and Hartwig for the arylation of amines using palladium or
nickel catalyst [4, 5]. Aryllead, arylbismuth, arylborane
and arylsilane compounds were also used as coupling
component [6–10].
˚
published [22]. In some cases 4 A molecular sieve was also
In the method developed by Chan and Lam boronic
acids were used as reagents for the arylation of compounds
added to the reaction mixture [15, 16, 23].
Working on the examination of heterogeneous catalytic
methods in the preparative organic chemistry we prepared
2
?
N. Debreczeni Á A. Fodor Á Z. Hell (&)
Department of Organic Chemistry and Technology, Budapest
University of Technology and Economics, M }u egyetem rkp 3,
Budapest 1111, Hungary
˚
copper(II) on 4 A molecular sieve (Cu /4A) by impreg-
nation of finely ground molecular sieve with copper(II)
chloride in deionized water. The targeted copper content of
this catalyst was 6.3 wt%, the experimental value was
e-mail: zhell@mail.bme.hu
123

1
548
N. Debreczeni et al.
Fig. 1 General scheme of the
Chan-Lam reaction
Y
B(OH)2
Cu(OAc)2
R'
Y = O, NH
R
+
R'
YH
R
Et N or
3
pyridine
CH Cl , rt, 24-72 h
40-90%
2
2
elaborated in the reaction of phenylboronic acid and mor-
pholine (Fig. 3). The results are summarized in Table 1.
Good results were obtained only in dichloromethane.
Methanol, which is also known solvent of the Chan-Lam
reaction, gave poor yield. Using Cu(II) on Mg-La mixed
2
?
oxide support (Cu /MgLaO) as catalyst the desired
2
?
product was no observed. Cu /4A gave moderate yield. In
all experiments large amount (20–40 %) of triphenylbo-
roxine (4, Fig. 2.) was also formed. Although in the liter-
ature mostly pyridine (sometimes triethylamine) has been
described as base in this reaction, we checked the possi-
bility of the use of other bases, too. Replacing pyridine
with triethylamine the yields decreased appreciably. Use of
other bases (sodium hydrogencarbonate or potassium car-
bonate) gave poor yield probably due to the multiple het-
erogeneous system.
2
Fig. 2 SEM image of the Cu /4A catalyst
?
5
.8 wt% (determined by ICP-OES). The surface analysis
by scanning electron microscope (SEM) showed cubic
zeolite crystals, most of the particles were in the 2.5–5 lm
range (Fig. 2, 10009 magnification). EDS showed that
copper covered the support’s surface evenly. The surface
2
?
0
Replacing Cu /4A with its reduced form (Cu /4A) the
conversion increased significantly, and the amount of 4
0
decreased below 5 %. As Cu /4A is sensitive to the
2
atmospheric oxygen, the weighing of the catalyst were
carried out under argon atmosphere. Increasing drastically
the amount of copper on the support’s surface the yield of
the desired product dropped dramatically while the amount
of 4 increased strongly (see Table 1, last entry).
area of the original molecular sieve (810 m /g) dropped to
2
60 m /g after the impregnation. This catalyst was applied
3
3
successfully in the A -coupling [24] as well as in the
transformation of oximes into nitriles [25] or nitriles into
2
amides [26]. Cu /4A was reduced with hydrazine hydrate
?
Further experiments were made under these reaction
conditions. The results of the reaction of phenylboronic
acid with different amines (Fig. 4.) are summarized in
Table 2.
using the proven method described for the preparation of
0
the supported Pd catalysts earlier [27, 28]. Copper content
0
of Cu /4A catalyst dropped to 5.5 wt%. There were no
remarkable changes in the surface area, the particle size
distribution remained practically the same. Copper distri-
bution on the surface was not modified during the reduc-
tion. The finely distributed copper made the catalyst
sensitive to the atmospheric oxygen.
The desired products were obtained with moderate to
good yield. A slight substituent effect was observed, see
compounds 3b-d. The aliphatic boronic acid 1f gave sim-
ilar result than the aromatic derivatives. A few amount
(\5 %) of the appropriate boroxine was obtained in all
cases, this could be separated easily by column chroma-
tography. XRF study showed that no remarkable amount of
copper could be found in the product.
2
Results and Discussion
We investigated the reactivity of our catalyst in the Chan-
Lam reaction. The optimal reaction conditions were
The recyclability of the catalyst was examined in the
reaction of phenylboronic acid and morpholine. In this case
Fig. 3 Model reaction for the
determination of the optimal
reaction conditions
OH
O
B
pyridine
O
B
O
B
B
+
N
O
+
OH
N
H
O
1
a
2a
3a
4
1
23

Coupling of boronic acids with amines
1549
Table 1 Optimization of the reaction conditions
as well as phenols. The yields were comparable with the
published ones. The workup of the reaction mixture vas
very simple, the catalyst was filtered out, then the solvent
was evaporated and the residue was purified by column
chromatography.
Solvent
Catalyst
Temperature Reaction Yield
a
(
°C)
time (h) (%)
2
?
Dichloromethane Cu /4A,
.2 g
40
24
20
20
35
24
42
7
0
2
?
Methanol
Cu /4A,
.2 g
65
0
2
?
3 Experimental
Toluene
Cu /4A,
.2 g
110
80
–
0
2
?
The commercial starting materials were purchased from
Merck-Hungary Ltd.
Acetonitrile
Cu /4A,
.2 g
–
0
2
?
1
Dichloromethane Cu /MgLaO, 40
.2 g
–
H NMR spectra were made on Bruker Avanche 500
0
spectrometer in CDCl using TMS as internal standard.
3
0
Dichloromethane Cu /4A, 0.2 g 40
0
Dichloromethane Cu /4A, 0.5 g 40
0
Dichloromethane Cu /4A, 0.5 g 40
0
Dichloromethane Cu /4A, 0.5 g 40
b
14
20
20
20
20
35
90
90
82
40
GC–MS spectra were made on Agilent 6890 N-GC-5973
N-MSD instrument, column: Restek, Rtx-5SILMS,
b
b
30 m 9 0.25 mm, 25 lm film layer. Temperature pro-
b,c
e
gram: 45 °C (1 min)?10 °C/min?310 °C (17 min).
Injector temperature: 250 °C, carrier gas: He. SEM images
were made on JEOL JSM-6380LA scanning electron
microscope, with 30 kV accelerating voltage, in vacuo.
0
d
Dichloromethane 5xCu /4A ,
.5 g
40
0
2
1
a
mmol phenylboronic acid, 1 mmol morpholine, 2 mmol pyridine,
0 ml solvent
Based on GC–MS analysis of the reaction mixture
In Ar atmosphere
3.1 Preparation of the Catalyst
b
c
d
e
2?
Cu /4A was prepared by treatment of powdered 4 A
Using triethylamine as base
˚
2
7.8 wt% Cu
molecular sieve with CuCl in deionized water as described
2
Biphenyl was formed as main product
in [19]. Thus, 2 g of support and 0.34 g (2 mmol) of
CuCl Á2H O in 200 ml deionized water were stirred at
2
2
the solid material filtered out from the reaction mixture
contained not only the catalyst, but the salt formed from the
boronic acid—pyridine salt, too, Thus, the pretreatment of
the catalyst was necessary before the reusability test. The
filtered solid was washed with water and then with alcohol,
then dried at 120 °C for 1 h. The yield of the 2nd run
dropped to 65 %. When this purification process was not
effectuated, only 58 % N-phenylmorpholine was obtained.
Perhaps, in this case the salts formed in the reaction might
precipitate onto the surface of the catalyst, covering and
thus blocking the active metal centers.
room temperature for 12 h. Then the light green solid was
filtered out, washed with deionized water and then with
acetone, and dried in an oven at 120 °C for 1 h.
1 g of this material in 10 ml ethanol was treated with
1 g hydrazine hydrate at room temperature for 3 h. Then
the light reddish-brown solid was filtered out under Ar
atmosphere, washed with ethanol and dried under vacuo.
As this material is sensitive to the atmospheric oxygen
(moderate warming), it was stored under Ar atmosphere.
2
?
Targeted copper content of Cu /4A: 6.3 wt%, mea-
0
sured value: 5.8 wt%, measured value for Cu /4A: 5.5 wt%
The Chan-Lam coupling has also been described with
phenols [18, 23]. We investigated the reaction of different
boronic acids with 4-nitrophenol (5, Fig. 5). The results are
summarized in Table 3. The desired products were
obtained with moderate yield.
(ICP-OES).
3.2 Typical Procedure for the Coupling of Boronic
Acids
˚
In summary, copper(0) on 4 A molecular sieve support
A mixture of boronic acid 1 (2 mmol), amine 2 or
4-nitrophenol 5 (1 mmol), pyridine (2 mmol) and 0.5 g
proved to be a suitable catalyst for the arylation of amines
Fig. 4 Chan-Lam reaction in the
0
presence of Cu /4A catalyst
OH
0
Cu /4A
pyridine
NR'R''
B
OH
+
R'R"'NH
R
dichloromethane
reflux, 20 h
R
1
2
3
123

1
550
N. Debreczeni et al.
Table 2 Coupling of phenylboronic acids with amines
a
b
Boronic acid
Amine
Product
Conversion
Yield
OH
B
9
0
77
68
57
2
2
a
HN
O
3a
N
O
1a
1a
1a
OH
OH
OH
OH
B
8
0
bHN
N
3b
N
N
OH
B
N
N
70
2c
H
3c
OH
B
6
6
5
0
0
5
53
50
43
2
2
2
a
a
a
HN
HN
HN
O
3d
N
O
1
1
b
c
OH
OH
B
O
O
3e
OH
N
O
OH
B
3f
1
d
e
OH
N
O
OH
B
5
5
50
56
2
2
a
a
HN
HN
O
O
3gF3C
N
O
1
1
OH
F3C
OH
n.d.
3h
N
O
f
B
OH
1
a
mmol amine, 2 mmol boronic acid and pyridine, 0.5 g catalyst, 10 ml dichloromethane
1
Based on the H NMR spectra of the crude product
b
Isolated yield
Fig. 5 Chan-Lam reaction with
phenols
OH
B
Cu /4A
0
HO
O
pyridine
+
OH
R
R
dichloromethane
reflux, 20 h
NO2
NO2
1
5
6
Table 3 Coupling of phenylboronic acids with 4-nitrophenol
dichloromethane, the filtrate was evaporated. The residue
was purified by column chromatography (Kieselgel, hex-
ane:acetone 4:1 eluent).
a
Boronic acid
Product
Yield
OH
B
O
O
O
1
5
5
4
5
0
8
All products have satisfactory spectral data ( H NMR,
1
a
b
c
OH
6a
MS). The spectral data of the known compounds were
identical with those reported in the literature.
O N
2
OH
B
6b
1
OH
O N
2
OH
B
3.3 Representative Spectroscopical Data
6c
O N
1
OH
2
of Compounds
1 mmol 5, 2 mmol boronic acid and pyridine, 0.5 g catalyst, 10 ml
dichloromethane
3.3.1 N-phenylmorpholine, 3a
a
Isolated yield
1
H NMR (300 MHz, CDCl ) d (ppm): d 7.30–7.26 (2H,
3
0
Cu /4A in boiling dichloromethane (10 ml) was stirred
m), 6.93–6.86 (3H, m), 3.86 (4H, t, J = 4.8 Hz), 3.15 (4H,
under Ar atmosphere for 20 h. then the mixture
was cooled, the solid was filtered, washed with
t, J = 4.8 Hz).
?
: 22,77 min; MS (m/z): M : 177.
GC: R
t
1
23

Coupling of boronic acids with amines
1551
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