Chan-Lam-Type C-N Cross-Coupling Reactions under Base- and Ligand-Free CuI-Zeolite Catalysis

Article abstract of DOI:10.1055/s-0036-1588652

Various representative copper(I)-exchanged zeolites were investigated for their catalytic potential in Chan-Lam cross-coupling reactions. Cu^I-USY appeared as the best catalyst and proved to efficiently promote C-N cross-coupling processes under attractive, simple, and practical conditions, namely refluxing in methanol under air and without any base.

Full text of DOI:10.1055/s-0036-1588652

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
A
paper
Synthesis
T. Garnier et al.
Paper
Chan–Lam-Type C–N Cross-Coupling Reactions under Base- and
I
Ligand-Free Cu -Zeolite Catalysis
Tony Garniera
Randa Saklya,b
Mathieu Danela
Stefan Chassaing*a
Patrick Pale*c
a
Institut des Technologies Avancées en sciences du Vivant
(
ITAV), Université de Toulouse, CNRS, UPS, 1 place Pierre
Potier, 31106 Toulouse Cedex 1, France
b
c
Laboratoire de Chimie Organique Hétérocyclique, Produits
Naturels et Réactivité (LCOHPNR), Faculté des Sciences de
Monastir, Université de Monastir, Monastir, Tunisie
Laboratoire de Synthèse, Réactivité Organique et Catalyse
(
LASYROC), Institut de Chimie, CNRS-UMR7177, Université
de Strasbourg, 4 rue Blaise Pascal, 67070 Strasbourg, France
stefan.chassaing@itav.fr
ppale@unistra.fr
Dedicated to the memory of Prof. J. F. Normant, a brilliant
scientist and a wonderful person, and in recognition of his
outstanding achievements in organometallic chemistry.
Received: 14.09.2016
Accepted: 20.10.2016
Published online: 22.11.2016
DOI: 10.1055/s-0036-1588652; Art ID: ss-2016-c0635-op
Due to harsh reaction conditions, the synthetic scope of
these Ullmann-type reactions was however restricted to a
limited range of substrates (Scheme 1). Nevertheless, at the
turn of the 21st century, new combinations of reagents and
copper/ligand systems unleashed the power of such cou-
pling reactions in organic synthesis and medicinal chemis-
Abstract Various representative copper(I)-exchanged zeolites were in-
vestigated for their catalytic potential in Chan–Lam cross-coupling re-
I
actions. Cu -USY appeared as the best catalyst and proved to efficiently
7
try. Among them, the mild conditions concomitantly pro-
promote C–N cross-coupling processes under attractive, simple, and
practical conditions, namely refluxing in methanol under air and with-
out any base.
posed by Chan,8 Lam,9 and Evans for, respectively, C–N
and C–O bond formation significantly improved the possi-
bility by allowing the coupling of arylboronic acids with
various N- or O-nucleophiles (Scheme 1). The N- or O-nu-
cleophiles could be as various phenols, amines, anilines,
amides, imides, ureas, carbamates, and sulfonamides, while
stannanes, siloxanes, and organobismuth derivatives can
replace boronic acids.11 These reactions are usually induced
by a stoichiometric amount of copper(II) in the presence of
excess base (Scheme 1). Catalysis could nevertheless be
achieved with various copper species, especially copper(II)
10
Key words copper, zeolites, heterogeneous catalysis, cross-coupling,
Chan–Lam reaction, C–N bond formation
Copper was among the very first metals used to pro-
mote organic transformations. This metal indeed contribut-
ed to the initiation of the long history of metal-mediated
formation of carbon–carbon bonds with the Glaser homo-
coupling reaction reported as early as the mid-19th centu-
1
2
12
ry, the Meerwein diazo decarboxylative coupling, and lat-
complexes, if the reaction is performed in air.
er on the Cadiot–Chodkiewicz cross-coupling in the mid-
Although such homogeneous catalysis provides huge
potential, product and catalyst recovery remains a problem
for practical and industrial applications. Heterogenization
of catalysts has thus become an important issue, especially
for the production of fine chemicals, due to the benefits of
this catalysis mode (i.e., easier isolation of products/cata-
lyst, recyclability of the catalyst, etc.) and its consequences
in industry.13 Surprisingly, and despite its interest, only a
handful of examples of heterogeneously catalyzed Chan–
Lam–Evans reactions have so far been reported. Fluorapa-
3
1950s. These works and others pioneered the tremendous
expansion of organocopper chemistry in the 1960s and
970s. Among them, it is worth mentioning the unique
1
contribution of Prof. J. F. Normant, to whom this paper is
dedicated, with, among others, the Normant carbocupra-
4
5
tion reaction and its developments.
Copper was also involved in the very first coupling reac-
tions producing carbon–heteroatom bonds, the so-called
6
Ullmann reaction, which have again initiated numerous
7
variations.
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

B
Synthesis
T. Garnier et al.
Paper
Ullmann reaction
ence of either pyridine or triethylamine, the bases com-
monly used in these couplings.8 The yields were accord-
ingly very low, equivalent to those obtained without base
–11
O
K
Br
O
Cu
210 °C
(entries 1 and 2 vs 3). Since we aimed to develop a base-free
87%
Evans reaction
version, we next screened other solvents in the presence of
OH (OH) B
O
X
I
2
only Cu -USY as the catalytic system (entries 4–7). Some-
1
equiv Cu(OAc)2
times used with copper(II) complexes, coordinating sol-
vents did not improve these results, except for DMF which
allowed for 67% yield to be achieved, even in the absence of
base (entry 4). More interestingly, protic solvents drastical-
ly changed the reaction course (entries 5–7). Indeed, water,
ethanol, and methanol gave good to excellent yields of the
expected coupling product in the absence of base. Methanol
provided the best results, (entry 7 vs 5 and 6), and neither
deborylation nor homocoupling products could be detect-
ed, despite their common observation in Chan–Lam–Evans
reactions. The ability of methanol to allow this coupling re-
5
equiv Et3N
R1
Chan reaction
XH (OH)2B
R1
R2
R2
CH2Cl2, 25 °C
1
–2 equiv Cu(OAc)2
2
equiv py or Et3N
CH2Cl2, 25 °C
R1
R2
R1
R2
3
3
X = NR , O
XH = NHR , OH
R3 = H, Alk, RC=O, SO2Ar
Lam–Chan reaction
(
OH)2B
X
N
X
X
X
X
X
1.5 equiv Cu(OAc)2
equiv py
CH2Cl2, 25 °C
I
R1
action in the presence of Cu -USY zeolite is quite surprising
NH
X
2
X
R2
R1
R2
since the original report mentioned that no reaction occurs
X = N, CH
9
in methanol. Remarkably, the addition of a base (pyridine
6
–88%
Scheme 1 From the pioneering Ullmann reaction to the Chan–Lam–
Evans versions involving arylboronic acids in place of aryl halides
tite in which calcium ions were exchanged for copper(II)
ions has been applied to the coupling of imidazole and a
few alkylamines with phenylboronic acid.14 Alternatively,
cuprous oxide particles have also been used, either as
15
16
such or supported on natural natrolite.
In connection with the heterogenization issue and with
the ‘greening’ of organic transformations as a goal,1
7,18
we
are currently developing the zeo-click concept, in which re-
agents should react through zeolites, metalated or not, ben-
efitting from zeolite size and shape selectivity under condi-
18
tions as mild as possible (Scheme 2, top). We have already
shown that copper(I) is stabilized in zeolites, their frame-
work acting as a polydentate ligand toward the metal ion,
I
and that the resulting Cu -zeolites are excellent heteroge-
neous catalysts, easy to handle, recyclable, and shape selec-
tive, for a variety of organic transformations, usually with-
out the need for an additional ligand (Scheme 2, bottom).19
To further extend this toolbox, we recently reported a
I
new Ullmann-type synthesis of diaryl ethers with Cu -USY
19k
zeolite as a ligand-free and recyclable catalyst. We now
demonstrate here that the Chan–Lam version could also be
I
catalyzed with Cu -zeolites under very mild conditions
without added base.
To set up the reaction conditions, we examined the ar-
chetypal coupling of imidazole (1a) and phenylboronic acid
I
(
2a), in the presence or absence of base and using Cu -USY
zeolite as the catalyst in various solvents (Table 1). In the
solvent commonly used for Chan–Lam–Evans reactions, i.e.
dichloromethane, very low conversion occurred in the pres-
Scheme 2 The zeo-click concept (top) and some reactions achieved
with Cu -zeolites (bottom)
I
19
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

C
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T. Garnier et al.
Paper
or triethylamine) did not enhance the efficiency of the cou-
pling reaction, pyridine even altering negatively the reac-
tion progress (entries 8 and 9 vs 7).
Table 2 Screening of Catalysts for the Coupling of Phenylboronic Acid
and Imidazolea
catalyst
NH
(10 mol%)
Ph
+
(HO)2B Ph
2a
N
I
N
Table 1 Screening of Conditions for the Cu -USY-Catalyzed Coupling
MeOH
N
a
65 °C, 17 h
of Phenylboronic Acid and Imidazole
1
a
3a
I
Cu -USY
(
Entry
Catalyst
Yield (%)b
Ph
NH
10 mol%)
+
(HO)2B Ph
N
N
N
base, solvent
I
1
2
3
4
5
6
Cu -USY
86
1
a
2a
3a
I
43c
Cu -ZSM5
I
47c
54c
15c
0d
Yield (%)b
Cu -MOR
Entry
Solvent
Base
Temp (°C)
Time (h)
I
Cu -Beta
1
2
3
4
5
6
7
8
9
CH
CH
CH
2
2
2
Cl
Cl
Cl
2
2
2
pyridine
45
45
45
65
65
65
65
65
65
20
65
65
65
65
48
48
48
17
17
17
17
17
17
48
17
17
17
17
<5
<5
<5
67
56
80
86
74
85
<5
88
68
86
33
CuCl
Et
–
–
–
–
–
3
N
NH
4
-USY
7
none
0d
DMF
a
Reaction run with phenylboronic acid (1.0 equiv with a 0.17 M concentra-
tion) and imidazole (1.5 equiv) under air, unless otherwise stated.
2
H O
b
Yields of isolated pure products.
Incomplete conversion.
No conversion.
EtOH
c
d
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
pyridine
Et
–
–
–
–
–
3
N
Control experiments with native commercial USY zeo-
lite or without any catalyst clearly evidenced the role of
copper in this reaction (entries 6 and 7). Interestingly, the
use of copper chloride itself only led to marginal reaction,
revealing the catalytic ability of copper embedded within
the (right) zeolite framework (entry 5 vs 1).
This copper zeolite catalyst can be easily recovered and
reused after a simple filtration-washing sequence. With the
same model reaction, two cycles could be performed with-
out change in catalyst efficacy (86% and 85% yields for re-
spectively run 1 and 2) but the third run induced a drop in
yield, with only 60% yield of isolated product being ob-
tained. Although the lowering of the catalyst amount inher-
ent to its recovery at each cycle could be responsible for
such decrease, some leaching might also explain these re-
sults. However, a Sheldon test performed under the same
conditions, has shown a significantly reduced conversion
1
1
1
1
0
1c
2d
3e
1 f
4
a
Reaction run with phenylboronic acid (1.0 equiv with a 0.17 M concentra-
tion) and imidazole (1.5 equiv) under air, unless otherwise stated.
b
Yields of isolated pure products.
c
Reaction run with imidazole (2.0 equiv).
d
Reaction run with imidazole (1.0 equiv) and phenylboronic acid (1.5
equiv).
e
Reaction run with a 0.5 M concentration of phenylboronic acid.
Reaction run with a 1 M concentration of phenylboronic acid.
f
In this reaction, heating proved necessary as almost no
conversion occurred at room temperature (entry 7 vs 10).
In terms of 1a/2a ratio, a slight excess of nucleophile rela-
tive to boronic acid provided better results (entries 7 and
I
after 24 hours at 65 °C upon removal of the Cu -USY cata-
1
1 vs 12). Regarding reagent concentration, the boronic
lyst. Overall, these results suggested a preference for a
‘catch and release’ mechanism for this heterogeneous cata-
lyst over leaching of catalytically active species in solution.
With these reaction conditions in hand, we then ex-
acid concentration proved important with an optimum
around 0.2–0.5 M (entries 8 and 12 vs 13), probably due to
equilibration with the corresponding boroxine.
Under the so-obtained conditions, the influence of zeo-
lite pore size and shape was examined in the same model
coupling reaction (Table 2). Various typical and readily
available zeolites were doped with copper(I) ions upon
heating in the presence of CuCl,
engaged as a catalyst in the Chan–Lam reaction. All of them
were able to promote the cross-coupling reaction, but Cu -
USY was clearly the best catalyst (entry 1 vs 2–4). In agree-
20
I
plored the scope of this base-free Cu -USY catalyzed Chan–
Lam alternative (Tables 3 and 4). In a first series of experi-
ments, the effect of the boronic acid nature was examined
(Table 3). Phenylboronic acids carrying electron-deficient
groups did not significantly affect the reaction efficacy (en-
tries 2 and 3 vs 1). However, those carrying electron-rich
substituents led to contrasted results. Although o-tolylbo-
ronic acid gave an improved and excellent yield of the cor-
responding product 3e (entry 5 vs 1), its o-methoxy ana-
logue led to a net decrease in yield (entry 5 vs 6), neverthe-
18,19i
characterized, and then
I
19
ment with our earlier results, USY zeolite which offers the
largest pores (7–11 Å) with a cage shape provided the best
results in terms of conversion, yield, and reaction time.
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T. Garnier et al.
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I
Table 3 Cu -USY-Catalyzed Coupling of Imidazole with Various Boronic
Acids
less these are better than the results obtained by Chan,
Lam, and co-workers. Surprisingly, the corresponding p-
a
8,9
methoxy analogue led to another decrease in yield (entry 7
vs 6), while the p-diethylamino derivative could only afford
I
Cu -USY
R
NH
(10 mol%)
+
(HO)2B
R
N
N
N
MeOH
65 °C, 17 h
1
a
3a–i
I
Table 4 Cu -USY-Catalyzed Coupling of Phenylboronic Acid with Vari-
ous Nucleophilesa
Entry
1
Product
Yield (%)b
86
I
Cu -USY
Ph
N
(10 mol%)
Ph
N
N
N
3a
3b
+
N
NH
(HO)2B Ph
MeOH
65 °C, 17 h
COOMe
2a
3a,j–n
2
3
84
83
Yield (%)b
N
N
Entry
1
Product
Number
Ph
N
N
N
3a
86
F
3c
Ph
–c
2
–
N
Br
N
N
Ph
3
4
5
3j
–
55
–c
–c
4
3d
73
N
N
Br
N
N
Ph
N
N
5
6
3e
3f
95
80
Ph
–
MeO
N
O
6
7
Ph
3k
3l
55
55
Ph
N
H
N
N
Ph
OMe
NEt2
N
7
3g
71
O
N
O
O
8
9
N
Ph
3m
56
8
9
3h
3i
28
72
N
N
O
N
N
O
N
Ph
37d
3n
–
OH
tBu
10
–c
Ph
–c
–c
O
10
–
–
N
N
N
N
11
–
–c
Me
Ph
11
O
a
Reaction run with boronic acid (1.0 equiv with a 0.17 M concentration)
a
and imidazole (1.5 equiv) under air, unless otherwise stated.
Reaction run with boronic acid (1.0 equiv with a 0.17 M concentration)
b
and imidazole (1.5 equiv) under air, unless otherwise stated.
Yields of isolated pure products.
Partial conversion but no traces of expected product detected.
b
c
Yields of isolated pure products.
Complete conversion but no traces of expected product detected.
c
d
No traces of O-arylated product detected.
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T. Garnier et al.
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the expected product 3h in poor yield (entry 8 vs 7 vs 1).
Interestingly, m-hydroxyphenylboronic acid reacted as ex-
pected, giving 3-(1H-imidazol-1-yl)phenol (3i) in good
yield, without further coupling as a phenol (entry 9). This
result suggests an attractive and possibly useful selectivity
in N- vs O-coupling reactions (vide infra).
the large oxygenated zeolite framework ligand could play a
role similar to the dedicated ligand designed by Stahl and
Ribas for the mechanism of the Ullmann coupling reac-
tion.24 Upon air oxidation and in the presence of a nucleo-
phile, a copper(III) intermediate E could be formed, stabi-
lized by the oxygenated zeolite framework and by H-bond-
ing with the incoming nucleophile. Reductive elimination
would then lead to the coupling product, while regenerat-
ing the zeolite framework coordinated to copper(I).
In sharp contrast to arylboronic acids, alkyl- or vinylbo-
ronic acids did not furnish the expected coupling products
(entries 10 and 11). Their ease of cyclization to boroxine
may be one of the reasons.
In another series of experiments, the effect of variations
in the nucleophile nature was investigated (Table 4). N-Het-
erocycles proved more or less reactive depending on their
structure, but often less reactive than imidazole under the
present conditions. Usually less reactive than imidazole it-
self in Chan–Lam coupling, benzimidazole unexpectedly
did not produce any coupling under the present conditions
O
O
R = H, Et, Me
O
R
O
O
CuI
CuI
ROH
B
OMe
OR
R
O
O
RO
H
O
H
O
O
CuI
O
O
B
C
OR
OR
MeO B
(entry 2 vs 1). In contrast, pyrazole could be arylated in
O
good yield, although less than imidazole (entry 3 vs 1).
Although known for its low or lack of reactivity, pyrrole
was nevertheless engaged under the present conditions,
aiming that a possible confinement effect due to the zeolite
O
A
O
O
O
O
R
CuI
CuIII
O2
R
R
N
N
O
H
O
21
framework could force them to react. Pyrrole unfortu-
nately did not lead to the expected coupling products, even
in the presence of base (entry 4). Similarly, simple amines
such as piperidine also did not form the corresponding N-
arylated product (entry 5). This lack of Chan–Lam-type
couplings could be linked to the basicity of the nucleophile,
H N
O
E
D
I
Scheme 3 Mechanistic proposal for the Cu -zeolite catalyzed Chan–
Lam cross-coupling reaction
22
in reminiscence of Cundy’s observations.
In conclusion, we have reported a new ligand-free and
base-free Cu-catalyzed protocol for the cross-coupling of
arylboronic acids with a variety of N-nucleophiles. Among
four representative and readily available copper(I)-ex-
Indeed, amides, including cyclic amides such as isatin
entries 6 and 7), and imides (entry 8) readily reacted and
(
gave the expected N-arylated products 3k–m in good
yields. However, pyridin-2(1H)-one only gave a modest
yield of the expected coupling product 3n. Interestingly,
only the N-arylated product was formed (entry 9), revealing
again the same N- vs O-selectivity in such coupling reac-
tions.
I
changed zeolites, Cu -USY proved to be the best catalyst by
efficiently promoting the cross-coupling process under at-
tractive, simple, and practical conditions, i.e. refluxing in
methanol under air and without any base. This catalyst
could be easily recovered and recycled at least three times.
Further works are in progress in our groups to expand
the scope of this heterogeneous Chan–Lam cross-coupling
version, to decipher its mechanism and to apply it to organ-
ic (total) synthesis.
To get more evidence of this selectivity, we engaged var-
ious phenols under the same conditions. In sharp contrast
to N-nucleophiles, these O-nucleophiles did not react at all
under the present conditions (entries 10 and 11). Therefore,
these conditions are exclusively selective for N-nucleo-
philes, offering numerous opportunities in organic synthesis.
In these Chan–Lam type reactions, the zeolite frame-
work can act as a large ligand, stabilizing copper species. It
can also favor proton transfer at various stages (Scheme 3).
In this regard, such large oxygenated ligands could help to
understand the special role of protic solvents (Scheme 3, in-
termediates A and B). Furthermore, the fact that boronic ac-
ids are only efficiently converted in protic solvents, particu-
larly methanol, is reminiscent of Jutand’s study on the key
role that water and related ligands could play in the Suzuki–
Miyaura coupling reaction, especially at the transmetala-
All starting materials were commercially available and were used as
received. The reactions were monitored by TLC carried out on silica
plates (silica gel 60 F254, Merck) using UV light for visualization. Col-
umn chromatography was performed on silica gel 60 (0.040–0.063
mm, Merck) using mixtures of EtOAc and cyclohexane. Evaporation of
solvents were conducted under reduced pressure at temperatures less
than 30 °C unless otherwise noted. Melting points were measured
with a Stuart SMP30 apparatus in open capillary tubes and are uncor-
rected. IR spectra were obtained from the ‘Service Commun de Spec-
troscopie Infrarouge et Raman’ of the Plateforme Technique, Institut
1
13
de Chimie de Toulouse. H and C NMR spectra were recorded on a
Bruker Avance 300 spectrometer at 300 and 75 MHz, respectively rel-
ative to residual solvent as an internal standard (CDCl : δ = 7.26 for H
23
tion step. From this background, transmetalation could
1
3
indeed occur through intermediate C. On the other hand,
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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Synthesis
T. Garnier et al.
Paper
and δ = 77.0 for 13C). Carbon multiplicities were determined by
DEPT135 experiments. Electrospray (ESI), Atmospheric-Pressure
Chemical Ionization (APCI) and Desorption Chemical Ionization (DCI)
low/high-resolution mass spectra were obtained from the ‘Service
Commun de Spectroscopie de Masse’ of the Plateforme Technique, In-
stitut de Chimie de Toulouse.
1
H NMR (300 MHz, CDCl ): δ = 7.84 (br s, 1 H), 7.67 (t, J = 1.5 Hz, 1 H),
3
7.51 (d, J = 1.5 Hz, 2 H), 7.26–7.23 (m, 2 H).
13
C NMR (75 MHz, CDCl ): δ = 139.1, 135.3, 133.0, 131.2, 123.9, 123.2,
3
1
17.2.
MS (DCI, +): m/z (%) = 145 (35) [M – Br + 2 H] , 223 (40) [M – 81Br + 2
H] , 225 (40) [M – Br + 2 H] , 301 (50) [M( Br, Br) + H] , 303 (100)
+
2
+
79
+
79
79
+
79
81
+
81
81
+
[
M( Br, Br) + H] , 305 (50) [M( Br, Br) + H] .
I
Cu -USY Catalyzed Cross-Coupling Reaction of Arylboronic Acids
with N-Nucleophiles; General Procedure
1
-(2-Methylphenyl)-1H-imidazole (3e)
CAS Reg. No. 25371-93-1]
Pale yellow oil; yield: 75 mg (95%); R = 0.40 (cyclohexane/EtOAc 1:4).
f
I
In a 10-mL round-bottom flask were successively added Cu -USY (ca.
[
15 mg, 10 mol% of copper species), the nucleophile (0.75 mmol, 1.5
equiv), the boronic acid (0.5 mmol, 1.0 equiv), and MeOH (3.0 mL).
The mixture was refluxed under air for 17 h and analyzed by LCMS.
After cooling to r.t., the solvent was removed and the desired com-
pound was isolated by purification on a short pad of silica gel (cyclo-
hexane/EtOAc mixture).
FTIR (ATR, neat): 3111, 2960, 1505, 1240, 1059, 765 cm–1
.
1
H NMR (300 MHz, CDCl ): δ = 7.62 (br s, 1 H), 7.39–7.27 (m, 3 H),
3
7.24–7.21 (m, 2 H), 7.07 (t, J = 1.2 Hz, 1 H), 2.19 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 137.4, 136.5, 133.8, 131.2, 129.2, 128.7,
3
1
26.8, 126.4, 120.4, 17.5.
1
-Phenyl-1H-imidazole (3a)
CAS Reg. No. 7164-98-9]
Pale yellow oil; yield: 62 mg (86%); R = 0.30 (cyclohexane/EtOAc 1:4).
MS (DCI, +): m/z (%) = 159 (100) [M + H]+.
[
f
1
-(2-Methoxyphenyl)-1H-imidazole (3f)
CAS Reg. No. 10040-93-4]
Pale yellow oil; yield: 70 mg (80%); R = 0.25 (cyclohexane/EtOAc 1:4).
FTIR (ATR, neat): 3107, 3059, 1600, 1509, 1304, 1058, 760 cm–1
.
[
1
H NMR (300 MHz, CDCl ): δ = 7.85 (br s, 1 H), 7.51–7.45 (m, 2 H),
3
f
7.41–7.34 (m, 3 H), 7.28 (t, J = 1.2 Hz, 1 H), 7.21 (br s, 1 H).
FTIR (ATR, neat): 3115, 2939, 2839, 1600, 1515, 1250, 1058, 754 cm–1
.
13
C NMR (75 MHz, CDCl ): δ = 137.1, 135.3, 130.2, 129.7, 127.2, 121.2,
3
1
H NMR (300 MHz, CDCl ): δ = 7.85 (br s, 1 H), 7.41–7.35 (m, 1 H),
118.0.
3
7.29 (dd, J = 1.5, 7.5 Hz, 1 H), 7.22–7.20 (m, 2 H), 7.08–7.02 (m, 2 H),
MS (DCI, +): m/z (%) = 145 (100) [M + H]+.
3
.86 (s, 3 H).
13
C NMR (75 MHz, CDCl ): δ = 152.5, 137.7, 128.9, 128.6, 126.4, 125.4,
3
Methyl 4-(1H-Imidazol-1-yl)benzoate (3b)
1
20.9, 120.2, 112.2, 55.7.
[
CAS Reg. No. 101184-08-1]
MS (DCI, +): m/z (%) = 175 (100) [M + H]+.
White solid; yield: 85 mg (84%); mp 127 °C; R = 0.20 (cyclohex-
f
ane/EtOAc 1:4).
1
-(4-Methoxyphenyl)-1H-imidazole (3g)
FTIR (ATR, neat): 3111, 3005, 2957, 2845, 1712, 1609, 1526, 1266,
[
CAS Reg. No. 10040-95-6]
–1
1
062, 851 cm .
Beige solid; yield: 62 mg (71%); mp 62–63 °C; R = 0.35 (cyclohex-
ane/EtOAc 1:4).
FTIR (ATR, neat): 3118, 3005, 2837, 1611, 1520, 1250, 1060, 832 cm–1
1
f
H NMR (300 MHz, CDCl ): δ = 8.19–8.15 (m, 2 H), 8.01 (br s, 1 H),
3
7.51–7.46 (m, 2 H), 7.36 (br t, J = 1.5 Hz, 1 H), 7.26 (br s, 1 H), 3.95 (s, 3
.
H).
1
13
H NMR (300 MHz, CDCl ): δ = 7.75 (br s, 1 H), 7.32–7.27 (m, 2 H),
3
C NMR (75 MHz, CDCl ): δ = 165.8, 140.5, 135.2, 131.4, 130.9, 128.8,
3
7
.19–7.17 (m, 2 H), 7.00–6.95 (m, 2 H), 3.84 (s, 3 H).
120.4, 117.6, 52.2.
13
MS (DCI, +): m/z (%) = 203 (100) [M + H]+.
C NMR (75 MHz, CDCl ): δ = 158.8, 135.7, 130.6, 129.9, 123.0, 118.6,
3
114.7, 55.5.
MS (DCI, +): m/z (%) = 175 (100) [M + H]+.
1
-(4-Fluorophenyl)-1H-imidazole (3c)
CAS Reg. No. 21441-24-7]
Pale yellow oil; yield: 67 mg (83%); R = 0.25 (cyclohexane/EtOAc 1:4).
[
N,N-Diethyl-4-(1H-imidazol-1-yl)aniline (3h)
f
[
CAS Reg. No. 1269166-04-2]
FTIR (ATR, neat): 3113, 3072, 1518, 1231, 1058, 837 cm–1
.
Brown solid; yield: 30 mg (28%); mp 55–57 °C; R = 0.20 (EtOAc).
1
f
H NMR (300 MHz, CDCl ): δ = 7.75 (br s, 1 H), 7.32–7.27 (m, 2 H),
3
1
H NMR (300 MHz, CDCl ): δ = 7.71 (br s, 1 H), 7.21–7.15 (m, 4 H),
7.19–7.17 (m, 2 H), 7.00–6.95 (m, 2 H).
3
6.71–6.66 (m, 2 H), 3.37 (q, J = 7.2 Hz, 4 H), 1.18 (t, J = 7.2 Hz, 6 H).
13
C NMR (75 MHz, CDCl ): δ = 161.5 (d, J = 246.7 Hz), 135.6, 133.5 (d,
3
13
C NMR (75 MHz, CDCl ): δ = 147.1, 135.9, 129.4, 125.9, 123.4, 118.9,
J = 2.2 Hz), 130.3, 123.4 (d, J = 8.2 Hz), 118.5, 116.6 (d, J = 22.7 Hz).
MS (DCI, +): m/z (%) = 163 (100) [M + H]+.
3
111.9, 44.5, 12.4.
+
+
MS (DCI, +): m/z (%) = 216 (100) [M + H] , 186 (70) [M – Et] .
1
-(3,5-Dibromophenyl)-1H-imidazole (3d)
3
-(1H-Imidazol-1-yl)phenol (3i)
[
CAS Reg. No. 149797-66-0]
[
CAS Reg. No. 10041-03-9]
White solid; yield: 110 mg (73%); mp 101–103 °C; R = 0.45 (cyclohex-
ane/EtOAc 1:4).
f
White solid; yield: 58 mg (72%); mp 162 °C; R = 0.15 (cyclohex-
ane/EtOAc 1:4).
FTIR (ATR, neat): 3118, 3005, 2837, 1611, 1520, 1250, 1060, 832 cm–1
.
f
FTIR (ATR, neat): 3131, 3060, 3015, 1591, 1570, 1497, 1304, 1267,
–1
1103, 1064, 842, 748 cm .
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

G
Synthesis
T. Garnier et al.
Paper
1
H NMR (300 MHz, CDCl ): δ = 8.07 (s, 1 H), 7.51 (s, 1 H), 7.31 (t, J = 8.1
White solid; yield: 32 mg (37%); mp 125–126 °C; R = 0.15 (cyclohex-
3
f
Hz, 1 H), 7.13 (s, 1 H), 7.00 (ddd, J = 0.9, 2.4, 8.1 Hz, 1 H), 6.94 (t, J = 2.4
Hz, 1 H), 6.82 (ddd, J = 0.9, 2.4, 8.4 Hz, 1 H).
ane/EtOAc 1:1).
FTIR (ATR, neat): 3054, 1660, 1603, 1581, 1529, 1492, 767 cm–1
.
13
C NMR (75 MHz, CDCl ): δ = 160.1, 139.5, 136.8, 131.9, 130.0, 119.7,
1
3
H NMR (300 MHz, CDCl ): δ = 7.52–7.32 (m, 7 H), 6.66 (ddd, J = 0.9,
3
115.7, 113.1, 109.3.
1.2, 9.3 Hz, 1 H), 6.23 (dt, J = 1.2, 6.6 Hz, 1 H).
MS (DCI, +): m/z (%) = 161 (100) [M + H]+.
13
C NMR (75 MHz, CDCl ): δ = 162.3, 140.8, 139.8, 137.9, 129.2, 128.4,
3
1
26.4, 121.8, 105.8.
1
-Phenyl-1H-pyrazole (3j)
CAS Reg. No. 1126-00-7]
Pale yellow oil; yield: 40 mg (55%); R = 0.80 (cyclohexane/EtOAc 1:4).
MS (DCI, +): m/z (%) = 172 (100) [M + H]+.
[
f
Recycling Procedure
FTIR (ATR, neat): 3110, 2922, 1600, 1521, 1501, 1393, 936, 755 cm–1
.
At the end of a run, the zeolite could be recovered by filtration over a
polypropylene Millipore membrane and further washed with EtOAc,
water, and acetone. After drying under reduced pressure, the so-ob-
tained solid was used as catalyst in the next run.
1
H NMR (300 MHz, CDCl ): δ = 7.93 (br d, J = 2.4 Hz, 1 H), 7.73–7.68
3
(m, 3 H), 7.48–7.43 (m, 2 H), 7.32–7.27 (m, 1 H), 6.47 (br t, J = 2.3 Hz, 1
H).
13
C NMR (75 MHz, CDCl ): δ = 141.0, 140.1, 129.3, 126.7, 126.4, 119.1,
3
1
07.5.
Acknowledgment
MS (DCI, +): m/z (%) = 145 (100) [M + H]+.
This work was supported by the Agence Nationale de la Recherche
(ANR-13-BS07-0017-02 ChOZe) and the CNRS. R.S. acknowledges the
Tunisian Ministry of Education and Research for financial support. We
thank Eric Wimmer and Doctor Valérie Bénéteau (LASYROC, Universi-
té de Strasbourg) for preparation of the copper(I)-exchanged zeolites.
N-Phenylbenzamide (3k)
[
CAS Reg. No. 93-98-1]
White solid; yield: 54 mg (55%); mp 160–162 °C; R = 0.80 (cyclohex-
ane/EtOAc 1:1).
f
FTIR (ATR, neat): 3343, 3053, 1654, 1599, 1527, 1464, 1321, 749 cm–1
.
1
Supporting Information
H NMR (300 MHz, CDCl ): δ = 7.90–7.86 (m, 2 H), 7.80 (br s, 1 H),
3
7
.66–7.63 (m, 2 H), 7.59–7.47 (m, 3 H), 7.41–7.35 (m, 2 H), 7.19–7.13
Supporting information for this article is available online at
(m, 1 H).
http://dx.doi.org/10.1055/s-0036-1588652.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
13
C NMR (75 MHz, CDCl ): δ = 165.8, 137.9, 135.0, 131.8, 129.0, 128.7,
3
127.0, 124.5, 120.2.
+
+
MS (DCI, +): m/z (%) = 198 (100) [M + H] , 215 (25) [M + NH ] .
References
4
(
1) (a) Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422. (b) Glaser, C.
N-Phenylisatin (3l)
Justus Liebigs Ann. Chem. 1870, 154, 137.
2) Meerwein, H.; Buchner, E.; van Emster, K. J. Prakt. Chem. 1939,
152, 237.
[
CAS Reg. No. 723-89-7]
(
Orange solid; yield: 61 mg (55%); mp 138–139 °C; R = 0.40 (cyclohex-
f
ane/EtOAc 4:1).
(3) (a) Chodkiewicz, W.; Cadiot, P. C. R. Hebd. Seances Acad. Sci.
1955, 241, 1055. (b) Chodkiewicz, W. Ann. Chim. (Paris) 1957, 2,
1
H NMR (300 MHz, CDCl ): δ = 7.69–7.66 (m, 1 H), 7.58–7.51 (m, 3 H),
3
819.
7.47–7.39 (m, 3 H), 7.16 (dt, J = 0.9, 7.5 Hz, 1 H), 6.89 (br d, J = 8.1 Hz,
(
4) For the first examples, see: (a) Normant, J. F.; Bourgain, M. Tet-
rahedron Lett. 1971, 27, 2583. For reviews, see: (b) Normant, J. F.
Synthesis 1972, 63. (c) Normant, J. F.; Alexakis, A. Synthesis
1
H).
13
C NMR (75 MHz, CDCl ): δ = 182.8, 157.2, 151.5, 138.3, 132.8, 129.9,
3
128.7, 125.9, 125.5, 124.2, 117.4, 111.2.
1981, 841.
+
+
MS (DCI, +): m/z (%) = 196 (90) [M – CO + H] , 167 (100) [M – 2 CO] .
(5) (a) Rappoport, Z.; Marek, I. The Chemistry of Organocopper Com-
pounds; Rappoport, Z.; Marek, I., Eds.; Wiley: Chichester, 2009.
(b) Krause, N. Modern Organocopper Chemistry; Wiley-VCH:
Weinheim, 2002.
N-Phenylphthalimide (3m)
[
CAS Reg. No. 520-03-6]
(
6) (a) Ullmann, F.; Lehner, A. Ber. Dtsch. Chem. Ges. 1904, 37, 853.
b) Ullmann, F.; Sponagel, P. Ber. Dtsch. Chem. Ges. 1905, 38,
211.
Orange solid; yield: 63 mg (56%); mp 207–208 °C; R = 0.40 (cyclohex-
ane/EtOAc 4:1).
f
(
2
1
H NMR (300 MHz, CDCl ): δ = 7.98–7.92 (m, 2 H), 7.82–7.75 (m, 2 H),
(7) For reviews, see: (a) Beletskaya, I. P.; Cheprakov, A. V. Coord.
Chem. Rev. 2004, 248, 2337. (b) Frlan, R.; Kikelj, D. Synthesis
2006, 2271. (c) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev.
3
7.54–7.38 (m, 5 H).
13
C NMR (75 MHz, CDCl ): δ = 167.2, 134.3, 131.7, 131.6, 129.0, 128.0,
3
2008, 108, 3054. (d) Monnier, F.; Taillefer, M. Angew. Chem. Int.
126.5, 123.7.
Ed. 2009, 48, 6954. (e) Fischer, C.; Koenig, B. Beilstein J. Org.
Chem. 2011, 7, 59. (f) Evano, G.; Theunissen, C.; Pradal, A. Nat.
Prod. Rep. 2013, 30, 1467. (g) Sambiagio, C.; Marsden, S. P.;
Blacker, A. P.; McGowan, P. C. Chem. Soc. Rev. 2014, 43, 3525.
(8) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P. Tetra-
hedron Lett. 1998, 39, 2933.
+
+
MS (DCI, +): m/z (%) = 196 (90) [M – CO + H] , 167 (100) [M – 2 CO] .
1-Phenylpyridin-2(1H)-one (3n)
[
CAS Reg. No. 13131-02-7]
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

H
Synthesis
T. Garnier et al.
Paper
(
9) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.;
Chan, D. M. T.; Combs, A. Tetrahedron Lett. 1998, 39, 2941.
10) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39,
937.
(19) (a) Chassaing, S.; Kumarraja, M.; Sani Souna Sido, A.; Pale, P.;
Sommer, J. Org. Lett. 2007, 9, 883. (b) Chassaing, S.; Sani Souna
Sido, A.; Alix, A.; Kumarraja, M.; Pale, P.; Sommer, J. Chem. Eur. J.
2008, 14, 6713. (c) Alix, A.; Chassaing, S.; Pale, P.; Sommer, J.
Tetrahedron 2008, 64, 8922. (d) Bénéteau, V.; Olmos, A.;
Boningari, T.; Sommer, J.; Pale, P. Tetrahedron Lett. 2010, 51,
3673. (e) Boringari, T.; Olmos, A.; Reddy, B. M.; Sommer, J.; Pale,
P. Eur. J. Org. Chem. 2010, 6338. (f) Keller, M.; Sani Souna Sido,
A.; Pale, P.; Sommer, J. Chem. Eur. J. 2009, 15, 2810. (g) Patil, M.
K.; Keller, M.; Reddy, B. M.; Pale, P.; Sommer, J. Eur. J. Org. Chem.
2008, 4440. (h) Kuhn, P.; Alix, A.; Kumarraja, M.; Louis, B.; Pale,
P.; Sommer, J. Eur. J. Org. Chem. 2009, 423. (i) Kuhn, P.; Pale, P.;
Sommer, J.; Louis, B. J. Phys. Chem. C 2009, 113, 2903. (j) Harkat,
H.; Borghèse, S.; De Nigris, M.; Kiselev, S.; Bénéteau, V.; Pale, P.
Adv. Synth. Catal. 2014, 356, 3842. (k) Magné, V.; Garnier, T.;
Danel, M.; Pale, P.; Chassaing, S. Org. Lett. 2015, 17, 4494.
(20) It has been shown that boroxine can participate in Chan–Lam–
Evans coupling reactions. For more details, see ref. 10 and:
Chan, D. M. T.; Monaco, K. L.; Li, R.; Bonne, D.; Clark, C. G.; Lam,
P. Y. S. Tetrahedron Lett. 2003, 44, 3863.
(
(
(
2
11) (a) Qiao, J. X.; Lam, P. Y. S. Synthesis 2011, 829. (b) Rao, K. S.; Wu,
T.-S. Tetrahedron 2012, 68, 7735.
12) (a) Collman, J. P.; Zhong, M. Org. Lett. 2000, 2, 1233. (b) Lan, J.-
B.; Chen, L.; Yu, X.-Q.; You, J.-S.; Xie, R.-G. Chem. Commun. 2004,
188. (c) Uemura, T.; Chatani, N. J. Org. Chem. 2005, 70, 8631.
(d) Moessner, C.; Bolm, C. Org. Lett. 2005, 7, 2667. (e) Wentzel,
M. T.; Hewgley, J. B.; Kamble, R. M.; Wall, P. D.; Kozlowski, M. C.
Adv. Synth. Catal. 2009, 351, 931.
(
(
(
13) Barboro, P.; Liguori, F. Heterogenized Homogeneous Catalysts for
Fine Chemicals Production; Springer: Dordrecht, 2010.
14) Kantam, M. L.; Venkanna, G. T.; Sridhar, C.; Sreedhar, B.;
Choudary, B. M. J. Org. Chem. 2006, 71, 9522.
15) Sreedhar, B.; Venkanna, G. T.; Kumar, K. B. S.;
Balasubrahmanyam, V. Synthesis 2008, 795.
(
(
16) Azarifar, D.; Soleimanei, F. RSC Adv. 2014, 4, 12119.
17) Chassaing, S.; Beneteau, V.; Pale, P. Catal. Sci. Technol. 2016, 6,
9
23.
(21) (a) Derouane, E. G. J. Mol. Catal. A 1998, 134, 29. (b) Sastre, G. A.;
Corma, A. J. Mol. Catal. A 2009, 305, 3.
(
18) (a) Chassaing, S.; Alix, A.; Boringari, T.; Sani Souna Sido, A.;
Keller, M.; Kuhn, P.; Louis, B.; Sommer, J.; Pale, P. Synthesis
(22) Cundy, D. J.; Forsyth, S. A. Tetrahedron Lett. 1998, 39, 7979.
(23) Amatore, C.; Le Duc, G.; Jutand, A. Chem. Eur. J. 2013, 19, 10082.
(24) Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; Ribas,
X. Chem. Sci. 2010, 1, 326.
2010, 1557. (b) Chassaing, S.; Alix, A.; Olmos, A.; Keller, M.;
Sommer, J.; Pale, P. Z. Naturforsch., B 2010, 65b, 783.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H