Synthesis of substituted acetylenes, aryl-alkyl ethers, 2-alkene-4-ynoates and nitriles using heterogeneous mesoporous Pd-MCM-48 as reusable catalyst

Article abstract of DOI:10.1016/j.tet.2011.05.132

Pd-MCM-48 has been employed as a heterogeneous catalyst for the synthesis of substituted acetylenes via Sonogashira reactions under copper and amine-free reaction conditions. In addition, the catalyst exhibited excellent regioselectivity for primary alcohols towards C-O coupling leading to formation of alkyl-aryl ethers in high yields. A green procedure for the stereoselective synthesis of 2-alkene-4-ynoates and nitriles from the reactions of vic-(E)-diiodoalkenes with activated alkenes has also been demonstrated using Pd-MCM-48 catalyst. The catalyst was easily recovered from the reaction mixture by filtration and reused for at least six times with minimal loss of activity.

Full text of DOI:10.1016/j.tet.2011.05.132

Tetrahedron 67 (2011) 5717e5724
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of substituted acetylenes, arylealkyl ethers, 2-alkene-4-ynoates and
nitriles using heterogeneous mesoporous Pd-MCM-48 as reusable catalyst
*
*
*
Subhash Banerjee , Hari Khatri, Vagulejan Balasanthiran, Ranjit T. Koodali , Grigoriy Sereda
Department of Chemistry, The University of South Dakota, 414E. Clark Street, Vermillion, SD 57069, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 May 2011
Received in revised form 29 May 2011
Accepted 31 May 2011
Available online 12 June 2011
Pd-MCM-48 has been employed as a heterogeneous catalyst for the synthesis of substituted acetylenes
via Sonogashira reactions under copper and amine-free reaction conditions. In addition, the catalyst
exhibited excellent regioselectivity for primary alcohols towards CeO coupling leading to formation of
alkylearyl ethers in high yields. A green procedure for the stereoselective synthesis of 2-alkene-4-
ynoates and nitriles from the reactions of vic-(E)-diiodoalkenes with activated alkenes has also been
demonstrated using Pd-MCM-48 catalyst. The catalyst was easily recovered from the reaction mixture by
filtration and reused for at least six times with minimal loss of activity.
Keywords:
Sonogashira coupling
Selective CeO coupling
1,3-Enyne unit
Ó 2011 Elsevier Ltd. All rights reserved.
Mesoporous Pd-MCM-48
Heterogeneous catalysis
1. Introduction
have been reported in the literature using Pd-MCM-48 as cata-
lyst4mep because of the challenging preparative method of MCM-48
The carbonecarbon and carboneheteroatom bond formation
via palladium-catalyzed coupling reactions1e3 plays a crucial role in
the organic synthesis. Conventionally, reactive and soluble palla-
dium complexes have been used as homogeneous catalysts for
these coupling reactions. However, non-reusability of the homo-
geneous catalysts remains a scientific challenge due to economical
and environmental concerns. As a result different strategies have
been reported for heterogenization of the homogeneous catalysts,
which enabled the easy separation of products from the reaction
mixture as well as recycling of the catalysts. The ordered meso-
porous siliceous material supported Pd catalysts2m,4 have attracted
much attention in recent years due to their unique physical char-
acteristics. Among various classes of mesoporous materials, the
cubic MCM-48 is attractive because its following features: (i)
involving long reaction times (1e7 days) and/or hydrothermal re-
action conditions.5 The simple and room temperature procedure
for preparation of MCM-48 reported by us6a has paved the way to
the exploration of MCM-48-based catalysts for organic synthesis.
As a part of our continued interest in the heterogeneous catalysis,6
we have reported a simple protocol for the synthesis of a novel,
heterogeneous, and versatile catalyst, Pd-MCM-48 at room tem-
perature as well as its application for chemo- and region-selective
hydrogenation and coupling (Heck and Suzuki) reactions under
ligand-free aerobic conditions.6j Excellent activity and selectivity of
the catalyst motivated us to better explore its potential in organic
synthesis. In this paper, we report the use of Pd-MCM-48 catalyst
for the synthesis of arylearyl or alkylearyl substituted acetylenes
via Sonogashira cross-coupling of aryl halides with terminal al-
kynes, arylealkyl ethers and 2-alkene-4-ynoates and nitriles by
a simple reaction of vic-(E)-diiodoalkenes with conjugated alkenes
in water (Scheme 1).
thermal stability (ii) large surface areas (1000e2500 m2 ꢀ1) en-
g
abling high dispersion of catalytic active sites, (iii) uniform pore
sizes, (iv) easily tunable pore volume that allow for facile encap-
sulation of nanoparticles (NPs) and finally, (v) interpenetrating
network of three-dimensional pores, which facilitate molecular
transport of reactants and products more efficiently than the one-
dimensional network of MCM-41.4d However, only a few studies
2. Results and discussion
Two different methods namely, impregnation and deposition
were designed to introduce Pd nanoparticles into MCM-48 support.
In the impregnation method, aqueous solution of pre-formed Pd
nanoparticles was added to the precursor mixture of MCM-48 us-
ing our recently published procedure for catalyst 1.6j Two more
catalysts were prepared in this manner, but with different amounts
* Corresponding authors. Tel.: þ1 605 677 6190; fax: þ605 677 6397; e-mail
addresses: ocsb2009@yahoo.com (S. Banerjee), ranjit.koodali@usd.edu (R.T. Koodali),
gsereda@usd.edu (G. Sereda).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.132

5718
S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
I
Pd-MCM-48 (1)
Pd-MCM-48 (2)
Pd-MCM-48 (3)
700
I2
ArX
H
R
Ar
R
R
600
Pd-MCM-48
I
500
R = alkyl, aryl
W
W
W = CO2R, CN
R
400
Pd-MCM-48
300
200
100
Scheme 1. Pd-MCM-48 catalyzed coupling reactions.
of the Pd nanoparticles. These catalysts are referred to as impreg-
nated Pd-MCM-48 (catalysts 1e3). Briefly, the required amount of
Pd NPs6j was added to an appropriate molar composition of cetyl-
trimethylammonium bromide, NH3 and tetraethyl orthosilicate in
ethanol/water mixture and stirred at room temperature for 4 h. The
mesoporous material was obtained through washing with water
followed by drying, calcination at 550 ꢁC in air and mild reduction
with H2 gas (see Experimental section for details). In the deposition
method,6j a precursor Pd salt was deposited on the synthesized
MCM-48 (referred to as deposited Pd-MCM-48) and then reduced
by H2 gas. The prepared catalysts were characterized by powder
X-ray diffraction (XRD), transmission electron microscopy (TEM)
imaging, nitrogen sorption, and chemisorption (CO-pulse) studies.
The quantity of Pd in the catalyst has been determined from atomic
absorption spectroscopic (AAS) study. The analytical and textural
data of catalysts 1e3 are given in Table 1. The XRD studies revealed
the formation of cubic mesoporous MCM-48 as evident from the
0.0
0.2
0.4
0.6
0.8
1.0
Relative Pressure(P/P )
0
Fig. 2. Nitrogen adsorptionedesorption isotherms of catalyst, 1e3.
This result is also in accordance with the previously published
results by Yasar et al.4k With increasing Pd loading, the chances of
agglomeration increase, whichled totheobserveddecreaseinthePd-
surface area and Pd-dispersion. While most of small Pd NPs (<2 nm)
were present inside the pores of MCM-48, some larger sized Pd NPs
(average size w6 nm) were detected on the surface of mesoporous
material as observed in the TEM image (Fig. 4). The TEM image also
indicates that the Pd NPs on the surface of the MCM-48 are well
dispersed. The CO pulse (chemisorption) study revealed that the
crystallite sizeof the Pd NPs wasincreased from5.8 nmincatalyst 1 to
28 nm in catalyst 3 with increasing Pd content in the samples.
small peak near 2q
3.2ꢁ (Fig. 1).
Table 1
Analytical and textural data of Pd-MCM-48 catalysts
Pd-MCM-48 Catalysts
Surface area [m2 gꢀ1
]
Pore diameter [nm]
Pd-surface area [m2 gꢀ1
]
Pd-dispersion [%]
Pd-content [%]
1
2
3
1357
1697
1788
2.2
1.9
1.8
95.3
35.4
17.7
20
8
4
0.6
1.6
2.6
6
5
4
3
2
1
15000
12500
10000
7500
Pd-MCM-48 (1)
Pd-MCM-48 (2)
Pd-MCM-48 (3)
Pd-MCM-48 (1)
Pd-MCM-48 (2)
Pd-MCM-48 (3)
5000
2500
0
0
2
3
4
5
6
20
40
60
80
100
2 θ
o
Pore diameter (A )
Fig. 1. Powder XRD pattern of Pd-MCM-48 catalyst, 1e3.
Fig. 3. Pore size distribution of catalyst, 1e3.
The pore size distribution of the catalysts was calculated from
the BarretteJoynereHalenda (BJH) equations using the nitrogen
desorption isotherm (Fig. 2), and surface area was calculated using
BrunauereEmmetteTeller (BET) equation (Table 1).
The data in Table 1 indicate that all three catalysts have narrow
pore size distribution (Fig. 3) with pore diameters ranging from 1.8
to 2.2 nm (See Table 1) and large surface area (1355e1788 m2 gꢀ1).
However, the pore diameter, metal surface area and dispersion
of the Pd NPs were found to decrease with increasing Pd content in
the sample. The decrease in pore diameter may be ascribed to the
presence of Pd species within the pores of the mesoporous
material.
The synthesized Pd-MCM-48 catalysts have been employed for
the synthesis of substituted acetylenes via Sonogashira cross-
coupling (sp2esp) of aryl halides with terminal alkynes. We
observed that the Pd-MCM-48 efficiently catalyzed this reaction
under copper-amine-free reaction conditions. It was observed that
the presence of copper always leads to unwanted dimerization of
alkyne, which often happens in presence of air or other oxidizing
agents.7
Moreover, amines often have a pungent smell that curtails
practicality of the process. The reaction conditions were optimized,

S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
5719
conditions. In some cases, the yields of these reactions are better
than reported Pd-salts or supported Pd catalysts (references were
given in Table 3). The comparison has been shown in the Table 3.
Most importantly, it is worth mentioning here, whereas Pd-MCM-
48 smoothly catalyzes Sonogashira coupling of bromobenzene
derivatives with terminal alkynes (Table 3, entries 3, 8, 13e17), Pd-
MCM-41 was not able initiate these reactions.2m However, chloro-
benzene did not react, and starting materials were recovered. Most
of the reactions (entries 1e12, 14e16) in Table 3 have been carried
out using ethanol and no ether formation was observed. However,
for nitro and cyano-substituted bromobenzene, ether was formed
at the yield w40%. The formation of ether was avoided by using
DMF as solvent (entries 13 and 17, Table 3).
Interestingly, reaction of some nitro-substituted aryl iodides and
bromides with ethanol always exclusively led to CeO coupling
products (Scheme 2). Various nitro-substituted aryl iodides and
bromides were found to be reactive under these conditions. Very
recently, Beller et al.8 reported a procedure for Pd(OAc)2-catalyzed
CeO coupling in presence of the bulky di-1-adamantyl-substituted
bipyrazolylphosphine ligand.
Importantly, the authors reported excellent and uncommon
chemoselectivity for a primary alcohol versus its secondary and
tertiary counterparts. Motivated by their results; we investigated
the selectivity of our mesoporous Pd-MCM-48 catalyst 1 towards
CeO coupling reactions and found by far higher reactivity of pri-
mary alcohol (Scheme 2). Thus, when a mixture of ethanol (pri-
mary), iso-propanol (secondary) and tert-butanol (tertiary) was
refluxed with 4-nitroiodobenzene in presence of Pd-MCM-48 1
(40 mg, 0.6%) only ethanol was consumed (forming 1-ethoxy-4-
Fig. 4. TEM images of Pd-MCM-48 catalyst 1.
and their synthetic outcome is summarized in Table 2. Addition of
copper (I) iodide as a co-catalyst always produced diyne 2 as major
product (entry 1e4, 7e8, Table 2) in aerobic conditions. The Pd-
MCM-48(1)/EtOH/K2CO3 reagent system was found to be the best.
It was also observed that the yield of the product did not increase
significantly for the increased amount of Pd over 0.6%.
Table 2
Optimization of reaction conditions for the Sonogashira cross-coupling reaction
Catalyst, base
Ph
Ph
Ph
PhI
Ph
Ph
Solvent, Temperature
1
2
Entry
Catalyst
Base
Et3N
Piperidine
Piperidine
Piperidine
NaOH
NaOAc
K2CO3
K2CO3
K2CO3
K2CO3
Solvent
Temp (ꢁC)
Time (h)
Products ratio (%)a
Yield (%)a
1
2
1
2
3
4
5
6
7
8
Pd-MCM-48b/CuIc
Pd-MCM-48b/CuIc
Pd-MCM-48b
EtOH
DMF
DMF
DMF
EtOH/H2O
EtOH/H2O
DMF
EtOH
DMF
80
120
100
120
80
100
100
80
120
80
80
80
80
12
12
10
10
24
24
10
10
10
10
10
10
10
0
0
0
0
0
100
100
100
100
0
70
74
82
90
0
Pd/Cu-MCM-48
Pd-MCM-48b
Pd-MCM-48b/CuIc
Pd-MCM-48b/CuIc
Pd-MCM-48b/CuIc
Pd-MCM-48b
0
0
0
20
25
55
100
100
100
100
80
75
45
0
0
0
86
90
80
85
88
83
75
9
b
10
11
12
13
Pd-MCM-48 (1)
EtOH
EtOH
EtOH
Pd-MCM-48 (2) (1.6%)
Pd-MCM-48 (3) (2.6%)
Pd-MCM-48 (Deposited)d
K2CO3
K2CO3
K2CO3
EtOH
0
Bold font shows the optimum reaction condition, which was used to carry out all the reactions listed within this Table.
a
The yields and ratio of the products was determined from the 1H NMR spectra.
Pd-MCM-48 (30 mg) was used for 1 mmol of phenylacetylene.
CuI (5 mol %) was used for 1 mmol of phenylacetylene.
Catalyst was prepared by depositing Pd-precursor on synthesized MCM-48.
b
c
d
The scope and general applicability of the Pd-MCM-48 (1) (0.6%)
catalyst have been investigated under optimized reaction condi-
tions (Table 2, entry 10). A series of alkyl and aryl-substituted ter-
minal alkynes were coupled with different aryl halides in presence
of Pd-MCM-48 (30 mg, 0.6%, 1.7ꢂ10ꢀ3 mmol of Pd) and K2CO3
(2 mmol) in ethanol at 80 ꢁC to produce alkylearyl or arylearyl
substituted acetylenes in good yields. The results are summarized
in Table 3. The reactions were very selective and always produced
the target disubstituted acetylenes under these reaction conditions
with no diynes observed.
nitro-benzene as the product) while the secondary and tertiary
alcohols remained intact under the ligand-free and aerobic reaction
conditions (Scheme 3).
The catalyst recyclability has been investigated for the synthesis
of diphenylacetylene (Table 3, entry 4). The catalytic material was
recovered from the reaction mixture by filtration, washed with
ethanol, dried in air, and reused for subsequent runs. It was ob-
served that the catalyst can be used for six times with minimal loss
of activity. The results are presented in Table 6.
After the successful application of the Pd-MCM-48 catalyst for
the Sonogashira and CeO coupling reactions, we explored its po-
tential for the synthesis of organic molecules with valuable
Aryl iodides and bromides with either an electron donating or
withdrawing substituent readily reacted under this reaction

5720
S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
Table 3
Pd-MCM-48 (1) catalyzed Sonogashira cross-coupling reaction
Pd-MCM-48
R1
R1
ArX
Ar
Solvent, K2CO3
Entry
1
ArX
R1
Time (h)
10
Yield (%)a
78
Ref
4h
2
3
2a
12
12
75
4h
2f
72 (43)b (18)c (16)d,e (0)f
4
5
1a
1b
2b
2b
8
8
85
82
2f
2f
6
7
2b
10
10
80
90
2f
2f
1a
8
9
10
1c
1b
1d
2c
2c
2c
12
12
12
70 (0)f
85 (30)d,e
78
2f
2f
2f
11
12
13
1a
1b
8
12
7
84
75
85
2f
2f
2i
2d
2a
14
15
16
2a
2b
2b
10
12
12
65
2i
2i
2i
1f
70
70 (57)b
17
2b
10
80 (60)b
2i
a
Yields refers to those of pure and isolated products characterized by 1H and 13C NMR. 30 mg (0.6%) of Pd-MCM-48 was used per 1 mmol of alkyne.
b
c
d
e
f
Catalyst¼PdCl2/PPh3/K2CO3.2i
Using Pd(PPh3)4/CuI.2j
Catalyst is PdeSiO2.2k
Yield obtained from Pd-Zeolite.2l
Using Pd-MCM-412m.The reactions listed in entries 1e12 and 14e15 have been carried out using ethanol and for entries 13 and 17 DMF was used.
R1
R1
Pd-MCM-48
I
OEt
(40 mg, 0.6 %)
Pd-MCM-48 (0.6 %)
O
X
CH2R2
+
iPrOH + t BuOH
K2CO3, Reflux, 12 h
K2CO3, R2CH2OH
Reflux, 12 h
O2N
O2N
EtOH +iPrOH + tBuOH
O2N
R2 = Me; X = I : Yield = 90 %
O2N
+
R1 = H;
Scheme 3. Pd-MCM-48 catalyzed selective CeO coupling.
R1 = NO2; R2 = Me; X = I : Yield = 95 %
R1 = NO2; R2
=
nPr; X = Br : Yield = 88 %
biological and optical properties. Thus, formation of the 1,3-enyne
unit opens a practical synthetic approach to molecules with vast
applications in biology,9 electronics and photonics.10 Generally,
Scheme 2. Pd-MCM-48 catalyzed CeO coupling.

S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
5721
these compounds are synthesized by homogeneous Pd- or Cu-
catalyzed coupling of alkynes or organometallic alkynes and vinyl
halides.11 Recently, Ranu et al.12a synthesized (E)-and (Z)-2-ene-4-
ynoates and nitriles by Pd NPs-catalyzed coupling of vic-diio-
doalkenes with conjugated alkenes. However, none of these cata-
lysts are reusable. To overcome this limitation, later on Ranu et al.12b
applied hydroxyapatite-supported Pd (Pd-HAP) as reusable catalyst
for the construction of the 2-ene-4-ynoate unit. However, this ma-
terial has not reported to catalyze coupling of vic-diiodoalkenes
with conjugated nitriles.12b Therefore, a heterogeneous catalyst
with wider applicability was long awaited. We found that Pd-MCM-
48 efficiently catalyzes the coupling of vic-diiodoalkenes with con-
jugated esters or nitriles, leading to (E)- and (Z)-2-alkene-4-ynoates
and 2-ene-4-yne-nitriles in good yields in presence of K2CO3 and
tetra-butyl ammonium bromide (TBAB) in water (Scheme 4).
aryl-substituted alkenes produced 1,3-eneyne esters and nitriles in
good yields (70e92%) within practical reaction time (4e6 h). The
coupling is highly stereoselective, thus only (E)-isomer was isolated
in case of acrylic esters. However, (Z)-stereoisomer was obtained as
a major product when acrylonitrile was used. Only 30 mg of Pd-
MCM-48 (1) catalyst containing 1.7ꢂ10ꢀ3 mmol of Pd were suffi-
cient to perform the reactions smoothly in presence of K2CO3 and
TBAB in water with no involvement of hazardous organic solvents.
Further, the catalyst was recovered from the reaction mixture
simply by filtration, washed with ethanol, dried, and reused for
subsequent runs.
In one example, (reaction of vic-(E) diiodostyrene and n-butyl
acrylate) we determined that the catalyst can be reused up to six
times with minimal loss of activity (See Table 6). Only after the
fourth cycle, the yield dropped to 58%. This could be due to the
blockage of the pores of the mesoporous MCM-48 with organic
compounds involved in the reaction.
I
Pd-MCM-48 (0.6 %)
W
For comparison, the most representative reported results for the
synthesis of the 1,3-enyne unit via coupling of vic-(E) diiodoalkenes
with conjugated alkenes on different Pd catalysts are summarized
in Table 7. It is evident from the data outlined in Tables 5 and 6, that
the Pd-MCM-48 catalyst is superior in terms of reaction time
(4e6 h), general applicability for conjugated alkenes (both CO2R-
H
W
R
R
H O/TBAB
2
o
I
K CO /90
C
2
3
R = alkyl, aryl
W = CO Me, CO Bu , CN
n
2
2
Scheme 4. Pd-MCM-48 catalyzed coupling of vic-diiodoalkenes with conjugated
alkenes.
and CN-substituted), and reusability versus the most common
12a
PdCl2/TBAB/K2CO3
and Pd-HAP systems reported previously.12b
Further, the new catalyst has proven to be a better alternative to
the existing catalysts for the construction of the 1,3-enyne unit via
coupling of vic-diiodoalkenes with conjugated alkenes.
In order to optimize the reaction of vic-(E)-diiodostyrene and n-
butyl acrylate (Table 4), we have screened several bases (K2CO3,
Na2CO3 and NaOH) in various solvents (DMF, EtOH, N-methyl pyr-
rolidone (NMP), H2O, etc.).
Table 5
Table 4
Pd-MCM-48 catalyzed coupling of vic-diiodoalkenes with conjugated alkenes
Optimization of reaction conditions for the synthesis of butyl 5-phenylpent-2-en-4-
ynoate
I
Pd-MCM-48 (0.6 %)
H2O/TBAB
W
H
I
W
R
R
CO2Bun
Catalyst
(E)
CO2Bun
H
K2CO3/ 90 o
C
I
Ph
Solvent, Base
(E)
Ph
80 o
C
I
Entry
R
W
Time (h)
Yield (%)a
E:Zb
Entry Catalyst
Base
Solvent
EtOH
Na2CO3 EtOH
Time (h) Yield (%)a
1
2
3
4
5
6
7
8
7
9
10
C4H9
C4H9
C6H13
C6H5
C6H5
C6H5
p-MeeC6H4
p-MeeC6H4
p-MeeC6H4
p-CleC6H4
m-OMeeC6H4
CO2Me
CO2nBu
CO2nBu
CO2Me
CO2nBu
CN
5
5
6
4
4
6
5
4.5
6
75
70
72
80
85
73
78
92
70
76
89
100:00
100:00
100:00
100:00
100:00
14:86
100:00
100:00
30:70
1
2
3
4
5
6
7
8
9
Pd-MCM-48
K2CO3
12
12
4
24
4
15
10
75
0
85
60
0
Pd-MCM-48
Pd-MCM-48
Pd-MCM-48
Pd-MCM-48
Pd-MCM-48
Pd-MCM-48
Pd-MCM-48
PdeC (10%)
K2CO3
K2CO3
K2CO3
DMF
H2O
TBABb/H2O
Na2CO3 TBABb/H2O
6
CO2Me
CO2nBu
CN
NaOH
K2CO3
K2CO3
TBABb/H2O 12
NMPc
EtOH
EtOH
6
6
6
45
0
0
CO2nBu
CO2nBu
4
4
100:00
100:00
10
Pd-MCM-48 (deposited)d K2CO3
a
Yields refer to those of pure and isolated products characterized by 1H and 13
C
a
Yields refer to those of pure and isolated products.
b
NMR data.
1.5 mmol of tetrabutyl ammonium bromide (TBAB) was used for 1 mmol of
diiodostyrene.
b
E/Z ratio was determined from analysis of 1H NMR spectra. 30 mg of Pd-MCM-48
c
(1) and 1.5 mmol of TBAB was used per 1 mmol of alkene. All the products were
known.
NMP is N-methyl pyrrolidine.
Catalyst was prepared by depositing Pd-precursor on synthesized MCM-48.
d
The reaction was inefficient (15% yield) with Pd-MCM-48 (1)
Table 6
and K2CO3 in ethanol (Table 4, entry 1) and failed in water without
TBAB (Table 4, entry 4). However, the use of TBAB along with water
led to the desired product, butyl 5-phenylpent-2-en-4-ynoate in
high yield (Table 4, entry 5). The reaction in DMF proved to be
successful as well (Table 4, entry 3). However, to avoid tedious
workup process, we have replaced DMF solvent with H2O. The
commercially available Pd/C (10%) (Table 4, entry 9) and Pd-MCM-
48 (deposited) (Table 4, entry 10) lead to the formation of an un-
identified product in both cases. The Pd-MCM-48(1)/K2CO3/H2O/
TBAB system exhibited the best catalytic performance (Table 4,
entry 5) for this coupling reaction. Therefore, this reagent has
been selected to explore its scope of applicability. Both alkyl- and
Recyclability of Pd-MCM-48 for coupling reactions
Number of times the
catalyst was reused
Yield (%)a
Diphenylacetylene
(entry 4, Table 3)
Butyl 5-phenylpent-2-ene-
4-ynoate (entry 5, Table 5)
1
2
3
4
5
6
85
85
82
80
75
75
85
84
76
65
58
45
a
Yield refer to pure and isolated products.

5722
S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
Table 7
Comparative results for the synthesis of 1,3-enyne unit using different Pd catalysts
I
Catalytic
system
(E)
W
H
W
R
R
I
Entry
Catalytic system
R
W
Time (h)
Yield (%)a
Recycle times
Ref
1
2
3
PdCl2, TBAB/H2O Na2CO3, 80 ꢁC
Pd-HAP, NMP K2CO3, 90 ꢁC
Pd-MCM-48, TBAB K2CO3, H2O/90 ꢁC
Alkyl/aryl
Alkyl/aryl
Alkyl/aryl
CO2R, CN
CO2R
CO2R, CN
6e24
5e7
4e6
65e82
67e90
70e92
2
3
6
12a
12b
Present
a
Yield refer to those of pure products.
In accordancewith Ranu et al.,12b the coupling reactions are likely
to proceed by two alternating pathways (Scheme 5). In path a, the
final product, 2-ene-4-yonate was produced via intermediate
iodoalkyne(I); weproved in a separateexperiment, that this product
(I) is exclusively produced as an intermediate fromvic-diiodostyrene
in presence of Pd-MCM-48/K2CO3. Treatment of this intermediate (I)
with butyl acrylate under the reaction conditions produces the final
enyne carboxylic ester through Heck coupling. The possibility of
path b has also been documented by Ranu et al., where initially Heck
reaction took place followed by HI elimination.12b
Table 8
Pd-MCM-48 catalyzed CeN coupling reaction
Pd-MCM-48
DMF, NaOAc
ArNRR'
RNHR'
ArX
Entry
1
ArX
Amine
Time (h)
12
Yield (%)a
80
CO2Me
2
3
4
5
15
8
75
95
80
75
CO2Me
Ph
I
Ph
I
I
(E)
Pd-MCM-48
K2CO3
Path a
Ph
I
(E)
(E)
(I)
Pd-MCM-48
K2CO3
Path b
H
H
K2CO3
- HI
CO2Me
Pd-MCM-48
K2CO3
CO2Me
CO2Me
(E)
(E)
Ph
Ph
8
Scheme 5. Possible mechanism for the synthesis of 1,3-eneyne unit.
The high E-selectivity for CO2R compared to the relatively small
CN group and also the conversion to higher energy Z-isomer for CN
group has been well addressed in Heck coupling.1g
PhNHMe
10
In earlier communication, we have presented two examples for
the carbon-nitrogen (CeN) bond formation (BuchwaldeHartwig
cross-coupling reaction) via cross-coupling reaction of 4-
nitroiodobenzene and pyrrolidine using our Pd-MCM-48 cata-
lyst.6j In this study, we have extended its scope for the CeN bond
formation reactions and results are presented in Table 8. Various
nitro and cyano-substituted aryl bromides and iodides were reac-
ted with aliphatic amines in presence of Pd-MCM-48 catalyst and
a base, NaOAc to yield CeN coupled products in good yields
(75e95%).
The heterogeneity of the Pd-MCM-48 catalyst was checked for
the synthesis of diphenylacetylene (Table 3, entry 4) as a model
reaction using the hot filtration method.4p Briefly, the hot reaction
mixture was filtered through a fritted funnel after 2 h (w25%
conversion by 1H NMR), and the filtrate was refluxed for additional
10 h. However, only an insignificant 3% increase in yield was ob-
served. This result proved that the reaction was catalyzed hetero-
geneously and Pd NPs did not leach from the mesoporous MCM-48
matrix during the course of the reaction.
6
12
78
a
Yields refer to those of pure products. All of the products gave 1H and 13C NMR
data consistent with the structures and data in the literature.
carried out under copper- and amine-free conditions with high
isolated yields. The excellent selectivity was observed for primary
alcohols towards CeO coupling, leading to arylealkyl ethers in
excellent yields (88e95%) under ligand-free conditions using Pd-
MCM-48. Moreover, the impregnated catalyst showed excellent
activity for the construction of 1,3-enyne units, whereas only un-
identified products were produced on the deposited Pd-MCM-48
catalyst. To the best of our knowledge, selective CeO coupling
and reactions of vic-diiodoalkenes with conjugated alkenes, docu-
mented in this study, have not been reported using Pd-mesoporous
materials. Sonogashira coupling has never been reported using Pd-
MCM-48. This body of work provides new knowledge regarding the
applicability of mesoporous materials for those reactions.
3. Conclusions
4. Experimental section
In conclusion, mesoporous heterogeneous Pd-MCM-48 has been
introduced as an efficient reusable catalyst for the synthesis of
arylearyl or arylealkyl substituted acetylenes, arylealkyl ethers,
(E)-and (Z)-2-alkene-4-ynoates, and nitriles under ligand-free and
aerobic reaction conditions. The Sonogashira reaction has been
4.1. Chemicals and reagents used
Hexadecyltrimethylammoniumbromide (CTAB, 99þ%, Acros),
ethanol (absolute 200 Proof, AAPER), aqueous ammonia (Fisher),

S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
5723
tetraethoxysilane (99%, Alfa Aesar), palladium(II) 2,4-
pentanedionate (Alfa Aesar), and sodium terachloropalladate(II)
(Na2[PdCl4]) (Pressure Chemicals) were used for the synthesis of
Pd-MCM-48 catalysts. Dimethylaminopyridine (DMAP, 99%, Acros),
sodium borohydride (98% Acros), toluene (Acros), tetra-n-octy-
lammoniumbromide (TOAB, 98þ% Alfa Aesar), and sodium sulfate
anhydrous powder (Fisher) were used for the synthesis of Pd
nanoparticles. All the chemicals, reagents and solvents used for the
Sonogashira, CeO coupling, and synthesis of the enyne system
were purchased from either SigmaeAldrich and (or) Alfa Aesar,
and used as received without any further purification. (E)-vic-
Diiodoalkenes were synthesized from corresponding alkenes using
molecular iodine in watereethanol mixture at room temperature
and were characterized by 1H NMR spectroscopy data before use for
reactions.
synthesized catalyst was determined by atomic absorption spec-
troscopy and found to be 0.6 wt %.
The above procedure was used for the synthesis of other two
catalysts; catalyst 2 and catalyst 3 by varying the amount of Pd NPs
(3 mL of Pd NPs solution for catalyst 2, and 5 mL of Pd NPs for
catalyst 3). Characterization data for all three catalysts are pre-
sented either in the main text or in Supplementary data.
4.4. General experimental procedure for the Sonogashira
coupling of iodobenzene with phenylacetylene (Table 3,
entry 4)
Iodobenzene (204 mg, 1 mmol), phenylacetylene (102 mg,
1 mmol), K2CO3 (276 mg, 2 equiv, 2 mmol) and Pd-MCM-48
(25 mg) were mixed in 5 mL of ethanol and refluxed for 12 h
with stirring. The reaction progress was monitored by TLC. The
reaction mixture was cooled to room temperature, and solvent
was removed under vacuum. The residue was extracted with
100 mL of ethyl acetate and organic layer was washed with water
(2ꢂ5 mL). The organic layer was dried over Na2SO4, and solvent
was evaporated to provide diphenylacetylene as a white solid
(151 mg, 85%). The 1H NMR and 13C NMR spectroscopic data of the
product were in good agreement with previously reported data.2f
This procedure was followed for all the reactions listed in Table 3.
All the products listed in Table 3 are known and all of the products
gave 1H and 13C NMR data consistent with the structures and data
in the literature. The reference for each compound is provided in
Table 3.
4.2. Synthesis of Pd(0) nanoparticles
Pd(0) Nanoparticles were synthesized by a published procedure,
which involves reduction of Na2PdCl4 with NaBH4, and stabilized by
tetra-octylammonium bromide (TOAB) as a capping agent. Briefly,
9.6 mL of a 47 mM aqueous solution of Na2PdCl4 (yellow colour)
was mixed with 40 mL of a 50 mM solution of TOAB dissolved in
toluene and magnetically stirred at 300 rpm for 15 min. A red-
brown organic solution and the colourless aqueous phase were
formed due to the complete transfer of PdCl24ꢀ to the organic phase.
The colourless aqueous phase was separated and the toluene phase
was dried with Na2SO4. Then, 11.4 mL of a freshly prepared
0.1e1.0 M of NaBH4 aqueous solution were added drop wise for
a period of 2 h under vigorous magnetic stirring. The mixture was
stirred overnight, consecutively washed with 40 mL of a 0.1 M
H2SO4, 40 mL of a 0.1 M aqueous NaOH and 40 mL of water. Finally,
the organic solution was dried over anhydrous Na2SO4. Then we
transferred the Pd(0) nanoparticles to the aqueous phase. For that
a solution (10 mL) of 4-dimethylaminopyridine (DMAP) (0.1 M) was
used as a phase transfer agent and prepared by dissolving 0.1 g of
DMAP in 10 mL of deionized water. Then, aqueous DMAP solution
was added to 40 mL of the as-synthesized Pd nanoparticles in
toluene. The mixture was stirred for 2 h to complete transfer of the
Pd nanoparticles to the aqueous phase.
4.5. General experimental procedure for synthesis of butyl
5-phenylpent-2-ene-4-ynoate via coupling of 1,2-
diiodovinylbenzene with butyl acrylate (Table 5, entry 5)
A mixture of 1,2-diiodovinylbenzene (356 mg, 1 mmol), n-butyl
acrylate (192 mg, 1.5 mmol), K2CO3 (276 mg, 2 equiv, 2 mmol), and
tetra-butyl ammonium bromide (TBAB) (483 mg, 1.5 mmol) in
H2O (5 mL) was stirred at 90 ꢁC for 4 h. Progress of the reaction
was monitored by TLC. The reaction mixture was extracted with
ethyl acetate (2ꢂ5 mL). The organic layer was dried over anhy-
drous Na2SO4 the solvent was evaporated to yield the crude
product, which was purified by flash chromatography over silica
gel (eluted by 5% ethyl acetate in hexane) to afford pure butyl 5-
phenylpent-2-en-4-ynoate (194 mg, 85%) as a yellow oil. The
spectroscopic data (1H NMR and 13C NMR) are in good agreement
with reported in the literature.12a This reaction procedure was
followed for all the reactions listed in Table 5. All the products
listed in Table 5 are known in the literature and were character-
ized by 1H NMR and 13C NMR spectroscopic data, which are in
good agreement with reported values. The reference for each
compound is given in Table 5.
4.3. Representative experimental procedure for the synthesis
of Pd-MCM-48 (1)
The Pd-MCM-48 (1) catalyst has been synthesized by im-
pregnating Pd nanoparticles into the cubic phase of MCM-48
matrix following our previously published procedure.6j Pd nano-
particles were synthesized according to the published procedure
by the reduction of Na2PdCl4 with NaBH4 in the presence of tetra-
n-octylammoniumbromide (TOAB) as a capping as well as stabi-
lizing agent. In a typical experimental procedure, 1 mL of the Pd
nanoparticles solution (the concentration was adjusted to the
required loading), 25 mL ethanol, 1.2 g (3.3 mmol) of CTAB, 6 mL
of aq NH3 (0.09 mol) and 1.8 mL (8 mmol) of TEOS were se-
quentially added to a 125 mL polypropylene bottle, and stirred for
4 h at 300 rpm. The molar composition of the formed siliceous gel
is 0.41 CTAB:11 aq NH3:1.0 TEOS:53 EtOH:344H2O. After 4 h, the
mesoporous material was washed extensively with deionized
water, and dried overnight at 100 ꢁC. The dried material was finely
ground with a mortar and pestle and calcined in air at 550 ꢁC
(ramp rate of 3 ꢁC per min.) for 6 h in an alumina crucible to
remove the surfactant molecules. Since the calcined Pd-MCM-48
may contain Pd in the þ2 oxidation state, after calcinations this
calcined material was reduced in hydrogen-gas flow (20 mL/min)
at 300 ꢁC for 2 h in a tubular furnace to improve consistency of the
composition of the catalyst. The content of palladium in the
4.6. General experimental procedure for synthesis of 1-(4-
nitro-phenyl)-pyrrolidine via cross-coupling of 1-iodo-4-
nitro-benzene and pyrrolidine (Table 8, entry 1)
A mixture of 1-iodo-4-nitro-benzene (1 mmol, 249 mg), pyr-
rolidine (2 mmol, 142 mg), Pd-MCM-48 (30 mg) and NaOAc
(2 mmol, 164 mg) was heated at 130 ꢁC in DMF (5 mL) for 12 h till
completion of reaction (TLC). The reaction mixture was cooled to
room temperature and catalyst was separated by filtration. The
filtrate was extracted with ethyl acetate (20 mL), washed with
water (5ꢂ1 mL), dried over Na2SO4. The solvent was evaporated to
leave the crude product, which was purified by column chroma-
tography over silica-gel (2% ethyl acetate in hexane) to provide
pure 1-(4-nitro-phenyl)-pyrrolidine (153 mg, 80%). All the prod-
ucts listed in Table 3 are known in the literature and gave 1H and

5724
S. Banerjee et al. / Tetrahedron 67 (2011) 5717e5724
13C NMR data consistent with the structures and data in the
literature.
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Science Division, of the U.S. Department of Energy under Contract
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