Silica-immobilized CuI: An efficient reusable catalyst for three-component coupling reaction of aldehyde, amine and alkyne

Article abstract of DOI:10.1055/s-2007-984921

Silica-supported copper catalysts were effectively used in the three-component coupling of aldehydes, amines and alkynes to afford the corresponding propargylamines in moderate to excellent yields. The catalyst was quantitatively recovered from the reaction by a simple filtration and reused for a number of cycles with almost consistent activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984921

LETTER
2301
Silica-Immobilized CuI: An Efficient Reusable Catalyst for Three-Component
Coupling Reaction of Aldehyde, Amine and Alkyne
a
a
a
a
a
b
S
P
ilica-Immobi
r
lizedCu
a
I
as
C
atalys
v
t
in
T
hree-C
i
ompon
n
ent
C
oupling React
R
ion . Likhar,* Sarabindu Roy, Moumita Roy, M. S. Subhas, M. Lakshmi Kantam, Rajib Lal De
a
Inorganic & Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
b
Department of Chemistry, Jadavpur University, Kolkata 700032, India
Fax +91(40)27160921; E-mail: plikhar@iict.res.in
Received 11 April 2007
primarily since silica displays many advantageous proper-
ties, namely, excellent stability (chemical and thermal),
high surface area, good accessibility, and organic groups
Abstract: Silica-supported copper catalysts were effectively used
in the three-component coupling of aldehydes, amines and alkynes
to afford the corresponding propargylamines in moderate to ex-
cellent yields. The catalyst was quantitatively recovered from the can be robustly anchored to the surface, to provide cata-
reaction by a simple filtration and reused for a number of cycles lytic centers.16 By exploiting these advantages of silica,
with almost consistent activity.
we recently reported imine-functionalized silica-immobi-
Key words: silica, copper, three-component coupling, propargyl- lized copper complex catalyzed N-arylation of amines
1
7
amines, reusable catalyst
(Scheme1). Herein we wish to report the silica-immobi-
3
lized copper-catalyzed A coupling reaction.
The catalytic one-pot multicomponent coupling reaction
is an attractive strategy in organic synthesis to introduce
several elements of diversity into a molecule in a single
N
SiO2
N
SiO2
1
step. Three-component coupling of aldehydes, amines
N
HO
SiO2–Sal
3
SiO2–Py
and alkynes (A coupling) is one of the best examples of
such a process and has received much attention in recent
2
3
times. The resultant propargylamines obtained by A
coupling reactions are important synthetic intermediates
for potential therapeutic agents and polyfunctional amino
N
N
SiO2
N
SiO2
3
N
derivatives. There are several transition-metal catalysts
S
SiO2–Thio
3
SiO2–BPy
able to carry out A coupling reaction via C–H activation.
4
5
These include Ag(I) salts, Au(I)/Au(III) salts, Au(III)–
Scheme 1 Different imine-functionalized silica supports
6
7
salen complexes, Cu(I) salts, and a Cu/Ru bimetallic
system under homogeneous conditions. But all of these
8
3
-Aminopropyl-functionalized silica (AFS, 9% function-
alization, purchased from Aldrich) was derivatized with
different carbonyl compounds to the corresponding imi-
ne. Thus appropriate imine-functionalized silica support
was then subsequently complexed with copper salts to
afford the final silica-immobilized copper catalysts
systems suffer from the loss of the precious catalysts at the
end of the reaction. To achieve the recyclability of the
9
10
metal catalyst, Li et al. and Park et al. used room-tem-
17
perature ionic liquid immobilized catalysts. Our group re-
11
ported hydroxyapatite-supported copper (Cu-HAP) and
layered double hydroxide supported gold (LDH-AuCl4),12
18
3
(
Table 1, entries 1–6). To find the best catalyst for the A
and Reddy et al. reported heteropolyacid-supported silver
(
Ag-HPA)-catalyzed13 A coupling reactions. Recently
3
coupling reaction, we have chosen the three-component
reaction of 4-bromobenzaldehyde, morpholine and phe-
nylacetylene in acetonitrile as the model reaction
Scheme 2) and the results are summarized in Table 1.
From Table 1, it can be seen that SiO –Py–CuI is the best
1
4
Kidwai et al. have reported gold nanoparticles reusable
for the A coupling reactions.
3
(
The development of heterogeneous catalysts for fine
chemicals synthesis has become a major area of research
recently, as the potential advantages of these materials
2
catalyst amongst the catalysts screened.
To check the solvent effect on the outcome of the reaction,
different solvents were employed in the A coupling reac-
tion and the results are summarized in Table 2. It was ob-
served that acetonitrile was the most effective solvent, so
it was used in all reactions. It is noteworthy that water can
also be used as solvent, albeit with moderate yields
(
simplified recovery and reusability, the potential for in-
3
corporation in continuous reactors and microreactors)
over homogeneous systems can have a major impact on
the environmental performance of a synthesis.15 The
majority of these novel catalysts are based on silica,
(
Table 2, entry 6). Even at room temperature SiO –Py–
2
SYNLETT 2007, No. 14, pp 2301–2303
Advanced online publication: 24.07.2007
0
3
.0
9
.2
0
0
7
CuI afforded 45% product in 48 hours (Table 2, entry1).
DOI: 10.1055/s-2007-984921; Art ID: D10807ST
©
Georg Thieme Verlag Stuttgart · New York

2
302
P. R. Likhar et al.
LETTER
O
N
CHO
O
catalyst (5 mol%)
+
+
MeCN, 90 °C, N2, 8 h
N
H
Br
Br
Scheme 2 Three-component coupling using silica-immobilized copper catalysts
Table 1 Catalyst Screening for the Three-Component Coupling of
Table 3 Coupling of Aldehyde, Amine and Alkyne Catalyzed by
a
a
4-Bromobenzaldehyde, Morpholine, and Phenylacetylene (see
SiO –Py–CuI
2
Scheme 1)
R2
R1
R3
N
1
2 3
R4
Entry
Catalyst (5 mol%)
Isolated yield (%)
R CHO
+
R R NH
+
1
2
3
4
5
6
SiO –Py–Cu(OAc)
68
39
42
56
65
95
90
2
2
1
2
3
4
R4
R , R , R , R = aryl, alkyl, H
SiO –Sal–Cu(OAc)
2
2
Entry R1
R , R
2
3
R4
Time Yield
b
SiO –Thio–Cu(OAc)
(h)
(%)
2
2
SiO –BPy–Cu(OAc)
1
2
Ph
Morpholine
Morpholine
Morpholine
Morpholine
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
8
90
2
2
SiO –Py–CuCl
4-BrC H
8
92, 89c
92
2
2
6
4
SiO –Py–CuI
3
4-ClC H
4
8
2
6
7
CuI
4
4-MeC H
12
14
24
8
78
6
4
a
Reaction conditions: aldehyde (1 mmol), amine (1.2 equiv), alkyne
5
4-MeOC H Morpholine
75
6
4
(
1.5 equiv), MeCN (3 mL), 90 ºC for 8 h, N atmosphere.
2
6
4-NO C H
4
Morpholine
n.r.d
90
2
6
Table 2 Solvent Effect on the Three-Component Coupling of 4-
Bromobenzaldehyde, Morpholine, and Phenylacetylene Using SiO –
Py–CuI Catalyst
7
Cyclohexyl Morpholine
2
a
8
Ph(CH2)2
Ph
Morpholine
Piperidine
Piperidine
Pyrrolidine
8
88
Entry
Solvent (3 mL)
MeCN
Isolated yield (%)
9
6
90
1
92, 45b
30
10
11
12
13
14
15
16
17
18
Ph(CH
2
)
2
6
89
2c
3
THF
Ph
6
93
2
3
Dioxane
MeOH
35
4-BrC
Ph
6
H
4
R = R = allyl
8
90
2
3
4
85
R = R = allyl
8
91
2
3
5
Toluene
Water
80
Ph
R = R = benzyl Ph
10
8
92
6
42, 40d
Ph
Morpholine
Morpholine
Morpholine
4-MeC
6
H
4
4
88
a
Reaction conditions: aldehyde (1 mmol), amine (1.2 equiv), alkyne
4-BrC H
4-MeC H
8
90
6
4
6
(
1.5 equiv), catalyst (5 mol%), 90 °C for 8 h, N atmosphere.
2
b
Reaction at r.t. for 48 h.
Ph
Ph
Bu
Ph
12
18
72
c
Reaction temperature: 66 ºC.
2
d
nd
R = 4-BrC H ,
R = H
54
Yield after 2 cycle (leaching: 1.01%).
6
4
3
To widen the scope of the SiO –Py–CuI catalyst in A3
a
Reaction conditions: aldehyde (1 mmol), amine (1.2 equiv), alkyne
2
(
1.5 equiv), catalyst (5 mol%), MeCN (3 mL), 90 °C, N atmosphere.
coupling, several other aldehydes, amines and alkynes
were allowed to react under the optimized conditions19
and the results are summarized in Table 3. Aromatic alde-
hydes with both electron-donating and electron-with-
drawing functionalities afforded good to excellent yields
of the corresponding propargylamines (Table 3, entries 2–
2
b
Isolated yields.
Yields after the 5 cycle.
c
th
d
n. r. = no reaction.
the cyclic and acyclic secondary amines gave good yields.
Aromatic amine also reacted to give the corresponding
product but yields were low (Table 3, entry 18). Aromatic
alkynes afforded better yields than the aliphatic alkyne
5
). 4-Nitrobenzaldehyde did not yield the desired product,
1
1,13
which is in accordance with the earlier studies.
Both
the cyclic and acyclic aldehydes reacted with equal ease to
give excellent yields (Table 3, entries 7, 8, and 10). Both
(
Table 3, entry 17).
Synlett 2007, No. 14, 2301–2303 © Thieme Stuttgart · New York

LETTER
Silica-Immobilized CuI as Catalyst in Three-Component Coupling Reaction
(8) Li, C. J.; Wei, C. Chem. Commun. 2002, 268.
2303
For any heterogeneous catalyst, it is important to know its
ease of separation and possible reusability. The catalyst
was separated by simple filtration and washed with ethyl
acetate followed by water and finally with acetone and
air-dried. The recovered catalyst was used in the next run
and almost consistent activity was noticed for five consec-
utive cycles (Table 3, entry 2). To check whether the reac-
tion occurs mainly due to the leached metal or supported
catalyst, a reaction was terminated after a small conver-
sion (1 h, 13% conversion) and the catalyst was filtered
off by hot filtration and the reaction was continued with
the filtrate for the required period of time. Almost no
change in conversion was observed. This confirmed that
no active species was leached during the reaction. More-
over, the copper content of the fresh catalyst, and the cat-
(
9) Li, Z.; Wei, C.; Chen, L.; Varma, R. S.; Li, C. J. Tetrahedron
Lett. 2004, 45, 2443.
(
(
10) Park, S. B.; Alper, H. Chem. Commun. 2005, 1315.
11) Choudary, B. M.; Sridhar, C.; Kantam, M. L.; Sreedhar, B.
Tetrahedron Lett. 2004, 45, 7319.
(
12) Kantam, M. L.; Prakash, B. V.; Reddy, C. R. V.; Sreedhar,
B. Synlett 2005, 2329.
(13) Reddy, K. M.; Babu, N. S.; Prasad, P. S. S.; Lingaiah, N.
Tetrahedron Lett. 2006, 47, 7563.
(14) Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green
Chem. 2007, in press.
(
15) (a) Mizuno, N.; Misono, M. Chem. Rev. 1998, 98, 199.
(
b) Sartori, G.; Ballini, R.; Bigi, F.; Bosica, G.; Maggi, R.;
Righi, P. Chem. Rev. 2004, 104, 199.
(16) Corma, A.; Garcia, H. Adv. Synth. Catal. 2006, 348, 1391.
(
17) Likhar, P. R.; Roy, S.; Roy, M.; Kantam, M. L.; De R, L.
J. Mol. Catal. A: Chem. 2007, in press.
th
alyst after the 5 cycle were found almost unchanged
(
18) Preparation of Imine-Modified Silica-Supported Copper
(
only 2% difference).
1
7
Catalysts:
In conclusion, we have developed an efficient hetero-
geneous protocol for the three-component coupling of
aldehydes, amines and alkynes to afford the correspond-
ing propargylamines using silica-immobilized CuI cata-
lyst, which is easily separable from the reaction mixture
and reusable with consistent activity.
SiO –Py–Cu(OAc) : SiO –Py (1 g) was stirred with a
2
2
2
solution of Cu(OAc)
(1 mmol) in acetone (25 mL) for 24 h
2
to get SiO –Py–(CuOAc) . The copper content was
2
2
measured by ICP–AES and it was found to be 0.43 mmol/g.
Similarly SiO –Sal–Cu(OAc) (Cu: 0.41 mmol/g), SiO –
2
2
2
BPy–Cu(OAc) (Cu: 0.39 mmol/g), and SiO –Thio–
2
2
Cu(OAc) (Cu: 0.41 mmol/g) were prepared from Cu(OAc)
2
2
in acetone. SiO –Py–CuCl (Cu: 0.47 mmol/g) was prepared
2
2
from an acetone solution of CuCl . SiO –Py–CuI was
2
2
Acknowledgment
prepared from a MeCN solution of CuI and the copper
content was 0.45 mmol/g.
We wish to thank the CSIR for financial support under the Task
Force Project COR-0003. S.R. and M.S.S. thank CSIR and M.R.
thanks UGC for providing research fellowships.
3
(
19) Typical Procedure for A Coupling Reaction: A mixture
of aldehyde (1 mmol), amine (1.2 mmol), alkyne (1.5 mmol)
and SiO –Py–CuI (110 mg, 5 mol%) in MeCN (3 mL) was
2
stirred in a round-bottomed flask at 90 °C under nitrogen.
After completion of the reaction (monitored by TLC) the
catalyst was filtered. After removing the solvent at reduced
pressure, the crude material was purified by chromatography
on silica gel using hexane–EtOAc mixture as eluent to afford
the corresponding propargylamines. Spectroscopic data of
the new compounds are given below:
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(
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(
2
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Diallyl-[1-(4-bromophenyl)-3-phenylprop-2-ynyl]amine
1
(
7
Table 3, entry 12): H NMR (300 MHz, CDCl ): d = 7.40–
3
.62 (m, 6 H), 7.28–7.38 (m, 3 H), 5.70–5.91 (m, 2 H), 5.24
(
3
d, J = 17.0 Hz, 2 H), 5.12 (d, J = 9.3 Hz, 2 H), 4.99 (s, 1 H),
.16–3.29 (m, 2 H), 2.90–3.06 (m, 2 H). C NMR (75 MHz,
13
(
(
2) Wei, C.; Zhang, L.; Li, C. J. Synlett 2004, 1472.
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CDCl ): d = 138.5, 136.3, 131.8, 131.1, 129.8, 128.4, 122.8,
3
1
+
21.4, 117.4, 88.1, 84.7, 55.9, 53.5. ESI–MS: m/z = 368 [M
1], 366 [M + 1], 271, 269, 146, 104. Anal. Calcd for
C H BrN: C, 66.67; H, 5.89; N, 4.09. Found: C, 66.71; H,
98, 2599. (b) Dyker, G. Angew. Chem. Int. Ed. 1999, 38,
1698.
1
9
20
(
4) (a) Yan, W.; Wang, R.; Xu, Z.; Xu, J.; Lin, L.; Shen, Z.;
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Lett. 2003, 5, 4473.
5.92; N, 4.01.
4
-[1-(4-Bromophenyl)-3-p-tolylprop-2-ynyl]morpholine
1
(
Table 3, entry 16): H NMR (300 MHz, CDCl ): d = 7.45–
3
7
2
2
1
6
2
.61 (m, 4 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.12 (d, J = 8.0 Hz,
H), 4.69 (s, 1 H), 3.61–3.79 (m, 4 H), 2.52–2.68 (m, 4 H),
(
(
(
5) (a) Wei, C.; Li, Z.; Li, C. J. Synlett 2004, 1472. (b) Wei, C.;
Li, C. J. J. Am. Chem. Soc. 2003, 125, 9584.
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13
.38 (s, 3 H). C NMR (75 MHz, CDCl ): d = 138.5, 137.1,
3
31.8, 131.3, 130.3, 129.0, 121.7, 119.8, 89.1, 83.5, 67.2,
+
+
1.4, 49.8, 21.4. EI–MS: m/z = 371 [M ], 369 [M ], 285,
2006, 8, 1529.
83, 214, 205, 189, 128, 86, 56. Anal. Calcd for
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2
0
20
5.47; N, 3.75.
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