A highly regioselective Cu-exchanged tungstophosphoric acid catalyst for hydroarylation and hydroamination of alkynes

Article abstract of DOI:10.1016/j.tetlet.2008.10.131

An efficient and reusable Cu-exchanged tungstophosphoric acid catalyst is demonstrated for the solvent free hydroarylation and hydroamination reactions of alkynes with numerous arene and amine derivatives, respectively. The catalyst exhibited exceptionally high activity and regioselectivity in both the reactions.

Full text of DOI:10.1016/j.tetlet.2008.10.131

Tetrahedron Letters 50 (2009) 239–242
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A highly regioselective Cu-exchanged tungstophosphoric acid
catalyst for hydroarylation and hydroamination of alkynes
Nayeem Pasha, N. Seshu Babu, K. T. Venkateswara Rao, P. S. Sai Prasad, N. Lingaiah *
Catalysis Laboratory, Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and reusable Cu-exchanged tungstophosphoric acid catalyst is demonstrated for the solvent
free hydroarylation and hydroamination reactions of alkynes with numerous arene and amine deriva-
tives, respectively. The catalyst exhibited exceptionally high activity and regioselectivity in both the
reactions.
Received 17 September 2008
Revised 23 October 2008
Accepted 28 October 2008
Available online 31 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Hydroarylation
Hydroamination
Friedal–Craft’s alkenylation
Cu-exchanged tungstophosphoric acid
8–10
palladium, platinum,11–13
1
. Introduction
such as rhodium,7 ruthenium,
1
4–16
17
,18 and transitional metal tri-
gold
or rare earth-metals, FeCl
3
1
9–23
The formation of new C–C and C–N bonds is of great importance
flates
in the presence of ionic liquid media also promote the
in both academia and synthetic organic chemistry. The alkenyla-
tion of arenes or hydroarylation of alkynes leading to the formation
of C–C bonds is an important transformation in the synthesis of
pharmaceuticals, agrochemicals, and fine chemicals. Friedel–
Craft’s alkylation of various arenes, especially electron-rich arenes
with alkyl halides, alcohols, or alkenes, involves the formation of
alkenylation of arenes.
On the other hand, the synthesis of nitrogen-containing build-
ing blocks has gained significant importance in the pharmaceutical
industry. One of the potential approaches for the synthesis of nitro-
gen-containing molecules is hydroamination, which is an atom-
economic process for the formation of amines, enamines, and imi-
nes. The hydroamination process converts inexpensive and readily
available starting materials into the desired products in a single
step reaction without the formation of any other side products.
Based on this concern, an efficient hydroamination reaction is al-
ways considered economically and environmentally benign. How-
ever, the hydroaminations of alkynes can only be achieved in the
presence of certain catalysts, as the amines generally do not react
spontaneously with alkynes due to the electron-rich nature of both
the species. The alkynes are converted into reactive species (enam-
ines and imines), which are reactive intermediates and can be used
for various sorts of subsequent transformations. The hydroamina-
tion of alkynes has been accomplished with different cationic met-
1
new C–C bonds via the alkylation/alkenylation of arenes. On the
other hand, C–N bond-forming processes are highly interesting
due to the presence of nitrogen-containing molecules as building
blocks in industrial applications.
Hydroarylation has received much attention due to its simple
approach when compared to existing methods such as Heck reac-
2
3
tions, cross-coupling reactions, and olefin cross-metathesis reac-
4
tions. Alkenylation of arenes with alkynes proceeds via alkenyl
carbocation intermediates, which is followed by an electrophilic
attack to the arene that can be promoted by Lewis acids. However,
due to the instability of vinyl cationic intermediates, the oligomer-
ization of alkynes takes place during the alkenylation5 of arenes.
1
+
2+
2+
2+
Some Lewis acid metal chlorides such as ZrCl
to produce the desired alkenylated products with lower yields. La-
ter, Tsuchimoto et al. reported several metal triflates, Sc(OTf) , In-
OTf) , and Zr(OTf) as catalysts for the alkenylation of arenes with
4
and AlCl
3
are known
als (e.g., Ag , Cu , Zn , and Pd ) supported on acidic materials
such as montmorillonite clay K-10, phosphotungstic acid, and zeo-
6
2
4–28
3
lite HBEA.
(
3
4
Despite the advantages of the above catalysts in both reactions,
a few drawbacks are associated with them such as moisture sensi-
tivity, high cost of metal, difficult catalyst preparation, and low
recyclability. Therefore, the use of new, mild, and efficient catalysts
remains to be explored for both hydroarylation and hydroamina-
tion protocols. As part of our ongoing programs on the use of
both internal and terminal alkynes through the formation of alke-
6
nyl cationic intermediates. Several other transition metal catalysts
*
Corresponding author. Tel: +91 40 27193163; fax: +91 40 27160923.
E-mail address: nakkalingaiah@iict.res.in (N. Lingaiah).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.131

2
40
N. Pasha et al. / Tetrahedron Letters 50 (2009) 239–242
heteropoly acid catalysts for various organic transformations such
as hydroamination, hydroarylation and the synthesis of propargyl
Table 1
a
Hydroarylation of phenyl alkyne derivatives with arenes
24,29–32
amines and selective oxidation of alcohols,
we sought to
Ar
R1
R1
evaluate the feasibility of a Cu-exchanged TPA catalyst for hydro-
arylation and hydroamination reactions under identical reaction
conditions. Herein, we disclose our preliminary findings toward
this end.
Cu-TPA, Solvent free
+
Ar
H
80 ºC
R2
R2
1
2
3
Entry
1
R
1
R
2
Ar–H
Time (h)
Yield of 3b (%)
2
2
. Experimental
H
H
6
86
.1. Preparation of Cu-exchanged tungstophosphoric acid
catalyst
2
3
H
H
H
4
89
The copper-exchanged TPA was prepared as a precipitate by
adding the required amount of barium hydroxide (to neutralize
the three protons) to an aqueous solution of TPA. Later, the Ba ions
were replaced by precipitating it as BaSO
4
by adding a calculated
H
4
93.91c
amount of CuSO O solution. The resultant Cu salt of TPA was
4
Á6H
2
recovered from the solution by recrystallization and then oven
dried at 120 °C for 12 h. The catalyst was finally calcined at
3
00 °C for 2 h. The retention of the Keggin structure after the ex-
4
5
H
H
H
H
5
4
81
88
change of Cu ions was confirmed by XRD, Laser Raman, and FT-IR
analysis.
OCH3
2
.2. Catalytic activity measurements: hydroarylation and
hydroamination of alkynes
In a general experimental procedure of hydroarylation reaction,
mmol of alkyne and 1.1 mmol of arene were taken in a 10 mL
6
H
OMe
3
95
1
round-bottomed flask, and the reaction mixture was allowed to stir
at 80 °C under a nitrogen atmosphere. After ensuring the reaction
was complete, the crude mixture was filtered to separate the cata-
7
8
9
H
H
Me
Cl
3
6
91
83
lyst, and the product mixture was purified by column chromatog-
1
raphy. The structure of the purified product was analyzed by
H
NMR spectroscopy. A similar procedure was adopted for the hydro-
amination of alkynes with amines, instead of arenes. The structures
1
of the compounds were determined by H NMR spectroscopy, and
the data were compared with reports in the existing literature.
3
. Results and discussion
Ph
Ph
H
H
12
12
69
67
The present catalyst is studied for both the C–C (hydroarylation)
and C–N (hydroamination) bond-forming reactions under mild and
solvent free conditions (Scheme 1). The results obtained from both
reactions are shown in Tables 1 and 2, respectively.
10
a
Reaction conditions: Alkyne derivative (1 mmol); arene derivative (1.1 mmol);
catalyst wt: 0.05 g; temperature: 80 °C.
3
.1. Hydroarylation of alkynes
b
Isolated yields.
C
Yield determined after 4th reaction cycle.
The hydroarylation of various substrates is carried out over Cu–
TPA catalysts, and the results are shown in Table 1. The results sug-
gest that the yields of hydroarylated products are varied according
to the electronic nature of the arene and alkyne. For example, in
the addition of phenyl acetylene to benzene (Table 1, entry 1),
the reaction proceeds slowly as compared to para-xylene, mesity-
lene, naphthalene, and anisole (Table 1, entries 2–5). The addition
of phenyl acetylene to chlorobenzene (electron-poor arene) results
in no net reaction even at longer reaction times (24 h) (not shown
in Table 1). This implies that more electron-rich arenes than ben-
R
N
Aniline
Ar-H
Ar
Cu-TPA
Cu-TPA
H
Solvent free,
Solvent free,
CH3
CH2
80 ºC
8
0 ºC
Hydroaminated product
Hydroarylated product
Scheme 1. Hydroarylation and hydroamination of alkyne.

N. Pasha et al. / Tetrahedron Letters 50 (2009) 239–242
241
Table 2
9 and 10). The hydroarylation activity of internal alkynes is rela-
tively lower when compared to that of terminal alkynes.
Hydroamination of phenyl acetylene with various amine derivatives using Cu–TPA
catalysta
3
.2. Hydroamination of alkynes
NH2
N
H
Based on the results during a hydroarylation reaction using a
Cu-TPA, Solvent free
Cu–TPA catalyst, we sought to evaluate the feasibility of the same
catalyst for the hydroamination of alkynes under the same reaction
conditions. To our delight, the hydroamination of alkynes with var-
ious amines takes place with good to excellent product yields. The
results are shown in Table 2. The results reveal that amines bearing
electron-withdrawing groups underwent hydroamination with
phenyl acetylene quickly as compared to electron-donating
amines. For example, in the reaction of phenyl acetylene and ani-
line, the corresponding ketimine is obtained with 92% yield within
3 h. With the addition of phenyl acetylene to electron-poor aniline
derivatives including naphthyl amine, hydroamination takes place
to give corresponding ketimines in excellent yields within 2 h of
reaction time irrespective of the position of the substituent (Table
+
80 ºC
R
1
2
3
Entry
1
Amine
Time (h)
3
Yield of 3b (%)
NH2
NH2
92
2
2.5
95
Cl
NH2
2
, entries 1–6). The addition of electron-rich amines such as para-
3
4
5
2
93
methyl and para-methoxy anilines to phenyl acetylene proceeds at
a slower reaction rate, and moderate product yields are obtained
compared to electron-poor anilines (Table 2, entries 8 and 9). These
results also lead to the conclusion that the electronic nature of the
amines plays a vital role in the hydroamination of alkynes as in the
case of hydroarylation.
Mechanistic illustrations of hydroarylation and the hydroamin-
ation reaction of alkynes are shown in Scheme 2. The hypothesis of
the reaction mechanism demonstrates that the presence of cationic
Cu species promotes the hydroarylation reaction due to the inter-
action of Cu with a triple bond of alkynes. Consequently, this
undergoes an electrophilic aromatic substitution with arenes to
Cl
NH2
2
97.93c
89
O N
2
NH2
2.5
NH2
6
2
2
91
92
F
+
form a vinyl-Cu intermediate (Ib) with the release of H that prot-
NH2
onates the complex and forms the product by regenerating the cat-
alyst. Unlike the preceding case, the hydroamination of alkynes
proceeds through the coordination of cationic Cu species with
amine rather than with alkyne, which subsequently attacks the
phenylacetylene resulting enamine intermediate (IIb), which is
further transformed into the desired ketimine (IIc).
In order to reiterate the significance of the Cu species for hydro-
arylation and hydroamination reactions, separate experiments
were conducted with a Cu-free TPA catalyst under the reaction
conditions used in the case of Cu–TPA. The results reveal that the
Cu-free TPA catalyst cannot facilitate both the reactions. Thus, it
is clear from the above results that the presence of cationic Cu spe-
cies promotes both hydroarylation and hydroamination reactions.
7
8
Br
NH2
4
4
86
83
NH2
9
MeO
a
Reaction conditions: Alkyne derivative (1 mmol); amine derivative (1.1 mmol);
catalyst wt: 0.05 g; temperature: 80 °C.
b
Isolated yields.
c
Yield determined after 4th reaction cycle.
4
. Recycled experiments
zene react easily with phenyl acetylene as compared to electron-
poor arenes, which is due to the characteristics of electrophilic
metallation of the aromatic C–H bond. It clearly demonstrates that
the electronic factors of arenes play a prominent role during the
hydroarylation of alkynes. In general, selectivity of the hydroary-
lated product is a challenging task, as the reaction forms both E
and Z isomers. Indeed, in all the reactions, it is interesting to ob-
serve that regioselectivity of the resulting hydroarylated product
is high (>98:2). With the success of the present catalyst, the sub-
strate scope of electronically varied alkynes is also studied under
the same reaction conditions. The terminal alkynes bearing elec-
tron-rich groups such as para-methoxy and para-methyl phenyl
acetylene react easier with mesitylene, affording high yields (Table
The reusability of the catalyst was studied for both hydroaryla-
tion and hydroamination reactions. The crude reaction mixture
was filtered to separate the catalyst, and washed with dichloro-
methane to wash off organic residues. Further, the catalyst was
oven dried at 120 °C for 2 h and used for the recycled experiments.
The results obtained from the recycled runs (Table 1, entry 3 and
Table 2, entry 4) showed the consistent activity of the Cu–TPA
catalyst.
5. Conclusions
1
, entries 6 and 7), while electron-poor alkynes, that is, para-chloro
In summary, Cu–TPA is demonstrated as an efficient and reus-
able catalyst for the new C–C and C–N bond formation reactions
under mild and neat reaction conditions. The presence of cationic
Cu species is deemed to be responsible for the exceptional activity
of both hydroamination and hydroarylation reactions. The present
phenyl acetylene reacted relatively slower (Table 1, entry 8). It is
noteworthy that the addition of electron-rich arenes such as mesit-
ylene and para-xylene to diphenylacetylene also takes place in
acceptable yields at their stipulated reaction time (Table 1, entries

2
42
N. Pasha et al. / Tetrahedron Letters 50 (2009) 239–242
Cu(n-1)+-TPA
H+
H
Cun+
-
Ar-H
+
Cun+-TPA
H
TPA
Ar
H
Ar
H
H
Ic
Ib
Cun+-TPA
Amine
Ph
N
H
Ph
N
CH
3
Cun+-TPA
+
Cu-TPA
Cun+-TPA
H
H
+
N
H
H
IIc
IIb
H
Ph
Scheme 2. Plausible reaction mechanism for the Cu–TPA catalyzed hydroarylation and hydroamination of alkynes.
protocol offers advantages due to catalyst reusability and neat
reaction conditions.
13. Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y. Org. Lett. 2000, 2, 2927–2930.
1
1
1
4. Reetz, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485–3496.
5. Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669–3671.
6. Ne-vado, C.; Echavarren, A. M. Chem. Eur. J. 2005, 11, 3155–3164.
Acknowledgement
17. Song, C.; Jung, D.; Choung, S.; Roh, E.; Lee, S. Angew. Chem., Int. Ed. 2004, 43,
183–6185.
8. Nakao, Y.; Kanyiva, K.; Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2006, 128, 8146–
147.
19. Bolm, C.; Legros, J.; Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217–6254.
6
1
The authors N.P. and K.T.V.R. thank the Council of Scientific and
Industrial Research (CSIR) for the award of senior and junior re-
search fellowships, respectively.
8
2
0. Jovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed. 2005,
4, 3913–3917.
1. Kischel, J.; Jovel, I.; Mertins, K.; Zapf, A.; Beller, M. Org. Lett. 2006, 8, 19–22.
4
2
References and notes
22. Nakamura, M.; Hirai, A.; Nakamura, E. J. Am. Chem. Soc. 2000, 122, 978–979.
2
2
2
3. Komeyama, K.; Morimoto, T.; Takaki, K. Angew. Chem., Int. Ed. 2006, 45, 2938–
2941.
1
.
Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. Friedel–Crafts Alkylations in
Comprehensive Organic Synthesis. In Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, UK, 1991.
4. Lingaiah, N.; Seshu Babu, N.; Mohan Reddy, K.; Sai Prasad, P. S.; Suryanarayana,
I. Chem. Commun. 2007, 3, 278–279.
5. Penzien, J.; Haeßner, C.; Jentys, A.; Köhler, K.; Müller, T. E.; Sievers, C.; Lercher,
J. A. J. Catal. 2004, 221, 302–312.
2.
3.
4.
5.
6.
Belteskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009–3066.
Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 32, 4704–4734.
Grubbs, R. H. Hand Book of Metathesis; Wiley-VCH: Weinheim, 2003.
Reilly, J. A.; Nieuwland, J. A. J. Am. Chem. Soc. 1928, 50, 2564–2566.
Tsuchimoto, T.; Maeda, T.; Shirakawa, E.; Kawakami, Y. Chem. Commun. 2000,
2
2
6. Penzien, J.; Müller, T. E.; Lercher, J. A. Chem. Commun. 2000, 1753–1754.
7. Ganapati, V.; Shanbhag, G. V.; Kumbar, S. M.; Joseph, T.; Halligudi, S. B.
Tetrahedron Lett. 2006, 47, 141–143.
2
2
3
3
3
8. Richmond, M. K.; Scout, S. L.; Alper, H. J. J. Am. Chem. Soc. 2001, 123, 10521–
1
573–1574.
10525.
7
8
.
.
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731–1770.
Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani,
N. Nature 1993, 366, 529–531.
9. Mohan Reddy, K.; Seshu Babu, N.; Suryanarayana, I.; Sai Prasad, P. S.; Lingaiah,
N. Tetrahedron Lett. 2006, 47, 7563–7566.
0. Nagaraj, P.; Pasha, N.; Sai Prasad, P. S.; Lingaiah, N. Green Chem. 2007, 9, 1126–
9
.
Merlic, C. A.; Pauly, M. E. J. Am. Chem. Soc. 1996, 118, 11319–11320.
1
129.
1. Seshu Babu, N.; Mohan Reddy, K.; Sai Prasad, P. S.; Lingaiah, N. Tetrahedron Lett.
007, 48, 7642–7645.
2. Mohan Reddy, K.; Seshu Babu, N.; Sai Prasad, P. S.; Lingaiah, N. Catal. Commun.
008, 9, 2525–2531.
1
0. Murakami, M.; Hori, S. J. Am. Chem. Soc. 2003, 125, 4720–4721.
1
1. Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Science 2000, 287,
2
1
992–1995.
1
2. Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J.
Am. Chem. Soc. 2000, 122, 7252–7263.
2