Palladium-catalyzed regiospecific aminocarbonylation of alkynes in the ionic liquid [bmim][Tf2N]

Article abstract of DOI:10.1021/ol061675v

Regiospecific construction of 2-substituted acrylamides was achieved by palladium-catalyzed aminocarbonylation of alkynes in the ionic liquid [bmim][Tf₂N] without any acid additive under relatively mild conditions. The ionic liquid was used as

Full text of DOI:10.1021/ol061675v

ORGANIC
LETTERS
2006
Vol. 8, No. 23
5199-5201
Palladium-Catalyzed Regiospecific
Aminocarbonylation of Alkynes in the
Ionic Liquid [bmim][Tf2N]
Yu Li,†,‡ Howard Alper,*,† and Zhengkun Yu*,‡
Centre for Catalysis Research and InnoVation, Department of Chemistry, UniVersity of
Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5, and Dalian Institute of
Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian,
Liaoning 116023, P. R. China
howard.alper@uottawa.ca; zkyu@dicp.ac.cn
Received July 7, 2006
ABSTRACT
Regiospecific construction of 2-substituted acrylamides was achieved by palladium-catalyzed aminocarbonylation of alkynes in the ionic
liquid [bmim][Tf2N] without any acid additive under relatively mild conditions. The ionic liquid was used as the reaction medium and also
acted as a promoter. Acrylamides were obtained in moderate to excellent yields, and an important feature is that the catalyst system can be
recycled five times without loss of catalytic activity.
In recent years, ionic liquids have emerged as green solvents
with unique properties such as high polarity, good thermal
stability, and the capacity to dissolve various organic,
inorganic, and organometallic compounds, as well as neg-
ligible vapor pressure and recyclability. Their high polarity
and the ability to solubilize both inorganic and organic
compounds can result in enhanced rates of chemical pro-
cesses and provide higher selectivities compared to conven-
tional solvents.1 Accordingly, ionic liquids are emerging as
novel replacements for volatile organic solvents in organic
synthesis. Moreover, ionic liquids are easily prepared and
recycled, and their properties can be fine-tuned by changing
the anion or the alkyl group attached to the cation.2
and cycloaddition reactions, to name just a few.3 They are
also extensively used in the synthesis of polymeric materials.4
Although currently the most widely utilized process for
synthesis of acrylamides is hydration of acrylonitriles,
synthesis of N-substituted acrylamides usually requires
stepwise methods starting from acrylic acid or its esters.5
Using a different approach, N-substituted acrylamides were
formed in 35-52% yields from reaction of alkylidenecar-
benes with isonitriles.6 An alternative method for direct and
clean synthesis of substituted acrylamides is carbonylation
of alkynes in the presence of amines, i.e., aminocarbonyla-
tion, Scheme 1).7 2-Substituted acrylamides were synthesized
via palladium-catalyzed aminocarbonylation of terminal
Acrylamides and derivatives are employed in a wide range
of organic reactions, which include nucleophilic additions
(3) (a) Tatee, T.; Narita, K.; Kurashige, S.; Ito, S.; Miyazaki, H.;
Yamanaka, H.; Mizugaki, M.; Sakamoto, T.; Fukuda, H. Chem. Pharm.
Bull. 1986, 34, 1643. (b) Kitagawa, O.; Aoki, K.; Inoue, T.; Taguchi, T.
Tetrahedron Lett. 1995, 36, 593. (c) Andres, C.; Duque-Soladana, J. P.;
Pedrosa, R. J. Org. Chem. 1999, 64, 4282.
† University of Ottawa.
‡ Chinese Academy of Sciences.
(1) Recent reviews: (a) Welton, T. Chem. ReV. 1999, 99, 2071. (b)
Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3772. (c)
Sheldon, R. Chem. Commun. 2001, 2399. (d) Wilkes, J. S. Green Chem.
2002, 4, 73. (e) Welton, T. Coord. Chem. ReV. 2004, 248, 2459.
(2) For selected references, see: (a) Mizushima, E.; Hayashi, T.; Tanaka,
M. Green Chem. 2001, 3, 76. (b) Kim, H. S.; Kim, Y. J.; Lee, H.; Park, K.
Y.; Lee, C.; Chin, C. S. Angew. Chem., Int. Ed. 2002, 41, 4300. (c) Ranu,
B. C.; Banerjee, S. Org. Lett. 2005, 7, 3049.
(4) Recent review: Caulfield, M. J.; Qiao, G. G.; Solomon, D. H. Chem.
ReV. 2002, 102, 3067.
(5) Ohara, T.; Sato, T.; Shimizu, N.; Prescher, G.; Schwind, H.; Weiberg,
O.; Marten, K. Ullmann’s Encyclopedia of Industrial Chemistry, Acrylic
Acid and DeriVatiVes, 6th ed., electronic release; Wiley-VCH: Weinheim,
1998.
(6) Stang, P. J.; Bjork, J. A. J. Chem. Soc., Chem. Commun. 1978, 1057.
(7) Reppe, W. Justus Liebigs Ann. Chem. 1953, 582, 1.
10.1021/ol061675v CCC: $33.50
© 2006 American Chemical Society
Published on Web 10/13/2006

Scheme 1. Carbonylation of Terminal Alkynes in the
Table 1. Optimization of Reaction Conditions for the
Palladium-Catalyzed Aminocarbonylation of Alkynesa
Presence of Amines
CO
yield productsc
alkynes in a strong acidic medium8 or in the presence of
organic iodides,9 p-TsOH or H2.10 Unfortunately, so far very
limited work has been done toward carbonylative coupling
of primary and secondary alkylamines with terminal alkyl
alkynes, and regioselectivities and yields for the aimed
products are rather unsatisfactory.9 The acid component of
the aminocarbonylation catalyst makes the process corrosive.
It would be desirable to develop new aminocarbonylation
catalysts that do not require an acid stabilizer or an activity
booster.11 Recently, Ryu and co-workers have reported tin-
radical-catalyzed aminocarbonylation of alkynes.12 A selec-
tive reaction for carbon monoxide insertion into the carbon
nitrogen bond of propargylamines to give 2,3-dienamides
or R-vinyl acrylamides was reported by Alper et al.13
Recently, we investigated the palladium-catalyzed carbony-
lative coupling of a variety of alkylamines with alkyl alkynes
in the ionic liquid [bmim][Tf2N] and found that the ionic
liquid efficiently promoted the reactions to proceed without
any acid additive and that the catalyst system can be recycled
for five runs without any significant loss of its catalytic
activity. Herein, we report these results.
An initial study was carried out using 1-octyne and
diethylamine as the substrates to optimize the reaction
conditions, and the results are summarized in Table 1. It was
found that the CO pressure affected the carbonylation, and
the reaction proceeded faster at a relatively low pressure,
i.e., 200 psi, (Table 1, entries 1-3). A similar behavior has
previously been noticed when the same catalytic system is
used in the alkoxycarbonylation of alkynes.14 It is likely that
CO competes with either the alkyne or amine for coordina-
tion to the active metal center in the catalytic cycle. The
reaction is sensitive to the solvent, as shown in Table 1. The
best result was achieved using Pd(OAc)2/dppp as the catalyst
in the ionic liquid [bmim][Tf2N]15 (Table 1, entry 8). It
should be noted that only a trace amount of the desired
entry catalyst /ligand (psi)
solvent
(%)b
3:4
1
2
3
4
5d
6
7
8
9f
10
11
12
13
Pd(OAc)2/dppp 400 [bmim]PF6
Pd(OAc)2/dppp 300 [bmim]PF6
Pd(OAc)2/dppp 200 [bmim]PF6
27
33
56
47
98:2
99:1
98:2
97:3
99:1
Pd(OAc)2/dppp
Pd(OAc)2/dppp
Pd(PhCN)2Cl2
50 [bmim]PF6
50 [bmim]PF6
200 [bmim]PF6
43
trace
trace
Pd(OAc) 2/PPh3 200 [bmim]PF6
Pd(OAc)2/dppp 200 [bmim][Tf2N] 66
Pd(OAc)2/dppp 200 [bmim][Tf2N] 64
Pd(OAc)2/dppp 400 [bmim][Tf2N] 50
Pd(OAc)2/dppp 200 [bmim]BF4
Pd(OAc)2/dppp 200 THF
Pd(OAc)2/dppp 200 DMF
>99e:<1
99:1
99:1
trace
0
0
a Reaction conditions: alkyne 1 (1 mmol), amine 2 (5 mmol), catalyst
(0.03 mmol), ligand (0.06 mmol), solvent (2 g), 110 °C, 22 h. b Yields after
isolation by flash column chromatography on SiO2. c Molar ratio is
determined by 1H NMR spectroscopy. d 90 °C. e Compound 4 was not
detected. f 120 °C.
carbonylation product was detected when THF, DMF, or
[bmim]BF4 was used as the reaction medium (Table 1, entries
11-13). Both Pd(CH3CN)2Cl2 and Pd(OAc)2/PPh3 instead
of Pd(OAc)2/dppp demonstrated very poor catalytic activity
under the same conditions (Table 1, entries 6 and 7).
Eventually, Pd(OAc)2/dppp was chosen to be the catalyst
precursor in [bmim][Tf2N] at 200 psi of carbon monoxide.
A variety of primary and secondary amines were employed
in the reaction, and very good results were obtained (Table
2). Terminal alkynes with substituents such as acetoxy,
nitrile, diethoxy, phenylsulfide, and tetrahydro-pyran-2-yloxy
were efficiently carbonylated, giving the corresponding
R-methylene amides in moderate to excellent yields with
excellent regioselectivities. It is assumed that the high
regioselectivity is due to the hydropalladation of the alkyne
occurring so as to place the palladium at the internal position
of the alkyne. However, carbonylation of the internal alkyne
1i afforded the desired product in low yield (Table 2, entry
16).
(8) (a) Mori, K.; Mizoroki, T.; Ozaki, A. Chem. Lett. 1975, 1673. (b)
Hiyama, T.; Wakasa, N.; Useda, T.; Kusumoto, T. Bull. Chem. Soc. Jpn.
1990, 63, 640.
(9) (a) Torri, S.; Okumoto, H.; Sadakane, M.; Xu, L. H. Chem. Lett.
1991, 1673. (b) Ouerfelli, O.; Isida, M.; Shinozaki, H.; Nakanishi, K.;
Ohfune, Y. Synlett 1993, 6, 409.
(10) (a) Ali, B. E.; El-Ghanam, A. M.; Fettouhi, M.; Tijani, J.
Tetrahedron Lett. 2000, 41, 5761. (b) Ali, B. E.; Tijani, J.; El-Gahanam,
A. M. Appl. Organomet. Chem. 2002, 16, 369. (c) Ali, B. E.; Tijani, J.;
El-Ghanam, A. M. J. Mol. Catal. A 2002, 187, 17. (d) Ali, B. E.; Tijani, J.
Appl. Organomet. Chem. 2003, 17, 921. (e) Matteoli, U.; Scrivanti, A.;
Beghetto, V. J. Mol. Catal. A 2004, 213, 183.
(11) Kiss, G. Chem. ReV. 2001, 101, 3435.
(12) Uenoyama, Y.; Fukuyama, T.; Nobuta, O.; Matsubara, H.; Ryu, I.
Angew. Chem., Int. Ed. 2005, 44, 1075.
(13) (a) Imada, Y.; Alper, H. J. Org. Chem. 1996, 61, 6766. (b) Imada,
Y.; Vasopollo, G.; Alper, H. J. Org. Chem. 1996, 61, 7982.
(14) Scrivanti, A.; Beghetto, V.; Campagna, E.; Zanato, M.; Matteoli,
U. Organometallics 1998, 17, 630.
The recyclability of the palladium catalyst system for the
aminocarbonylation of alkynes was investigated in [bmim]-
[Tf2N] (Table 3). As a result of the good solubility of Pd-
(OAc)2 and dppp in the ionic liquid, reuse of the catalyst
was performed without any significant loss of its catalytic
activity after five runs with 4 mL of toluene per extraction.
Because of the strong delocalization of the negative charge
(15) The ionic liquid were synthesized according to published proce-
dures: Huddleston, G. J.; Visser, A. E.; Reichert, W. M.; Willauer, H. D.;
Broker, G. A.; Rogers, R. D. Green Chem. 2001, 3, 156. Subsequent washing
of the ionic liquid with a biphasic mixture H2O-CH2Cl2 eliminated sodium
and chloride impurities. Water was removed by vacuum drying.
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Org. Lett., Vol. 8, No. 23, 2006

Table 2. Palladium-Catalyzed Aminocarbonylation of Alkynes
in [bmim][Tf2N]a
Table 3. Recycling of the Catalytic System for the
Palladium-Catalyzed Aminocarbonylation of Alkynes
similar to those of polar organic solvents, which makes this
ionic liquid a promising solvent for the stabilization of
charged metal centers and recycling of the catalytic system.
In conclusion, the palladium-catalyzed aminocarbonylation
of alkynes with amines proceeds efficiently in [bmim][Tf2N]
under mild conditions, without any acid additive, regiospe-
cifically affording R-methylene amides in good yields. As
the reaction medium, the ionic liquid gave improved product
yields and regioselectives compared with use of a conven-
tional solvent. A competitive advantage is that the catalyst
system can be recycled and reused five times without the
loss of catalytic activity.
Acknowledgment. We are grateful to the Natural Sci-
ences and Engineering Research Council of Canada (NSERC),
and the National Science Foundation of China (grant no.
20406020) for support of this research.
Supporting Information Available: Experimental pro-
cedures, spectroscopic data, and copies of 1H and 13C NMR
spectra for the acrylamide products. This material is available
free of charge via the Internet at http://pubs.acs.org.
a Alkyne 1 (1 mmol), amine 2 (5 mmol), Pd (OAc) 2 (0.03 mmol), dppp
(0.06 mmol), CO (200 psi), [bmim][Tf2N] (2 g), 110 °C, 22 h. b Yields
after isolation by flash column chromatography on SiO2. c,d <6% linear
aminde was detected.
OL061675V
(16) (a) Deetlefs, M.; Hardacre, C.; Nieuwenhuyzen, M.; Padua, A. A.
H.; Sheppard, O.; Soper, A. K. J. Phys. Chem. B 2006, 110, 12055 (b)
Kilingshirn, M. A.; Broker, G. A.; Holbrey, J. D.; Saughnessy, K. H.;
Rogers, R. D. Chem. Commun. 2002, 1394.
over all atomic centers and the high flexibility of the C-S-
N-S-C backbone, the Tf2N- is regarded as a weakly
coordinating anion,16 and the ionic liquid exhibits polarities
Org. Lett., Vol. 8, No. 23, 2006
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