Aquapalladium complex: A stable and convenient catalyst for the intermolecular hydroamination of alkynes

Article abstract of DOI:10.1002/ejoc.200400568

The intermolecular hydroamination of alkynes proceeds very smoothly in the presence of a catalytic amount of the aquapalladium complex [Pd(dppe)(H ₂O)₂](TfO)₂. This reaction most probably proceeds through the formation of an equilibrium between the hydroxopalladium and the amidopalladium complexes, and subsequent aminopalladation of alkynes. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400568

SHORT COMMUNICATION
Aquapalladium Complex: A Stable and Convenient Catalyst for the
Intermolecular Hydroamination of Alkynes
Tomohiro Shimada,[a] Gan B. Bajracharya,[a] and Yoshinori Yamamoto*[a]
Keywords: Aquapalladium catalyst / Hydroamination / Alkynes / Arylamines / Imines
The intermolecular hydroamination of alkynes proceeds very
smoothly in the presence of a catalytic amount of the aqua-
palladium complex [Pd(dppe)(H2O)2](TfO)2. This reaction
most probably proceeds through the formation of an equilib-
ium complexes, and subsequent aminopalladation of al-
kynes.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
rium between the hydroxopalladium and the amidopallad- Germany, 2005)
Introduction
stituted analogues of the aromatic ring produced the corre-
sponding products with poor yields.
Stoichiometric conversion of a hydroxopalladium com-
plex into its amido complex by treatment with amines was
Recently, the transition-metal-catalyzed intermolecular
hydroamination of alkynes has been widely investigated.[1]
This reaction is regarded as an atom-economical route by
which to transform CϪC unsaturated bonds into functional
compounds. Moreover, this reaction provides a wide range
of useful compounds that are utilized as fine chemicals and
intermediates for pharmaceutical and industrial products.
As a result of the great research efforts in this area, it is now
feasible to carry out the intermolecular hydroamination of
unactivated alkynes in the presence of different kinds of me-
tal catalysts.[2Ϫ4] However, a major drawback of some cata-
lysts lies in their air and/or light sensitivity, which demands
they be handled with great care,[2e,2f,3] and in addition they
can only be used for the hydroamination of terminal
alkynes.[2aϪ2d] Recently, we reported that the intermolecular
hydroamination of alkynes proceeds smoothly with o-amino-
phenols in the presence of a palladium catalyst that is eas-
ily handled without special care.[5] We assumed that the pal-
ladium phenoxide complex A would be formed from the
reaction of o-aminophenol with PdX2, which would be con-
verted into the amidopalladium complex B by proton trans-
fer, and then the amino-palladation of alkynes would take
place (Scheme 1a).[5a] Accordingly, the key to the pal-
ladium-catalyzed hydroamination step must be the facile
formation of the amido complex B by neighboring-group
assistance of the o-phenolic OH group. This catalytic sys-
tem could be applied to various alkynes, but the amine was
limited to o-aminophenol and in some instances monosub-
reported by Lopez[6a] and Hartwig[6bϪ6d] and their co-work-
´
ers; the thermodynamically more stable PdϪNH complexes
D were yielded from the corresponding PdϪOH complexes
(Scheme 1, b). Furthermore, Sodeoka and co-workers re-
cently reported that Michael addition of activated methynes
to α,β-unsaturated ketones was catalyzed by a aquapallad-
ium complex.[7] It occurred to us that palladium-catalyzed
hydroamination might proceed with aquapalladium and/or
hydroxopalladium complexes if activation of an amine
NϪH bond occurs catalytically as shown in Scheme 1 (b).[8]
Herein, we report that the intermolecular hydroamination
of nonactivated internal alkynes with both nonactivated
and activated arylamines takes place at 80 °C in the pres-
ence of the aquapalladium catalyst, [Pd(dppe)(H2O)2]2ϩ [9]
.
Results and Discussion
First, we examined the reaction of 6-dodecyne (1a,
0.60 mmol) with aniline (2a) (0.50 mmol) in the presence
of several different palladium catalysts [Equation (1)]. The
imine product 3a, obtained by hydroamination, was con-
verted into the ketone 4a upon treatment with silica gel.[3a]
The use of Pd(NO3)2, which was an effective catalyst in the
hydroamination reactions with o-aminophenol,[5a] gave 4a
in 37% yield. The other catalysts, such as [PdCl2(dppe)],
[PdCl2(CH3CN)2] and [Pd2(dba)3]·CHCl3, afforded no 4a at
all. However, the use of [Pd(dppe)(H2O)2](TfO)2 gave 4a in
64% yield; the yield of 4a was increased to 74% by the use
of 1.5 equiv. of 1a in 1,4-dioxane (see Table 1, Entry 1).
Interestingly, the use of [Pd(PPh3)4] (10 mol %) as catalyst
gave a mixture of 6-phenylamino-7-dodecene and 5-phe-
nylamino-6-dodecene in a combined yield of 42%, which
[a]
Department of Chemistry, Graduate School of Science,
Tohoku University,
Sendai 980-8578, Japan
Fax: (internat.) ϩ81-22-217-6784
E-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2005, 59Ϫ62
DOI: 10.1002/ejoc.200400568
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
59

T. Shimada, G. B. Bajracharya, Y. Yamamoto
SHORT COMMUNICATION
Scheme 1. Palladium-catalyzed hydroamination of alkynes
Table 1. Palladium-catalyzed intermolecular hydroamination of alkynes 1 with aniline 2a
Entry[a]
R1
R2
1
Reaction time [h]
Yield [%][b]
4:5
1
2
nPent
Ph
Ph
4-MeO-C6H4
3-MeO-C6H4
4-Br-C6H4
4-CF3-C6H4
Ph
nPent
Ph
nBu
nBu
nBu
nBu
nBu
(CH2)3OAc
1a
1b
1c
1d
1e
1f
24
18
24
24
10
24
24
20
74
96
99
82
63
Ͼ 99
41
Ͼ 99
Ϫ
Ϫ
3
2:1
3:1
1:1
1:2
1:2
4:1
4[c]
5
6
7
8
1g
1h
[a]
Reaction conditions: i) aniline (0.50 mmol), alkyne (0.75 mmol), [Pd(dppe)(H2O)2](TfO)2 (10 mol %), 1,4-dioxane (10 m), 80 °C; ii)
[b]
[c]
SiO2, CH2Cl2, room temp., 2 h. Isolated yields. Three equivalents of alkyne were used.
would have been obtained by
a hydropalladationϪ the reaction conditions and the products were obtained in
dehydropalladation sequence.[10] This strongly suggests that a quantitative yield (Entry 8).
this hydroamination reaction [Equation (1)] does not pro-
ceed through the hydropalladation mechanism.[11]
Next, we examined the scope of this reaction [Equa-
tion (2)], and the results obtained after hydrolytic work up
are given in Table 1. Among the solvents examined, 1,4-
dioxane gave the best result (Entry 1).[12] The reaction of
the simple alkynes 1aϪc with aliphatic and aromatic sub-
stituents proceeded quite smoothly (Entries 1Ϫ3). The use
of three equivalents of 1d, which has an electron-donating
group at the para-position, gave a 3:1 mixture of 4d and 5d
in 82% yield (Entry 4). The arylalkynes 1e and 1f reacted
similarly, giving a mixture of 4e (4f) and 5e (5f) in good to
high yields (Entries 5 and 6), but 1g, which has a CF3 group
at the para-position, gave a low yield (Entry 7). The ace-
toxy-substituted alkyne 1h also reacted with aniline under
(2)
We attempted to isolate the hydroamination product in
the amine form prior to converting it into the ketone form.
The aquapalladium complex catalyzed reaction of 1b with
2a, followed by reduction with NaBH3CN, produced the
corresponding amine 6 in 48% yield [Equation (3)].
(3)
As can be seen in Equation (4) and Table 2, various sub-
stituted anilines 2 react with diphenylacetylene (1b) at 80
°C in 1,4-dioxane with 10 mol % [Pd(dppe)(H2O)2](TfO)2
as catalyst.[13] The substituents on the aromatic ring of ani-
line had no significant effect on this reaction. The aniline
derivatives that have an electron-donating group at the
(1)
60
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 59Ϫ62

Intermolecular Hydroamination of Alkynes
SHORT COMMUNICATION
A plausible mechanism for the hydroamination reaction
is shown in Scheme 2. First, the hydroxopalladium complex
E is produced in situ from the aquapalladium complex. The
aminopalladium complex F is then generated from inter-
mediate E by coordination of the amine. An equilibrium
between F and the amidopalladium complex G forms, fol-
lowed by the coordination of alkynes and subsequent inser-
tion gives the vinylpalladium intermediate H.[14] Pro-
tonolysis of H yields the enamine 3Ј and reproduces the
palladium catalyst. Finally, enamine 3Ј is converted into im-
ine 3 under the reaction conditions.
para-position reacted smoothly with 1b under the standard
conditions to give ketone 4b. Although these reactions re-
quired a relatively long reaction time, very high product
yields were achieved (Entries 1Ϫ3). The aniline derivatives
that have an electron-withdrawing group at the para-posi-
tion also provided the desired product in quantitative yield
(Entries 4 and 5); however, the reaction with p-nitroaniline
(2g) gave a lower yield (Entry 6). The product 4b was ob-
tained from 3-(trifluoromethyl)aniline (2h) and 3,5-dimeth-
ylaniline (2i) in Ͼ 99 and 68% yields, respectively (Entries
7 and 8). With the sterically hindered 2,6-dimethylaniline
(2j) and pentafluoroaniline (2k), the hydrolysis product 4b
was isolated together with the corresponding (2,6-dimeth-
ylphenyl)(1,2-diphenylethylidene)amine (3b) and (1,2-di-
phenylethylidene)(pentafluorophenyl)amine (3c) with quan-
titative conversion after hydrolytic work up (Entries 9 and
10). This reaction also took place with 1-naphthylamine
(Entry 11). A secondary amine that could not be used as
an amine substrate in the hydroamination reaction with an
early transition metal catalyst[2f,3] can be employed in this
reaction; the reaction of N-methylaniline 2m with diphenyl-
acetylene (1b) and phenyl(butyl)acetylene (1c) proceeded
smoothly and the corresponding products were obtained in
high yields (Entries 12 and 13). In one set of experiments,
the enamine product derived from 1b and 2m was reduced
with H2/Pd-C to give 7 in 45% yield [Equation (5)].
Conclusion
In this communication, we have demonstrated that a
stable and convenient aquapalladium complex can be used
as a catalyst for the intermolecular hydroamination of in-
ternal alkynes with arylamines. Compared with the pre-
viously known lanthanide and early transition metal cata-
lysts, special care is not needed in the handling of the aqua
complex. Further applications of the aqua complex are be-
ing investigated.
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded with
JEOL JNM LA-300 (300 MHz) and JEOL JMTC-400/54/SS
(400 MHz) spectrometers. 1H NMR spectroscopic data are re-
ported as follows: Chemical shift in ppm (δ) relative to the chemical
shift of CDCl3 at δ ϭ 7.24 ppm, integration, multiplicities (s ϭ
singlet, d ϭ doublet, t ϭ triplet, q ϭ quadruplet, m ϭ multiplet
and br ϭ broadened), and coupling constants (Hz). 13C NMR
spectroscopic data are reported in ppm (δ) relative to the central
line of the triplet of CDCl3 at δ ϭ 77 ppm. IR spectra were re-
corded with a SHIMADZU FTIR-8200A spectrometer; absorption
bands are reported in cmϪ1. High-resolution mass spectra were ob-
tained with JEOL JMS-DX303, JEOL JMS-AX500 and BRUKER
APEXIII spectrometers. Column chromatography was carried out
by employing silica gel 60 n (spherical, neutral, 40Ϫ100 µm,
KANTO Chemical Co.). Analytical thin-layer chromatography
(TLC) was performed on 0.2 mm Kieselgel 60 F254 (Merck) pre-
coated plates. All manipulations were conducted under an argon
atmosphere using standard Schlenk techniques.
Table 2. Palladium-catalyzed intermolecular hydroamination of di-
phenylacetylene (1b) with arylamines 2
Entry[a] ArNH2
2
Reaction time [h] Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13[e]
4-HO-C6H4NH2
4-MeS-C6H4NH2 2c
4-Me-C6H4NH2
4-F-C6H4NH2
4-CF3-C6H4NH2
4-NO2-C6H4NH2 2g 55
3-CF3-C6H4NH2 2h 46
3,5-Me2-C6H3NH2 2i
2,6-Me2-C6H3NH2 2j
C6F5NH2
2b 50
96
Ͼ 99
91
Ͼ 99
Ͼ 99
40
47
2d 46
2e
2f
24
19
Ͼ 99
68
22
22
2k 18
15[c]
45[d]
94
1-naphthylamine
N-methylaniline
N-methylaniline
2l
2m
2m
47
3
7
84
83[f]
[a]
Typical Procedure for the Aquapalladium-Catalyzed Hydroamin-
ation Reaction. The Synthesis of 6-Dodecanone (4a): 6-Dodecyne 1a
(124.7 mg, 0.75 mmol) was added to the reaction vial containing a
1,4-dioxane solution (0.05 mL) of aniline (2a, 46.6 mg, 0.5 mmol)
and [Pd(dppe)(H2O)2](TfO)2 (42.0 mg, 0.050 mmol) under argon.
The solution was heated at 80 °C for 24 hours and then cooled to
room temperature. After dilution with dichloromethane, SiO2 was
added successively and the suspension was stirred for 2 hours. The
product was filtered through a short SiO2 pad using diethyl ether
as eluent, and the resulting filtrate was concentrated. The residue
was purified by column chromatography [silica gel, hexane/ethyl
acetate, 50:1 (200 mL) Ǟ 10:1 (until complete elution)] to afford
6-dodecanone (4a) in 74% yield (68.0 mg). 1H NMR (300.40 MHz,
CDCl3): δ ϭ 0.80Ϫ0.92 (m, 6 H), 1.15Ϫ1.37 (m, 10 H), 1.47Ϫ1.61
(m, 4 H), 2.36 (2t, J ϭ 7.4, 7.4 Hz, 4 H) ppm. 13C NMR
(75.45 MHz, CDCl3): δ ϭ 13.90, 14.01, 22.44, 22.48, 23.55, 23.83,
28.92, 31.42, 31.59, 42.76, 42.81, 211.77 (CO) ppm. IR (neat): ν˜ ϭ
Reaction conditions: i) aniline (0.50 mmol), alkyne (0.75 mmol),
[Pd(dppe)(H2O)2](TfO)2 (10 mol %), 1,4-dioxane (10 m), 80 °C; ii)
SiO2, CH2Cl2, room temp., 2 h. [b] Isolated yields. [c] Imine 3b (85%)
was isolated. [d] Imine 3c (55%) was isolated. [e] Instead of diphenyl-
[f]
acetylene 1b, phenyl(butyl)acetylene 1c was used. The isomeric
ratio of the corresponding products was 2:1.
(4)
(5)
Eur. J. Org. Chem. 2005, 59Ϫ62
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61

T. Shimada, G. B. Bajracharya, Y. Yamamoto
SHORT COMMUNICATION
Scheme 2. Plausible mechanism for the hydroamination reaction
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lower yields were obtained under similar conditions:
[Pd(dppp)(H2O)2](TfO)2 (33%), [Pd(dppf)(H2O)2](TfO)2 (24%),
[Pd(µ-OH)(dppe)]2(TfO)2 (41%). We also examined the reac-
tion of [Pd(dppe)(CH3CN)2](TfO)2, which would act as a Lewis
acid, and confirmed that the yield was low (50%).
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Received August 10, 2004
62
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Eur. J. Org. Chem. 2005, 59Ϫ62