A novel (2,2-diarylvinyl)phosphine/palladium catalyst for effective aromatic amination

Article abstract of DOI:10.1002/adsc.200700220

A new series of diarylvinylphosphine ligands was designed and synthesized. A catalyst system, consisting of the ligands and palladium species, effectively catalyzed the coupling reaction of aryl bromides and chlorides with amines to afford the corresponding products in good to excellent yields. The efficiency is likely derived from an interaction between the palladium center and the cisaryl moiety on the diarylvinylphosphine ligand stabilizing a catalytic intermediate during the coupling reaction.

Full text of DOI:10.1002/adsc.200700220

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DOI: 10.1002/adsc.200700220
A Novel (2,2-Diarylvinyl)phosphine/Palladium Catalyst for
Effective Aromatic Amination
Ken Suzuki,a,* Yoji Hori,a Takenobu Nishikawa,a and Tohru Kobayashia
a
Takasago International Corporation, Corporate Research & Development Division, 1-4-11, Nishi-Yawata, Hiratsuka,
Kanagawa 254-0073, Japan
Fax : (+81)-463-25-2093; e-mail: ken_suzuki@takasago.com
Received: May 2, 2007; Published online: September 11, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A new series of diarylvinylphosphine li-
gands was designed and synthesized. A catalyst
system, consisting of the ligands and palladium spe-
cies, effectively catalyzed the coupling reaction of
aryl bromides and chlorides with amines to afford
the corresponding products in good to excellent
yields. The efficiency is likely derived from an inter-
action between the palladium center and the cis-
aryl moiety on the diarylvinylphosphine ligand sta-
bilizing a catalytic intermediate during the coupling
reaction.
Characteristics that these ligands have in common
are electron-richness and steric hindrance. To synthe-
size a more effective phosphine ligand by strengthen-
ing these characteristics, we investigated vinylphos-
phine 1 due to its three vacant positions, although
ligand 1 has not been previously used for this cou-
pling (Figure 1). Based on the vinylphosphine struc-
ture, a new ligand, diarylvinylphosphine 2 was de-
signed. A substituent group (R1) at the a-position on
phosphine 2 was introduced to make the ligand more
sterically hindered around the phosphorus atom. To
increase electron density of the ligand, the b-position
was substituted by two aryl moieties (Ar) with elec-
tron-donating groups, which were conjugated to the
phosphorus atom through the vinyl moiety. Accord-
ingly, we synthesized a series of diarylvinylphosphines
3–9, which are white solids and stable to air and mois-
ture (Figure 2).[9]
Keywords: amination; cross-coupling; ligand
design; P ligands; palladium
The palladium-catalyzed coupling reaction of aryl hal-
First, the effect of substituent groups on the ligands
ides with amines has become one of the most power- was examined in the reaction of 4-tert-butylbromo-
ful methods for the synthesis of aromaticamines. [1] In- benzene with diphenylamine in toluene using 1 mol%
itial efforts towards the coupling reaction with appli- of PdACTHRE(UNG OAc)2 and 4 mol% of the ligand as shown in
cable aryl halides have used generally available phos- Table 1. As is the case with alkylphosphines reported
phine ligands such as (o-tolyl)3P and BINAP.[2] Al- previously,[3–8] entries 2–5 show that alkylphosphines
though aryl bromides have successfully been used for 3b–d are more active than arylphosphine 3a. Intro-
the coupling reaction, employment of less active aryl duction of two electron-donating groups at the para-
chlorides has had limited success. Considering appli- position of the aryl moiety on phosphines 4a–c afford-
cations for industrial processes, the choice of aryl ed excellent coupling product yields, but a longer re-
chloride is extremely significant because of its lower action time was needed with ligands 3b–d (entries 6–
cost, better availability and lower toxicity. Recently, 8). Although the reason is unclear, ligand 5 resulted
there has been a noteworthy advance in the reaction in a poor yield. Ligands 8 and 9, with phenyl and iso-
of aryl chlorides using newly discovered ligands that propyl groups introduced into the a-position for bulk-
sharply improve the effectiveness of the coupling re- iness, gave low yields (entries 12 and 13). Contrary to
action.[3–8] For example, Buchwald,[3] Hartwig,[4]
Beller[5] and Koie[6] as well as others[7,8] reported ex-
cellent ligands such as biphenylphosphine, pentaaryl-
ferrocenylphosphine, diadamantylbutylphosphine and
tris-tert-butylphosphine. These advances have led us
to develop a new catalyst.
Figure 1. Structures of vinylphosphines.
Adv. Synth. Catal. 2007, 349, 2089 – 2091
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Ken Suzuki et al.
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center.[10] Considering the fact that ligand 7 has a sim-
ilar structure to ligand 10, it must be proved that the
vinyl moiety on ligand 7 could work as a spacer to
control the spatial relationship between the cis-phenyl
group at the b-position and the phosphorus atom. As
the result, we believe that an interaction between the
palladium center and the cis-phenyl group stabilizes
the catalyst in the unstable step when an actual cata-
lyst species is generated. At the same time, steric re-
pulsion, which is caused by the cis-phenyl moiety and
that is around the palladium center, could accelerate
a reductive elimination step.
Next, we examined the general coupling reaction of
aryl halides with amines using ligand 3c, which was
one of the most effective in our series of ligands. Re-
sults are summarized in Table 2. Reactions of para-
and ortho-substituted aryl bromides with primary
amines in the presence of 2 mol% of ligand 3c and 1
Figure 2. A series of diarylvinylphosphines.
Table 1. Effect of substituent groups of the diarylvinylphos-
mol% of PdCAHTRE(UNG OAc)2 proceeded to selectively give the
phines.[a]
secondary amines in 89% and 90% yield, respectively
(entries 1 and 2). The tertiary amine was also ob-
tained by the reaction of anisyl bromide with diben-
zylamine. The catalyst system that consists of ligand
3c/Pd was active for the reaction of aryl chlorides. In
entry 4, the reaction of chlorobenzene with diphenyl-
amine gave triphenylamine in 95% yield under the
same conditions. Both electron-rich and electron-poor
aryl chlorides could be converted to the correspond-
ing products (entries 5 and 6).
Entry Ligand Time Yield[b] Entry Ligand Time Yield[b]
[h]
[%]
[h]
[%]
1
2
3
4
5
6
7
–
8
8
3
3
3
8
3
<1
88
97
97
89
85
87
8
9
4c
5
6
7
8
9
1
8
8
8
8
8
8
8
88
25
26
45
40
40
1
3a
3b
3c
3d
4a
4b
10
11
12
13
14
In summary, we have demonstrated that the cata-
lyst system using the new series of diarylvinylphos-
phine ligands was effective for the coupling reaction
of aryl bromides and chlorides with amines, and gave
the desired product in good to excellent yields. Our
current efforts focus on expanding the scope of aro-
[a]
Reaction conditions: 4-tert-butylbromobenzene (1.1 equivs.),
diphenylamine (1.0 equiv.), Pd(OAc)2, (1 mol%), ligand (4
mol%), NaO-t-Bu (1.2 equivs.), toluene, 1008C.
AHCTREUNG
[b]
Yields were determined by GC analysis.
our original expectations, we found that the simple matic amination and the related coupling reactions.
phosphines 3b–d were more effective.
Then we examined the reaction with vinylphos-
phine 1 under the same reaction conditions, which Experimental Section
gave the coupling product in 1% yield (entry 14). A
comparison of entry 11 with entry 14 indicates that Typical Procedure for the Amination
the phenyl group at the b-position of ligand 7 strongly
affects the activity (Figure 3).
Buchwaldꢁs group reported ligand 10 as being effec-
tive for coupling reactions, and suggested that this ef-
fectiveness is related to an interaction between the
ortho-phenyl group on ligand 10 and the palladium
Amine (1.0 equiv.) and aryl halide (1.1 equivs.) were added
to a solution of PdACHTRE(UNG OAc)2 (1.0 mol%), the ligand (2.0–4.0
mol%) and NaO-t-Bu (1.2 equivs.) in toluene (0.5M) at
room temperature under an argon atmosphere. Then the
mixture was stirred at 1008C for 3 h. After cooling to room
temperature, the reaction mixture was diluted with toluene,
and washed with water and brine, and the organiclayer was
extracted from the aqueous layer with toluene. The com-
bined organicphase was dried over anhydrous magnesium
sulfate and concentrated under reduced pressure. The crude
material was purified by column chromatography on silica
gel to afford the coupling product.
Figure 3. Structures of phosphines.
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Adv. Synth. Catal. 2007, 349, 2089 – 2091

A Novel (2,2-Diarylvinyl)phosphine/Palladium Catalyst
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Table 2. Arylamination using ligand 1c/Pd.[a]
[a]
Reaction conditions: aryl halide (1.1 equivs.), amine (1.0 equivs.), PdCAHTRE(UNG OAc)2, (1 mol%), ligand (2 mol%), NaO-t-Bu
(1.2 equivs.), toluene, 1008C.
Isolated yields.
Aryl halide (1.0 equiv.) and amine (1.1 equivs.) were employed.
[b]
[c]
Eur. J. 2004, 10, 2983; b) A. Zapf, M. Beller, Chem.
Commu. 2005, 431.
Acknowledgements
[6] a) M. Nishiyama, T. Yamamoto, Y. Koie, Tetrahedron
Lett. 1998, 39, 617; b) T. Yamamoto, M. Nishiyama, Y.
Koie, Tetrahedron Lett. 1998, 39, 2367; c) M. Watanabe,
M. Nishiyama, T. Yamamoto, Y. Koie, Tetrahedron
Lett. 2000, 41, 481.
We are grateful to Dr. T. Hagiwara for support of this work
and useful suggestions. We also thank Dr. M. Fujiwhara for
fruitful discussion, and Mr. Y. Yaguchi, Mr. T. Kobayashi and
Mr. A. Kawaraya for their excellent analytical support.
[7] a) X. Bei, A. S. Guram, H. W. Turner, W. H. Weinberg,
Tetrahedron Lett. 1999, 40, 1237; b) S. Urgaonkar, M.
Nagarajan, J. G. Verkade, Org. Lett. 2003, 5, 815;
c) G. Y. Li, Angew. Chem. Int. Ed. 2001, 40, 1513;
d) G. Y. Li, G. Zheng, A. F. Noonan, J. Org. Chem.
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[8] For other coupling reactions using phosphine ligands,
see: a) A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed.
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