Clean synthesis of triarylamines: Buchwald-Hartwig reaction in water with amphiphilic resin-supported palladium complexes

Article abstract of DOI:10.1039/b918424d

Catalytic aromatic amination was achieved in water under heterogeneous conditions by the use of palladium complexes anchored to the amphiphilic PS-PEG resin with little palladium leaching to provide a green and clean (metal-uncontaminated) protocol for the preparation of triarylamines, including the optoelectronically active N,N,N′,N′-tetraaryl-1,1′- biphenyl-4,4′-diamines (TPDs).

Full text of DOI:10.1039/b918424d

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Clean synthesis of triarylamines: Buchwald–Hartwig reaction in water
with amphiphilic resin-supported palladium complexesw
Yoshinori Hiraiz and Yasuhiro Uozumi*
Received (in Cambridge, UK) 7th September 2009, Accepted 3rd December 2009
First published as an Advance Article on the web 23rd December 2009
DOI: 10.1039/b918424d
Catalytic aromatic amination was achieved in water under
heterogeneous conditions by the use of palladium complexes
anchored to the amphiphilic PS-PEG resin with little palladium
leaching to provide a green and clean (metal-uncontaminated)
protocol for the preparation of triarylamines, including the
optoelectronically active N,N,N0,N0-tetraaryl-1,10-biphenyl-
4,40-diamines (TPDs).
palladium complexes of resin-supported hindered alkyl-
phosphines, and explore their catalytic ability for the
Buchwald–Hartwig amination in water.9,10 Considering the
utility of the products as optoelectroactive materials,11 we
elected to study the catalytic aromatic amination with
diarylamines affording triarylamines (Scheme 1).12,13
When the coupling reaction of bromobenzene (3A) with
diphenylamine (4) was carried out in refluxing 20 M aqueous
KOH for 24 h with 5 mol% Pd of the polymeric complex 1-Pd
prepared by mixing the polymeric phosphine 114 and
Since the discoveries of Buchwald and Hartwig that the
coupling of aryl halides and various amines can be catalyzed
by palladium complexes, the catalytic amination of aryl
halides, the so-called Buchwald–Hartwig reaction, has intrigued
synthetic chemists, and is generally recognized as one of the
most powerful methods for preparing a variety of arylamines.1
However, in spite of increasing concern for the environment
and the safety of chemical processes, only scattered attention
has been paid to the catalytic amination in water with a
recyclable heterogeneous catalyst, which would provide a
green alternative to the Buchwald–Hartwig reaction.2,3 In
addition, efficient removal of the metal complexes from the
reaction mixture of the catalytic amination process would
allow not only the recovery of costly noble metal species but
also the production of arylamines uncontaminated by metal
species to provide clean compounds with improved biological
and electronic utility. Here we report the development of an
environmentally benign and safe heterogeneous catalytic system
for palladium-promoted amination of aryl halides, which is
carried out in water with a readily recyclable immobilized
catalyst to achieve the clean (metal-uncontaminated) synthesis
of triarylamines, such as optoelectronically active N,N,N0,N0-
tetraphenyl-1,10-biphenyl-4,40-diamine (TPD) derivatives.
It has been well-documented that the aromatic amination is
efficiently catalyzed by palladium complexes of sterically
hindered alkylphosphine ligands, e.g., RP(t-C4H9)2 and
RP(cyclo-C6H11)2.4 However, to the best of our knowledge,
no catalyst system has yet been developed to accomplish the
aromatic amination with immobilized complexes5,6 in water7
in one system. We have recently developed amphiphilic
polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported
transition metal catalysts8 which promote various catalytic
transformations smoothly in water under heterogeneous
conditions. As a result, we decided to design and prepare the
di(m-chloro)bis(Z3-allyl)dipalladium(II)
([PdCl(Z3-C3H5)]2)
(P/Pd = 2/1) prior to their catalytic use, we were pleased to
find that the desired Ph3N (5A) was obtained in 92% yield
(conversion of 4 = 100%, isolated yield of 5A = 92%, purity
of 5A = 498%). The polymeric palladium complex 2-Pd
generated from the PS-PEG-(dicyclohexyl)phosphine
2
hardly catalyzed the amination, giving only o2% yield of
5A under otherwise similar conditions. Next, we examined the
recyclability of the catalyst beads and found that the recovered
catalyst beads (P/Pd
=
2/1) showed high catalytic
performance under the same conditions to afford 5A in
92% yield through five recycling runs. In the absence of one
or both of the polymeric ligand 1 and palladium sources, the
coupling reaction of 3A and 4 did not take place under
otherwise identical conditions.
The heterogeneous catalytic amination was examined in
water with
a
variety of haloarenes under similar
reaction conditions and exhibited wide substrate tolerance
(Table 1).15
Thus, the amination catalysis with phenyl chloride and
iodide proceeded in water as smoothly as that with phenyl
bromide under the same conditions to afford triphenylamine
(5A) in 82% and 89% yield, respectively. Electron-withdrawing
and electron-donating aromatic substituents, such as CF3,
Institute for Molecular Science, Myodaiji, Okazaki, Aichi 444-8787,
Japan. E-mail: uo@ims.ac.jp; Fax: +81 564 95 5574;
Tel: +81 564 59 5571
w Electronic supplementary information (ESI) available: Experimental
details and spectroscopic data of compounds 5A–L, 7a–g, 9, 11, and
13. See DOI: 10.1039/b918424d
Scheme 1 Synthesis of triarylamine via aqueous heterogeneous
z Visiting scientist from KANEKA Corporation.
Buchwald–Hartwig reaction.
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Table 1 Diphenylamination of haloarenesa
Table 2 Double arylation of anilinesa
Entry
H2NAr (6)
Product
Yield (%)b
Entry
Ar–X (3)
Product
Yield (%)b
1
2
3
4
5
6
7
6a (R = H)
7a (= 5A)
7b
88
85
83
87
85
85
92
6b (R = 2-CF3)
6c (R = 2-CH3)
6d (R = 3-CH3)
6e (R = 4-CH3)
6f (R = 4-CH3O)
6g (R = 4-(CH3)2N)
1
2
3
4
5
6
7
8
3A-Cl (R = H, X = Cl)
3A-Br (R = H, X = Br)
3A-I (R = H, X = I)
5A
5A
5A
5B
5C
5D
5E
5F
5G
5H
5I
82
92
89
85
91
44
88
95
96
65
84
91
20
87
7c (= 5D)
7d (= 5E)
7e (= 5F)
7f (= 5H)
7g
3B (R = 3-CF3, X = Br)
3C (R = 4-CF3, X = Br)
3D (R = 2-CH3, X = Br)
3E (R = 3-CH3, X = Br)
3F (R = 4-CH3, X = Br)
3G (R = 3-CH3O, X = Br)
3H (R = 4-CH3O, X = Br)
3I (R = 3-(C2H5)2N, X = Br)
3J (R = 4-C6H5, X = Br)
3K (1-bromonaphthalene)
3L (2-bromonaphthalene)
a
Reaction conditions: 3 (0.90 mmol), 6 (0.30 mmol), 1 (0.03 mmol
P residue), [PdCl(Z3-C3H5)]2 (7.5 mmol), 20 M KOH (0.6 mL), 100 1C,
24 h, under N2. Isolated yield.
b
9
10
11
12
13
14
5J
5K
5L
process with sublimation is often required to provide TPDs
with a high level of metal-uncontaminated purity. With a
clean aromatic amination protocol in hand, we set about
demonstrating its applicability for the preparation of TPD
derivatives (Scheme 2).17 The reaction of 4,40-dibromobiphenyl
(8) with 3 equiv. of diphenylamine (4) was carried out with
5 mol% palladium (2.5 mol% to bromo residue) of the
polymeric 1-Pd complex (P/Pd = 2/1) in aqueous KOH
solution under reflux for 24 h. The aromatic amination took
place successively at two of the bromo groups of 8 to give a
67% isolated yield of the N,N,N0,N0-tetraphenyl-1,10-
biphenyl-4,40-diamine (9). Little palladium leaching was
observed (lower than the detection limit of ICP-AES
analysis) even in the crude product, and analytically pure 9
was isolated by simple chromatographic purification.
Amination of 8 with phenyl(meta-tolyl)amine (10) and naphthyl-
phenylamine (12) gave N,N0-diphenyl-N,N0-di(meta-tolyl)-1,10-
biphenyl-4,40-diamine (11) and N,N0-dinaphthyl-N,N0-diphenyl-
1,10-biphenyl-4,40-diamine (13) in 33% and 59% yield,
respectively.
a
Reaction conditions: 3 (0.45 mmol), 4 (0.30 mmol), 1 (0.03 mmol
P residue), [PdCl(Z3-C3H5)]2 (7.5 mmol), 20 M KOH (0.6 mL), 100 1C,
24 h, under N2. Isolated yield.
b
CH3, OCH3, N(C2H5)2, and Ph groups, were tolerated under
similar conditions to give the corresponding triarylamines
5B–5J in good to excellent yield. The catalytic efficiency
of the amination was strongly affected by substituents
at the ortho position of the bromoarenes. Thus, the amination
of ortho-tolyl bromide (3D) gave 44% yield of 5D, whereas
that of meta- and para-tolyl bromides (3E and 3F) afforded
the corresponding 5E and 5F in 88% and 95% yield,
respectively. A similar steric effect was also observed with
1- and 2-bromonaphthalene (3K and 3L), where the desired
triarylamines 5K and 5L were obtained in 20% and 87% yield,
respectively.
Considering the lack of commercially available diarylamine
derivatives (Ar2NH), the double arylation of primary anilines
with haloarenes should offer a practical alternative synthetic
route to various triarylamines (Table 2). The double arylation
was achieved by the catalytic amination with 3 mol equiv. of
bromobenzene with the aniline 6. Thus, when the arylation of
anilines 6a–e with bromobenzene was carried out with the
palladium complex of PS-PEG resin-supported di(tert-butyl)-
phosphine ligand 1 in water in the presence of KOH, the
arylation took place twice successively on the nitrogen of the
aniline substrates to give the corresponding triarylamines 7a,
7b, 7c, 7d and 7e in 88%, 85%, 83%, 87% and 85% isolated
yield, respectively, where 2.5 mol% of palladium vs. the
reactive bromo residue was enough to promote the double
arylation. The double N-arylation took place successfully
also with the electron-rich anilines 6f and 6g to afford the
N,N-diphenylanilines 7f and 7g in 85% and 92% yield,
respectively.
In summary, the Buchwald–Hartwig amination was
achieved in water under heterogeneous conditions by use of
an immobilized palladium complex, coordinated with an
amphiphilic polystyrene-poly(ethylene glycol) resin-supported
di(tert-butyl)phosphine ligand, which was designed and
prepared with a view toward using it in water. Aromatic
amination of aryl halides with diphenylamine and N,N-double
arylation of anilines with bromobenzene were found to
proceed smoothly in water with broad substrate tolerance to
give triarylamines in high yield with high recyclability
of the polymeric catalyst beads. Since little palladium
leached from the polymeric catalyst under the water-based
reaction conditions, this method provides a green and clean
(metal-uncontaminated) protocol for the preparation of
triarylamines. The catalytic system was applied to successive
amination of dibromoarenes and N,N,N0N0-quadruple
arylation of phenylenediamine producing N,N,N0N0-tetraaryl-
phenylenediamines. With the heterogeneous catalytic system,
electroactive N,N,N0,N0-tetraaryl-1,10-biphenyl-4,40-diamines
(TPDs) were obtained without metal contamination.
N,N,N0,N0-Tetraphenyl-1,10-biphenyl-4,40-diamine derivatives
(TPDs) are known as optoelectroactive organic materials due
to their hole-transport properties.16 Because of their utility in
optoelectronic devices (e.g., EL devices), a costly purification
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6 Aromatic amination with heterogeneous palladium sources and
external alkylphosphine ligands: (a) R. Nishio, S. Wessely,
M. Sugiura and S. Kobayashi, J. Comb. Chem., 2006, 8, 459;
(b) T. Inasaki, M. Ueno, S. Miyamoto and S. Kobayashi,
Synlett, 2007, 3209; (c) M. Guino and K. K. Hii, Tetrahedron
´
Lett., 2005, 46, 7363; (d) Y. Monguchi, K. Kitamoto, T. Ikawa,
T. Maegawa and H. Sajiki, Adv. Synth. Catal., 2008, 350, 2767.
7 Aromatic amination in water, see: (a) X. Huang, K. W. Anderson,
D. Zim, A. B. Klapars and S. L. Buchwald, J. Am. Chem. Soc.,
2003, 125, 6653; (b) K. W. Anderson, R. E. Tundel, T. Ikawa,
R. A. Altma and S. L. Buchwald, Angew. Chem., Int. Ed., 2006, 45,
6523; (c) C. Xu, J.-F. Gong and Y.-J. Wu, Tetrahedron Lett., 2007,
48, 1619; (d) B. H. Lipshutz, D. W. Chung and B. Rich,
Adv. Synth. Catal., 2009, 351, 1717.
8 For recent examples of studies on polymer-supported transition
metal complex catalysts from the author’s group, see:
(a) Y. Uozumi and K. Shibatomi, J. Am. Chem. Soc., 2001, 123,
2919; (b) Y. Uozumi, H. Tanaka and K. Shibatomi, Org. Lett.,
2004, 6, 281; (c) H. Hocke and Y. Uozumi, Synlett, 2002, 12, 2049;
(d) H. Hocke and Y. Uozumi, Tetrahedron, 2003, 59, 619;
(e) H. Hocke and Y. Uozumi, Tetrahedron, 2004, 60, 9297;
(f) Y. Nakai and Y. Uozumi, Org. Lett., 2005, 7, 291;
(g) Y. Uozumi and M. Kikuchi, Synlett, 2005, 1775;
(h) Y. Uozumi and M. Kimura, Tetrahedron: Asymmetry, 2006,
17, 161; (i) Y. Nakai, T. Kimura and Y. Uozumi, Synlett, 2006,
3065; (j) Y. Kobayashi, D. Tanaka, H. Danjo and Y. Uozumi,
Adv. Synth. Catal., 2006, 348, 1561; (k) Y. Uozumi, T. Suzuka,
R. Kawade and H. Takenaka, Synlett, 2006, 2109; (l) Y. Uozumi
and T. Suzuka, J. Org. Chem., 2006, 71, 8644; (m) Y. Uozumi and
T. Suzuka, Synthesis, 2008, 1960; (n) Y. Uozumi, H. Takenaka and
T. Suzuka, Synlett, 2008, 1557; (o) Y. Oe and Y. Uozumi,
Adv. Synth. Catal., 2008, 350, 1771–1775; (p) Y. Uozumi,
Y. Matsuura, T. Arakawa and Y. M. A. Yamada, Angew. Chem.,
Int. Ed., 2009, 48, 2708.
9 Soluble non-crosslinked polymer-supported aryl(dicyclohexyl)-
phosphines have been developed for solution-phase aromatic
amination under homogeneous conditions; see: A. Leyva,
H. Garcia and A. Corma, Tetrahedron, 2007, 63, 7097.
10 PS-PEG resin-supported aryl(dicyclohexyl)phosphine has been
reported to promote the Suzuki–Miyaura coupling under
heterogeneous conditions; see: K. Glegola, E. Framery,
K. M. Pietrusiewicz and D. Sinou, Adv. Synth. Catal., 2006, 348,
1728.
Scheme 2 Clean synthesis of N,N,N0,N0-tetraaryl-1,10-biphenyl-4,40-
diamines (TPDs).
Notes and references
1 For recent reviews, see: (a) J. F. Hartwig, Acc. Chem. Res., 2008,
41, 1534–1544; (b) D. S. Surry and S. L. Buchwald, Angew. Chem.,
Int. Ed., 2008, 47, 6338–6361; (c) R. Martin and S. L. Buchwald,
Acc. Chem. Res., 2008, 41, 1461–1473.
11 (a) Y. Shirota, J. Mater. Chem., 2000, 10, 1; (b) Y. Shirota,
J. Mater. Chem., 2005, 15, 75.
2 For recent reviews on immobilized catalysts, see: (a) S. V. Ley,
I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G. Leach,
D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer and
S. J. Taylor, J. Chem. Soc., Perkin Trans. 1, 2000, 3815;
(b) Q.-H. Fan, Y.-M. Li and A. S. C. Chan, Chem. Rev., 2002,
102, 3385; (c) Y. Uozumi, Top. Curr. Chem., 2004, 242, 77;
12 In contrast to the vast amount of research on aromatic amination
with alkylamines, only scant attention has been focused on
aromatic amination with diarylamines, see: (a) N. Kataoka,
Q. Shelby, J. P. Stambuli and J. F. Hartwig, J. Org. Chem.,
2002, 67, 5553; (b) Q. Shen, T. Ogata and J. F. Hartwig, J. Am.
Chem. Soc., 2008, 130, 6586. Also see ref. 4b.
(d) M. Guino and K. K. Hii, Chem. Soc. Rev., 2007, 36, 608;
´
(e) Z. Wang, G. Chen and K. Ding, Chem. Rev., 2009, 109, 322;
(f) J. Lu and P. H. Toy, Chem. Rev., 2009, 109, 815.
3 For recent reviews on catalytic organic transformation in water,
see: (a) C.-J. Li, Chem. Rev., 2005, 105, 3095–3165; (b) C.-J. Li and
L. Chen, Chem. Soc. Rev., 2006, 35, 68–82.
13 For recent examples of aromatic amination with diarylamines, see:
(a) H. Xu and C. Wolf, Chem. Commun., 2009, 1715 (Cu catalysis);
(b) J. L. Bolliger and C. M. Frech, Tetrahedron, 2009, 65, 1180
(transition metal-free conditions).
14 The reaction with 2 mol% palladium of 1-Pd did not complete
after 30 h (monitored by GC).
4 Typical examples, see: (a) M. Nishiyama, T. Yamamoto and
Y. Koike, Tetrahedron Lett., 1998, 39, 617; (b) J. F. Hartwig,
M. Kawatsura, S. I. Hauck, K. H. Shaughnessy and L. M. Aleazer-
Roma, J. Org. Chem., 1999, 64, 5575; (c) K. Suzuki, Y. Hori and
T. Kobayashi, Adv. Synth. Catal., 2008, 350, 652; (d) Q. Shen,
S. Shekhar, J. P. Stambuli and J. F. Hartwig, Angew. Chem., Int.
Ed., 2005, 44, 1371.
15 Alkylamines were also tolerated as aminating substrates. Thus, for
example, the coupling reaction of PhBr and morpholine gave 90%
yield of N-phenylmorpholine under similar conditions. Further
studies on the substrate tolerance are in progress.
16 For a recent example, see: J. A. Bardecker, H. Ma, T. Kim,
F. Haung, M. S. Liu, Y.-J. Cheng, G. Ting and A. K.-Y. Jen,
Adv. Funct. Mater., 2008, 18, 3964.
5 Aromatic amination with a polymer-supported Pd complex, see:
C. A. Parrish and S. L. Buchwald, J. Org. Chem., 2001, 66, 3820.
17 D. S. Surry and S. L. Buchwald, J. Am. Chem. Soc., 2007, 129,
10354.
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This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 1103–1105 | 1105