Diazabutadiene: a simple and efficient ligand for copper-catalyzed N-arylation of aromatic amines

Article abstract of DOI:10.1016/j.tetlet.2006.10.103

Diazabutadienes (DABs) were chosen as ancillary ligands in the Cu-catalyzed C-N coupling reaction for the synthesis of triarylamines. A combination of CuI/DAB (1) [1: N,N′-bis(2,6-diisopropylphenyl)-1,4-diaza-1,3-butadiene] was found to be an efficient catalyst system for N-arylation of diarylamines and anilines with aryl iodides, affording the desired products in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2006.10.103

Tetrahedron Letters 47 (2006) 9275–9278
Diazabutadiene: a simple and efficient ligand for
copper-catalyzed N-arylation of aromatic amines
Yu-Hua Liu,a,b Chen Chena,b and Lian-Ming Yanga,*
aBeijing National Laboratory for Molecular Sciences (BNLMS), New Materials Laboratory, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, China
bGraduate School of Chinese Academy of Sciences, Beijing 100049, China
Received 15 August 2006; revised 20 October 2006; accepted 23 October 2006
Available online 9 November 2006
Abstract—Diazabutadienes (DABs) were chosen as ancillary ligands in the Cu-catalyzed C–N coupling reaction for the synthesis
of triarylamines. A combination of CuI/DAB (1) [1: N,N0-bis(2,6-diisopropylphenyl)-1,4-diaza-1,3-butadiene] was found to be an
efficient catalyst system for N-arylation of diarylamines and anilines with aryl iodides, affording the desired products in good to
excellent yields.
Ó 2006 Elsevier Ltd. All rights reserved.
Triarylamine compounds are attractive targets for
chemical synthesis because of their importance as build-
ing blocks of organic materials with electronic, photo-
electronic and magnetic properties.1 This has led to the
development of many synthetic protocols using the tran-
sition metal-catalyzed C–N coupling. The most remark-
able advances have been made in the Pd-catalyzed
process, which can realize the coupling reaction of form-
ing various C–N bonds under very mild conditions and
becomes the most powerful tool for laboratory-scale
preparation.2 On the other hand, the Ullmann reaction,3
a venerable method for the Cu-mediated C–N coupling,
has also received a steady increase of interest. From a
standpoint of large-scale or industrial preparation, Ull-
mann-type reactions are more preferred because copper
catalysts have the advantages of cost savings, low toxi-
city, and air- and moisture-stability. Recently, much
work has been done to overcome the inborn drawbacks
(harsh reaction conditions, requirement for large
amounts of copper agents, and moderate yields) of the
conventional Ullmann reaction, and proved that the
activity of copper catalysts could be greatly improved
by the use of proper ligands.4 The more practical
ligand-promoted Cu-catalyzed chemistry (so-called
post-Ullmann reactions) is being developed, and various
types of ligands, such as aliphatic diamines, 8-hydroxy-
quinoline, phosphines, ethylene glycol, glycine and pro-
line, have been employed.4 With regard to the synthesis
of triarylamines by the ligand-promoted Cu-catalyzed
coupling, some successful examples involved the use of
Cu(I)/phenanthroline system,5 Cu(I)-neocuproine com-
plex,6 CuI/N- or P-based bidentate ligand systems,7
CuI/P(Bu)3 system,8 CuI/pyridine-based systems,9 as
well as Cu(I)-phenanthroline complexes.6,10
As part of our research, we are interested in the
exploration of other efficient ligands, but simple and
inexpensive, for the copper-catalyzed synthesis of tri-
arylamines. We notice a known family of ligands with
the chelating nature, 1,4-diazabuta-1,3-dienes (DABs).
DABs are readily available from the condensation of
glyoxal with primary amines, and conveniently manipu-
lated due to their insensitivity to air or moisture. Their
coordination versatility stems from the flexibility of
the N@C–C@N backbone and the strong r-donating
and p-accepting properties. The steric factors of DABs
can be easily modulated by the change of groups on
the amine section of DAB. These features of DABs
would be favorable for stabilizing catalytic species and
assisting catalytic cycle. Their coordination capability
was well documented in the DAB–metal complexes,11
but they were rarely used as additive ligands in the cat-
alytic coupling reaction.12,13 Here, we wish to report our
preliminary investigation in the employment of DABs as
ancillary ligands in Cu-catalyzed N-arylation of aro-
matic amines for the synthesis of triarylamines.
With DABs as ligand, a set of experiments was carried
out to optimize the reaction conditions. We determined
*
Corresponding author. E-mail: yanglm@iccas.ac.cn
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.103

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Y.-H. Liu et al. / Tetrahedron Letters 47 (2006) 9275–9278
KOtBu as the base of choice, toluene as the solvent of
choice, and the catalytic system composed of 1.2:1 molar
ratio of DAB to Cu. The N-arylation of diphenylamine
with iodobenzene in the presence of 5 mol % CuI and
6 mol % of DAB (1) [1: N,N0-bis(2,6-diisopropylphen-
yl)-1,4-diaza-1,3-butadiene] proceeded at 120 °C to
give an excellent isolated yield (Table 1, entry 2). The
role of DAB (1) was confirmed by running a control
experiment (Table 1, entry 1). The use of other several
diazabutadienes led to the observation that aryl-diaza-
butadienes are superior to alkyl-diazabutadienes
(Table 1, entries 2 and 3 vs entries 4 and 5) as ligands
for this Cu-catalyzed N-phenylation. This reactivity
trend could result from the fact that there exists a better
balance between the electronic and steric effects in the
aryl-DAB. It was shown that the aryl-DAB has a com-
parable performance to the commercially available
ligands phenanthrolines5,6 and 2,20-bipyridyl.4c,7
the less hindered (2-naphthyl)phenylamine (entry 7 vs
8). For aryl iodides, the one with the p-methoxy group
gave the decreased yields compared to that with the p-
methyl group (entry 3 vs 2; and entry 6 vs 5). Addition-
ally, the double amination proceeded smoothly under
similar conditions when diiodobiphenyl was treated with
Table 2. N-arylation of diarylamines catalyzed by the CuI/DAB (1)
system
R1
R2
R1
5 mol% CuI, 6 mol% DAB(1)
I
NH
+
N
R2
t-BuOK
Toluene
R3
R3
Entry Amine
1
Aryl halide
Yielda (%)
94
With the optimum conditions in hand, we checked the
reactivity of a few diarylamines and some un-activated
aryl iodides (Table 2). In most cases, this protocol affor-
ded the desired products in good to excellent yields
(entries 1–5, 7, and 9–11). The iodide with electron-
donating substituents led to the reduced yields (entries
2, 3, 5, and 6). For diarylamines, the effect of the steric
factor on this reaction appeared to be greater than that
of the electronic factor. For instance, the reaction of
di(p-tolyl)amine gave comparable yields to that of di-
phenyamine (comparing entries 1–3 with entries 4–6),
while the sterically hindered (1-naphthyl)phenylamine
reacted with iodobenzene to afford a far lower yield than
I
N
H
2
3
4
5
6
7
79
72
88
87
63
88
I
N
H
O
I
N
H
I
N
H
I
Table 1. CuI-catalyzed N-phenylation of iodobenzene using different
DABs as ligand
N
H
O
I
N
H
5 mol% CuI, 6 mol% Ligand
I
NH
N
+
1.5 eq t-BuOK
Toluene
1.25 eq
I
I
N
Yielda (%)
67
H
Entry
1
Ligand
No ligand
8
38
HN
2
3
94
90
(1)
N
N
9
85b
83b
87b
I
I
I
I
I
I
N
H
N
N
N
N
(2)
10
11
N
H
4
5
64
75
(3)
(4)
N
H
But
But
N
N
Reaction conditions: aryl amine: 1.0 mmol; aryl halide: 1.25 mmol;
CuI: 5 mol %; DAB (1): 6 mol %; KOtBu: 1.5 mmol; toluene: 5 mL;
reaction temperature: 120 °C; reaction time: 20 h.
a Isolated yields.
Reaction conditions: aryl halide: 1.25 mmol; diarylamine: 1 mmol;
CuI: 5 mol %; DAB ligand: 6 mol; KOtBu: 1.5 mmol; solvent: toluene,
5 mL; temperature: 120 °C; reaction time: 20 h.
a Isolated yields.
b Molar ratio of amine to halide: 2.5:1.

Y.-H. Liu et al. / Tetrahedron Letters 47 (2006) 9275–9278
Table 3. N-diarylation of anilines catalyzed by the CuI/DAB (1) system
9277
R1
R2
+
5 mol% CuI, 6 mol% DAB (1)
R1
I
NH2
N
3 eq t-BuOK
Toluene
R2
R2
4 eq
Entry
1
Amine
Aryl halide
Yielda (%)
97
92
82
NH2
I
2
3
NH2
I
I
NH2
I
I
4
5
82
84
NH2
NH2
NH2
6
73
I
I
7
8
76
75
O
O
NH2
NH2
I
Reaction conditions: aryl iodide: 4.0 mmol; aryl amine: 1.0 mmol; CuI: 5 mol %; DAB (1): 6 mol %; KOtBu: 3 mmol; toluene: 5 mL; reaction time
48 h; reaction temperature: 120 °C.
a Isolated yields.
diarylamines (entries 9–11). In this reaction, the side
reaction was the homocoupling of the aryl iodide to
form biaryls.
ligands on the coupling reactions. This work is ongoing
in our laboratory.
We also found that the CuI/DAB (1) system was effec-
tive for the coupling reaction of primary arylamines
with aryl iodides, and N-diarylation proceeded in good
to excellent yields as shown in Table 3. The use of larger
excess of aryl iodides was favorable for avoiding the for-
mation of a mixture of triarylamine and diarylamine.
The experiment demonstrated that 3 equiv of iodobenz-
ene was coupled with 1 equiv of diphenylamine to give
only an 80% yield of triphenylamine (compare entry 1
in Table 3). Anilines with p- and m-methyl or p-methoxy
group are all viable coupling partners in this reaction
(Table 3, entries 3–8).
Acknowledgments
The authors thank the National 863 Program of China
(Z36-1-715-98) and the National Natural Science Foun-
dation of China (Project No. 60276007) for financial
support of this work.
Supplementary data
Detailed experimental procedure and characterization
of the products. This material is available free of charge.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.10.103.
In summary, a simple and efficient method for Cu-cata-
lyzed N-arylation of diarylamines and anilines has been
developed based on CuI/DAB systems. This CuI/DAB
(1) catalytic system represents an interesting alternative
to the existing copper catalytic systems. Further effort
is directed at extending the scope of electrophilic sub-
strates used in the CuI/DAB catalytic systems from aryl
iodides to aryl bromides or even chlorides, and studying
the influence of the steric and electronic factors of DAB
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