7
08
Chemistry Letters Vol.38, No.7 (2009)
A Simple Access to Symmetric Diarylamines via Copper(II)-catalyzed Coupling
of Aqueous Ammonia with Arylboronic Acids
ꢀ
ꢀ
Changfeng Zhou, Fan Chen, Dongpeng Yang, Xiaofei Jia, Lixue Zhang, and Jiang Cheng
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325027, P. R. China
(Received April 23, 2009; CL-090405; E-mail: jiangcheng@wzu.edu.cn)
II
Table 1. Screening for the optimum conditionsa
A simple and efficient Cu -catalyzed coupling reaction of
arylboronic acids with aqueous ammonia under air is described.
The reaction was conducted under atmospheric pressure and no
additional ligand was required. Benzoic acid was added to tune
the basicity of the reaction system.
b
Entry
Copper
.
Solvent
DCE
Acid/equiv Yield/%
PhCOOH (0.5)
1
2
3
4
5
6
7
8
9
Cu(OAc)2 H2O
50
60
<5
70
65
91
70
66
60
24
67
69
61
76
75
29
84
73
<5
.
Cu(OAc)2 H2O Toluene PhCOOH (0.5)
.
Cu(OAc)2 H2O
THF
PhCOOH (0.5)
.
Cu(OAc)2 H2O CH3CN PhCOOH (0.5)
.
Direct access to aryl amines from ammonia is attractive not
only because ammonia is one of the cheapest and most abundant
Cu(OAc)2 H2O
EtOAc PhCOOH (0.5)
.
Cu(OAc)2 H2O EtCOOEt PhCOOH (0.5)
1
.
nitrogen sources in chemical synthesis, but also because aryl
amines are useful intermediates in the pharmaceutical, agro-
Cu(OAc)2 H2O EtCOOEt
TsOH (0.5)
HOAc (0.5)
.
Cu(OAc)2 H2O EtCOOEt
2
.
chemical, and polymer industries. However, examples of em-
ploying ammonia in such transformation have rarely been re-
Cu(OAc)2 H2O EtCOOEt HCOOH (0.5)
.
10 Cu(OAc) H O EtCOOEt
2
2
—
H O EtCOOEt PhCOOH (0.1)
3
ported which is at least partly due to the high N–H bond disso-
11 Cu(OAc)2
12 Cu(OAc)2
13 Cu(OAc)2
.
.
.
2
ꢂ1
4
ciation energy (104 ꢁ 2 kcal mol ). Moreover, in coupling re-
actions, ammonia is an excellent ligand for many metals and will
often bind to the metal center to form catalytically unactive spe-
cies. The stability of the amido–metal complexes also inhibits
the key reductive elimination to form C–N bonds.
H O EtCOOEt PhCOOH (2.0)
2
H O EtCOOEt PhCOOH (3.0)
2
EtCOOEt PhCOOH (0.5)
14
CuSO
4
15
16
17
18
19
CuBr2
CuO
Cu(OTf)2
CuF2
—
EtCOOEt PhCOOH (0.5)
EtCOOEt2 PhCOOH (0.5)
EtCOOEt PhCOOH (0.5)
EtCOOEt PhCOOH (0.5)
EtCOOEt PhCOOH (0.5)
Recently, the palladium-catalyzed amination of aryl halides
5
a
with ammonia has been described by Surry and Buchwald and
Shen and Hartwig5b in which bulky ferrocene or electron-rich
phosphine ligands were used. The copper-catalyzed amination
of aryl halides using ammonia was reported by Lang et al. and
aAll reactions were run with phenylboronic acid (1a) (0.2
mmol), NH3 H2O (0.6 mmol), copper (20 mol %), indicated
acid, EtCOOEt (2 mL), 80 C, 24 h. Isolated yields.
.
6
Thadani et al., respectively. However, the reactions were per-
ꢃ
b
formed under pressures along with a competitive C–O arylation
of the ethylene glycol solvent in Lang’s procedure. Very recent-
ly, a very simple copper-catalyzed coupling reaction of aqueous
equiv of benzoic acid, the yield increased to 50% in DCE
(Table 1, Entry 1). Among the solvents tested, ethyl propionate
was the best and the yield was sharply increased to 90% in the
presence of 0.5 equiv of benzoic acid (Table 1, Entry 6). Trace
aniline was obtained and no triaryl amines was detected under
the procedure. Other acids, such as TsOH, acetic acid, and for-
mic acid, were also efficient for such transformation and benzoic
acid was the best (Table 1, Entries 6–9). Further investigations
revealed that the amount of benzoic acid had a significant effect
on the reaction. Several copper(II) sources were also examined,
7
ammonia with aryl bromides was reported by Xia and Taillefer.
Copper salts and complexes have been extensively utilized
as catalysts for the Chan–Lam reaction between boronic acids
and amines. However, to the best of our knowledge, the employ-
ment of aqueous ammonia in the Chan–Lam reaction has rarely
8
been reported or studied. We envisioned that the in situ formed
copper(II)/NH3 complex would be an efficient catalyst for such
transformation. Recently, Fu described the coupling reaction of
aromatic boronic and aqueous ammonia at room temperature af-
9
.
fording primary arylamines. Herein, we wish to report a simple
and Cu(OAc)2 H2O turned out to be better than the others. No
II
and cheap copper(II)-catalyzed coupling reaction of aqueous
ammonia with arylboronic acids, providing symmetric diaryl-
amines in good to excellent yields.
Initial studies were conducted using aqueous ammonia (3
equiv) and phenylboronic acid (1a) (0.2 mmol) in 1,2-dichloro-
ethane (DCE) as a model reaction under air in the presence of
product was formed in the absence of Cu .
With the optimized conditions in hand, we turned our atten-
tion to study the substrate scope. The results are summarized in
Table 2.
As expected, a series of arylboronic acids ran smoothly
under the reaction conditions. Arylboronic acids possessing
electron-donating groups delivered symmetric diaryl amines in
good to excellent yields. For example, 2b, 2c, 2d, and 2e were
isolated in 85, 75, 85, and 70% yields, respectively (Table 2,
Entries 1–4). However, arylboronic acids possessing electron-
withdrawing groups provided the products in lower yields, and
primary amines were found to some extent. Fortunately, the
yields for the arylboronic acids possessing electron-withdrawing
.
Cu(OAc)2 H2O (20 mol %). Disappointingly, after the extensive
screening of copper sources and solvents, no synthetically useful
results were obtained. We realized that the distribution of the in
situ formed copper species depended on the basicity of the reac-
tion system and would have great effect on the reaction. Thus,
benzoic acid was added to tune the basicity of the reaction sys-
tem in a series of solvents. To our delight, in the presence of 0.5
Copyright Ó 2009 The Chemical Society of Japan
Zhou, Changfeng
