Nickel-catalyzed cross-coupling of diarylamines with haloarenes

Article abstract of DOI:10.1039/b911286c

The cross-coupling reaction of diarylamines with aryl bromides/iodides can be effected by the Ni(ii)-(σ-aryl) complex/PPh₃/NaH system, and a preliminary investigation was conducted into the mechanism of this reaction.

Full text of DOI:10.1039/b911286c

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Nickel-catalyzed cross-coupling of diarylamines with haloarenes†
Cai-Yan Gao,a,b Xingbo Caoa,b and Lian-Ming Yang*a
Received 10th June 2009, Accepted 23rd July 2009
First published as an Advance Article on the web 3rd August 2009
DOI: 10.1039/b911286c
The cross-coupling reaction of diarylamines with aryl
bromides/iodides can be effected by the Ni(II)–(r-aryl)
complex/PPh3/NaH system, and a preliminary investigation
was conducted into the mechanism of this reaction.
readily available, cheaper, and convenient to manipulate due to
their air-/moisture-stability. For catalytic C–N coupling reactions,
bases are required to deprotonate the amine or neutralize the
protons that the amine released in the reaction course. Further,
considering the fact that facile reduction of the Ni(II) center may
make the reaction more efficient, the use of bases possessing
reducing ability should be desirable. Thus, sodium hydride, a cheap
and easy-to-use base, was employed in this study as it was reported
to be able to reduce Ni(II) to the catalytically active low-valent Ni
species.3e
Nickel-catalyzed aromatic C–N coupling reactions have received
intense investigations and made remarkable advances over the past
decade. A considerably wide range of arylamine derivatives can
be obtained from the catalytic couplings of haloarenes (primarily
chloroarenes) with various types of nitrogen-containing substrates
involving primary amines, secondary cyclic and acyclic amines,
anilines and N-alkyl anilines.1–6 In contrast, the Ni-catalyzed
N-arylation of diarylamines or anilines for triarylamine synthesis
has been a challenging task. Triarylamines are an important class
of building blocks for organic materials with unique photoelectric
properties;7 currently their preparation depends primarily on
Pd-8 and Cu-catalyzed9 C–N coupling reactions. Thus, the nickel-
catalyzed triarylamine synthesis merits exploration whether from
the angle of synthetic methodology or material preparation.
Our previous work displayed an interesting procedure for the
Ni(II)-catalyzed N-arylation of bromomagnesium diarylamides
for triarylamine synthesis.4a However, this protocol seems to be
somewhat cumbersome and complicated in manipulation since
the diarylamidomagnesium bromides needed to be produced by
treatment of diarylamines with the Grignard reagent and the
reaction solvent THF be replaced (entirely or partly) with other
solvents such as toluene or dioxane. On the other hand, a recent
publication6 provided a single special case where a triarylamine
product was afforded by the coupling of diphenylamine with
4-bromobenzophenone in the presence of Ni(II)–NHC complex
as a catalyst. It was concluded from the above-mentioned
outcomes that: (1) nickel-based catalytic systems would likely
cause aromatic C–N couplings for triarylamine synthesis if the
proper reaction conditions are chosen; and (2) more convenient,
general protocols are awaiting development. Herein, we want to
present a simple protocol for the nickel-catalyzed triarylamine
synthesis from N-arylation of diarylamines through employing
an easily-available Ni(II)–(s-aryl) complex, which were previously
applied to the aminations of aryl chlorides4b and tosylates,4c as a
pre-catalyst.
As shown in Table 1, a combination of NiCl2(PPh3)2 and PPh3
can give triphenylamine in toluene at 120 ◦C upon the use of
NaH as base, albeit in only 30% yield (entry 1). After some
experimentation, it was found that a Ni(II)–(s-aryl) complex,
Ni(PPh3)2(1-naphthyl)Cl, worked far better than NiCl2(PPh3)2
under similar conditions, giving an excellent yield of 88% (entry 2).
The difference in the catalytic activity between Ni(PPh3)2(1-
naphthyl)Cl and NiCl2(PPh3)2 might be ascribed to their different
reactivity toward the reductive base NaH. Phosphine-based biden-
tate ligand (entry 3) was slightly inferior to triphenylphosphine,
while the strongly s-donating N-heterocyclic carbene (entry 4)
and nitrogen-based bidentate ligand (entry 5) were ineffective. An
◦
◦
attempt to reduce reaction temperatures from 120 C to 100 C
led to a decreased yield (entry 6). To our surprise, elevating the
reaction temperature (up to 140 ◦C in m-xylene) seemed to be very
unfavorable for this reaction (entry 7). The change of reaction
solvents from toluene to dioxane (entry 8) or THF (entry 9)
brought a reduced yield or even no product due to the nature of the
solvents and reaction temperatures. It is worth noting that almost
no reaction occurred upon replacement of NaH with other bases,
such as KtOBu (entry 10) and NatOBu (entry 11), used normally
in nickel-catalyzed C–N couplings, whether the Ni(II) or Ni(0) was
utilized as the nickel source. This indicated that the use of strong
bases possessing reducing ability is essential for this reaction. The
role of the nickel-based catalyst system was confirmed by a control
experiment (entry 12). It must be mentioned that biphenyl as a by-
product was always detected, to a greater or lesser degree, in these
coupling reactions involving NaH as both base and reductant.
Finally, the optimized reaction conditions were set up as entry 2
in Table 1.
Next, we performed the coupling reaction between a range of
haloarenes and representative diarylamines under the optimized
reaction conditions. The results are summarized in Table 2.
Generally, both aryl bromides and iodides are substrates suit-
able for this reaction, and the iodide performed a bit bet-
ter than the corresponding bromide. Electron-neutral bromo-
and iodobenzene were smoothly coupled with diarylamines in
good to excellent yields (entries 1, 2, and 15–18); electron-rich
p-bromotoluene gave a relatively low yield of the expected product
(entries 6 and 7). The aryl chloride was resistant to the reaction
The cross-coupling of diphenylamine and bromobenzene was
used as a model reaction for the screening of reaction conditions.
Ni(II) compounds were chosen as pre-catalysts because they were
aBeijing National Laboratory for Molecular Sciences (BNLMS), Lab-
oratory of New Materials, Institute of Chemistry, Chinese Academy of
Sciences, Beijing, 100190, China. E-mail: yanglm@iccas.ac.cn; Fax: 00-
8610-62559373; Tel: 00-8610-62565609
bGraduate School of Chinese Academy of Sciences, Beijing, 100049, China
† Electronic supplementary information (ESI) available: Experimental
procedures and spectral data. See DOI: 10.1039/b911286c
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Table 1 Screening of conditions for Ni(II)-catalyzed arylation of diphenylaminea
Entry
[Ni]b (mol%)
Ligand (mol%)
Base
Solvent
Temp./◦C
Yield (%)c
1
2
C-1 (5)
C-2 (5)
C-2 (5)
C-2 (5)
C-2 (5)
C-2 (5)
C-2 (5)
C-2 (5)
C-2 (5)
C-2 (5)
Ni(0) (ca. 5)g
none
PPh3 (10)
PPh3 (10)
DPPEd (5)
SIPr·HCle (10)
Phenf (5)
PPh3 (10)
PPh3 (10)
PPh3 (10)
PPh3 (10)
PPh3 (10)
PPh3 (10)
none
NaH
NaH
toluene
toluene
toluene
toluene
toluene
toluene
m-xylene
dioxane
THF
120
120
120
120
120
100
140
120
70
30
88
75
3
NaH
NaH
NaH
NaH
NaH
NaH
NaH
KOtBu
NaOtBu
NaH
4
5
6
7
8
9
10
11
12
0
trace
78
11
60
trace
trace
trace
0
toluene
toluene
toluene
120
120
120
a Reaction conditions: diphenylamine (1 equiv), bromobenzene (2 equiv), base (1.5 equiv), 12 h. b C-1: Ni(PPh3)2Cl2; C-2: Ni(PPh3)2(1-naphthyl)Cl.
c Isolated yield. d 1,2-Bis(diphenylphosphino)ethane. e 1,3-Bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolium chloride. f 1,10-Phenanthroline. g The Ni(0)
species was in situ generated from Ni(PPh3)2Cl2 and CH3MgBr following the literature procedure (see ref. 1).
conditions (entry 3). Thus, a selective amination of 4-bromo-1-
chlorobenzene (entry 4) and 3-bromo-1-chlorobenzene (entry 5)
may be carried out. The nature of electron-withdrawing groups
on haloarenes affected the reaction substantially. For example,
the bromoarene bearing the inert chlorine–aryl bond could offer
acceptable yields (entries 4 and 5). Rather, those containing
the carbonyl group, such as 4-bromobenzophenone (entry 12),
4-bromobenzaldehyde (entry 13) and 4-bromobenzoate (entry 14),
provided only small amounts of or no desired product, although
the starting bromides were found to be consumed completely. This
might be because the carbonyl group may capture the electrons
resulting from the NaH-related electron transfer process to form
the carbonyl radical anion,10 leading to a failure in the reduction of
the Ni(II) into the catalytically active low-valent Ni species. On the
other hand, this reaction is very sensitive to the steric hindrances
of both types of substrates. For example, o-methyl-substituted
haloarenes (entries 8–10) furnished far lower yields than those
without ortho-substituents; a similar outcome was observed in
the case of 1-bromonaphthalene (entry 11). And unhindered
4,4¢-dimethyldiphenylamine with the electron-donating group
provided high yields similar to diphenylamine (entries 15 and 16),
but the yields rapidly decreased from diphenylamine, phenyl(2-
naphthyl)amine to phenyl(1-naphthyl)amine with increasing the
steric bulk of amine substrates (entry 1 versus entry 17; and entry
2 versus entry 18 versus entry 19).
Ni(II)–(s-aryl) complexes11 that may be regarded as the oxidative
adducts of haloarenes to Ni(0) as shown in eqn (1). As a result, no
triarylamine product was detected. Thus, it should be safe to rule
out the mechanism to follow an usual Ni(0)–Ni(II) cycle for this
nickel-catalyzed triarylamine synthesis.
It was presumed that the catalytically active species might be the
Ni(I) species in this reaction. The Ni(I) may be generated in situ by
one-electron transfer of the in situ-generated Ni(0) species to the
haloarene12 following the reaction steps as shown in Scheme 1.
Combining previous studies13 with our experimental results, a
plausible mechanism is proposed that might follow a catalytic
cycle of the Ni(I)–Ni(III) shuttle involving sequential oxidative
addition, transmetallation and reductive elimination (Scheme 2).
This conclusion may partly explain the reasons why aryl chlorides
do not react under the conditions and there always existed a
considerable amount of biaryl by-product. The rate-determining
step of the reaction is unclear at present.
(1)
It was found that this reaction is quite different from most of
the nickel-catalyzed aromatic C–N couplings reported previously.
For instance, chloroarenes were inert in the reaction; the homo-
coupling of bromo-/iodoarenes producing biaryls occurred as a
major side reaction to a greater or lesser degree in almost all
cases; the conversion efficiencies increased with the increase of the
concentration of bromo-/iodoarenes; and the reaction proceeded
only in the presence of strong bases with reducing ability such
as sodium hydride, the Grignard reagent or the organolithium
reagent. To discern the mechanism of the reaction, we con-
ducted a stoichiometric reaction of sodium diphenylamide with
Scheme 1 A proposed route to in situ generation of the catalytically active
Ni(I) species.
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Table 2 Nickel-catalyzed arylation of diarylamines with haloarenesa
Entry Aryl bromide (iodide)
1
Diarylamine
Isolated yield (%)
88
2
3
90
no reaction
4
60
63
65
68
45
40
47
5
Scheme 2 A proposed mechanism for the arylation of diarylamines with
bromo-/iodoarenes catalyzed by the Ni(II)–(s-aryl) complex/PPh3/NaH
system.
6
7
In conclusion, we have once again demonstrated the possibility
of the nickel-catalyzed aromatic C–N coupling for triarylamine
synthesis. A preliminary investigation suggested that the mecha-
nism of this reaction might be different from that of the normal
nickel-catalyzed C–N couplings following a catalytic cycle of the
Ni(0)–Ni(II) shuttle. Meanwhile, this simple, practical protocol
for triarylamine synthesis functions, to a certain extent, as a
complement or alternative to the corresponding palladium and
copper catalyses, and further enhances the utility of Ni(II)–(s-aryl)
complexes as catalysts for the cross-coupling reactions. Studies are
underway in our laboratory to improve the reaction conditions for
expansion of the substrate scope as well as to detail information
on the mechanism of this reaction.
8
9
10
11
35
12
13
23b
0b
Experimental section
General procedure for the nickel-catalyzed arylation of
diarylamine with aryl halide
14
15
16
17
18
19
0b
85
87
61
63
29
An oven-dried 50-mL three-necked flask was charged with sodium
hydride (120 mg of 60% NaH in white oil, 3 mmol), Ni(PPh3)2(1-
naphthyl)Cl (74 mg, 5 mol % relative to diarylamine), and
PPh3 (52 mg, 10 mol% relative to diarylamine). The diarylamine
(2 mmol) and the aryl halide (3–4 mmol) were added at this time
if solid. The flask was evacuated and backfilled with nitrogen,
with the operation being repeated twice. Dried toluene (10 mL)
was added via syringe, followed by the aryl halide (4 mmol) if
◦
liquid. The reaction mixture was heated in an oil bath at 120 C
for 12 h. The reaction mixture was allowed to cool to room
temperature, quenched with H2O (20 mL), and filtered through a
pad of silica gel. The organic layer was separated and the aqueous
phase extracted with toluene (20 mL ¥ 2). Then the combined
organic phases were dried over anhydrous MgSO4 and filtered.
The filtrate was evaporated under reduced pressure and the residue
purified by column chromatography on silica gel with petroleum
ether to afford the analytically pure product in the isolated yields
indicated in Table 2.
a Reaction conditions◦: diarylamine (1 equiv), haloarenes (1.5–2 equiv),
NaH (1.5 equiv), 120 C, 12 h. b Aryl bromide was consumed completely.
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Triphenylamine (Table 2, entry 1)
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According to the general procedure, sodium hydride (120 mg of
60% NaH in white oil, 3 mmol), Ni(PPh3)2(1-naphthyl)Cl (74 mg,
5 mol %), PPh3 (52 mg, 10 mol%), diphenylamine (338 mg,
2 mmol), and bromobenzene (628 mg, 4 mmol) were transformed
into the product as a white solid (430 mg, 88%): mp 127–128 ◦C
◦
1
(lit.,14 mp 127 C). H NMR (CDCl3, 400 MHz): d 7.01 (t, J =
7.6 Hz, 3H), 7.10 (d, J = 7.6 Hz, 6H), 7.25 (t, J = 7.6 Hz, 6H);
MS (EI): m/z 245 (M+). CAS Number: 603-34-9.
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complex and sodium diphenylamide
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Under N2 atmosphere, to a solution of diphenylamine (1.2 mmol,
203 mg) in toluene (5 mL) was added sodium hydride (48 mg of
60% NaH in white oil, 1.2 mmol) at room temperature and the
mixture was stirred for 1 h. Then the nickel(II)–(s-aryl) complex
(1 mmol) was added to the reaction mixture, followed by heating
in an oil bath at 120 ◦C for 12 h. The reaction mixture was worked
up via the normal procedure and examined by TLC and GC-MS
techniques.
Acknowledgements
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The authors thank the National Natural Science Foundation of
China (Project Nos. 20672116 and 20872142) for financial support
of this work.
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This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 3922–3925 | 3925
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