CL-131075
Received: November 15, 2013 | Accepted: December 7, 2013 | Web Released: December 12, 2013
Silicon-based C-N Cross-coupling Reaction
Kenta Shimizu,1 Yasunori Minami,*2,3 Osamu Goto,4 Hideyuki Ikehira,5 and Tamejiro Hiyama*2,3
1Department of Applied Chemistry, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551
2Research and Development Initiative, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551
3JST, ACT-C, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551
4Tsukuba Research Laboratory, Sumitomo Chemical, 6 Kitahara, Tsukuba, Ibaraki 300-3294
5Organic Synthesis Research Laboratory, Sumitomo Chemical,
1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558
(E-mail: yminami@kc.chuo-u.ac.jp, thiyama@kc.chuo-u.ac.jp)
Palladium-catalyzed C-N bond-forming cross-coupling re-
action of N-trimethylsilylamines with aryl bromides and
chlorides is found to proceed in the presence of a fluoride
activator in 1,3-dimethyl-2-imidazolidinone (DMI), giving
triarylamines in excellent yields. When aryl bromide and
bis(silyl)amine were used in this reaction, double C-N bond-
forming products were obtained in high yields. The present
reaction was successfully applied to C-N bond-forming
polymerization.
Table 1. Cross-coupling reaction of aryl halides with N-
(trimethylsilyl)diphenylaminea
[Pd(dba)2] (1 mol%)
Xphos (2 mol%)
+
TMS NPh2
Ar NPh2
Ar
X
CsF (1.5 equiv)
DMI, 100 °C
1
2a
3
(1.1 equiv)
Entry
1
Ar
X
Time/h
3
Yield/%b
X
R
1
2
3
4
5
6
7
8
9
1a R = 4-Me
1¤a R = 4-Me
1b R = H
1c R = 4-MeO
1d R = 4-NMe2
1e R = 4-NPh2
Br
Cl
Br
Br
Br
Br
0.5
4
1
1
1
3aa
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
97
77
97
94
89
99
99
99
98
97
99
98
Arylamines are an important structural motif for various
pharmaceuticals, natural products, dyes, agrochemicals, and
functionalized polymers,1 and can be prepared straightforwardly
by the metal-catalyzed cross-coupling reaction of aryl halides or
pseudohalides with nitrogen nucleophiles.2,3 Particularly, the
Pd-catalyzed reaction, so-called Buchwald-Hartwig amination,2
is of great significance because of a straightforward approach
and better functional group compatibility. The reaction usually
requires strong bases for effective aromatic amination. Naturally,
base-sensitive functional groups cannot tolerate the presence of
such bases. In order to fulfill this drawback, milder reaction
conditions were developed: use of active catalyst systems4 and/
or weak bases5 and aqueous conditions.6 However, improvement
of nucleophilic nitrogen source has been largely absent since
stannylamines were applied by Migita, Kosugi, et al.7
3
1f R = 4-CO2Me Br
0.5
0.5
0.5
0.5
12
1
1g R = 4-PhCO
1h R = 4-CF3
1i R = 4-NO2
1j R = 2-Me
1k R = 3,5-Me2
X
Br
Br
Br
Br
Br
10
11
12
3ja
3ka
13
1l
Br
3
3la
94
X
14
1m
Br
1
3ma
99
Our group has studied silicon-based C-C bond-forming
cross-coupling reactions.8 These reactions proceed under mild
conditions since carbon nucleophiles are generated smoothly
by the reaction of organosilicon compounds with a fluoride
activator. The concept of organosilicon and fluoride activation to
generate active nucleophiles has been applied to C-N coupling
reaction with limited success. Barluenga and co-workers
reported cross-coupling reaction of aryl halides with silylal-
dimines to give N-arylated aldimines.9 Smith, Holmes, and co-
workers developed the reaction of aryl halides with silylamines
in supercritical carbon dioxide (scCO2).10 The latter is seminal.
However, the use of scCO2 limits its scope: substrates such as
monosilyl primary amines cannot be applicable as they react
with scCO2. Moreover, the reaction needs special pressure
bottles. Herein we report the Pd-catalyzed cross-coupling
reaction of aryl halides with silylamines under mild conditions
in 1,3-dimethyl-2-imidazolidinone (DMI).
aUnless otherwise noted, a mixture of 1 (0.50 mmol), 2a
(0.55 mmol), [Pd(dba)2] (5.0 ¯mol), Xphos (10 ¯mol), CsF
(0.75 mmol), and DMI (0.50 mL) were heated at 100 °C.
bIsolated yields.
(1 mol %), Xphos (2-dicyclohexylphosphino-2¤,4¤,6¤-triisopro-
pylbiphenyl)11 (2 mol %), and CsF (1.5 equiv) in DMI at
100 °C for 30 min gave diphenyl(p-tolyl)amine (3aa) in 97%
yield with the generation of TMS-F detected by gas chroma-
tography (Table 1, Entry 1). Other fluoride ion sources such as
TBAF and KF decreased the yield of 3aa.12 The reaction
conditions were applied to various aryl halides. Less reactive 4-
chlorotoluene (1¤a) also underwent the C-N coupling to form
3aa in 77% yield (Entry 2). On the contrary, the reaction using
4-iodotoluene resulted in 35% yield. Phenyl and electron-rich
aryl bromides having OMe, NMe2, and NPh2 groups on their
para-positions did not hamper the reaction to give correspond-
ing coupling products in excellent yields (Entries 3-6).
On the basis of the silicon-based cross-coupling reaction,
we examined the prototypical standard reaction conditions and
soon found that 4-bromotoluene (1a) coupled with N-(tri-
methylsilyl)diphenylamine (2a) in the presence of [Pd(dba)2]
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