Novel robust benzimidazolylidene palladium complexes: Synthesis, structure, and catalytic applications in amination of chloroarenes

Article abstract of DOI:10.1016/j.tet.2012.11.003

A series of novel pyridine stabilized PdeNHC complexes were developed, which revealed high activities and broad substrates tolerance in the amination of various (hetero)-aryl chlorides. Besides various secondary amines, a wide range of primary anilines and aliphatic amines were also well tolerated. The results highlight us a new strategy to increase catalyst activity in the future catalyst design by alternating the σ-donor property and flexibility of NHC ligands.

Full text of DOI:10.1016/j.tet.2012.11.003

Tetrahedron 69 (2013) 673e679
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Novel robust benzimidazolylidene palladium complexes: synthesis,
structure, and catalytic applications in amination of chloroarenes
*
Weiwei Fang, Jian Jiang, Yong Xu, Juefei Zhou, Tao Tu
Department of Chemistry, Fudan University, 220 Handan Road, 200433 Shanghai, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 August 2012
Received in revised form 23 October 2012
Accepted 2 November 2012
Available online 9 November 2012
A series of novel pyridine stabilized PdeNHC complexes were developed, which revealed high activities
and broad substrates tolerance in the amination of various (hetero)-aryl chlorides. Besides various
secondary amines, a wide range of primary anilines and aliphatic amines were also well tolerated. The
results highlight us a new strategy to increase catalyst activity in the future catalyst design by alternating
the s-donor property and flexibility of NHC ligands.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Amination
Benzimidazoles
Carbenes
Chloroarenes
Palladium
1. Introduction
elimination steps did speed up, which enhanced the catalytic ac-
tivity and improved yields. As the catalytic active species, Pd(0)
species played the crucial role in coupling process and the stability
of the Pd(0)ecarbon bond is considered as another key issue to
During the last several decades, significant efforts have been
devoted to the development of transition metal catalyzed cross-
coupling reactions,1 which implicated the fact that these re-
actions have been constituted as the most powerful and practical
protocols to construct carbonecarbon or carboneheteroatom
bonds. Until now, versatile catalytic systems based on Pd(II) com-
plexes have been reported,2 in which much attention was mainly
focused on developing ‘universal’ (robust, highly efficient, readily
prepared and tolerating broad substrate scopes) catalysts for the
transformation. In contrast with bulky tertiary monophosphines,3
N-heterocyclic carbenes (NHCs) represent a type of air, heat and
moisture stable as well as environmental friendly ligands, which
also exhibit much potential in Pd-catalyzed cross-coupling reac-
tions.2b,4 Since the first NHC was reported,5 the design, synthesis,
and catalytic application of novel NHCs have become a very active
and intriguing research field.6,7
influence the catalytic efficiency. Therefore, tuning s-donor prop-
erty of NHC may offer us another optional strategy to create more
robust and active PdeNHC complexes with steady metalecarbon
bonds.
Influenced by the ‘flexible steric bulky’ concept proposed by
Glorius,8 recently, Organ and co-workers developed a series of
pyridine stabilized NHCePd complexes 1 (Fig. 1), which demon-
strated high activity toward several CeC and CeN formation re-
actions, such as SuzukieMiyaura cross-coupling reactions,
aminations, and etc.2b By increasing steric bulky environment
around Pd center, the metalemetal exchange and the reductive
Fig. 1. A selection of palladiumeNHC complexes.
Along with our recent research on the synthesis of metal com-
plexes and their potential applications in catalysis and soft matter
aspects,9,10 we notified that the less intensive studied ylidenes
derived from benzimidazolium salts behave differently, which may
* Corresponding author. E-mail address: taotu@fudan.edu.cn (T. Tu).
be attributed to their stronger s-donor and weaker p-acceptor
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.003

674
W. Fang et al. / Tetrahedron 69 (2013) 673e679
properties.11 Therefore, pyridine stabilized benzimidazolylidene
palladium complexes 2 were proposed to verify our hypothesis:
besides the ‘flexible steric bulky’ environment around the catalytic
As a class of useful compounds, aryl amines have diverse ap-
plications in chemistry, pharmaceutical, and material science,14 it is
a very active and intriguing research field to develop ‘universal’
protocol to synthesize them. Although, palladium catalyzed ami-
nation reactions constitute as a powerful protocol for its high se-
lectivity, mild conditions, and broad substrate scopes, the efficient
catalyst is still rare especially for sluggish chloroarenes and espe-
cially for bulky substrates, nowadays which is still considered as
a challenging task. Therefore, the amination of a variety of chlor-
oarenes was selected to explore the catalytic activities of PdeNHC
4aec. Initially, the amination of chlorobenzene with morpholine
was picked as a model reaction to optimize the various reaction
conditions (Table 1). In the presence of t-BuOK and 2 mol %
PdeNHC complex 4a, the reactions proceeded well and similar
center, s-donor property of NHC ligands is another vital factor to
impact on the efficiency of the catalyst.11 Due to the steric hin-
drance between i-Pr groups and benzene ring, steric bulky NHCePd
complex 2, unfortunately, is hardly accessible, even after various
attempts.12 Alternatively, another two kinds of ylidenes derived
from other
benzimidazolium salts with benzyl type substitutions were se-
lected to study the influence of catalytic activity by tuning the
donor property of NHC ligands (Fig. 1). To our delight, the PdeNHC
complex 3 with a large -extended acenaphthoimidazolium ring
p-extended arylimidazolium salts or unsymmetrical
s
-
p
revealed extremely high catalytic activity in several cross-coupling
reactions even with a catalyst loading as low as 0.075 mol %.13 In
order to further confirm the concept and gain direct insight into the
Table 1
Condition screening and optimizationa
relationship between s-donor property and the steric environment
around Pd center, in this article, we synthesized novel complexes
4aec, and explored their structure properties and catalytic poten-
tials toward amination reactions.
Entry
[Cat.]
(mol %)
Solvent
T (ꢀC)
Yieldb (%)
2. Results and discussion
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4a
4b
4c
4a
4a
\
2
2
2
2
2
1
1
1
Dioxane
THF
DME
80
80
80
80
80
90
85
91
66c
93
84
98
82
60
88
20
10
By heating with PdCl2 and K2CO3 in neat 3-chloropyridine at
80 ꢀC, robust PdeNHC complexes 4aec were synthesized in good
yields from the corresponding unsymmetrical benzimidazolium
salts 5aec (Fig. 2), which were readily accessible in excellent yields
by the N-alkylation of the 2,6-diisopropyl-phenyl-benzimidazole
DME
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
80
100
100
100
100
100
100
9
1
10
11
12
0.5
0.1
\
a
1 mmol scale for 24 h.
Isolated yield.
With t-BuONa as a base.
b
c
isolated yields of product 6 were obtained when dioxane, DME and
THF were applied (85e91%, entries 1e3, Table 1). When t-BuONa
was used instead in DME, only a 66% yield was observed (entry 4,
Table 1). Other inorganic and organic bases, such as KOH, Cs2CO3,
Et3N, and DBU all fell out in unsatisfied yields (<46%, see
Supplementary data), which additionally confirmed that the choice
of base is critical for the transformation.2b,15 The best result (93%,
entry 5, Table 1) was obtained with nonpolar solvent toluene under
the identical reaction conditions with t-BuOK as base. Further re-
ducing the catalyst loading to 1 mol %, only an 84% yield was pre-
sented (entry 6, Table 1). To our delight, upon increasing the
reaction temperature to 100 ꢀC, the amination reaction went along
well and resulted in an excellent isolated yield (98%, entry 7, Table
1). When less bulky PdeNHC precatalysts 4b and 4c were applied,
slightly low yields were revealed (82% and 60%, entries 8 and 9,
Table 1). Further decreasing the catalyst loading to 0.5 and
0.1 mol %, 88% and 20% isolated yields were still observed (entries
10 and 11, Table 1) and suppressed the blank test (entry 12, Table 1).
In order to directly compare the catalytic activity of complex 4a
with other pioneering catalysts, the catalysts 1 and their allylic
analog as well as Buchwald’s bulky tertiary monophosphines were
involved the model reaction, and all revealed less effective activi-
ties than complex 4a under the optimal reaction condition (see
Supplementary data).
Fig. 2. Synthesis and structure of PdeNHCs 4aec.
with the corresponding substituted benzyl bromides (see
Supplementary data). By slow diffusion of petroleum ether into the
solution of complexes 4aec in dichloromethane, yellow needle
crystals were obtained, which were suitable for single crystal dif-
fraction analysis. The molecular structure of complex 4a was
depicted in Fig. 2 (for 4bec, see Supplementary data). In contrasted
with their imidazol-2-ylidene and acenaphtho-imidazol-2-ylidene
analogs (1 and 3), the space around the Pd centers of complexes
4aec is less congested, which may be aroused by the less bulky
methylene group attached to the benzimidazole ring. Whereas, the
methylene linker also offered another flexible means for substrates
easily approaching the Pd center, which is also a strategy to in-
crease the activity of the catalyst. Due to the size of substituted
groups (i-Pr, Me, and H) of the benzyl rings, the steric environment
of complex 4a is much more congested than what observed in
complexes 4b and 4c, and which may assist the reductive elimi-
nation step and concomitant regeneration Pd(0) to accelerate
cross-coupling reactions. From X-ray analysis, the bond distance of
ꢀ
PdeNCN in the complex 4a is 1.972(4) A, which is longer than what
we observed in the complex 313 and indicate the
s-donor property
With the optimized reaction condition in hand, the substrate
scope with various amines was then explored. As shown in Table 2,
the protocol well tolerates diverse electronic and steric substituents
on both sides of the reacting partners, as well as for heterocyclic
of the benzene ring is worse than that of the acenaphtho-ring. To
our surprise, the bond distance of PdeNCN in the complex 4b is
shortest among three complexes (4aec), which is 1.945(5) A and
ꢀ
may be influenced by the appropriate steric effect of Mes group.
substrates. When morpholine was utilized as a nucleophile,

W. Fang et al. / Tetrahedron 69 (2013) 673e679
675
Table 2
electron-donating groups are slightly more efficient than those
with electron-deficient groups (95e>99% vs 93%, 18, 20 and 21 vs
19). Spectacularly, satirically more hindered substrates, such as
2,4,6-trimethylaniline and 2,6-diisopropyl-aniline, were also well
tolerated and resulted in similar yields (48e96%, 22e27) even with
a catalyst loading down to 1 mol %. Furthermore, aliphatic primary
amines were also involved; again bulky amine resulted in a better
yield (85% vs 53%, 29 vs 28). Other steric bulkier substrates also
were exploited and good isolated yields (30 and 31, 86% and 70%)
were obtained.
Amination of chloroarenes with secondary aminesa
Table 3
Amination of chloroarenes with primary aminesa
H
N
H
N
H
N
H
N
a 1 mol % 4a, 1 mmol scale for 24 h.
b Isolated yield.
c With 2 mol % 4a.
O
F
16: 94%
17: 94%
19: 93%
18: >99%
d With 5 mol % 4a.
e Cs2CO3 with 2 mol % 4a.
H
N
H
N
H
N
H
N
a variety of (hetero)-chloroarenes was inspected, which all resulted
in good to excellent isolated yields (Table 2). The relative position of
substituents impacted the coupling efficiency; p-chlorotoluene
resulted in a slightly lower yield than its m-analog (7b vs 7c, 97% vs
89%); but even with 2 mol % PdeNHC complex 4a, only a 53% yield
of 7a was observed with the o-isomer. In the presence of 2.0 mol %
catalyst, similar moderate yields were obtained with p-chlor-
oanisole and p-piperidylchlorobenzene (8a and 8b, 64% and 65%).
Further increasing the catalyst loading to 5.0 mol %, the yield was
enhanced to 76%, which revealed that strong electron-donating
group slightly hampered the coupling process. To our delight,
electron-deficient, heterocyclic, and even bulky chloroarenes all
gave out good to excellent yields (9e11, 72e94%) indicating the
broad protocol applicability. With nitro group substituted chlor-
oarene, even weak base Cs2CO3 accelerated the amination reaction
of 4-chloronitro-benzene (9c, 72%). For sterically congested sub-
strate like 9-chloroanthracene, the amination also operated well to
produce 12 in a 77% yield.
d
d
23: 63%
20: 95%
21: 95%
22: 95%
H
N
H
N
H
N
H
N
X
c
25a: 83%(X = H)
d
c
d
d
24: 48%
25b: 12% (X = N)
27: 92%
26: 96%
H
N
H
N
H
N
H
N
O
O
e
30: 86%
29: 85%
31: 70%
28: 53%
a 1 mmol scale for 24 h, 5 mol % 4a.
b
Isolated yield.
c with 2 mol % 4a.
d with 1 mol % 4a.
e
with 9-bromoanthracene as a substrate.
In consideration of broad applications of fluorine containing
aromatic compounds in pharmaceuticals, pesticides, and functional
materials,16 p-chlorotrifluoromethylbenzene was selected for the
further substrate scope study. At first, N-methylpiperazine and N-
phenylpiperazine were selected as nucleophiles instead of mor-
pholine and resulted in 80% and 68% yields, respectively (13a and
13b). The ring size of cyclic amines affected coupling reactions
slightly; pyrrolidine, piperidine, and azepane all resulted in similar
good yields (71e84%, 14aec). Besides cyclic alkylamines, several
anilines with different electronic substituents were also involved,
and resulted in 92%, 91%, and 81% yields, respectively (15aec).
Due to their sluggish properties in the Pd-catalyzed amination
reactions, primary amines were regarded as rather poor substrates
in the previous reports, even with precatalysts like 1.2 Recently, we
revealed that PdeNHC complex 3 exhibited high activity toward
amination of a variety of chloroarenes with primary amines.13
Therefore, we would like to further evaluate the capability of the
new catalytic system of catalyst 4a with various primary amines
(Table 3). To our delight, under optimal conditions, the amination
by aniline proceeded very well and afforded compound 16 in a 94%
yield. The identical yield of compound 17 was achieved with o-
toluidine, indicating an inconspicuous stereo-electronic effect for
the protocol. Good to quantitative isolated yields (83e>99%) were
also observed with products 18e31, which further confirmed the
general capability of the catalyst 4a. The amination by anilines with
3. Conclusion
In summary, a series of pyridine stabilized PdeNHC catalysts
4aec were developed and complex 4a exhibited high activity in the
amination of various (hetero)-aryl chlorides. Besides various sec-
ondary amines, a wide range of primary anilines and aliphatic
amines were also well tolerated. Although, in comparison with
previous reported PdeNHC catalysts, the steric environment
around Pd center is less congested, by alternating the
s-donor
properties of benzimidazoles and flexibility of methylene group in
PdeNHC 4aec, the catalytic activity of the catalyst is also enhanced.
Further studies on the potential application of PdeNHC complexes
4aec in other related cross-coupling reactions are under in-
vestigation in our laboratory.
4. Experimental section
4.1. General
All commercial reagents were used directly without further
purification, unless otherwise stated. Dry N,N-dimethylformamide
(DMF), N,N-dimethylacetamide (DMA), and dimethyl-sulfoxide
(DMSO) were purchased from Alfa Aesar and Acros, stored over
ꢀ
4 A molecular sieves and handled under N2. Anhydrous methanol

676
W. Fang et al. / Tetrahedron 69 (2013) 673e679
(MeOH) and tert-butanol (t-BuOH) were distilled from anhydrous
calcium chloride prior to use. Tetrahydrofuran (THF) was distilled
from sodium/benzophenone prior to use. 1,2-Dimethoxy-ethane
(DME), 1,4-dioxane, and toluene were distilled from calcium hy-
dride prior to use. t-BuOK was purchased from Acros. 1H, 13C NMR
were recorded on Jeol ECA-400 and Bruker 400 DRX spectrome-
ters. GCeMS spectra were recorded on a Bruker micrOTOF II
instrument.
7.42 (d, J¼3.6 Hz, 2H), 7.24e7.20 (m, 1H), 6.99e6.98 (m, 1H),
6.91e6.80 (m, 2H), 6.59e6.54 (m, 2H), 6.46e6.25 (m, 1H),
3.64e3.57 (m, 2H), 3.98e2.94 (m, 1H), 2.92e2.79 (m, 2H), 1.42 (d,
J¼3.5 Hz, 6H), 1.33e1.00 (m, 18H), 0.83 (d, J¼4.4 Hz, 6H); 13C NMR
(CDCl3, 100 MHz, 298 K):
d
¼163.45, 151.59, 151.04, 150.60, 150.32,
150.05, 149.26, 148.07, 137.77, 134.02, 132.37, 131.50, 130.72, 125.29,
124.66, 123.05, 122.21, 121.74, 112.30, 50.37, 34.30, 29.78, 28.58,
28.48, 25.90, 24.58, 24.45, 24.04.
4.2. Synthesis of 1-(benzyl)-3-(2,6-diisopropylphenyl)-3H-
benzimidazolium bromide salts (5aec)
4.3.2. (Compound 4b). Yield: 63%. 1H NMR (CDCl3, 400 MHz,
298 K):
d
¼8.88 (d, J¼5.6 Hz, 1H), 8.77 (t, J¼4.4 Hz, 1H), 7.69 (d,
J¼8.0 Hz, 1H), 7.59 (t, J¼7.8 Hz, 1H), 7.42 (d, J¼8.0 Hz, 2H),
7.24e7.21 (m, 1H), 7.08e7.03 (m, 1H), 7.00e6.92 (m, 3H), 6.86 (t,
J¼7.2 Hz, 1H), 6.61e6.51 (m, 1H), 6.46e6.43 (m, 2H), 2.90e2.74 (m,
2H), 2.40 (s, 6H), 2.35 (s, 3H), 1.41 (d, J¼6.4 Hz, 6H), 0.87 (t,
According to the literature,17 to the solution of 1-(2,6-
diisopropylphenyl)-1H-benzimidazole (2.43 g, 8.7 mmol) in
20 mL EtOAc, 2-(bromomethyl)-1,3,5-triisopropylbenzene (2.53 g,
8.7 mmol) was added, the resulting mixture was stirred at room
temperature for 24 h, then at 60 ꢀC for another 12 h until the re-
action was completed (monitored by TLC). After cooling to the room
temperature, the mixture was filtered and washed with Et2O to
afford the salt 5a as a white solid 4.28 g.
J¼6.4 Hz, 6H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼163.71, 151.50,
d
150.97, 150.49, 150.26, 149.96, 148.82, 148.03, 147.46, 138.50,
137.71, 135.79, 133.60, 132.26, 131.39, 130.70, 129.70, 127.70, 124.62,
124.30, 123.41, 122.47, 112.34, 111.55, 51.81, 28.65, 25.94, 24.44,
24.07, 21.04, 20.82.
4.2.1. (Compound 5a). Yield: 86%, 1H NMR (CDCl3, 400 MHz,
4.3.3. (Compound 4c). Yield: 73%. 1H NMR (CDCl3, 400 MHz,
298 K):
d
¼10.89 (s, 1H), 7.63 (t, J¼10.6 Hz, 1H), 7.56e7.47 (m, 2H),
298 K):
d
¼8.88 (s, 1H), 8.87 (d, J¼4.0 Hz, 1H), 7.67 (d, J¼6.8 Hz, 3H),
7.42 (t, J¼10.4 Hz, 3H), 7.18 (d, J¼10.6 Hz, 1H), 7.13 (s, 2H), 6.48 (s,
2H), 3.32 (sept, J¼8.8 Hz, 2H), 2.94 (sept, J¼9.4 Hz, 1H), 2.15 (sept,
J¼9.0 Hz, 2H), 1.28 (t, J¼8.2 Hz, 12H), 1.18 (d, J¼8.8 Hz, 12H), 1.03 (d,
7.61 (t, J¼7.6 Hz, 1H), 7.43 (t, J¼7.6 Hz, 4H), 7.36 (t, J¼7.6 Hz, 1H),
7.23e7.12 (m, 4H), 6.92e6.88 (m, 1H), 6.45e6.43 (m, 2H), 2.93e2.76
(m, 2H), 1.42 (d, J¼6.4 Hz, 6H), 0.90e0.88 (m, 6H); 13C NMR (CDCl3,
J¼9.2 Hz, 6H); 13C NMR (CDCl3, 100 MHz, 298 K):
d
¼151.20, 148.83,
100 MHz, 298 K):
d
¼164.63, 151.65, 151.11, 150.66, 150.38, 150.12,
146.14, 141.79, 133.37, 132.20, 131.16, 127.93, 127.70, 127.05, 124.99,
122.15,122.04,115.48,112.77, 47.12, 34.14, 29.91, 28.73, 24.53, 24.20,
23.86, 23.72.
149.39, 148.30, 137.96, 135.21, 133.51, 132.44, 131.42, 130.95, 129.11,
128.36, 128.18, 124.82, 123.72, 123.02, 112.66, 111.77, 54.65, 28.75,
26.28, 24.68, 24.23.
4.2.2. (Compound 5b). Yield: 85%, 1H NMR (CDCl3, 400 MHz,
298 K):
d
¼11.53 (s,1H), 7.63 (t, J¼7.8 Hz,1H), 7.54e7.45 (m, 2H), 7.41
4.4. General procedure for Pd-catalyzed amination12
(d, J¼8.0 Hz, 2H), 7.27 (t, J¼4.0 Hz, 1H), 7.19 (d, J¼8.0 Hz,1H), 6.94 (s,
2H), 6.47 (s, 2H), 2.41 (s, 6H), 2.31 (s, 3H), 2.17 (sept, J¼6.8 Hz, 2H),
1.27 (d, J¼6.8 Hz, 6H), 1.05 (d, J¼6.8 Hz, 6H); 13C NMR (CDCl3,
To a 50 mL Schlenk tube containing base (1.5 mmol) and pre-
catalyst 4a (1 mol %, 0.0083 g) purged with N2 (three times), amine
(1.2 mmol) was added via syringe, and the resulted mixture was
allowed to stir at room temperature for 2e3 min. Solvent (1 mL)
was then injected via syringe followed by the aryl chloride
(1.0 mmol). If the aryl chloride was a solid, it was introduced into
the vial prior to purging with N2. At this time, the reaction was
stirred for 24 h at 100 ꢀC. After cooling to the room temperature, the
reaction mixture was concentrated in vacuo and directly purified
via silica gel flash chromatography.
100 MHz, 298 K):
d
¼146.07, 142.95, 142.84, 139.29, 139.60, 133.23,
132.10, 130.63, 130.02, 127.85, 127.71, 127.00, 125.35, 124.88, 114.58,
112.82, 48.43, 28.74, 24.71, 23.45, 20.83, 20.05.
4.2.3. (Compound 5c). Yield: 72%. 1H NMR (CDCl3, 400 MHz,
298 K):
d
¼11.64 (s, 1H), 7.82 (d, J¼8.0 Hz, 1H), 7.66e7.55 (m, 5H),
7.41e7.34 (m, 5H), 7.30 (d, J¼8.4 Hz, 1H), 6.39 (s, 2H), 2.14 (sept,
J¼6.4 Hz, 2H), 1.27 (d, J¼6.8 Hz, 6H), 1.03 (d, J¼6.8 Hz, 6H); 13C NMR
(CDCl3, 100 MHz, 298 K):
d¼146.05, 142.77, 133.22, 132.95, 132.01,
130.45, 129.03, 128.83, 128.20, 127.89, 127.69, 127.12, 124.80, 114.34,
112.78, 50.98, 28.66, 24.60, 23.39.
4.4.1. 4-Phenylmorpholine (6). 1H NMR (CDCl3, 400 MHz, 298 K):
d
¼7.32e7.27 (m, 2H), 6.93 (d, J¼8.4 Hz, 2H), 6.89 (t, J¼7.2 Hz, 1H),
3.87 (t, J¼4.8 Hz, 4H), 3.17 (t, J¼4.8 Hz, 4H); 13C NMR (CDCl3,
4.3. Synthesis of pyridine-stabilized palladiumeNHC com-
plexes (4aec)
100 MHz, 298 K):
d
¼151.11, 139.03, 119.86, 115.54, 66.78, 49.18;
GCeMS: tR¼12.517 min, m/z¼163.1 [M]þ, 163.1, 132.0, 77.0, 51.0.
According to the similar literature,12 3-chloropyridine (10.0 mL)
was added to a Schlenk tube containing PdCl2 (532 mg, 3.0 mmol),
5a (1.73 g, 3.0 mmol), K2CO3 (2.07 g, 15.0 mmol) and a stirrer bar.
The reaction mixture was heated with vigorous stirring for 16 h at
80 ꢀC. After cooling to room temperature, the reaction mixture was
diluted with CH2Cl2 and passed through a short pad of silica gel
covered with a pad of Celite eluting with CH2Cl2 until the product
was completely recovered. Most of the CH2Cl2 was removed (rotary
evaporator), and the 3-chloropyridine was then distilled (under
water aspirator vacuum) and saved for reuse. Pure complex 4a was
isolated after triturating with pentane, decanting of the superna-
tant and drying in high vacuum to afford 2.31 g solid.
4.4.2. 4-(o-Tolyl)morpholine (7a). 1H NMR (CDCl3, 400 MHz,
298 K):
J¼7.2 Hz, 1H), 3.86 (t, J¼4.4 Hz, 4H), 2.92 (t, J¼4.4 Hz, 4H), 2.33 (s,
3H); 13C NMR (CDCl3, 100 MHz, 298 K):
d
¼7.20 (t, J¼7.2 Hz, 2H), 7.04 (d, J¼7.2 Hz, 1H), 7.01 (d,
d
¼151.20, 132.53, 131.09,
126.59, 123.33, 118.87, 67.38, 52.17, 17.79; GCeMS: tR¼12.528 min,
m/z¼177.1 [M]þ, 177.1, 132.0, 91.1, 65.0.
4.4.3. 4-(m-tolyl)morpholine (7b). 1H NMR (CDCl3, 400 MHz, 298
K):
(m, 4H), 2.38 (s, 3H); 13C NMR (CDCl3, 100 MHz, 298 K):
138.68, 128.87, 120.80, 116.38, 112.72, 66.81, 49.30, 21.64.
d
]7.22 (t, J]7.2 Hz, 1H), 6.79e6.77 (m, 3H), 3.89 (m, 4H), 3.18
d]151.22,
4.4.4. 4-(p-Tolyl)morpholine (7c). 1H NMR (CDCl3, 400 MHz, 298 K):
4.3.1. (Compound 4a). Yield: 93%. 1H NMR (CDCl3, 400 MHz,
d
¼7.09 (d, J¼8.4 Hz, 2H), 6.84 (d, J¼8.0 Hz, 2H), 3.86 (t, J¼4.8 Hz,
298 K):
d¼8.92 (s, 1H), 8.81 (s,1H), 7.66 (s,1H), 7.58 (t, J¼7.2 Hz,1H),
4H), 3.11 (t, J¼4.8 Hz, 4H), 2.28 (s, 3H); 13C NMR (CDCl3, 100 MHz,

W. Fang et al. / Tetrahedron 69 (2013) 673e679
677
298 K):
d
¼149.02, 129.51, 129.22, 115.82, 66.75, 49.68, 20.25;
400 MHz, 298 K):
d
¼ꢁ61.18; GCeMS: tR¼17.769 min, m/z¼244.1
GCeMS: tR¼13.381 min, m/z¼177.1 [M]þ, 177.1, 146.1, 91.1, 65.0.
[M]þ, 244.0, 173.0, 145.0, 71.0.
4.4.5. 4-(4-Methoxyphenyl)morpholine (8a). 1H NMR (CDCl3,
4.4.15. 1-Phenyl-4-(4-(trifluoromethyl)phenyl)piperazine (13b). 1H
400 MHz, 298 K):
d
¼6.90e6.84 (m, 4H), 3.85 (t, J¼4.6 Hz, 4H), 3.77
NMR (CDCl3, 400 MHz, 298 K):
d
¼7.56 (d, J¼8.0 Hz, 2H), 7.36 (t,
(s, 3H), 3.05 (t, J¼4.6 Hz, 4H); 13C NMR (CDCl3, 100 MHz, 298 K):
J¼7.0 Hz, 2H), 7.04e6.95 (m, 5H), 3.46 (t, J¼3.2 Hz, 4H), 3.38 (t,
d¼153.84, 145.52, 117.67, 114.37, 66.91, 55.36, 50.63.
J¼2.8 Hz, 4H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼153.16, 150.99,
d
129.21, 126.40, 123.37, 120.85, 120.53, 120.25, 116.35, 114.68, 49.11,
4.4.6. 4-(4-(Piperidin-1-yl)phenyl)morpholine (8b). 1H NMR (CDCl3,
48.07; 19F NMR (CDCl3, 400 MHz, 298 K):
d
¼ꢁ61.12; GCeMS:
400 MHz, 298 K):
d¼6.94e6.86 (m, 4H), 3.85 (t, J¼4.2 Hz, 4H),
tR¼27.955 min, m/z¼306.1 [M]þ, 305.9, 172.9, 90.9, 76.9.
3.06e3.02 (m, 8H), 1.72 (t, J¼4.2 Hz, 4H), 1.58e1.52 (m, 2H); 13C
NMR (CDCl3, 100 MHz, 298 K):
66.84, 51.66, 50.33, 25.88, 24.03.
d
¼146.52, 144.77, 118.02, 117.01,
4.4.16. 1-(4-(Trifluoromethyl)phenyl)pyrrolidine (14a). 1H NMR
(CDCl3, 400 MHz, 298 K):
d
¼7.43 (d, J¼8.8 Hz, 2H), 6.54 (d, J¼8.8 Hz,
2H), 3.32 (t, J¼6.6 Hz, 4H), 2.03 (q, J¼3.2 Hz, 4H); 13C NMR (CDCl3,
4.4.7. 4-(4-Fluorophenyl)morpholine
(9a). 1H
NMR
(CDCl3,
100 MHz, 298 K):
d
¼149.74, 126.35, 124.04, 116.68, 116.35, 110.80,
400 MHz, 298 K):
d
¼6.98 (d, J¼8.4 Hz, 2H), 6.92 (d, J¼8.8 Hz, 2H),
47.45, 25.39; 19F NMR (CDCl3, 400 MHz, 298 K):
d¼ꢁ60.42; GCeMS:
3.86 (t, J¼4.8 Hz, 4H), 3.08 (t, J¼4.8 Hz, 4H); 13C NMR (CDCl3,
tR¼16.202 min, m/z¼215.1 [M]þ, 214.0, 158.9, 144.9.
100 MHz, 298 K):
d
¼158.37, 155.99, 147.83, 117.35, 115.49, 66.79,
50.19; 19F NMR (CDCl3, 400 MHz, 298 K):
d
¼ꢁ124.12; GCeMS:
4.4.17. 1-(4-(Trifluoromethyl)phenyl)piperidine (14b). 1H NMR (CDCl3,
tR¼11.216 min, m/z¼181.0 [M]þ, 181.0, 109.0, 95.0, 75.0.
400 MHz, 298 K):
d
¼7.46 (d, J¼8.4 Hz, 2H), 6.92 (d, J¼8.4 Hz, 2H), 3.27
(t, J¼4.8 Hz, 4H), 1.69e1.63 (m, 6H); 13C NMR (CDCl3, 100 MHz,
4.4.8. 4-(4-(Trifluoromethyl)phenyl)morpholine
(9b). 1H
NMR
298 K):
d
¼153.79, 126.28, 123.56, 119.60, 119.28, 114.52, 49.23, 25.38,
(CDCl3, 400 MHz, 298 K):
d¼7.50 (d, J¼8.8 Hz, 2H), 6.92 (d, J¼8.8 Hz,
24.23; 19F NMR (CDCl3, 400 MHz, 298 K):
d¼ꢁ61.06; GCeMS:
2H), 3.86 (t, J¼4.8 Hz, 4H), 3.23 (t, J¼4.8 Hz, 4H); 13C NMR (CDCl3,
tR¼16.379 min, m/z¼229.1 [M]þ, 228.1, 210.1, 188.0, 172.0, 145.0.
100 MHz, 298 K):
d
¼153.29, 126.31, 126.00, 123.31, 120.89, 120.57,
114.16, 66.49, 47.97; 19F NMR (CDCl3, 400 MHz, 298 K):
d
¼ꢁ61.28;
4.4.18. 1-(4-(Trifluoromethyl)phenyl)azepane (14c). 1H NMR (CDCl3,
GCeMS: tR¼16.757 min, m/z¼231.1 [M]þ, 231.1, 173.1, 145.0.
400 MHz, 298 K):
d
¼7.41 (d, J¼8.8 Hz, 2H), 6.68 (d, J¼8.8 Hz, 2H),
3.48 (t, J¼5.8 Hz, 4H), 1.80e1.78 (m, 4H), 1.56e1.53 (m, 4H); 13C
4.4.9. 4-(4-Nitrophenyl)morpholine (9c). 1H NMR (CDCl3, 400 MHz,
NMR (CDCl3, 100 MHz, 298 K):
d
¼150.93, 126.51, 123.96, 116.56,
298 K):
d
¼8.14 (d, J¼9.6 Hz, 2H), 6.83 (d, J¼9.6 Hz, 2H), 3.86 (t,
116.25, 110.29, 49.15, 27.29, 26.87; 19F NMR (CDCl3, 400 MHz,
J¼4.8 Hz, 4H), 3.37 (t, J¼4.8 Hz, 4H); 13C NMR (CDCl3, 100 MHz,
298 K):
214.1, 172.0, 159.0, 145.0.
d
¼ꢁ60.51; GCeMS: tR¼19.280 min, m/z¼243.1 [M]þ, 243.1,
298 K):
d
¼154.87, 138.69, 125.74, 112.47, 66.21, 46.92; GCeMS:
tR¼17.403 min, m/z¼208.1 [M]þ, 207.9, 149.9, 119.9, 77.0, 51.0.
4.4.19. N-Methyl-N-phenyl-4-(trifluoromethyl)aniline (15a). 1H NMR
4.4.10. 4-(Pyridin-2-yl)morpholine (10a). 1H NMR (CDCl3, 400 MHz,
(CDCl3, 400 MHz, 298 K):
d
¼7.46e7.39 (m, 4H), 7.23e7.19 (m, 3H),
298 K):
d
¼8.19 (d, J¼4.0 Hz, 1H), 7.49 (t, J¼8.8 Hz, 1H), 7.01
6.87 (d, J¼8.8 Hz, 2H), 3.37 (s, 3H); 13C NMR (CDCl3, 100 MHz,
(t, J¼7.2 Hz, 2H), 3.82 (t, J¼4.8 Hz, 4H), 3.49 (t, J¼4.8 Hz, 4H); 13C NMR
298 K):
d
¼151.48, 147.70, 129.77, 126.18, 125.28, 124.94, 123.55,
(CDCl3, 100 MHz, 298 K):
d¼159.39, 147.73, 137.35, 113.63, 106.78,
119.98, 119.66, 114.75, 40.09; 19F NMR (CDCl3, 400 MHz, 298 K):
66.54, 45.40; GCeMS: tR¼12.728 min, m/z¼164.0 [M]þ,164.0,133.0,
d
¼ꢁ60.99; GCeMS: tR¼18.868 min, m/z¼250.1 [M]þ, 251.2, 167.1,
119.0, 107.0, 51.0.
145.0, 77.0.
4.4.11. 4-(4-methylquinolin-2-yl)morpholine (10b). 1H NMR (CDCl3,
4.4.20. N,4-Dimethyl-N-(4-(trifluoromethyl)phenyl)aniline (15b). 1H
400 MHz, 298 K):
d
]7.73e7.68 (m, 2H), 7.50 (dt, J]1.6 Hz, J]8.4
NMR (CDCl3, 400 MHz, 298 K):
J¼8.0 Hz), 7.12 (d, J¼8.4 Hz, 2H), 6.80 (d, J¼8.8Hz, 2H), 3.34 (s, 3H),
2.40 (s, 3H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼151.66, 145.10,
135.17,130.45,126.10,125.89,123.64,119.12,113.78, 40.16, 20.91; 19F
d
¼7.43 (d, J¼8.8 Hz, 2H), 7.23 (d,
Hz, 1H), 7.20 (dt, J]1.2 Hz, J]8.2 Hz, 1H), 6.68 (s, 1H), 3.75 (t, J]4.8
Hz, 4H), 3.60 (t, J]4.8 Hz, 4H), 2.50 (s, 3H); 13C NMR (CDCl3, 100
d
MHz, 298 K):
d]157.00, 147.37, 144.83, 128.98, 126.90, 123.31,
123.18, 122.06, 109.26, 66.52, 45.16, 18.87.
NMR (CDCl3, 400 MHz, 298 K):
d¼ꢁ60.91; GCeMS: tR¼20.453 min,
m/z¼265.1 [M]þ, 265.1, 145.0, 91.1.
4.4.12. 4-(Naphthalen-1-yl)morpholine (11). 1H NMR (CDCl3,
400 MHz, 298 K):
(m, 4H), 7.12 (d, J¼7.2 Hz,1H), 4.02 (t, J¼4.8 Hz, 4H), 3.14 (t, J¼4.8 Hz,
4H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼149.19, 134.58, 128.56,
128.26, 125.64, 125.21, 123.53, 123.19, 114.46, 114.37, 67.17, 53.22.
d
¼8.35e8.28 (m,1H), 7.92e7.85 (m,1H), 7.65e7.43
4.4.21. 4-Fluoro-N-methyl-N-(4-(trifluoromethyl)-phenyl)-aniline
(15c). 1H NMR (CDCl3, 400 MHz, 298 K):
d
¼7.41 (d, J¼8.8 Hz, 2H),
7.18e7.15 (m, 2H), 7.12e7.08 (m, 2H), 6.75 (d, J¼8.8 Hz, 2H), 3.31 (s,
3H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼161.50, 159.06, 151.59,
143.73, 127.87, 126.25, 126.15, 123.58, 119.68, 119.36, 116.62, 113.85,
d
d
4.4.13. 4-(Anthracen-9-yl)morpholine
400 MHz, 298 K):
(12). 1H NMR (CDCl3,
¼8.56 (d, J¼8.8 Hz, 2H), 8.34 (s, 1H), 8.03 (d,
113.78, 40.23; 19F NMR (CDCl3, 400 MHz, 298 K):
d
¼ꢁ60.99, ꢁ116.34;
d
GCeMS: tR¼18.879 min, m/z¼269.1 [M]þ, 269.1, 185.1, 145.0, 95.0.
J¼8.0 Hz, 2H), 7.53e7.46 (m, 4H), 4.06 (t, J¼4.2 Hz, 4H), 3.54 (t,
J¼4.2 Hz, 4H); 13C NMR (CDCl3, 100 MHz, 298 K):
d
¼143.37, 132.49,
4.4.22. 2,6-Dimethyl-N-phenylaniline
(16). 1H
NMR
(CDCl3,
130.44, 128.95, 125.30, 125.23, 125.06, 124.48, 68.41, 51.60; GCeMS:
tR¼19.658 min, m/z¼263.1 [M]þ, 263.0, 204.0, 176.0, 88.0.
400 MHz, 298 K):
d
¼7.14e7.07 (m, 5H), 6.71 (t, J¼6.8 Hz, 1H), 6.47
(d, J¼7.6 Hz, 2H), 5.09 (br s, 1H), 2.18 (s, 6H); 13C NMR (CDCl3,
100 MHz, 298 K):
118.08, 113.41, 18.28.
d
¼146.19, 138.14, 135.84, 129.16, 128.47, 125.68,
4.4.14. 1-Methyl-4-(4-(trifluoromethyl)phenyl)piperazine (13a). 1H
NMR (CDCl3, 400 MHz, 298 K):
J¼8.4 Hz, 2H), 3.29 (t, J¼4.4 Hz, 4H), 2.56 (t, J¼4.4 Hz, 4H), 2.35 (s,
3H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼153.20, 126.28, 123.36,
120.45, 120.12, 114.39, 54.71, 47.80, 46.01; 19F NMR (CDCl3,
d
¼7.47 (d, J¼8.4 Hz, 2H), 6.92 (d,
4.4.23. 2,6-Dimethyl-N-(o-tolyl)aniline (17). 1H NMR (CDCl3,
d
400 MHz, 298 K): ¼7.28e7.22 (m, 4H), 7.15e7.05 (m,1H), 6.88e6.80
d
(m, 1H), 6.33e6.25 (m, 1H), 5.04 (br s, 1H), 2.46 (s, 3H), 2.33 (s, 6H);

678
W. Fang et al. / Tetrahedron 69 (2013) 673e679
13C NMR (CDCl3, 100 MHz, 298 K):
128.48, 126.86, 125.48, 122.32, 118.03, 111.64, 18.16, 17.58.
d
¼114.05, 138.67, 135.46, 130.18,
128.74, 128.34, 120.91, 20.55, 19.06, 18.96; GCeMS: tR¼16.270 min,
m/z¼239.1 [M]þ, 239.1, 222.1, 208.1, 132.0, 120.0.
4.4.24. N-(4-Methoxyphenyl)-2,6-dimethylaniline (18). 1H NMR
4.4.34. N-(2,6-Diisopropylphenyl)-2,6-dimethylaniline (27). 1H NMR
(CDCl3, 400 MHz, 298 K):
2H), 6.51 (d, J¼8.8 Hz, 2H), 5.03 (br s, 1H), 3.76 (s, 3H), 2.21 (s, 6H);
13C NMR (CDCl3, 100 MHz, 298 K):
d
¼7.13e7.03 (m, 3H), 6.77 (d, J¼8.8 Hz,
(CDCl3, 400 MHz, 298 K):
d
¼7.18e7.11 (m, 3H), 6.95 (d, J¼7.6 Hz,
2H), 6.74 (t, J¼7.4 Hz, 1H), 4.81 (br s, 1H), 3.20e3.13 (m, 2H), 1.99 (s,
d¼152.66, 140.06, 139.20, 134.83,
6H), 1.13 (d, J¼6.8 Hz, 12H); 13C NMR (CDCl3, 100 MHz, 298 K):
128.53, 124.97, 115.20, 114.65, 55.61, 18.31.
d
¼144.07, 143.08, 138.74, 129.48, 125.57, 124.81, 123.20, 119.59,
28.00, 23.44,19.31; GCeMS: tR¼16.556 min, m/z¼281.2 [M]þ, 281.3,
4.4.25. N-(4-Fluorophenyl)-2,6-dimethylaniline
(19). 1H
NMR
236.2, 208.1, 196.1.
(CDCl3, 400 MHz, 298 K):
d
¼7.10e7.03 (m, 3H), 6.83 (t, J¼7.8 Hz,
2H), 6.41 (t, J¼4.1 Hz, 2H), 5.05 (br s, 1H), 2.17 (s, 6H); 13C NMR
4.4.35. N-Cyclohexyl-2,6-dimethylaniline (28). 1H NMR (CDCl3,
(CDCl3, 100 MHz, 298 K):
d
¼157.38, 155.04, 142.45, 138.51, 135.45,
400 MHz, 298 K):
d
¼7.02 (d, J¼7.6 Hz, 2H), 6.83 (t, J¼7.6 Hz, 1H),
128.61, 125.61, 115.60, 114.43, 18.23; 19F NMR (CDCl3, 400 MHz,
298 K):
¼ꢁ126.83.
3.04e2.97 (m, 1H), 2.92 (br s, 1H), 2.31 (s, 6H), 2.05e1.98 (m, 2H),
d
1.81e1.76 (m, 2H), 1.69e1.64 (m, 1H), 1.35e1.11 (m, 6H); 13C NMR
(CDCl3, 100 MHz, 298 K):
34.94, 25.94, 25.54, 18.98.
d
¼145.08, 128.92, 128.67, 121.03, 56.13,
4.4.26. N-(4-Isopropylphenyl)-2,6-dimethylaniline (20). 1H NMR
(CDCl3, 400 MHz, 298 K):
¼7.08e6.98 (m, 5H), 6.42 (d, J¼7.2 Hz,
2H), 5.03 (br s, 1H), 2.78 (m, 1H), 2.18 (s, 6H), 1.19 (d, J¼6.8 Hz, 6H);
13C NMR (CDCl3, 100 MHz, 298 K):
d
4.4.36. N-(2,6-dimethylphenyl)adamantan-1-amine (29). 1H NMR
(CDCl3, 400 MHz, 298 K):
¼7.10e7.04 (m, 2H), 6.98e6.92 (m, 1H),
d¼143.99, 138.70, 138.61, 135.40,
d
128.45, 126.95, 125.29, 113.66, 33.08, 24.16, 18.37.
2.70 (br s, 1H), 2.42 (s, 6H), 2.15e2.05 (m, 3H), 1.86e1.80 (m, 6H),
1.70e1.62 (m, 6H); 13C NMR (CDCl3, 100 MHz, 298 K):
134.61, 128.24, 122.86, 55.41, 44.27, 36.33, 30.01, 20.57.
d¼142.95,
4.4.27. N-(3,5-Dimethylphenyl)-2,6-dimethylaniline (21). 1H NMR
(CDCl3, 400 MHz, 298 K):
2H), 5.03 (br s, 1H), 2.21e2.15 (m, 12H); 13C NMR (CDCl3, 100 MHz,
298 K):
d
¼7.12e7.03 (m, 3H), 6.39 (s, 1H), 6.12 (s,
4.4.37. N-(4-Methoxyphenyl)naphthalen-1-amine (30). 1H NMR
(CDCl3, 400 MHz, 298 K):
d
¼146.16, 138.80, 138.37, 135.76, 128.42, 125.48, 120.18,
d
¼7.96 (d, J¼8.0 Hz, 1H), 7.82 (d, J¼5.2 Hz,
111.34, 21.40, 18.36.
1H), 7.47e7.41 (m, 3H), 7.30 (t, J¼8.0 Hz, 1H), 7.08 (d, J¼7.6 Hz, 1H),
7.02 (d, J¼8.8 Hz, 2H), 6.85 (d, J¼8.8 Hz, 2H); 13C NMR (CDCl3,
4.4.28. 2,4,6-Trimethyl-N-(o-tolyl)aniline (22). 1H NMR (CDCl3,
100 MHz, 298 K):
125.95, 125.28, 121.78, 121.03, 120.84, 114.71, 111.64, 55.54.
d
¼155.01, 140.84, 136.83, 134.56, 128.53, 126.12,
400 MHz, 298 K):
(t, J¼7.4 Hz, 1H), 6.15 (d, J¼8.0 Hz, 1H), 4.87 (br s, 1H), 2.33e2.32 (m,
6H), 2.16 (s, 6H); 13C NMR (CDCl3, 100 MHz, 298 K):
d
¼7.13 (d, J¼7.2 Hz, 1H), 6.99e6.96 (m, 3H), 6.69
d
¼144.02,
4.4.38. N-(4-methoxyphenyl)anthracen-9-amine (31). 1H NMR
(CDCl3, 400 MHz, 298 K): d]8.34 (s,1H), 8.18 (d, J]8.4 Hz, 2H), 8.04
135.93, 135.53, 135.05, 130.12, 129.15, 126.88, 121.94, 117.67, 111.29,
20.84, 18.02, 17.52; GCeMS: tR¼22.130 min, m/z¼225.2 [M]þ, 225.2,
208.1, 194.1, 121.1.
(d, J]8.4 Hz, 2H), 7.49e7.41 (m, 4H), 6.73 (d, J]8.8 Hz, 2H), 6.56 (d,
J ]8.8Hz, 2H), 5.92 (br s, 1H), 3.72 (s, 3H); 13C NMR (CDCl3, 100
MHz, 298 K):
125.39, 124.65, 123.76, 115.32, 114.79, 55.66.
d]152.80, 141.98, 132.26, 128.75, 128.60, 125.69,
4.4.29. 2,4,6-Trimethyl-N-(m-tolyl)aniline (23). 1H NMR (CDCl3,
400 MHz, 298 K):
J¼7.6 Hz, 1H), 6.46e6.41 (m, 2H), 5.14 (br s, 1H), 2.45 (s, 3H), 2.38 (s,
3H), 2.32 (s, 6H); 13C NMR (CDCl3, 100 MHz, 298 K):
138.91, 135.85, 135.56, 135.17, 129.11, 129.01, 118.76, 113.86, 110.32,
21.51, 20.85, 18.19.
d
¼7.16 (t, J¼7.6 Hz, 1H), 7.08 (s, 2H), 6.69 (d,
Acknowledgements
d
¼146.56,
Financial support from the National Natural Science Foundation
of China (No. 21172045 and 20902011), the Changjiang Scholars
and Innovative Research Team in University (IRT1117), the Shanghai
Leading Academic Discipline Project (B108), and Department of
Chemistry, Fudan University is gratefully acknowledged.
4.4.30. 2,4,6-Trimethyl-N-(p-tolyl)aniline (24). 1H NMR (CDCl3,
400 MHz, 298 K):
(br s, 1H), 2.44 (s, 3H), 2.38 (s, 3H), 2.31 (s, 6H); 13C NMR (CDCl3,
100 MHz, 298 K):
d
¼7.10e7.07 (m, 4H), 6.55 (d, J¼8.0 Hz, 2H), 5.11
d
¼144.20, 135.89, 135.57, 134.95, 129.66, 129.12,
Supplementary data
126.96, 113.35, 20.83, 20.37, 18.16.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.11.003.
4.4.31. 2,4,6-Trimethyl-N-phenylaniline (25a). 1H NMR (CDCl3,
400 MHz, 298 K):
J¼7.0 Hz, 1H), 6.47 (d, J¼7.6 Hz, 2H), 5.06 (br s, 1H), 2.29 (s, 3H), 2.16
(s, 6H); 13C NMR (CDCl3, 100 MHz, 298 K):
¼146.60, 135.92, 135.48,
135.34, 129.17, 117.82, 113.20, 20.88, 18.20.
d
¼7.13 (t, J¼7.6 Hz, 2H), 6.93 (s, 2H), 6.71 (t,
References and notes
d
1. Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich, F.,
Eds.; Wiley-VCH: Weinheim, 2004.
2. (a) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (b) Valente, C.;
C¸ alimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.; Organ, M. G. Angew. Chem., Int. Ed.
2012, 51, 3314; (c) Fortman, G. C.; Nolan, S. P. Chem. Soc. Rev. 2011, 40, 5151.
3. Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27.
4. Díez-Gonzalez, S.; Nolan, S. P. Chem. Rev. 2009, 109, 3612.
5. Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361.
4.4.32. N-mesitylpyridin-2-amine (25b). 1H NMR (CDCl3, 400 MHz,
298 K): ]8.12 (dd, J]0.8 Hz, J]4.8 Hz, 1H), 7.34 (dt, J]1.6 Hz, J]
d
7.2 Hz, 1H), 6.95 (s, 2H), 6.62e6.59 (m, 1H), 6.25 (br s, 1H), 6.00
ꢁ
(d, J]8.4 Hz, 1H), 2.31 (s, 3H), 2.19 (s, 6H); 13C NMR (CDCl3, 100
6. For selected examples, see: (a) Benhamou, L.; Chardon, E.; Lavigne, G.;
Bellemin-Laponnaz, S.; Cesar, V. Chem. Rev. 2011, 111, 2705; (b) Nair, V.; Menon,
MHz, 298 K):
129.28, 113.36, 105.55, 20.90, 18.22.
d]158.02, 148.36, 137.75, 136.55, 136.35, 133.73,
ꢁ
R. S.; Biju, A. T.; Sinu, C. R.; Paul, R. R.; Josea, A.; Sreekumar, V. Chem. Soc. Rev.
2011, 40, 5336; (c) Bierenstiel, M.; Cross, E. D. Coord. Chem. Rev. 2011, 255, 574;
(d) Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39.
7. (a) Wu, L.; Falivene, L.; Drinkel, E.; Grant, S.; Linden, A.; Cavallo, L.; Dorta, R. Angew.
Chem., Int. Ed. 2012, 51, 2870; (b) Wu, L.; Drinkel, E.; Gaggia, F.; Capolicchio, S.;
Linden, A.; Falivene, L.; Cavallo, L.; Dorta, R. Chem.dEur. J. 2011, 17, 12886.
8. Wurtz, S.; Glorius, F. Acc. Chem. Res. 2008, 41, 1523.
4.4.33. N-(2,6-Dimethylphenyl)-2,4,6-trimethylaniline (26). 1H NMR
(CDCl3, 400 MHz, 298 K):
3H), 4.71 (br s, 1H), 2.25 (s, 3H), 1.99e1.95 (m, 12H); 13C NMR
(CDCl3, 100 MHz, 298 K):
¼142.14, 138.94, 131.43, 130.40, 129.17,
d¼6.97 (d, J¼7.6 Hz, 2H), 6.81e6.78 (m,
d

W. Fang et al. / Tetrahedron 69 (2013) 673e679
679
€
9. (a) Tu, T.; Fang, W.; Bao, X.; Li, X.; Dotz, K. H. Angew. Chem., Int. Ed. 2011, 50, 6601;
12. During this paper in the hand of referees, an unexpected synthesis of benzi-
midazolium salts (the precursor of complex 2, R¼Me, R0¼Me) through dihy-
drophenazines en route was reported, more detail see: Adv. Synth. Catal. 2012,
354, 1356.
13. Tu, T.; Fang, W.; Jiang, J. Chem. Commun. 2011, 12358.
14. (a) Suwanprasop, S.; Nhujak, T.; Roengsumran, S.; Petsom, A. Ind. Eng. Chem.
Res. 2004, 43, 4973; (b) Amines: Synthesis, Properties and Application; Lawrence,
S. A., Ed.; Cambridge University: Cambridge, 2004; (c) Industrial Organic
Chemistry; Weissermel, K., Arpe, H.-J., Eds.; Wiley-VCH: Weinheim, Germany,
1997.
€
(b) Tu, T.; Bao, X.; Assenmacher, W.; Peterlik, H.; Daniels, J.; Dotz, K. H. Chem.dEur.
J. 2009,15,1853; (c) Tu, T.; Assenmacher, W.; Peterlik, H.; Schnakenburg, G.; Dotz,
K. H. Angew. Chem., Int. Ed. 2008, 47, 7127; (d) Tu, T.; Assenmacher, W.; Peterlik, H.;
Weisbarth, R.; Nieger, M.; Dotz, K. H. Angew. Chem., Int. Ed. 2007, 46, 6368.
€
€
10. (a) Wang, Z.; Feng, X.; Fang, W.; Tu, T. Synlett 2011, 951; (b) Tu, T.; Feng, X.;
Wang, Z.; Liu, X. Dalton Trans. 2010, 10598; (c) Tu, T.; Mao, H.; Herbert, C.; Xu,
€
€
M.; Dotz, K. H. Chem. Commun. 2010, 7796; (d) Tu, T.; Malineni, J.; Bao, X.; Dotz,
K. H. Adv. Synth. Catal. 2009, 351, 1029; (e) Tu, T.; Malineni, J.; Dotz, K. H. Adv.
€
Synth. Catal. 2008, 350, 1791.
11. (a) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47, 3122; (b) Marion, N.;
15. Schlummer, B.; Scholz, U. Adv. Synth. Catal. 2004, 346, 1599.
16. (a) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37,
320; (b) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119 and references
therein.
ꢁ
€
Díez-Gonzalez, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988; (c) Kuhl, O.
Chem. Soc. Rev. 2007, 36, 592; (d) Hahn, F. E. Angew. Chem., Int. Ed. 2006, 45,1348; (e)
€
Hahn, F. E.; Wittenbecher, L.; Le Van, D.; Frohlich, R. Angew. Chem., Int. Ed. 2000, 39,
€
541; (f) Hahn, F. E.; Wittenbecher, L.; Boese, R.; Blaser, D. Chem.dEur. J.1999, 5,1931.
17. Hirano, K.; Biju, A. T.; Glorius, F. J. Org. Chem. 2009, 74, 9570.