Macrocyclic Aryl-Nickel(II) Complexes: Synthesis, Structure, and Reactivity Studies

Article abstract of DOI:10.1021/acs.organomet.5b00733

The synthesis, characterization, and reactivity of the monoaryl-Ni(II) compound 2 and the diaryl-Ni(II) compound 4 formed through the direct electrophilic metalation of two macrocyclic azacalix[m]arene[n]pyridine ligands are described. Compound 4 was much more stable in protic solvents and acids than the monoaryl-Ni(II) compound 2. Moreover, 2 can react with a variety of nucleophiles, resulting in the formation of C-C, C-O, C-Br, and C-N bonds. In contrast, compound 4 exhibited very inert reactivity upon reaction with a large numberof nucleophiles. Interestingly, compound 2 was also capable of reacting with several less bulky alkyl halides to form new C-C bonds, while the same procedure is inapplicable to 4. The study reported in this work provides a thorough investigation on the reactivity of aryl-Ni(II) species that should facilitate comprehension of the detailed mechanism of nickel-catalyzed C-H functionalization.

Full text of DOI:10.1021/acs.organomet.5b00733

Article
pubs.acs.org/Organometallics
Macrocyclic Aryl−Nickel(II) Complexes: Synthesis, Structure, and
Reactivity Studies
Chi Yang, Wen-Di Wu, Liang Zhao,* and Mei-Xiang Wang*
The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry,
Tsinghua University, Beijing 100084, People’s Republic of China
S
* Supporting Information
ABSTRACT: The synthesis, characterization, and reactivity of
the monoaryl−Ni(II) compound 2 and the diaryl−Ni(II)
compound 4 formed through the direct electrophilic metal-
ation of two macrocyclic azacalix[m]arene[n]pyridine ligands
are described. Compound 4 was much more stable in protic
solvents and acids than the monoaryl−Ni(II) compound 2.
Moreover, 2 can react with a variety of nucleophiles, resulting
in the formation of C−C, C−O, C−Br, and C−N bonds. In
contrast, compound 4 exhibited very inert reactivity upon
reaction with a large numberof nucleophiles. Interestingly,
compound 2 was also capable of reacting with several less
bulky alkyl halides to form new C−C bonds, while the same
procedure is inapplicable to 4. The study reported in this work provides a thorough investigation on the reactivity of aryl−Ni(II)
species that should facilitate comprehension of the detailed mechanism of nickel-catalyzed C−H functionalization.
catalyst loading, high temperature requirements, and limitations
in substrate scope restrict the practicality of the nickel-catalyzed
C−H functionalization. Obviously, insightful comprehension of
the detailed mechanism of the nickel-catalyzed C−H activation
and the subsequent C−C and C−heteroatom bond formation
would be very helpful in improving the catalytic efficiency of
various nickel catalysts.
INTRODUCTION
■
From the standpoints of economics and versatility, nickel is a
privileged metal for the direct conversion of C−H bonds into
C−C, C−O, C−N, and C−halogen bonds.1 In contrast to its
precious-metal congeners Pd and Pt, nickel is widely recognized
as a low-cost and sustainable commodity metal. The unique
electron configuration of Ni ([Ar]4s23d8), different from that of
Pd ([Kr]4d10) and Pt ([Xe]4f145d96s1), engenders the nickel
element with a wide range of oxidation states from 0, +1, +2,
and +32 to the recently reported +4,3 which greatly increases its
chemical versatility in catalytic reactions. Therefore, the use of
nickel in C−H functionalization processes has recently received
particular attention.4 Many unique transformations have been
reported for the functionalization of sp2 and sp3 C−H bonds.5
For example, Hiyama and co-workers have reported indole C−
H bond activation by Ni(COD)2 followed by the insertion of
different alkynes to yield a series of hydroheteroarylation
products.6 A similar transformation was also reported by
Chatani to synthesize various isoquinolone derivatives.7 In
addition to the Ni(0) compounds, Ni(II) salts can also be
utilized in C−H functionalizations. Miura and co-workers have
reported nickel(II)-catalyzed direct C−H arylation and
alkenylation of heteroarenes with organosilicon reagents.8 A
postulated catalytic mechanism involved several steps, including
electrophilic aromatic metalation, transmetalation, reductive
elimination, and oxidation by Ni(II). In addition, despite the
absence of a C−H activation step, Fu’s seminal work reported a
novel Ni(I/II/III) catalytic cycle for nickel-catalyzed Negishi
arylations of propargylic bromides.9 However, despite the great
number of Ni-catalyzed organic transformations, relatively high
In the reported nickel-catalyzed aryl C−H bond functional-
ization reactions,4 aryl−Ni(II) complexes are thought to be the
key intermediate regardless of their generation by oxidative
addition or direct electrophilic aromatic metalation. In most
cases, subsequent reductive elimination of the intermediates
derived from the ligand exchange of aryl−Ni(II) complexes
with various nucleophiles accounts for the generation of the
final C−C and C−heteroatom coupling compounds. Kochi and
co-workers have previously synthesized a series of
arylalkylnickel(II) complexes and systematically investigated
the kinetics of the reductive elimination step.10 Recently, Itami
and co-workers detailedly investigated the mechanism of the
Ni(0)-catalyzed C−H/C−O coupling of benzoxazole and
naphthalen-2-yl pivalate by isolating the key C−O oxidative
addition intermediate Ar−NiII−OR.11 Nevertheless, to date the
systematic reactivity studies of aryl−Ni(II) complexes have
remained very poor. Herein we report the syntheses of two
aryl−Ni(II) compounds formed through the direct electrophilic
metalation of two macrocyclic azacalix[m]arene[n]pyridine
ligands (m, n = 1, 3 and 2, 2).12 The structure and
Received: August 26, 2015
© XXXX American Chemical Society
A
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physicochemical properties of the monoaryl−Ni(II) compound
2 and the diaryl−Ni(II) compound 4 have been thoroughly
characterized by different techniques, including X-ray crystal-
lography, X-ray photoelectron spectroscopy (XPS), and cyclic
voltammetry (CV). In contrast to the chemical passivity of the
diaryl−Ni(II) compound 4, the monoaryl−Ni(II) compound 2
can react with a large number of nucleophiles and electrophiles
to construct C−C, C−O, C−N, and C−Br bonds. Elucidation
of the reactivity difference between monoaryl− and diaryl−
Ni(II) compounds provides basic information for under-
standing Ni-catalyzed or -mediated C−H functionalization
reactions.
procedure of aryl−Pd(II) complexes14 and carried out the
synthesis of the diaryl−Ni(II) compound 4 in acetic acid at
elevated temperature. Finally, compound 4 was obtained in
76% yield.
Crystals of compound 2 of quality suitable for X-ray
crystallography were obtained by diffusing diethyl ether into
the dichloromethane/methanol solution of 2. As shown in
Figure 1, the crystal structure of 2 contains the encapsulated
nickel atom Ni1 coordinated by a deprotonated azacalix[1]-
arene[3]pyridine. A perchlorate counteranion is located at the
top of the nickel atom but at a distance far beyond that of a
Ni−O coordination bond. Ni1 exhibits a typical square-planar
coordination configuration, which is evidenced by the linear
∠N1−Ni1−N5 and ∠N3−Ni1−C24 bond angles of 178.6(2)
and 178.3(2)°. It is notable that the Ni1−C24 bond length
(1.881(5) Å) is approximately 0.02 Å shorter than the other
three Ni−N bond lengths in the range of 1.897(4)−1.908(5) Å.
Upon the occurrence of coordination, the azacalix[1]arene[3]-
pyridine macrocycle adjusts its 1,3-alternate conformation in
the free state12 to this saddlelike conformation in 2. In this way,
the four coordinated atoms are almost located on the same
plane with a very small deviation of 0.023 Å.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Aryl−Ni(II) Com-
pounds 2 and 4. We have recently shown that the
azacalix[1]arene[3]pyridine 1 can undergo electrophilic
aromatic metalation to generate arylcopper(II) compounds.13
According to a similar procedure (Scheme 1), reaction of 1
Scheme 1. Synthesis of Monoaryl−Ni(II) Compound 2 and
Diaryl−Ni(II) Compound 4
In the crystal structure of 4, the azacalix[2]arene[2]pyridine
macrocycle adopts a similar saddle conformation, thus
constituting a square-planar coordination geometry for the
nickel atom (deviation ∼0.035 Å) as well. The two C−Ni bond
lengths Ni1−C6 = 2.001 (7) Å and Ni1−C19 = 2.017(7) Å are
shorter than the Ni−N bond lengths (2.043(5)−2.045(5) Å).
In general, due to electrostatic interaction the doubly
deprotonated azacalix[2]arene[2]pyridine macrocycle in 4
should form a more compact coordination environment in
comparison to that of azacalix[1]arene[3]pyridine in 2. A
survey of the biaryl−bipyridine nickel compounds reported in
the literature15 suggests that the Ni−C and Ni−N bond lengths
in these compounds lie in the range of 1.85−2.00 Å,
comparable to the values in complex 2. We speculate that the
abnormally elongated bond lengths in 4 may be ascribed to the
unique cyclic skeleton of the azacalix[2]arene[2]pyridine. A
detailed structural comparison of the macrocyclic ligands in 2
and 4 indicates that the separation between two opposite
bridging nitrogen atoms in 2 is about 0.4 Å shorter than the
values in 4, suggesting a more curved conformation of the
macrocycle in 2. The more planar conformation of azacalix[2]-
arene[2]pyridine in 4 may be attributed to the fact that the
with 2 equiv of Ni(ClO4)2 in acetonitrile at room temperature
resulted in the formation of the monoaryl−Ni(II) compound 2
as a yellow powder in 90% yield. However, the same procedure
was unsuccessful in the metalation of azacalix[2]arene[2]-
pyridine 3. We therefore referred to the previous synthetic
Figure 1. X-ray crystal structure of (a) the monoaryl−Ni(II) compound 2 and (b) the diaryl−Ni(II) compound 4 with ellipsoids at the 40%
probability level.
B
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Figure 2. XPS spectra of (left) 2 and (right) 4.
Figure 3. (a) Cyclic voltammograms of 2 and 4 in CH3CN at 298 K. (b) DPV of 2 and 4 in CH3CN at 298 K. The concentration of 2 and 4 is 2.0 ×
10−3 M. (c) UV/vis spectra of 1 and 2 in CH3CN at 298 K. (d) UV/vis spectra of 3 and 4 in CH3CN at 298 K. The concentration of 2 and 4 in (c)
and (d) is 2.0 × 10−5 M.
separated N−N and C−C arrangement can weaken the
electrostatic and dipole−dipole repulsion.
To understand the physicochemical properties of com-
pounds 2 and 4, their electrochemistry and absorption spectra
were investigated. The redox properties were examined by
means of CV and differential pulse voltammetry (DPV). As
shown in Figure 3a, cyclic voltammograms of 2 and 4 showed a
similar reversible redox couple resulting from one-electron
reduction and oxidation of the nickel(II) center. The half-wave
reduction potentials (E1/2) measured by CV agreed quite well
with the values obtained by means of DPV (Figure 3b). The
In order to ensure the +2 oxidation state of the nickel center
in 2 and 4, the XPS measurement was conducted. As shown in
Figure 2, the XPS spectra revealed a pair of peaks for each
sample (854.4 and 871.6 eV for 2 and 854.5 and 871.8 eV for
4), which were assigned to the typical 2p2/3 and 2p1/2 peaks of
the nickel(II) on the basis of previously reported data.16
C
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Table 1. Summary of Physicochemical Properties of 2 and 4
a
b
c
d
e
λmax, nm (ε)
λmax, nm (ε)
λmax, nm (ε)
Egopt, eV]
E1/2, mV
HOMO, eV]
LUMO, eV]
2
4
285 (1.85)
282 (2.45)
318 (1.42)
345 (1.25)
2.77
3.02
−693
−867
−4.24
−4.01
−1.47
−0.99
358 (1.26)
b
a
c
ε is given in units of 104 M−1 cm−1. Egopt = 1240/λabsonset. Reduction potentials measured by cyclic voltammetry with ferrocene as the standard.
HOMO = −(Eox
d
e
+ 4.8 eV). LUMO = HOMO + Egopt
.
onset
acquired data indicated that compound 2 had a higher E1/2
potential of −693 mV in comparison to that of compound 4
(−867 mV). This implied that compound 2 had a greater
tendency to be reduced than compound 4, thus possibly
favoring the reductive elimination step. The UV/vis spectra of 2
in acetonitrile exhibited three absorption bands at λmax 285,
318, and 345 nm with molar extinction coefficients (ε) of
around 1.25−1.85 × 104 M−1 cm−1 (Table 1). Relative to the
three absorption bands of the neat azacalix[1]arene[3]pyridine,
all absorption bands of 2 were shifted bathochromically. As for
the diaryl−Ni(II) compound 4, its UV/vis spectra included two
absorption bands at λmax 282 and 358 nm with molar extinction
coefficients (ε) of 2.45 × 104 and 1.26 × 104 M−1 cm−1 (Table
1). A red shift of the absorption bands in comparison with
those of the azacalix[2]arene[2]pyridine was observed as well.
From the absorption spectra and the reduction potentials,
the estimated energy gap between the LUMO and HOMO
(Eg) and both the HOMO and LUMO energy levels of 2 and 4
were obtained and summarized in Table 1. The energy gap of 4
is 0.25 eV larger than that of 2, while the LUMO orbital of 2 is
approximately 0.5 eV lower than that of 4. In general, the
reaction of 2 with nucleophiles, which is mostly related to the
LUMO orbital of 2, is expectedly more favored than that of 4.
Reactivity Comparison between 2 and 4 with
Nucleophiles and Electrophiles. We next embarked on
the reactivity studies of the monoaryl−Ni(II) compound 2 and
the diaryl−Ni(II) compound 4. First, the stabilities of 2 and 4
in solution were quite different. In protic solvents such as
methanol compound 2 was gradually protonated to give the
neat azacalix[1]arene[3]pyridine ligand 1. The use of acetic
acid accelerated this process and generated 1 quantitatively
within 4 h. In contrast, compound 4 was stable in protic
solvents and even on heating in mild acids. Only the strong acid
trifluoroacetic acid can drive the protonated transformation of
4.
We next employed various nucleophiles, including organo-
lithium reagents, azide, halide, phenol, and hydroxyl, to react
with 2 and 4 with the aim of elucidating the reaction difference
of these two organonickel(II) compounds. Organolithium
reagents 5a−c were first applied to react with 2 to produce
alkylated or arylated azacalix[1]arene[3]pyridine compounds
6a−c (Scheme 2). Optimization of reaction conditions revealed
that the best yield of 60% was achieved when 2 equiv of
organolithium was used and the reaction was conducted at 0 °C
to reflux temperature, no matter what kind of organolithium
(alkyl- or aryllithium) was utilized. However, it has to be
pointed out that this carbon−carbon bond formation reaction
is time consuming. Generally, over 60 h is necessary for total
conversion. Moreover, a similar reaction procedure was
applicable to the formation of C−N and C−Br bonds as well.
When 2 equiv of sodium azide and potassium bromide was
respectively reacted with 2 in acetonitrile, after 24 h the azido-
or bromo-substituted azacalix[1]arene[3]pyridine derivatives 7
and 8 were obtained in high yield (90%). In sharp contrast,
reaction of the diaryl−Ni(II) compound 4 with the
Scheme 2. Cross-Coupling Reaction between Ar−Ni(II)
Complex 2 and Different Nucleophiles
aforementioned nucleophiles (organolithium reagents, NaN3,
and KBr) under the same reaction conditions did not produce
any coupling products.
The C−O bond formation was also attempted by conducting
the reaction of 2 with different alcohols and phenol in the
presence of bases (Table 2). With reference to our previously
Table 2. Reaction Conditions of 2 with O-Containing
Nucleophiles
Nu
base
(amt, equiv)
solvent
(amt, equiv)
temp
reflux
time, h yield, %
MeOH (2)
i-PrOH (2)
acetonitrile
acetonitrile
DBU (2)
DBU (2)
48
48
48
48
6
trace
trace
trace
67
reflux
reflux
reflux
room
MeONa (2) acetonitrile
PhOH (2)
KOH (4)
acetonitrile
DBU (2)
a
DMSO/H2O
30/1
82
temp
a
The parent macrocyclic azacalix[1]arene[3]pyridine was isolated in
15% yield after workup.
reported C−O coupling reaction of the aryl−Cu(III) analogue
of 2,17 we carried out the reaction of 2 with methanol in
refluxing acetonitrile with 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) as a base. Only a trace amount of methoxy-substituted
azacalix[1]arene[3]pyridine derivative was obtained. Isopropyl
alcohol gave the same negative result. Moreover, it is puzzling
that the direct use of CH3ONa also cannot facilitate the C−O
bond formation. In contrast, under the same conditions the
cross-coupling reaction between phenol and 2 afforded
compound 9 in 67% yield. We hypothesize that very different
dissociation constants of CH3O−Na+ and [PhO−][H-DBU]+ in
the organic solvent acetonitrile may account for their biased
performance in the C−O coupling reaction. The latter
compound has a larger dissociation constant due to the
existence of the organic cationic species [H-DBU]+. Remark-
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ably, when the typical ionic compound potassium hydroxyl was
employed in a mixed solvent of dimethyl sulfoxide (DMSO)
and water, a good yield (82%) for the formation of hydroxyl-
substituted compound 10 was achieved. Therein water is
prerequisite for this reaction. Unfortunately, there were no C−
O coupling reactions taking place between 4 and the oxygen-
containing nucleophiles.
Table 3. Optimization of the Reaction Conditions for 2 and
Benzoxazole
entry
solvent
base (amt, equiv)
temp, °C
yield, %
23
1
acetonitrile
toluene
dioxane
THF
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
K2CO3 (1)
K3PO4 (1)
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
90
2
17
3
15
4
none
5
DMSO
DMF
29
6
45
In addition to the above diverse nucleophiles, it is amazing to
find that the monoaryl−Ni(II) complex 2 can react with alkyl
halides (Scheme 3). To date, the alkylation of aryl−metal
7
DMF
25
8
DMF
none
9
DMF
t-BuOK (1)
DIPEA (1)
Et3N (1)
19
10
11
12
13
14
15
16
17
18
19
20
DMF
none
Scheme 3. Cross-Coupling Reaction between Ar−Ni(II)
Complex 2 and Alkyl Halides
DMF
23
DMF
DBU (1)
13
DMF
DABCO (1)
Cs2CO3 (0.2)
Cs2CO3 (0.5)
Cs2CO3 (1.5)
Cs2CO3 (2)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
14
DMF
8
DMF
38
DMF
30
DMF
32
DMF
14
DMF
110
120
34 (mess)
23 (mess)
DMF
complexes via the oxidative addition of alkyl halides is quite
limited,7c−e,f since such a process involves unfavorable
formation of a high-valence metal center and the resulting
alkyl metal complexes tend to favor β-hydride elimination
rather than the desired reductive elimination. When 2 was
mixed with methyl iodide in toluene in the presence of the two
additives sodium iodide and cesium carbonate and the mixture
was heated to 140 °C for 48 h, the alkylation product 6a was
obtained in 47% yield. It should be pointed out that the two
additives are necessary for this transformation. The reactions
for the two other primary alkyl halides nBuBr and
BrCH2COOMe also worked very well according to the same
dioxane, THF, and DMSO did not improve the yield. Finally,
N,N-dimethylformamide (DMF) was chosen as the reaction
medium, since it gave the best yield (45%). Screening of other
bases, such as the inorganic bases K2CO3, K3PO4, and t-BuOK
and organic bases including diisopropylethylamine (DIPEA),
Et3N, DBU, and 1,4-diazabicyclo[2.2.2]octane (DABCO)
revealed that cerium carbonate was a suitable base for this
transformation. Interestingly, the unique role of Cs2CO3 was
also mentioned in Itami’s work.18 Decreasing or increasing the
amount of Cs2CO3 was detrimental to the reaction. We also
attempted to utilize other heterocycles such as oxazole, thiazole,
and benzothiazole to realize the formation of biaryl carbon−
carbon bonds. However, these substrates were all inapplicable
to this reaction.
t
procedure. However, the reaction of 2 with BuCl did not
produce any desired coupling products, implying a detrimental
effect of the bulky group of alkyl halides. Until now, the
mechanism of the reaction between aryl−Ni(II) and electro-
philes is still unknown. No reactions took place between 4 and
alkyl halides.
CONCLUSIONS
■
Biaryl Coupling Reaction between 2 and Benzox-
azole. Recently, Itami and co-workers separated an aryl−
Ni(II) compound via the oxidative addition of Ni(0) by a C−O
bond.11 They reported that this aryl−Ni(II) species is
responsible for the following C−H bond activation of the
heterocyclic benzoxazole. We thus attempted to investigate
whether 2 and 4 can also be applied in this transformation to
realize C−H functionalization. As shown in Table 3 (entry 1),
the monoaryl−Ni(II) compound 2 was initially mixed with
benzoxazole and cesium carbonate in acetonitrile in a sealed
tube. When the mixture was heated for 24 h, the benzoxazole-
decorated macrocycle compound 6c was obtained in 23% yield
(entry 1). The use of other solvents such as toluene, 1,4-
In summary, we have reported the facile synthesis of aryl−
Ni(II) complexes by the direct electrophilic metalation of
azacalixaromatic macrocycles. The structure and properties of
the two aryl−Ni(II) complexes 2 and 4 were fully characterized.
The reactivity difference between the monoaryl−Ni(II)
compound 2 and the diaryl−Ni(II) compound 4 have been
systematically investigated through conducting the coupling
reactions with various nucleophiles and electrophiles. The
reactivity study will hopefully spur the development of new
synthetic methodologies by using cheap Ni(II) salts. Detailed
mechanistic studies for the transformations reported in this
work are still in progress.
E
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slowly. The resulting mixture was extracted with dichloromethane (3 ×
15 mL), and the organic phase was then washed with water (3 × 15
mL) and saturated brine (3 × 15 mL) and dried over anhydrous
MgSO4. After filtration and concentration, the residue was flash-
chromatographed on a silica gel column (petroleum ether/ethyl
acetate/dichloromethane 12/2/1) to afford the products: 6a (55 mg,
53%) as a white solid, mp 230−232 °C (lit.19 mp 230−232 °C); 6b
(59 mg, 61%) as a white solid, mp 182−184 °C (lit.19 mp 182−184
°C).
EXPERIMENTAL SECTION
■
General Procedures. All of the anhydrous solvents were purified
and dried via the reported standard process. Unless otherwise noted,
all the glassware used in reactions was dried in an oven. Commercially
available reagents were used as received. Reactions were monitored by
TLC, which was performed on precoated glass-backed silica gel plates
and visualized under UV light. Silica gel (200−300 mesh) was used to
perform flash column chromatography. A JEOL ECX-400 400 MHz
spectrometer was used to record 1H NMR and 13C NMR spectra using
CDCl3/CD3CN as solvent, and abbreviations are used to describe
NMR spectral data as follows: chemical shift (ppm), coupling constant
(J, Hz), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m
= multiplet). The electron spray ionization mass spectra (ESI-MS)
were recorded on an Esquire-LC-00136 spectrometer, and high-
resolution electrospray ionization (ESI) mass spectra were recorded
on a Thermo Fisher Exactive mass spectrometer. Infrared spectra were
recorded using a PerkinElmer Spectrum 100 FT-IR spectrometer in an
anhydrous environment. UV spectra were recorded using a
PerkinElmer Lamber35 UV/vis spectrophotometer at room temper-
ature.
Synthesis of 6c (Method A). At −78 °C and under an N2
atmosphere, 161 μL n-butyllithium (2.5 M in hexane) was injected
into a 10 mL Schlenk tube and then 1 mL of a THF solution of
benzoxazole (47.6 mg, 0.4 mmol) was injected slowly into the n-
butyllithium and the mixture stirred for 0.5 h at −78 °C. The resulting
mixture was then slowly added to a mixture of 2 (116 mg, 0.2 mmol)
and 10 mL of THF inside a three-neck round-bottom flask under N2
pressure and at a temperature of −78 °C within 30 min. After the
addition, the reaction temperature was raised to room temperature and
then the mixture was refluxed for 60 h until compound 2 was
consumed (monitored by TLC). The reaction mixture was cooled to
room temperature, and saturated NH4Cl was added slowly. The
resulting mixture was extracted with dichloromethane (3 × 15 mL),
and the organic phase was then washed with water (3 × 15 mL) and
saturated brine (3 × 15 mL) and dried over anhydrous MgSO4. After
filtration and concentration, the residue was flash chromatographed on
a silica gel column (petroleum ether/ethyl acetate 6/1) to afford 6c
(64 mg, 59%): mp 278−279 °C; 1H NMR (400 MHz, CDCl3) δ 7.80
(m, 1 H), 7,59 (m, 1 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.40−7.37 (m, 2
H), 7.14 (t, J = 7.6 Hz, 1 H), 6.88 (dd, J = 6.8 Hz, J = 7.2 Hz, 1 H),
6.81−6.80 (m, 2 H), 6.56 (d, J = 8.0 Hz, 2 H), 6.09 (d, J = 8.0 Hz, 2
H), 6.03 (d, J = 8.0 Hz, 2 H), 3.26 (s, 6 H), 3.10 (s, 6 H); 13C NMR
(100 MHz, CDCl3) δ 158.9 (s), 158.8 (s), 157.4 (s), 152.6 (s), 150.0
(s), 140.7 (s), 140.1 (s), 139.1 (s), 137.4 (s), 137.3 (s), 128.5 (s),
125.7 (s), 124.7 (s), 124.5 (s), 120.7 (s), 120.2 (s), 111.1 (s), 96.1 (s),
94.7 (s), 38.4 (s), 36.3 (s); IR (KBr, cm−1) ν 1584, 1572, 1466, 1419,
1365, 1248, 1130; HRMS (ESI) calcd for C32H29N8O [M + H]+
541.2464, found 541.2464. Anal. Calcd for C32H28N8O: C, 71.09; H,
5.22; N, 20.73. Found: C, 71.12; H, 5.27; N, 20.70.
Synthesis of 7 or 8. Under an N2 atmosphere, a mixture of 2 (116
mg, 0.2 mmol) and sodium azide or potassium bromide (0.4 mmol) in
dried acetonitrile (20 mL) was stirred for 24 h at room temperature in
a 50 mL three-neck round-bottom flask until all 2 was consumed.
Then 10 mL of ammonia was added. The resulting mixture was
extracted with dichloromethane (3 × 15 mL), and the organic phase
was then washed with water (3 × 15 mL) and saturated brine (3 × 15
mL) and dried over anhydrous MgSO4. After filtration and
concentration, the residue was flash-chromatographed on a silica gel
column (petroleum ether/ethyl acetate/dichloromethane 12/2/1) to
afford the target products: 7 (80 mg, 91%) as a white powder, mp
171−172 °C (lit.20 mp 170−171 °C); 8 (93 mg, 93%) as a white
powder, mp 257−258 °C (lit.21 mp 257−258 °C).
Synthesis of 9. Under an N2 atmosphere, a mixture of 2 (116 mg,
0.2 mmol), phenol (0.4 mmol), and DBU (0.4 mmol) in dried
acetonitrile (20 mL) was refluxed for 48 h in a 50 mL three-neck
round-bottom flask until all 2 was consumed. Then 10 mL of ammonia
was added. The resulting mixture was extracted with dichloromethane
(3 × 15 mL), and the organic phase was then washed with water (3 ×
15 mL) and saturated brine (3 × 15 mL) and dried over anhydrous
MgSO4. After filtration and concentration, the residue was flash-
chromatographed on a silica gel column (petroleum ether/ethyl
acetate/dichloromethane 12/2/1) to afford 9 as a white solid: mp
228−229 °C (lit.17 mp 228−229 °C).
Synthesis of 10. In a 25 mL three-neck round-bottom flask, 2 (58
mg, 0.1 mmol) was dissolved in 10 mL of DMSO/H2O (30/1) mixed
solvent, and potassium hydroxide solid (22.4 mg, 0.4 mmol) was
added in one portion. The mixture was stirred at room temperature for
6 h until 2 was consumed (monitored by TLC). A 5 mL portion of
water was poured into the flask, and hydrochloric acid (0.1 M) was
added until the solution became neutral. Dichloromethane was used to
extract the organic materials. Then the organic phase was washed with
Synthesis of 2. To a solution of reactant 1 (212 mg, 0.5 mmol) in
anhydrous acetonitrile (50 mL) was added a solution of Ni(ClO4)2·
6H2O (274 mg, 1.0 mmol) in 5 mL of acetonitrile slowly with a
syringe pump within 1 h. After addition was complete, the solution
was stirred for 10 h until the reactant 1 disappeared. Solvent was
removed under reduced pressure without heating, and a yellow-green
mixture was obtained. Chloroform (30 mL) was then added, the
resulting mixture was centrifuged, and the supernatant was removed.
These operations were repeated another two times, and then methanol
was used for the centrifugation. The solid from centrifugation was
dried to give the yellow powder 2 in 90% yield: mp >300 °C; 1H NMR
(400 MHz, CDCl3) δ 8.17 (t, J = 8.1 Hz, 1 H), 8.10 (t, J = 7.8 Hz, 2
H), 7.50 (t, J = 7.8 Hz, 1 H), 7.39 (d, J = 7.8 Hz, 2 H), 7.32 (d, J = 7.8
Hz, 2 H), 7.19 (d, J = 7.8 Hz, 2 H), 7.07 (t, J = 7.8 Hz, 4 H), 3.68 (s, 6
H), 3.53 (s,6 H); 13C NMR (100 MHz, CDCl3) δ 153.4 (s), 152.3 (s),
151.9 (s), 145.7 (s), 144.0 (s), 139.2 (s), 137.0 (s), 131.4 (s), 115.9
(s), 112.5 (s), 110.9 (s), 109.8 (s), 38.5 (s), 38.2 (s); IR (KBr, cm−1) ν
−
1578, 1484, 1423, 1341, 1091; ESI-MS m/z [M − ClO4 ]+: 480.2.
−
HRMS (ESI) calcd for C25H24N7Ni [M − ClO4 ]+ 480.1447, found
480.1435. Anal. Calcd for C25H24ClN7NiO4: C, 51.71; H, 4.17; N,
16.89. Found: C, 51.66; H, 4.19; N, 16.85.
Synthesis of 4. A mixture of azacalix[2]arene[2]pyridine 3 (211
mg, 0.50 mmol) and Ni(ClO4)2·6H2O (274 mg, 0.75 mmol) in acetic
acid was stirred and refluxed in 15 mL of acetic acid for 12 h. When 3
was consumed, which was monitored by TLC analysis, the reaction
mixture was cooled to room temperature. The solvent was removed,
and the residue was dissolved in dichloromethane and washed with
water (2 × 10 mL) and saturated brine (2 × 15 mL). The organic
phase was dried over anhydrous MgSO4. After filtration and
concentration under vacuum, the residue was recrystallized in a
mixture of dichloromethane, methanol, and hexane to give pure 4 (182
1
mg, yield: 76%) as a yellow powder: mp >300 °C; H NMR (400
MHz, CDCl3) δ 7.59 (t, J = 8.2 Hz, 2 H), 7.12 (t, J = 7.8 Hz, 2 H),
6.81 (t, J = 7.8 Hz, 4 H), 6.68 (t, J = 7.8 Hz, 4 H), 3.46 (s, 12 H); 13C
NMR (100 MHz, CDCl3) δ 156.7 (s), 145.8 (s), 140.8 (s), 138.0 (s),
125.1 (s), 109.4 (s), 105.7 (s), 40.3 (s); IR (KBr, cm-1) ν 1576, 1451,
1415,1316, 1116; ESI-MS [M + H]+ m/z 480.1; HRMS calcd for
C26H25N6Ni [M + H]+ 479.1494, found 479.1484. Anal. Calcd for
C26H24N6Ni: C, 65.17; H, 5.05; N, 17.54. Found: C, 65.13; H, 5.08; N,
17.57.
Synthesis of 6a or 6b (Method A). A mixture of 2 (116 mg, 0.2
mmol) and 20 mL of anhydrous THF was stirred at 0 °C for 0.5 h in a
50 mL three-neck round-bottom flask. Then 134 μL of lithium
methide (3 M in diethoxymethane) or 161 μL of n-butyllithium (2.5
M in n-hexane) was injected slowly into the reaction mixture over 5
min. The reaction mixture was stirred for 10 min at 0 °C and 10 min at
room temperature and then refluxed for 72 h under an Ar atmosphere
until the starting compound 2 was consumed. The reaction mixture
was cooled to room temperature, and saturated NH4Cl was added
F
DOI: 10.1021/acs.organomet.5b00733
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
water (3 × 10 mL) and saturated brine (3 × 10 mL) and dried over
anhydrous MgSO4. After filtration and concentration, the residue was
first flash-chromatographed on a silica gel column using petroleum
ether/ethyl acetate (3/1) mixed solvent as eluent to afford the crude
product. Then the crude product was flash-chromatographed again on
a silica gel column using petroleum ether/ethyl acetate (10/1) as
eluent to afford 10 as a white solid in 90% yield: mp 207−208 °C
(lit.12c mp 207−208 °C).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.5b00733.
■
S
NMR spectra and XPS and CV data for the compounds
and X-ray crystallographic data for 2 and 4 (PDF)
X-ray crystallographic data for 2 and 4 (CIF)
Synthesis of 6a,b (Method B) or 11: General Procedure. In
the glovebox, a 35 mL sealed tube was charged with compound 2 (116
mg, 0.2 mmol), electrophilic reagents (1.2 mmol), cesium carbonate
powder (65 mg, 0.2 mmol), sodium iodide (30 mg, 0.2 mmol), and 15
mL of toluene (anhydrous and deoxgenized). Then the sealed tube
was moved out of the glovebox and the mixture was heated to 140 °C
and stirred. After 48 h, the reaction mixture was cooled to room
temperature and insoluble substances were removed by filtration.
Toluene was removed under reduced pressure, and 20 mL of
dichloromethane was added. The resulting organic phase was washed
with water (5 × 10 mL) and saturated brine (2 × 10 mL) and dried
over anhydrous MgSO4. After filtration and concentration, the residue
was flash-chromatographed on a silica gel column (petroleum ether/
ethyl acetate/dichloromethane 12/2/1) to afford product 6a (47%),
6b (43%), or 11 (36%). Data for 11 (as yellow powder): mp 204−206
°C; 1H NMR (400 MHz, CDCl3) δ 7.43 (t, J = 8.0 Hz, 2 H), 7.14 (t, J
= 7.4 Hz, 1 H), 6.89 (dd, J = 6.8 Hz, J = 6.8 Hz, 1 H), 6.81−6.78 (m, 2
H), 6.54 (d, J = 7.8 Hz, 2 H), 6.06 (d, J = 8.0 Hz, 2 H), 6.00 (d, J = 8.0
Hz, 2 H), 3.84 (s, 2 H),3.79 (s, 3 H), 3.26 (s, 6 H), 3.10 (s, 6 H); 13C
NMR (100 MHz, CDCl3) δ 167.8 (s), 158.8 (s), 158.7 (s), 157.4 (s),
141.0 (s), 139.1 (s), 137.4 (s), 137.3 (s), 128.0 (s), 124.0 (s), 120.5
(s), 96.0 (s), 94.1 (s), 38.4 (s), 36.3 (s); IR (KBr, cm−1) ν 2902, 1742,
1598, 1567, 1474, 1421, 1248, 1133; HRMS [ESI] calcd for
C28H30N7O2 [M + H]+ 496.2461, found 496.2460. Anal. Calcd for
C28H29N7O2: C, 67.86; H, 5.90; N, 19.78. Found: C, 67.84; H, 5.88;
N, 19.74.
AUTHOR INFORMATION
Corresponding Authors
*E-mail for L.Z.: zhaolchem@mail.tsinghua.edu.cn.
*E-mail for M.-X.W.: wangmx@mail.tsinghua.edu.cn.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support by MOST (973 program, 2013CB834501),
NNSFC (21132005, 21421064, 21522206), and Beijing Higher
Education Teacher Project (YETP0130) is gratefully acknowl-
edged.
REFERENCES
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