Palladium(II)-catalyzed regioselective arylation of naphthylamides with aryl iodides utilizing a quinolinamide bidentate system

Article abstract of DOI:10.1021/jo400017v

A palladium(II)-catalyzed quinolinamide-directed 8-arylation of 1-naphthylamides with aryl iodides is reported. The bidentate directing group (quinolinamide) proved to be crucial for a highly regioselective transformation. In addition, the amide directing group can be easily hydrolyzed under basic conditions to offer a range of 8-aryl-1-naphthylamine derivatives. The theoretical calculations suggest that the C-H arylation reaction proceeds through a sequential C-H activation/oxidative addition pathway.

Full text of DOI:10.1021/jo400017v

Article
pubs.acs.org/joc
Palladium(II)-Catalyzed Regioselective Arylation of Naphthylamides
with Aryl Iodides Utilizing a Quinolinamide Bidentate System
Lehao Huang,† Qian Li,†,‡ Chen Wang,† and Chenze Qi*,†
†Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Institute of Applied Chemistry, Shaoxing
University, Shaoxing, Zhejiang Province 312000, People’s Republic of China
‡College of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 310014, People’s Republic of China
S
* Supporting Information
ABSTRACT: A palladium(II)-catalyzed quinolinamide-direc-
ted 8-arylation of 1-naphthylamides with aryl iodides is
reported. The bidentate directing group (quinolinamide)
proved to be crucial for a highly regioselective transformation.
In addition, the amide directing group can be easily hydrolyzed
under basic conditions to offer a range of 8-aryl-1-naphthyl-
amine derivatives. The theoretical calculations suggest that the C−H arylation reaction proceeds through a sequential C−H
activation/oxidative addition pathway.
group.11 Based on the previous work, we expected that the
bidentate system would bind tightly to catalysts, thereby
bringing the catalyst into close proximity to the 8-C−H bond of
1-naphthylamides to form intermediate A (Scheme 1). Herein
we report on the palladium(II)-catalyzed quinolinamide-
directed regioselective C-8 arylation of 1-naphthylamides with
a range of aryl iodides without the use of silver salt.
INTRODUCTION
■
8-Aryl-1-naphthylamine scaffolds as an important structural
unit widely exist in functional molecules,1 such as potential
chiral ligands,1a,b organic semiconductors,1e,f and electro-
luminescent materials.1f−h This key scaffold can be accessed
by representative cross-coupling reactions between an arylmetal
and an aryl halide.1a,b In recent years, emerging strategies for
making C−C biaryl linkages based on C−H arylation of arenes
have been developed.2 The newer transformations do not
require preparation of arylmetals and/or aryl halides in advance
as coupling partners. Hence, these transformations provide
rapid and environmentally benign access to biaryls. However,
the desired regioselectivity of C−H arylation remains a major
concern.3 Monodentate group-assisted transformation has
emerged as a powerful alternative method for ortho-C−H
arylation to control the regiochemistry.4 For example, Daugulis
and co-worker reported a palladium(II)-catalyzed ortho-
arylation of anilides with aryl iodides; the only C-2 arylated
product was formed when naphthylpivalamide was used as a
substrate (Scheme 1).5
RESULTS AND DISCUSSION
■
To evaluate the feasibility of this methodology, naphthylquino-
line-2-carboxamide 1a was chosen as a test substrate reacted
with iodobenzene under various palladium-catalyzed condi-
tions. The initial trial using Pd(OAc)2 as the catalyst and
AgOAc as the additive in xylene provided only trace amounts of
product 3a (Table 1, entry 1). Replacing AgOAc with
Cu(OAc)2 as the additive gave a slight improvement (Table
1, entry 2). Addition of HOAc only moderately improved the
yield, and CF3COOH completely suppressed product 3a
formation (Table 1, entries 3 and 4). Variation in inorganic
base additives was then investigated (Table 1, entries 5−10).
Most of the examined inorganic base additives displayed low
efficiencies except for K3PO4·3H2O and KOAc. Addition of
K3PO4·3H2O increased the yield of 3a to 75% (Table 1, entry
9). To our delight, the optimal reaction was achieved with 2
equiv of KOAc as the additive in xylene at 130 °C for 12 h
(Table 1, entry 10). A control experiment without the use of
additive resulted in a decreased yield (Table 1, entry 11). The
result demonstrated that inorganic base additives play a critical
role on the transformation. Other palladium catalysts such as
PdCl2, Pd2(dba)3, and Pd(CH3CN)2Cl2 also worked in this
transformation but delivered slightly lower yields (Table 1,
In view of the value of 8-aryl-1-naphthylamine scaffolds, our
goal was to seek strategies for the efficient and regioselective C-
8 arylation of 1-naphthylamine. A bidentate system that has
been used for the successful arylation of C−H bonds drew our
attention.6 A pioneering work by Daugulis and co-workers
describes the method by employing bidentate system for the
direct arylation of unactivated sp3 C−H bonds.7 This
methodology by Corey et al. has been used in β-C−H arylation
of α-amino acid derivatives.8 Chen and co-workers have applied
their strategy of arylation to total synthesis of natural product
celogentin and (+)-obafluorin.9 The method by Zhang et al. has
also been utilized for arylation/oxidation of benzylic C−H
bonds in sequential process.10 Very recently, Chatani et al. have
reported on the ruthenium-catalyzed ortho-arylation of aromatic
amides with aryl bromides assisted by a bidentate directing
Received: January 5, 2013
Published: February 20, 2013
© 2013 American Chemical Society
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Scheme 1. Pd(II)-Catalyzed Regioselective C−H Arylation of 1-Naphthylamides with Aryl Iodides
a
Table 1. Optimization of Reaction Conditions
reaction efficiency (Table 2, entry 4). Furthermore, the
structure of 3b was confirmed by X-ray crystallography (see
the Supporting Information).
Various 1-naphthylamides were then evaluated as shown in
Scheme 2. When the analogue N-(naphthalen-1-yl)-
picolinamides were used in place of 1a as the substrates, the
aryl iodides with both electron-withdrawing (COOEt) and
electron-donating substituents (OMe) underwent this trans-
formation to form the corresponding products in moderate to
good yields (Scheme 2, 3n−p). But no arylated products (3q,r)
were obtained when the corresponding benzamide or
acetamide was used in place of 1a as the substrate, indicating
that the coordination in a bidentate N,N fashion is a key step
for the reaction to proceed.
Since the 8-aryl-1-naphthylamine scaffolds widely exist in
functional molecules, especially electroluminescent materials,
we applied this protocol to test on polycyclic aromatic amines.
To our disappointment, no reaction occurred when 1- or 9-
anthracenamide (1c,d) was used in place of 1a as the substrate
presumably due to the steric factor or rigid structure (Scheme
3). Furthermore, no desired product was achieved when 1-
hexahydronaphthalenamide 1e was employed as the substrate.
Some preliminary mechanistic studies have been carried out
to probe the details of this C−H arylation reaction. The H/D
exchange in 1a was examined by heating the substrate with a
catalytic amount of Pd(OAc)2 in a D2O (40 equiv)/xylene
mixture (Scheme 4). After 12 h at 130 °C, 91% deuterium
incorporation was observed at the 8-position of 1-naphthyla-
mide 3s. No deuterated product was observed in the absence of
Pd(OAc)2 (Scheme 4). These experiments indicated that the
palladation process was reversible and C−H activation could
take place under the reaction conditions without the
involvement of the ArI substrate and KOAc. However, our
efforts to obtain the putative palladacycle intermediate have
been unsuccessful.
entry
catalyst (mol %)
additive
AgOAc
solvent
xylene
yield (%)
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
5
2
Cu(OAc)2
HOAc
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
toluene
DMF
23
34
trace
22
28
34
32
75
96
40
72
88
90
82
N.D
32
5
3
4
CF3COOH
NaOAc
5
6
NaOTf
7
Na2CO3
Cs2CO3
8
9
K3PO4·3H2O
KOAc
10
11
12
13
14
15
16
17
18
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
Pd2(dba)3
Pd(CH3CN)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
ClCH2CH2Cl
t-BuOH
a
Reaction conditions: 1a (0.5 mmol), Pd catalyst (0.075 mmol), PhI
(2.0 mmol, 408 mg), additive (1.0 mmol), solvent (5 mL), 130 °C, 12
h.
entries 12−14). Screening of the solvents indicated that xylene
gave the best yield (Table 1, entries 10, 15−18).
Under the optimal reaction conditions, the substrate scope of
aryl iodides was examined as shown in Table 2. Aryl iodides
with both electron-withdrawing and electron-donating groups
presented excellent compatibility (Table 2, entries 1−13). Even
the sensitive free-hydroxyl and amine group substituted aryl
iodides were not affected in the reaction (Table 2, entries 6 and
7) and efficiently participated in the reaction giving the
corresponding arylated products 3f and 3g in 80% and 82%
yields, respectively. Notably, introducing functional groups such
as Cl, Br, COOEt, OH, and NH2 added flexibility to further
elaborate the arylated products (Table 2, entries 6−9, 12). As
for the substitution pattern, meta-substituted aryl iodides also
worked well in the reaction to give the desired product (Table
2, entries 3 and 11). However, an attempt to employ the ortho-
substituted aryl iodides failed to yield the expected product in
the reaction, showing that steric factors clearly reduced the
Based on the previous studies12 and our experimental results,
two plausible reaction paths were proposed as shown in
Scheme 5. First, intermediate B was formed by the
coordination of Pd(OAc)2 with substrate 1a.13 In path a,
intermediate B underwent a sequential C−H activation14/
oxidative addition with aryl iodides to produce the Pd(IV)
intermediate D,15 which was followed by a reductive
elimination to result in the arylation product 3a and
regenerated the catalyst. Through a different order than path
a, the intermediate B underwent a sequential oxidative
addition/C−H activation with aryl iodides to produce the
Pd(IV) intermediate D in path b. To determine the order of
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a
Table 2. Scope of the Aryl Iodides
a
Reaction conditions: 1a (0.5 mmol, 149 mg), Pd(OAc)2 (0.075 mmol, 16 mg), ArI (2.0 mmol), KOAc (1.0 mmol, 98 mg), xylene (5 mL), 130 °C,
b
12 h. Isolated yield on a 5.0 mmol scale, 66 h.
C−H activation process versus the oxidative addition of ArI to
Pd(II), we performed theoretical calculations on the two
pathways (Figure 1).16 The optimized structures of selected
transition states were shown in Figure 2. As can be seen in
Figure 1, the energy barrier of path a was 25.3 kcal/mol, and
the oxidative addition step via transition state TSC′‑D was the
rate-determining step. On the other hand, the oxidative
addition step in path b required higher activation energy of
28.8 kcal/mol. Although not conclusive, our calculations
favored a sequential C−H activation/oxidative addition path-
way for this C−H arylation reaction.
Futhermore, the amide directing group could be simply
hydrolyzed (Scheme 6). The arylated substrates 3a and 3n were
heated with NaOH in ethanol to afford 92% and 85% yields of
8-phenyl-1-naphthylamine 3t, respectively.
CONCLUSIONS
■
In conclusion, we have demonstrated a powerful methodology
for the Pd-catalyzed regioselective arylation of the 1-
naphthylamides by employing a bidentate system. This
transformation tolerates a broad range of aryl iodides, even
including the sensitive free-hydroxyl and amine group
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Scheme 2. Screening of 1-Naphthylamides Auxiliaries
Other materials were purchased from common commercial sources
and used without additional purification.
Scheme 3. Unreactive Substrates
Preparation of Amide Compounds 1a−e.10 Amine (20 mmol),
picolinic acid, or quinoline-2-carboxylic acid (20 mmol), and Et3N (40
mmol, 5.6 mL) were dissolved in CH2Cl2 (40 mL) followed by
dropwise addition of POCl3 (3.76 mL) at 0 °C. The resulting mixture
was stirred at 0 °C for 0.5 h and warmed to room temperature for 2 h.
Then the reaction mixture was cooled to 0 °C. Ice−water was added
slowly to quench the reaction. The organic layer was collected, and the
aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The
combined organic phase was washed by saturated NaHCO3 (2 × 40
mL) and dried over MgSO4. The solvent was evaporated under
reduced pressure, and the residue was crystallized from CH2Cl2/
petroleum ether to give the desired product.
Scheme 4. Preliminary Mechanistic Studies
N-(Naphthalen-1-yl)quinoline-2-carboxamide (1a, CAS no.
1
298193-67-6): 4.29 g, 72% yield; pink solid; mp = 146−147 °C; H
NMR (400 MHz, CDCl3) δ 10.95 (s, 1 H), 8.43 (d, J = 8.4 Hz, 2 H),
8.36 (d, J = 8.0 Hz, 1 H), 8.25 (d, J = 8.4 Hz, 1 H), 8.16 (d, J = 8.4 Hz,
1 H), 7.91 (d, J = 8.0 Hz, 2 H), 7.81 (t, J = 7.2 Hz, 1 H), 7.71 (d, J =
8.4 Hz, 1 H), 7.59 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 162.4,
149.9, 146.3, 138.0, 134.2, 132.5, 130.4, 129.9, 129.5, 128.9, 128.2,
127.9, 126.5, 126.3, 126.1, 126.0, 125.1, 120.5, 118.8, 118.7. HRMS
(ESI) calcd for C20H14N2O [M + H]+ 299.1179, found 299.1182.
N-(Naphthalen-1-yl)picolinamide (1b, CAS no. 75358-95-
1):14 2.98 g, 60% yield; pink solid; mp = 128−129 °C; 1H NMR (400
MHz, CDCl3) δ 10.75 (s, 1 H), 8.70 (d, J = 5.2 Hz, 1 H), 8.41 (d, J =
7.2 Hz, 1 H), 8.36 (d, J = 7.6 Hz, 1 H), 8.09 (d, J = 8.4 Hz, 1 H), 7.91
(m, 2 H), 7.70 (d, J = 8.4 Hz, 1 H), 7.55 (m, 4 H); 13C NMR (100
MHz, CDCl3) δ 162.3, 150.1, 148.2, 137.8, 134.1, 132.4, 128.8, 126.5,
126.4, 126.3, 126.0, 125.9, 125.0,122.5, 120.5, 118.6. HRMS (ESI)
calcd for C16H12N2O [M + H]+ 249.1022, found 249.1020.
substituted. The amide auxiliary is effectively detached under
mild conditions to provide a synthetic method for 8-phenyl-1-
naphthylamine. Furthermore, the comparison of two plausible
reaction paths is conducted by theoretical calculations. The
result indicates that a sequential C−H activation/oxidative
addition pathway is favorable for the C−H arylation reaction.
EXPERIMENTAL SECTION
■
General Methods. Unless otherwise stated, all reactions were
carried out in an oven-dried flask in air. 1H NMR spectra were
recorded at 400 MHz, and the chemical shifts were reported in parts
per million (δ) relative to internal standard TMS (0 ppm) for CDCl3
or DMSO-d6. The peak patterns are indicated as follows: s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet; dd, doublet of doublet. The
coupling constants, J, are reported in hertz (Hz). 13C NMR spectra
were recorded at 100 MHz and referenced to the internal solvent
signals (center peak is 77.00 ppm in CDCl3 or 39.90 ppm in DMSO-
d6). High-resolution mass spectra (HRMS-ESI) were obtained on a
FT-ICR spectrometer. Amide derivatives 1a−e10 were synthesized
according to the literature procedure. N-(Naphthalen-1-yl)benzamide
and N-(naphthalen-1-yl)acetamide17 were prepared by known method.
N-(Anthracen-9-yl)picolinamide (1c): 1.49 g, 25% yield; light
yellow solid; mp =197−198 °C; 1H NMR (400 MHz, CDCl3) δ 10.27
(s, 1 H), 8.72 (s, 1 H), 8.45 (s, 1 H), 8.37 (d, J = 8.0 Hz, 1 H), 8.12 (d,
J = 8.4 Hz, 2 H), 8.02 (d, J = 8.4 Hz, 2 H), 7.94 (m, 1 H), 7.49 (m, 5
H); 13C NMR (100 MHz, CDCl3) δ 163.9, 149.7, 148.4, 137.7, 131.8,
128.7, 128.4, 127.9, 127.0, 126.8, 126.4, 125.4, 123.5, 122.9; HRMS
(ESI) calcd for C20H14N2O [M + H]+ 299.1179, found 299.1181.
N-(Anthracen-1-yl)quinoline-2-carboxamide (1d): 4.66 g, 67%
1
yield; dark green solid; mp = 196−197 °C; H NMR (400 MHz,
CDCl3) δ 11.06 (s, 1 H), 8.58 (s, 1 H), 8.41 (m, 3 H), 8.34 (d, J = 8.0
Hz, 1 H), 8.26 (d, J = 8.0 Hz, 1 H), 8.05 (d, J = 6.8 Hz, 1 H), 7.95 (d, J
= 6.8 Hz, 1 H), 7.88 (d, J = 7.6 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 2 H),
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Scheme 5. Plausible Mechanism
Figure 1. Potential energy surfaces of path a (sequential C−H activation/oxidative addition) and path b (sequential oxidative addition/C−H
activation).
7.63 (t, J = 8.0 Hz, 1 H), 7.49 (m, 3 H); 13C NMR (100 MHz, CDCl3)
δ 162.4, 149.9, 146.3, 138.0, 132.2, 132.1, 131.6, 131.5, 130.4, 129.9,
129.5, 128.5, 128.2, 128.0, 127.9, 127.2, 125.8, 125.5, 125.4, 125.2,
119.1, 118.8, 117.3; HRMS (ESI) calcd for C24H16N2O [M + H]+
349.1335, found 349.1338.
N-(1,2,3,4-Tetrahydronaphthalen-1-yl)quinoline-2-carboxa-
mide (1e, CAS no. 781628-15-7): 3.02 g, 50% yield; white solid; mp
= 133−134 °C; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 9.2 Hz, 1
H), 8.37 (d, J = 8.4 Hz, 1 H), 8.26 (d, J = 8.8 Hz, 1 H), 8.02 (d, J = 8.8
Hz, 1 H), 7.81 (d, J = 8.0 Hz, 1 H), 7.67 (t, J = 8.0 Hz, 1 H), 7.54 (t, J
= 8.0 Hz, 1 H), 7.38 (d, J = 8.0 Hz, 1 H), 7.16 (m, 3 H), 5.47 (m, 1
H), 2.83 (m, 2 H), 2.20 (m, 1 H), 1.94 (m, 3 H); 13C NMR (100
MHz, CDCl3) δ 163.9, 149.9, 146.5, 137.7, 137.5, 136.8, 130.1, 129.7,
129.3, 129.2, 128.8, 127.9, 127.8, 127.3, 126.4, 119.0, 47.8, 30.5, 29.4,
20.5.
Typical Procedure for Arylation Products 3a−r. A mixture of
naphthylamide (0.5 mmol, 1.0 equiv), aryl iodides (2.0 mmol, 4.0
equiv), Pd(OAc)2 (0.075 mmol, 15 mol %), anhydrous KOAc (1.0
mmol, 2.0 equiv), and xylene (5 mL) was placed in a 35 mL Schlenk
tube with a rubber plug under air. The tube was heated at 130 °C for
12 h. The reaction mixture was cooled to rt, diluted with ethyl acetate,
filtered through Celite, and concentrated in vacuo. The residue was
purified by silica gel column chromatography with ethyl acetate/
petroleum ether to afford the desired product.
N-(8-Phenylnaphthalen-1-yl)quinoline-2-carboxamide (3a):
183 mg, 96% yield; light yellow solid after purification by column
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Figure 2. Optimized structures of selected transition states in paths a and b. Bond lengths in angstroms.
Hz, 1 H), 7.19 (d, J = 7.2 Hz, 1 H), 7.05 (d, J = 7.2 Hz, 1 H), 7.02 (s, 1
H), 6.67 (t, J = 7.6 Hz, 1 H), 6.01 (d, J = 7.6 Hz, 1 H), 1.77 (s, 3 H);
13C NMR (100 MHz, CDCl3) δ 162.1, 149.5, 145.9, 142.6, 138.0,
Scheme 6. Hydrolysis of Amide 3
137.2, 137.0, 135.6, 132.7, 130.3, 129.8, 129.6, 129.2, 128.6, 127.8,
127.8, 127.6, 127.2, 127.0, 125.9, 125.8, 125.1, 124.2, 118.4, 21.1.
HRMS (ESI) calcd for C27H20N2O [M + H]+ 389.1648, found
389.1651.
N-(8-(4-Methoxyphenyl)naphthalen-1-yl)quinoline-2-car-
boxamide (3e). 186 mg, 92% yield; light yellow solid after
purification by column chromatography (eluent, ethyl acetate/
petroleum ether =1/6, v/v); mp =168−169 °C; 1H NMR (400
MHz, CDCl3) δ 9.57 (s, 1 H), 8.26 (t, J = 8.4, 1 H), 8.24 (t, J = 8.4 Hz,
1 H), 8.10 (d, J = 7.6 Hz, 1 H), 7.87 (m, 4 H), 7.78 (t, J = 7.6 Hz, 1
H), 7.62 (t, J = 8.0, 1 H), 7.60 (t, J = 8.4 Hz, 1 H), 7.50 (t, J = 8.0 Hz,
1 H), 7.34 (d, J = 6.8 Hz, 1 H), 7.30 (t, J = 8.4 Hz, 2 H), 6.44 (d, J =
8.4 Hz, 2 H), 2.90 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 162.0,
158.2, 149.8, 145.7, 137.5, 137.2, 135.6, 135.0, 132.7, 130.4, 130.2,
129.9, 129.7, 129.3, 128.4, 127.7, 127.6, 126.7, 125.9, 125.7, 125.0,
123.6, 118.5, 113.2, 54.1. HRMS (ESI) calcd for C27H20N2O2: [M +
H]+ 405.1598; Found, 405.1595.
N-(8-(4-hydroxyphenyl)naphthalen-1-yl)quinoline-2-carbox-
amide (3f): 156 mg, 80% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/3,
v/v); mp = 256−257 °C; 1H NMR (400 MHz, C2D6SO) δ 9.85 (s, 1
H), 8.81 (s, 1 H), 8.51 (d, J = 8.8, 1 H), 8.13 (d, J = 7.6 Hz, 1 H), 8.08
(d, J = 8.4 Hz, 1 H), 8.04 (d, J = 8.4 Hz, 1 H), 7.98 (d, J = 7.6 Hz, 2
H), 7.92 (d, J = 8.0 Hz, 1 H), 7.87 (t, J = 7.6 Hz, 1 H), 7.72 (t, J = 7.6
Hz, 1 H), 7.63 (t, J = 7.6 Hz, 1 H), 7.56 (t, J = 7.2 Hz, 1 H), 7.31 (d, J
= 6.8 Hz, 1 H), 7.19 (d, J = 8.4 Hz, 2 H), 6.49 (d, J = 8.4 Hz, 2 H);
13C NMR (100 MHz, C2D6SO) δ 161.9, 157.0, 149.5, 145.8, 138.2,
chromatography (eluent, ethyl acetate/petroleum ether = 1/10, v/v);
mp = 134−135 °C; 1H NMR (400 MHz, CDCl3) δ 9.47 (s, 1 H), 8.20
(m, 2 H), 8.10 (d, J = 7.6 Hz, 1 H), 7.89 (d, J = 7.6 Hz, 1 H), 7.84 (m,
3 H), 7.74 (t, J = 7.2 Hz, 1 H), 7.59 (m, 2 H), 7.49 (t, J = 7.2 Hz, 1 H),
7.38 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 7.2 Hz, 1 H), 6.93 (t, J = 7.6 Hz,
2 H), 6.39 (t, J = 7.2 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 162.0,
149.6, 145.7, 142.8, 137.9, 137.1, 135.6, 132.7, 130.4, 130.3, 129.6,
129.2, 128.8, 128.7, 127.9, 127.7, 127.6, 126.8, 126.3, 125.9, 125.7,
125.0, 123.7, 118.4; HRMS (ESI) calcd for C26H18N2O [M + H]+
375.1492, found 375.1497.
N-(8-Tolylnaphthalen-1-yl)quinoline-2-carboxamide (3b):
165 mg, 85% yield; light yellow solid after purification by column
chromatography (eluent, ethyl acetate/petroleum ether = 1/10, v/v);
mp =145−146 °C; 1H NMR (400 MHz, CDCl3) δ 9.50 (s, 1 H), 8.25
(d, J = 8.4, 1 H), 8.22 (t, J = 8.4 Hz, 1 H), 8.08 (d, J = 7.2 Hz, 1 H),
7.87 (m, 4 H), 7.78 (t, J = 8.4 Hz,1 H), 7.62 (t, J = 8.4 Hz, 1 H), 7.60
(t, J = 8.0 Hz, 1 H), 7.49 (t, J = 7.2 Hz, 1 H), 7.33 (d, J = 7.2 Hz, 1 H),
7.26 (d, J = 8.0 Hz, 2 H), 6.69 (d, J = 7.2 Hz, 2 H), 1.25 (s, 3 H); 13C
NMR (100 MHz, CDCl3) δ 162.0, 149.7, 145.7, 139.7, 137.9, 137.1,
136.2, 135.5, 132.6, 130.3, 130.2, 129.7, 129.2, 128.7, 128.6, 128.5,
127.7, 127.6, 126.8, 125.9, 125.7, 125.0, 123.8, 118.4, 20.0. HRMS
(ESI) calced for C27H20N2O [M + H]+ 389.1648, found 389.1651.
N-(8-m-Tolylnaphthalen-1-yl)quinoline-2-carboxamide (3c):
159 mg, 82% yield; light yellow solid after purification by column
chromatography (eluent, ethyl acetate/petroleum ether = 1/10, v/v);
mp = 128−129 °C; 1H NMR (400 MHz, CDCl3) δ 9.31 (s, 1 H), 8.07
(s, 2 H), 7.91 (d, J = 7.6 Hz, 1 H), 7.71 (m, 4 H), 7.59 (t, J = 7.2 Hz, 1
H), 7.46 (t, J = 7.6 Hz, 1 H), 7.43 (t, J = 6.8 Hz, 1 H), 7.33 (t, J = 7.6
138.1, 135.7, 133.4, 132.8, 131.0, 130.7, 130.3, 130.1, 129.3, 128.4,
128.2, 126.7, 126.1, 125.7, 125.2, 122.7, 118.4, 115.3; HRMS (ESI)
calcd for C26H18N2O2 [M + H]+ 391.1441, found 391.1437.
N-(8-(4-Aminophenyl)naphthalen-1-yl)quinoline-2-carboxa-
mide (3g): 160 mg, 82% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/2,
1
v/v); mp = 154−155 °C; H NMR (400 MHz, CDCl3) δ 9.71 (s, 1
H), 8.24 (s, 2 H), 8.18 (d, J = 7.6, 1 H), 7.96 (d, J = 8.4 Hz, 1 H), 7.80
(m, 4 H), 7.59 (t, J = 8.0 Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.46 (t, J
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= 8.0 Hz, 1 H), 7.32 (d, J = 7.2 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 2 H),
6.23 (d, J = 8.8 Hz, 2 H), 2.56 (s, 2 H); 13C NMR (100 MHz, CDCl3)
δ 162.0, 150.1, 145.9, 145.2, 138.0, 137.1, 135.6, 132.9, 132.7, 130.4,
129.8, 129.5, 129.2, 128.2, 127.7, 127.6, 126.5, 125.8, 125.4, 125.1,
122.8, 118.6, 114.6; HRMS (ESI) calcd for C26H19N3O [M + H]+
390.1601, found 390.1597.
N-(8-(4-Bromophenyl)naphthalen-1-yl)quinoline-2-carboxa-
mide (3h): 168 mg, 74% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/
10, v/v); mp = 162−163 °C; 1H NMR (400 MHz, CDCl3) δ 9.47 (s, 1
H), 8.30 (d, J = 8.4, 1 H), 8.23 (d, J = 8.4 Hz, 1 H), 8.03 (d, J = 7.8
Hz, 1 H), 7.92 (d, J = 7.6 Hz, 1 H), 7.87 (t, J = 8.4 Hz, 3 H), 7.79 (t, J
= 8.0 Hz, 1 H), 7.64 (t, J = 8.4 Hz, 1 H), 7.61 (t, J = 8.4 Hz, 1 H), 7.50
(t, J = 8.0 Hz, 1 H), 7.31 (d, J = 7.2 Hz, 1 H), 7.24 (d, J = 7.6 Hz, 2
H), 7.01 (d, J = 8.4 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 162.0,
149.2, 145.8, 141.7, 137.5, 136.6, 135.5, 132.3, 130.8, 130.4, 130.2,
130.1, 130.0, 129.6, 129.1, 127.9, 127.8, 127.1, 126.1, 125.8, 125.0,
124.6, 120.7, 118.2; HRMS (ESI) calcd for C26H17BrN2O [M + H]+
453.0597, found 453.0591.
N-(8-(4-Chlorophenyl)naphthalen-1-yl)quinoline-2-carboxa-
mide (3i): 182 mg, 89% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/
10, v/v); mp = 158−159 °C; 1H NMR (400 MHz, CDCl3) δ 9.46 (s, 1
H), 8.28 (d, J = 8.4, 1 H), 8.21 (d, J = 8.4 Hz, 1 H), 8.03 (d, J = 7.6
Hz, 1 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.86 (m, 3 H), 7.78 (t, J = 8.0 Hz,
1 H), 7.61 (m, 2 H), 7.49 (t, J = 8.0 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 3
H), 6.86 (d, J = 8.4, 2 H); 13C NMR (100 MHz, CDCl3) δ 162.0,
149.3, 145.8, 141.2, 137.5, 136.6, 135.5, 132.7, 132.3, 130.3, 130.1,
130.0, 129.9, 129.5, 129.1, 127.9, 127.8, 127.1, 126.1, 125.8, 125.0,
124.5, 118.2; HRMS (ESI) calcd for C26H17ClN2O [M + H]+
409.1102, found 409.1107.
N-(8-(4-Fluorophenyl)naphthalen-1-yl)quinoline-2-carboxa-
mide (3j): 174 mg, 89% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/
10, v/v); mp = 172−173 °C; 1H NMR (400 MHz, CDCl3) δ 9.50 (s, 1
H), 8.25 (t, J = 8.4, 1 H), 8.23 (t, J = 8.4 Hz, 1 H), 8.08 (d, J = 7.2 Hz,
1 H), 7.86 (m, 4 H), 7.77 (t, J = 7.6 Hz, 1 H), 7.62 (m, 2 H), 7.48 (t, J
= 7.6 Hz, 1 H), 7.30 (m, 3 H), 6.62 (t, J = 8.4 Hz, 2 H); 13C NMR
(100 MHz, CDCl3) δ 162.9, 161.9, 160.4, 149.4, 145.7, 138.8, 138.7,
137.5, 136.7, 135.6, 132.5, 130.5, 130.4, 130.3, 129.9, 129.8, 129.3,
128.9, 127.9, 127.7, 126.9, 126.0, 125.8, 125.0, 124.1, 118.4, 114.8,
114.6; HRMS (ESI) calcd for C26H17FN2O [M + H]+ 393.1398, found
393.1393.
HRMS (ESI) calcd for C29H22N2O3 [M + H]+ 447.1703, found
447.1709.
N-(8-(4-Nitrophenyl)naphthalen-1-yl)quinoline-2-carboxa-
mide (3m): 171 mg, 82% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/6,
1
v/v); mp = 211−212 °C; H NMR (400 MHz, CDCl3) δ 9.31 (s, 1
H), 8.23 (d, J = 8.4, 1 H), 8.17 (d, J = 8.4 Hz, 1 H), 7.96 (t, J = 8.6 Hz,
2 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.76 (d, J =
3.2 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H), 7.62 (m, 2 H), 7.51 (m, 3 H),
7.31 (d, J = 7.2 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 162.0,
150.1, 148.9, 145.9, 145.2, 137.7, 135.6, 135.5, 131.9, 130.5, 130.2,
130.0, 129.6, 129.3, 129.2, 128.3, 127.9, 127.6, 126.4, 126.1, 125.7,
125.0, 122.9, 118.2. HRMS (ESI) calcd for C26H17N3O3 [M + H]+
420.1343, found 420.1349.
N-(8-Phenylnaphthalen-1-yl)picolinamide (3n): 136 mg, 84%
yield; light yellow solid after purification by column chromatography
(eluent, ethyl acetate/petroleum ether = 1/10, v/v); mp = 125−126
°C; 1H NMR (400 MHz, CDCl3) δ 9.58 (s, 1 H), 8.26 (d, J = 7.6 Hz,
1 H), 8.14 (d, J = 4.8 Hz, 1 H), 8.07 (d, J = 7.6 Hz, 1 H), 7.87 (d, J =
8.0 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 1 H), 7.72 (t, J = 7.6 Hz, 1 H), 7.57
(t, J = 8.0 Hz, 1 H), 7.46 (t, J = 8.0 Hz, 1 H), 7.38 (d, J = 7.2 Hz, 2 H),
7.33 (m, 2 H), 7.16 (t, J = 7.6 Hz, 2 H), 6.98 (t, J = 7.6 Hz, 1 H); 13C
NMR (100 MHz, CDCl3) δ 162.0, 149.8, 147.4, 142.8, 137.7, 137.0,
135.5, 132.9, 130.5, 129.2, 128.8, 128.1, 126.8, 126.4, 125.9, 125.7,
125.0, 124.9, 122.5, 121.8; HRMS (ESI) calcd for C22H16N2O [M +
H]+ 325.1335, found 325.1331.
N-(8-(4-Methoxyphenyl)naphthalen-1-yl)picolinamide (3o):
129 mg, 73% yield; light yellow solid after purification by column
chromatography (eluent, ethyl acetate/petroleum ether = 1/6, v/v);
mp = 154−155 °C; 1H NMR (400 MHz, CDCl3) δ 9.71 (s, 1 H), 8.29
(d, J = 7.6, 1 H), 8.19 (d, J = 4.4 Hz, 1 H), 8.11 (d, J = 8.0 Hz, 1 H),
7.86 (d, J = 7.6, 1 H), 7.78 (t, J = 7.6 Hz, 2 H), 7.57 (t, J = 7.6, 1 H),
7.47 (t, J = 8.4 Hz, 1 H), 7.32 (m, 4 H), 6.72 (d, J = 8.4 Hz, 2 H), 3.59
(s, 3 H); 13C NMR (100 MHz, CDCl3) δ 161.9, 158.9, 150.0, 147.4,
137.3, 136.9, 135.5, 135.1, 133.0, 130.5, 130.3, 128.5, 126.3, 125.9,
125.7, 125.0, 124.9, 122.2, 121.9, 113.6, 55.0; HRMS (ESI) calcd for
C23H18N2O2 [M + H]+ 355.1441, found 355.1440.
Ethyl 4-(8-(picolinamido)naphthalen-1-yl)benzoate (3p): 109
mg, 55% yield; light yellow solid after purification by column
chromatography (eluent, ethyl acetate/petroleum ether = 1/6, v/v);
mp = 109−110 °C; 1H NMR (400 MHz, CDCl3) δ 9.35 (s, 1 H), 8.12
(m, 2 H), 8.07 (t, J = 7.6 Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.83 (m,
3 H), 7.73 (t, J = 7.6 Hz, 1 H), 7.59 (t, J = 8.0 Hz, 1 H), 7.50 (d, J =
8.0 Hz, 1 H), 7.44 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 7.2 Hz, 1 H), 7.24
(dd, J = 7.6, 4.8 Hz, 1 H), 4.30 (q, J = 7.2 Hz, 2 H), 1.36 (t, J = 7.2 Hz,
3 H); 13C NMR (100 MHz, CDCl3) δ 166.2, 161.9, 149.5, 147.6,
147.4, 137.0, 136.7, 135.5, 132.4, 130.1, 129.3, 129.2, 129.1, 128.8,
126.8, 126.1, 125.8, 125.3, 124.9, 123.7, 121.9, 60.7, 14.4; HRMS
(ESI) calcd for C25H20N2O3 [M + H]+ 397.1547, found 397.1543.
Procedure for Deuteration of Naphthylquinoline-2-carbox-
amide 1a. A mixture of naphthylquinoline-2-carboxamide 1a (0.5
mmol, 149 mg), Pd(OAc)2 (0.075 mmol, 16 mg), D2O (20.0 mmol,
400 mg), and xylene (5 mL) was placed in a 35 mL Schlenk tube with
rubber plug under air. The tube was heated at 130 °C for 12 h. The
reaction mixture was cooled to rt, diluted with ethyl acetate, filtered
through Celite, and concentrated in vacuo. The residue was purified by
silica gel column chromatography with ethyl acetate/petroleum ether
to afford the desired product.
N-(8-(3-Fluorophenyl)naphthalen-1-yl)quinoline-2-carboxa-
mide (3k): 174 mg, 89% yield; light yellow solid after purification by
column chromatography (eluent, ethyl acetate/petroleum ether = 1/
10, v/v); mp = 125−126 °C; 1H NMR (400 MHz, CDCl3) δ 9.48 (s, 1
H), 8.24 (t, J = 8.4, 1 H), 8.22 (t, J = 8.4 Hz, 1 H), 8.06 (d, J = 7.6 Hz,
1 H), 7.91 (t, J = 8.8 Hz, 2 H), 7.85 (d, J = 8.0 Hz, 2 H), 7.77 (t, J =
6.8 Hz, 1 H), 7.61 (m, 2 H), 7.49 (t, J = 7.2 Hz, 1 H), 7.31 (d, J = 6.0
Hz, 1 H), 7.19 (d, J = 8.4 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 6.80 (td,
J = 8.0, 7.6 Hz, 1 H), 6.07 (t, J = 8.4 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 163.5, 162.1, 161.0, 149.3, 145.8, 145.1, 145.0, 137.3, 136.5,
136.4, 135.5, 132.4, 130.3, 130.1, 129.8, 129.3, 129.2, 129.1, 127.9,
127.6, 127.0, 126.1, 125.8, 125.0, 124.9, 124.4, 118.4, 116.0, 115.8,
113.3, 113.1; HRMS (ESI) calcd for C26H17FN2O [M + H]+ 393.1398,
found 393.1403.
Ethyl 4-(8-quinoline-2-carboxamido)naphthalen-1-yl)-
benzoate (3l): 187 mg, 84% yield; light yellow solid after purification
by column chromatography (eluent, ethyl acetate/petroleum ether =
1/6, v/v); mp = 127−128 °C; 1H NMR (400 MHz, CDCl3) δ 9.34 (s,
1 H), 8.21 (t, J = 8.4, 1 H), 8.20 (t, J = 8.8 Hz, 1 H), 7.98 (d, J = 7.6
Hz, 1 H), 7.94 (d, J = 8.4 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 1 H), 7.81 (d, J
= 9.2 Hz, 2 H), 7.75 (t, J = 6.8 Hz, 1 H), 7.62 (m, 2 H), 7.56 (d, J =
8.4 Hz, 2 H), 7.51 (t, J = 8.0 Hz, 1 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.33
(d, J = 7.2 Hz, 1 H), 3.81 (q, J = 7.2 Hz, 2 H), 1.09 (t, J = 7.2 Hz, 3
H); 13C NMR (100 MHz, CDCl3) δ 165.1, 162.1, 149.2, 147.5, 145.5,
137.3, 136.9, 135.5, 132.2, 130.1, 130.0, 129.9, 129.3, 129.0, 128.8,
128.2, 127.7, 127.5, 127.3, 126.1, 126.0, 125.0, 118.3, 60.3, 14.0;
D-N-(Naphthalen-1-yl)quinoline-2-carboxamide (3s): 140 mg,
94% yield (91% D); light yellow solid after purification by column
chromatography (eluent, ethyl acetate/petroleum ether = 1/10, v/v);
1
mp = 146−147 °C; H NMR (400 MHz, CDCl3) δ 10.86 (s, 1 H),
8.43 (d, J = 7.2 Hz, 1 H), 8.35 (d, J = 8.4 Hz, 1 H), 8.23 (d, J = 8.4 Hz,
1 H), 8.16 (d, J = 8.4 Hz, 1 H), 8.08 (d, J = 8.4 Hz, 0.09 H), 7.83 (d, J
= 8.4 Hz, 1 H), 7.78 (d, J = 7.6 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H),
7.64 (d, J = 8.4 Hz, 1 H), 7.51 (m, 4 H); 13C NMR (100 MHz,
CDCl3) δ 162.3, 149.8, 146.2, 137.9, 134.2, 132.5, 130.4, 129.8, 129.4,
128.9, 128.2, 127.8, 126.4, 126.2, 126.1, 126.0, 125.9, 125.0, 118.8,
118.5; HRMS (ESI) calcd for C20H13DN2O [M + H]+ 300.1242,
found 300.1246.
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Procedure for Hydrolysis of Amides 3a and 3n. Quinoline-2-
carboxamide 3a or picolinamide 3n (0.25 mmol) and NaOH (240 mg,
6 mmol) were heated in ethanol (3 mL) for 12 h at 80 °C. After
completion, the mixture was diluted with ethyl acetate, filtered through
Celite, and concentrated in vacuo. The residue was purified by silica
gel column chromatography with ethyl acetate/petroleum ether to
afford the desired product.
Nakamura, M. WO2010104047A1, 2010. (h) Kim, T. H.; Kim, H. M.;
Baek, Y. M.; Kim, Y. B. KR2012095832A, 2012.
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D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174.
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8-Phenylnaphthalen-1-amine (3t, CAS no. 1254293-67-8):1b
50 mg, 92% yield; brown oil after purification by column
chromatography (eluent, ethyl acetate/petroleum ether = 1/20, v/
v); 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 1 H), 7.35 (m,
7 H), 7.23 (d, J = 8.0 Hz, 1 H), 7.11 (d, J = 7.2 Hz, 1 H), 6.55 (d, J =
7.2 Hz, 1 H), 3.57 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 163.9,
149.7, 148.3, 137.7, 131.8, 128.7, 128.4, 127.8, 127.0, 126.7, 126.4,
125.4, 123.5, 122.9.
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COMPUTATIONAL METHODS
■
All the calculations were performed using Gaussian 09 programs.18
Geometry optimization was conducted using B3LYP method19 with
the combined basis set, i.e., LANL2DZ for Pd, I atoms and 6-31+G(d)
for the other elements. Frequency analysis was conducted at the same
level of theory to confirm the stationary points to be minima or saddle
points. For all of the saddle points, intrinsic reaction coordinate
analysis (IRC)20 was performed to verify that them connect the right
reactants and products on the potential energy surface. Single-point
energy calculations in solution phase were calculated using the M06-L
method21 with a larger basis set, i.e., LANL2DZ with an added f-
polarization shell for Pd, I and 6-311++g(2df,2p) for the other
elements. Solvent effect was accounted for using the polarizable
continuum model (PCM) with the radii and nonelectrostatic terms for
the Truhlar and co-workers’ universal solvation model (SMD).22
Xylene was used as the solvent. Single-point energy corrected by the
Gibbs free energy correction from frequency calculation was used as
Gibbs free energy to describe the reaction energetics.
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H arylation, see: (a) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M.
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Borduas, N.; Dong, V. M. Chem. Sci. 2010, 1, 331. (c) Song, W.;
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, full spectroscopic data for all new
compounds, crystallographic data of compound 3b, energy
properties, and Cartesian coordinates of reactants, intermedi-
ates, and transition states. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: qichenze@usx.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Funding from NSFC (No. 21172149), the Science and
Technology Department of Zhejiang Province, and the
Foundation of Shaoxing University (2012LG1005) is greatly
acknowledged.
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