CuSO4·5H2O-catalyzed aminobenzannulation of ortho-alkynylaromatic ketones with anilines approach towards 1-aminonaphthalenes

Article abstract of DOI:10.1016/j.tet.2016.06.036

An efficient catalyst system for the aminobenzannulation of ortho-alkynylaromatic ketones with amines affording substituted 1-aminonaphthalene derivatives with high atom-efficiency in the presence of CuSO₄·5H₂O was developed.

Full text of DOI:10.1016/j.tet.2016.06.036

Accepted Manuscript
CuSO ·5H O-catalyzed aminobenzannulation of ortho-alkynylaromatic ketones with
4
2
anilines approach towards 1-aminonaphthalenes
Biao Guo, Ruimao Hua
PII:
S0040-4020(16)30549-X
10.1016/j.tet.2016.06.036
TET 27850
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 April 2016
Revised Date: 9 June 2016
Accepted Date: 12 June 2016
Please cite this article as: Guo B, Hua R, CuSO ·5H O-catalyzed aminobenzannulation of ortho-
4
2
alkynylaromatic ketones with anilines approach towards 1-aminonaphthalenes, Tetrahedron (2016), doi:
10.1016/j.tet.2016.06.036.
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ACCEPTED MANUSCRIPT
Graphical Abstract
.
CuSO4 5H2O-catalyzed aminobenzannulation of ortho-alkynylaromatic ketones with
anilines approach towards 1-aminonaphthalenes
1

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.
CuSO4 5H2O-catalyzed aminobenzannulation of ortho-alkynylaromatic ketones with
anilines approach towards 1-aminonaphthalenes
Biao Guo, Ruimao Hua*
Department of Chemistry, Tsinghua University, Beijing 100084, China
Fax: +86-10-62771149
E-mail: ruimao@mail.tsinghua.edu.cn
Abstract:
An efficient catalyst system for the aminobenzannulation of ortho-alkynylaromatic ketones
with amines affording substituted 1-aminonaphthalene derivatives with high atom-efficiency
.
in the presence of CuSO4 5H2O was developed.
Key Words: o-Alkynylaromatic ketones; Aminobenzannulation; 1-Aminonaphthalene; Amines;
Cupric sulfate pentahydrate
1. Introduction
As the simplest class of polycyclic aromatic hydrocarbons (PAHs), naphthalenes are
particularly appealing due to their unique biological activities,1 outstanding optoelectronic
properties2 and versatile roles in synthetic chemistry and material science.3 In view of these
significant applications, the development of efficient reactions for the construction of
naphthalene ring from simple and readily available starting compounds is very important. Up
to now numerous benzannulation pathways have been developed to access naphthalenes.4-10
Among them, Asao and Yamamoto did remarkable pioneering work in the [4+2]
benzannulation of o-alkynylaromatic ketones/aldehydes with alkynes or carbonyl compounds
via isochromenylium intermediates to provide multi-substituted naphthyl ketones, which is
usually called Asao-Yamamoto benzannulation.5 Meanwhile, the aminobenzannulation
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reactions were also established for the synthesis of 1-aminonaphthalenes. For example,
Herndon and co-workers developed a PdCl2/CuI-catalyzed one-pot Sonogashira-
aminobenzannulation sequence to produce 1-aminonaphthalenes in amine solvents, and the
reactions were limited to o-bromoacetophenone and terminal aliphatic alkynes (Scheme 1a).6
Lu and Wang further studied Herndon’s reaction by using terminal aromatic alkynes and
Pd(PPh3)4 to replace PdCl2.7 Fujii and Ohno developed a gold-catalyzed aminobenzannulation
via cascade intermolecular addition/intramolecular carbocyclization reaction of
dialkynylbenzenes with amine to give 1-aminonaphthalenes.8 In addition, amino-substituted
acridines,9 amino-substituted quinolines, dibenzofurans and carbazoles10 could be also
prepared by aminobenzannulation. However, the reported aminobenzannulation procedures
are mostly limited to secondary alkyl amines, and the primary amines and anilines were
hardly involved. It may attribute to the less nucleophilicity of aniline with respect to alkyl
amines, and the favorable forming of the corresponding imines rather than enamines when
primary amines were used.
Recent years, we have developed the efficiently synthetic routes for the construction of
naphthalene ring by the cycloaddition of 1,3-butadiynes,11 and the synthesis of
N-heterocyclic12 and carbocyclic13 compounds by using o-alkynylaromatic ketones/aldehydes
as starting materials or intermediates. In the case of the formation of chrysene derivatives via
copper-catalyzed homo-dimerization of o-alkynylacetophenones,13a isochromenylium is
proposed to be one of the key intermediates (Scheme 1a). With further interest in exploring
the aminobenzannulation of o-alkynylaromatic ketones with anilines via the similar
.
intermediates (vide infra), in this paper we wish to report an efficient CuSO4 5H2O-catalyzed
synthesis of 1-aminonaphthalene derivatives (Scheme 1b).14
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Scheme 1. Aminobenzannulation of o-alkynyl aromatic ketones
2. Results and discussion
Our initial investigation was carried out by treating 2-(phenylethynyl)acetophenone (1a)
.
with 1.4 equiv of 4-methylaniline (2b) using CuSO4 5H2O (5 mol %) as catalyst in toluene
o
under N2 atmosphere at 100 C for 14 h. To our delight, the desired aminobenzannulation
product of 1-aminonaphthalene 3ab could be isolated in 48% yield (Table 1, entry 1).15
Repeating the same reaction in dioxane or THF resulted in the considerable increase of yields
(Table 1, entries 2-3), but when DMF and EtOH were used, the yields of 3ab were decreased
greatly (Table 1, entries 4-5), and 3ab could be obtained in 83% yield with the use of DCE
.
(1,2-dichloroethane) as solvent (Table 1, entry 6). Noted that CuSO4 5H2O showed the best
choice of the copper catalyst, since the use of other copper salts as catalysts such as
.
.
Cu(OAc)2 H2O, Cu(OTf)2, CuCl2 H2O, CuCl, CuBr and CuI led to low yield or trace amount
o
of 3ab (Table 1, entries 7-12). Decrease of the reaction temperature to 80 C resulted in the
decrease of yield (Table 1, entry 13), but the reaction at 120 oC afforded 3ab in a similar yield
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o
as obtained at 100 C (Table 1, entry 14). In addition, when an equivalent of 2b (0.5 mmol)
was used, the yield of 3ab was declined to 62% (Table 1, entry 15).
Entry
1
Catalyst (mol %)
Solvent
toluene
dioxane
THF
Temp (oC) Yield (%)b
.
CuSO4 5H2O (5)
100
100
100
100
100
100
100
100
100
100
100
100
80
48
76
.
2
CuSO4 5H2O (5)
.
3
CuSO4 5H2O (5)
71
.
4
CuSO4 5H2O (5)
DMF
EtOH
DCE
52
.
5
CuSO4 5H2O (5)
20
.
6
CuSO4 5H2O (5)
83
.
7
Cu(OAc)2 H2O (5)
DCE
46
8
Cu(OTf)2 (5)
DCE
23
.
9
CuCl2 H2O (5)
DCE
35
10
11
12
13
14
15c
CuCl (5)
CuBr (5)
CuI (5)
DCE
trace
trace
trace
55
DCE
DCE
.
CuSO4 5H2O (5)
DCE
.
CuSO4 5H2O (5)
DCE
120
100
84
.
CuSO4 5H2O (5)
DCE
62
a Reaction conditions: 1a (0.5 mmol), 2b (0.7 mmol), solvent (2.0 mL), under N2 atmosphere,
14 hours in a screw-capped pyrex tube.
b Isolated yield. c 2b (0.5 mmol).
With the optimized conditions (Table 1, entry 6), we then studied the scope of the
substrates (Table 2). We first investigated the substitution effect of anilines. The anilines
bearing electron-donating groups such as Me, OMe and tBu at para-position could proceed in
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good yield. However, electron-withdrawing groups on the aromatic ring decreased the
reaction reactivity to some extent. Especially, the aniline bearing ester group at para-position
could just give the corresponding annulation product 3ah in 52% yield even with the use of
o
2.0 equiv. of 3h at 120 C with a prolonged reaction time (30 h). The dramatical substitution
effect could be demonstrated easily by the nucleophilicity of aniline. ortho-Substituted (3ai,
70%) and meta-substituted (3aj, 77%) anilines could also react with 1a smoothly, affording
corresponding products in modest to excellent yields. Notably, polysubstituents (3ak, 81%;
3al, 54%) were compatible in the catalytic system as well. When using 1-aminonaphthalene
as amine, dinaphthylamine 3am was obtained in 72% yield. For aliphatic amines, both
primary and secondary aliphatic amines could afford the desired aminobenzannulation
products in good yields (3an, 83%; 3ao, 82%).
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Subsequently, the scope of o-alkynylaromatic ketones 1 was investigated (Table 3). It was
apparently observed that aromatic alkyne with electron-withdrawing group of COMe on the
benzene ring showed relatively low reactivity to give 3eb in mild yield. o-Alkynylaromatic
ketones having aliphatic alkynyl groups (Table 3, R3 = n-hexyl 1f, t-butyl 1g and isopropenyl
1h) could also react with 2b affording the desired products in relatively low yields. In
addition, the reactions of fluoro-substituted o-alkynylaromatic ketones (1i-k), phenylacetyl (1l)
and hexanoyl (1m)-bearing o-alkynylaromatic ketones also gave the corresponding
1-aminonaphthalenes in good yields.
Table 3
Scope of o-alkynylaromatic ketones for 1-aminonaphthalenes synthesisa
NH2
O
R2
HN
.
CuSO4 5H2O (5 mol%)
R2
R3
R1
+
DCE, 100 oC, N2 , 14 h
R1
R3
1
2b
3
HN
HN
HN
R
R
3bb, R = Me, 81%
3cb, R = OMe, 90%
3db, R = Br, 82%
3fb, R = Hexyl, 55%
3gb, R = tBu, 54%
3hb, 52%
3eb, R = COMe, 65%
HN
HN
HN
Ph
F
R
3ib, R = H, 69%
3jb, R = Cl, 65%
3kb, R = OMe, 79%
3lb, 61%
3mb, 54%
a Reaction conditions: 1a (0.5 mmol), 2 (0.7 mmol), DCE (2 mL), N2, 14 h, isolated yield.
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In order to figure out the mechanism of the present reaction, a series of
condition-controlled experiments were done. By taking into consideration that the
aminobenzannulation might occur via a hydrolysis/dehydration mechanism with diketone 4a
as intermediate, the reactions of 4a with 2b in the standard conditions with or without catalyst
were conducted, and the reactions afforded 3ab in 78% and 80% yields, respectively (eq 1).
The results strongly indicated that the reaction of 4a with 2b was very easy even in the
absence of catalyst. Although the formation of 4a could not be observed in the absence of 2b
in the reaction of 1a with water (5.0 equiv) under the standard conditions, in the presence of N,
N-dimethylaniline (1.0 equiv), 4a formed in 23% yield, indicating that 4a might be an
intermediate for the formation of 3 (eq 2). In addition, it was found that under the standard
conditions, with the use of 5.0 equiv of D2O as shown in eq 3, the reaction afforded 3ab-d in
77% yield with 47% deuteration at C-2 and 52% deuteration at C-4 position (see
Supplementary data), and Wen and co-workers also reported the similar control experiments
to support the similar mechanism hypothesis.14
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Scheme 2. Condition-controlled experiments
Although the detailed mechanism remained unclear, on the basis of previous studies of
o-alkynylaromatic ketones and our experimental results, we propose two possible
mechanisms for the formation of 1-aminonaphthalenes as depicted in Scheme 3.
In route A, it involves the first formation of imine A1, and Cu(II)-promoted
tautomerization of imine A1 with enamine A2. A2 then undergoes a Cu(II)-catalyzed
6-endo-dig annulation affording intermediate A3, which takes place the subsequent
protonolysis and aromatization producing 3.
As mentioned above, in the presence of Cu(II), o-alkynylaromatic ketones can be
transferred to isochromenylium as intermediate in their transformation,13a and in the case of
using strong Brønsted acid of HOTf to replace Lewis acid of Cu(II), isochromenylium can be
isolated.13b Therefore, the other route (route B) for the formation of 1-aminonaphthalenes is
also proposed. It includes the formation of isochromenylium B1, and imine-enol Cu(II) salt
B2 derived from aminolysis of B1 or diketone B2’, derived from the hydrolysis of B1. The
metal-hydrogen exchange and enol-one tautomerization of B2 will generate intermediate B3,
which can also be generated from condensation of B2’ and aniline, and B3 is converted to its
enamine isomer B4 and then a cyclic intermediate B5 by intramolecular nucleophilic attack.
The aromatization of B5 by dehydration produces 3.
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As shown in eq 3, the apparent deuteration at C-2 position undoubtedly supports the
procedure of imine-enamine tautomerization, and the deuteration at C-4 position is resulted
from the procedure of metal-hydrogen exchange (protonolysis) of intermediate A3 (in route A)
and B2 (in route B).
Ph
HN
Cu(II)
Ph
Ph
+
N
N
H
Ph
Cu(II)
A2
H
Route A
Ph
A1
Ph
A3
Cu(II)
PhNH2
O
Ph
H2O
HN
H2O
Ph
1
Ph
3
Cu(II)
+
N
H
Ph
Route B
+
O
H
H2O
O
Ph
Ph
B1
Cu(II)
B5
O
H
OH
PhNH2
H+
Ph
PhNH2
B2'
H
Ph
NPh
N
Ph
Ph
N
OH
Ph
Ph
B2
B4
Cu(II)
O
H+
B3
O
Scheme 3. Proposed mechanism
3. Conclusion
We have developed a facile synthetic route for substituted 1-aminonaphthalenes via
.
CuSO4 5H2O-catalyzed aminobenzannulation of o-alkynylaromatic ketones with amines. The
9

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scope investigation indicated that both aliphatic amines and anilines could react smoothly
under the optimized conditions, providing an alternatively efficient catalyst system for the
synthesis of 1-aminonaphthalenes.
4. Experimental section
4.1. General Methods
All commercial reagents are analytically pure and used without further purification.
Nuclear magnetic resonance (NMR) spectra were recorded using CDCl3 as solvent at 298 K.
1H NMR (400 MHz) chemical shifts (δ) were referenced to internal standard TMS (for 1H, δ =
13
0.00 ppm). C NMR (100 MHz) chemical shifts were referenced to internal solvent CDCl3
(for 13C, δ = 77.16 ppm). High resolution mass spectra (HRMS) were obtained on a TOF-MS
instrument with ESI source. o-alkynylaromatic ketones were prepared according to literature
procedures.13
4.2. A typical experimental procedure for the synthesis of 1-aminonaphthalene 3ab
A mixture of 2-(phenylethynyl)acetophenone (1a, 110 mg, 0.5 mmol), 4-methyl-aniline
.
(2b, 75 mg, 0.7 mmol), CuSO4 5H2O (7 mg, 0.025 mmol, 5 mol %) and DCE (2.0 mL) was
heated at 100 °C (oil bath temperature) with stirring in a 25 mL screw-capped thick-walled
Pyrex tube under nitrogen atmosphere. When TLC control showed the completion of the
reaction (after 14 h), the reaction mixture was quenched with H2O. The mixture was extracted
with dichloromethane (DCM) three times, and dried over Na2SO4. The solvent was
evaporated and the crude residue was purified by column chromatography on silica gel to
afford 3ab as a white solid in 83% yield (128 mg).
4.3. Characterization data of products
1
All the products were characterized by H-NMR, 13C-NMR, and HRMS (ESI). The
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copies of NMR charts were reported in Supplementary data.
1
4.3.1. N,3-Diphenylnaphthalen-1-amine (3aa). Light yellow solid (119 mg, 81% yield); H
NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.72 (s, 1H),
7.66 – 7.58 (m, 3H), 7.50 – 7.43 (m, 1H), 7.40 (m, 3H), 7.31 (m, 1H), 7.26 – 7.19 (m, 2H),
7.02 – 6.95 (m, 2H), 6.90 (m, 1H), 5.89 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 144.6, 141.1,
139.3, 138.9, 135.1, 129.5, 129.0, 128.9, 127.5, 127.4, 126.9, 126.7, 125.8, 121.8, 120.9,
120.7, 117.6, 115.2; HRMS (ESI) calcd for C22H18N, [M + H]+ 296.1434, found 296.1430.
1
4.3.2. 3-Phenyl-N-(p-tolyl)naphthalen-1-amine (3ab). White solid (128 mg, 83% yield); H
NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.68 (s, 1H),
7.65 – 7.61 (m, 2H), 7.55 (m, 1H), 7.47 (m, 1H), 7.42 (m, 3H), 7.31 (t, J = 7.3 Hz, 1H), 7.07
(d, J = 8.2 Hz, 2H), 6.97 (d, J = 8.3 Hz, 2H), 5.90 (s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 141.6, 141.3, 140.2, 139.0, 135.1, 130.7, 130.1, 129.0, 128.9, 127.5, 126.6, 126.2,
125.6, 121.5, 120.0, 118.8, 113.4, 20.8; HRMS (ESI) calcd for C23H20N, [M + H]+ 1310.1590,
found 310.1596.
4.3.3. N-(4-Methoxyphenyl)-3-phenylnaphthalen-1-amine (3ac). Light yellow oil (140 mg,
86% yield); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 1H), 7.69 (d, J = 7.9 Hz, 1H),
7.50 – 7.42 (m, 3H), 7.34 – 7.11 (m, 6H), 6.89 (d, J = 8.8 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H),
13
5.72 (s, 1H), 3.60 (s, 3H); C NMR (100 MHz, CDCl3) δ 155.2, 141.4, 141.4, 139.0, 136.7,
134.97, 129.0, 128.8, 127.4, 126.5, 125.4, 125.1, 122.1, 121.0, 118.8, 114.9, 111.0, 55.6;
HRMS (ESI) calcd for C23H20NO, [M + H]+ 326.1539, found 326.1537.
4.3.4. N-(4-(t-Butyl)phenyl)-3-phenylnaphthalen-1-amine (3ad). White solid (149 mg, 85%
yield); 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.65
11

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(s, 1H), 7.60 (m, 3H), 7.45 – 7.31 (m, 4H), 7.30 – 7.21 (m, 3H), 6.99 – 6.92 (m, 2H), 5.83 (s,
1H), 1.28 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 143.8, 141.7, 141.3, 139.8, 139.0, 135.0,
129.0, 128.9, 127.5, 127.4, 126.6, 126.4, 126.3, 125.6, 121.5, 120.2, 117.8, 113.9, 34.2, 31.6;
HRMS (ESI) calcd for C26H26N, [M + H]+ 352.2060, found 352.2064.
4.3.5. N-(4-Fluorophenyl)-3-phenylnaphthalen-1-amine (3ae). Light yellow solid (111 mg,
71% yield); 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H),
7.70 (s, 1H), 7.62 (d, J = 7.4 Hz, 2H), 7.52 – 7.38 (m, 5H), 7.33 (t, J = 7.3 Hz, 1H), 6.97 (m,
4H), 5.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ158.0 (d, J = 239.7 Hz), 141.5, 140.3 (d, J =
1.6 Hz), 140.2, 139.0, 135.1, 129.1, 128.9, 127.6, 127.4, 126.7, 126.1, 125.8, 121.4, 120.4,
120.3 (d, J = 7.7 Hz), 116.2 (d, J = 22.3 Hz), 113.6; HRMS (ESI) calcd for C22H17FN, [M +
H]+ 314.1340, found 314.1338.
4.3.6. N-(4-Chlorophenyl)-3-phenylnaphthalen-1-amine (3af). White solid (125 mg, 76%
yield); 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.76
(s, 1H), 7.66 – 7.61 (m, 2H), 7.56 (s, 1H), 7.54 – 7.46 (m, 1H), 7.43(m, 3H), 7.34 (t, J = 7.3
Hz, 1H), 7.17 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.88 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 143.5, 140.9, 138.9, 138.9, 135.1, 129.4, 129.0, 129.0, 127.6, 127.4, 127.0, 126.8,
126.0, 125.2, 121.8, 121.5, 118.5, 116.0; HRMS (ESI) calcd for C22H17ClN, [M + H]+
330.1044, found 330.1047.
4.3.7. N-(4-Bromophenyl)-3-phenylnaphthalen-1-amine (3ag). Light yellow solid (125 mg,
67% yield); 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H),
7.79 (s, 1H), 7.69 – 7.63 (m, 2H), 7.60 (d, J = 1.4 Hz, 1H), 7.51 (m, 1H), 7.45 (m, 3H), 7.39 –
13
7.30 (m, 3H), 6.86 (d, J = 8.7 Hz, 2H), 5.93 (s, 1H); C NMR (100 MHz, CDCl3) δ 144.1,
12

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140.9, 139.0, 138.7, 135.1, 132.4, 129.1, 129.0, 127.7, 127.4, 127.2, 126.8, 126.1, 121.8,
121.7, 118.8, 116.4, 112.4; HRMS (ESI) calcd for C22H17BrN, [M + H]+ 374.0539, found
374.0537.
4.3.8. Methyl 4-((3-phenylnaphthalen-1-yl)amino)benzoate (2ah). White solid (92 mg, 52%
yield); 1H NMR (400 MHz, CDCl3) δ 7.99 – 7.94 (m, 1H), 7.93 – 7.89 (m, 3H), 7.74 (m, 1H),
7.69 (m, 2H), 7.57 – 7.44 (m,4H), 7.40-7.36 (m, 1H), 6.92 – 6.87 (m, 2H), 6.25 (s, 1H), 3.86
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.2, 150.0, 140.6, 138.9, 137.1, 135.1, 131.7, 129.0,
128.2, 127.7, 127.4, 126.9, 126.3, 123.1, 122.2, 120.8, 119.7, 114.5, 51.8; HRMS (ESI) calcd
for C24H20NO2, [M + H]+ 354.1489, found 354.1495.
4.3.9. 3-Phenyl-N-(o-tolyl)naphthalen-1-amine (3ai). Light yellow solid (108 mg, 70% yield);
1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.70 (s, 1H),
7.65 – 7.60 (m, 2H), 7.52 – 7.38 (m, 4H), 7.23 (d, J = 7.4 Hz, 1H), 7.09 (d, J = 7.4 Hz, 1H),
7.02 (d, J = 7.9 Hz, 1H), 6.94 (d, J = 7.3 Hz, 1H), 5.79 (s, 1H), 2.33 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 142.5, 141.3, 140.1, 139.1, 135.1, 131.1, 129.0, 128.9, 127.8, 127.5, 127.1,
126.6, 126.3, 125.7, 121.9, 121.6, 120.2, 119.0, 114.3, 18.1; HRMS (ESI) calcd for C23H20N,
[M + H]+ 310.1590, found 310.1592.
4.3.10. 3-Phenyl-N-(m-tolyl)naphthalen-1-amine (3aj). Orange red solid (119 mg, 77% yield);
1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.74 (s, 1H),
7.65 (d, J = 8.5 Hz, 3H), 7.49 (dd, J = 7.7, 7.0 Hz, 1H), 7.43 (m, 3H), 7.33 (m, 1H), 7.14 (m,
1H), 6.85 (m , 2H), 6.74 (d, J = 7.4 Hz, 1H), 5.92 (s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 144.7, 141.2, 139.5, 139.0, 135.1, 129.4, 129.0, 128.9, 127.5, 127.5, 126.9, 126.7,
13

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125.8, 121.8, 121.7, 120.8, 118.4, 115.3, 114.8, 21.7; HRMS (ESI) calcd for C23H20N, [M +
H]+ 310.1590, found 310.1589.
4.3.11. N-(3-Methoxy-2-methylphenyl)-3-phenylnaphthalen-1-amine (3ak). Light white solid
(137 mg, 81% yield); 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.1
Hz, 1H), 7.70 (s, 1H), 7.66 – 7.60 (m, 2H), 7.56 – 7.45 (m, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.37
– 7.30 (m, 2H), 7.07 (t, J = 8.2 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 6.59 (d, J = 8.2 Hz, 1H),
13
5.86 (s, 1H), 3.87 (s, 3H), 2.23 (s, 3H); C NMR (101 MHz, CDCl3) δ 158.6, 143.3, 141.3,
140.4, 139.1, 135.0, 129.0, 128.9, 127.5, 127.4, 126.7, 126.6, 126.2, 125.7, 121.6, 120.0,
116.5, 114.1, 112.5, 104.3, 55.8, 10.1; HRMS (ESI) calcd for C24H22NO, [M + H]+ 340.1696’
found 340.1695.
4.3.12. N-(3-Fluoro-2-methylphenyl)-3-phenylnaphthalen-1-amine (3al). Light white solid
(88 mg, 54% yield); 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.3
Hz, 1H), 7.75 (s, 1H), 7.63 (d, J = 7.4 Hz, 2H), 7.53 – 7.36 (m, 5H), 7.33 (t, J = 7.3 Hz, 1H),
13
7.02 – 6.94 (m, 1H), 6.74 – 6.63 (m, 2H), 5.78 (s, 1H), 2.24 (d, J = 1.5 Hz, 3H); C NMR
(100 MHz, CDCl3) δ162.0 (d, J = 242.3 Hz), 144.7 (d, J = 6.8 Hz), 141.0, 139.4, 139.0, 135.1,
129.0, 128.9, 127.6, 127.4, 127.1 (d, J = 10.3 Hz), 126.8, 126.7, 125.9, 121.8, 121.1, 116.0,
114.2 (d, J = 18.3 Hz), 113.6 (d, J = 2.3 Hz), 108.0 (d, J = 23.2 Hz), 9.3 (d, J = 5.8 Hz);
HRMS (ESI) calcd for C23H19FN, [M + H]+ 328.1496, found 328.1496.
4.3.13. N-(Naphthalen-1-yl)-3-phenylnaphthalen-1-amine (3am). Light yellow oil (124 mg,
72% yield); 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.2 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H),
7.92 (d, J = 8.0 Hz, 1H), 7.90 – 7.86 (m, 1H), 7.74 (s, 1H), 7.60 – 7.42 (m, 7H), 7.40 – 7.26
(m, 5H), 7.09 (d, J = 7.4 Hz, 1H), 6.39 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 141.2, 140.8,
14

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140.2, 139.2, 135.1, 134.8, 129.1, 128.9, 128.8, 127.4, 127.1, 126.7, 126.3, 126.3, 126.2,
125.9, 1822.6, 121.8, 121.8, 120.4, 115.6, 115.0; HRMS (ESI) calcd for C26H20N, [M + H]+
346.1590, found 346.1589.
4.3.14. 3-Phenyl-N-propylnaphthalen-1-amine (3an). Light yellow solid (108 mg, 83% yield);
1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.73 – 7.69
(m, 2H), 7.53 – 7.29 (m, 6H), 6.82 (s, 1H), 4.35 (s, 1H), 3.28 (t, J = 7.1 Hz, 2H), 1.84 – 1.74
(m, 2H), 1.07 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 144.1, 142.3, 139.6, 134.7,
129.1, 128.8, 127.6, 127.3, 126.2, 124.8, 122.7, 119.8, 115.5, 104.1, 46.2, 22.8, 12.0; HRMS
(ESI) calcd for C19H20N, [M + H]+ 262.1590, found 262.1592.
4.3.15. N,N-Diethyl-3-phenylnaphthalen-1-amine (3ao). Light yellow oil (113 mg, 82% yield).
1H NMR (400 MHz, CDCl3) δ 8.33 – 8.27 (m, 1H), 7.88 – 7.81 (m, 1H), 7.74 (s, 1H), 7.72 –
7.67 (m, 2H), 7.51 – 7.43 (m, 4H), 7.37 (dd, J = 5.8, 1.5 Hz, 2H), 3.25 (q, J = 7.1 Hz, 4H),
1.09 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 148.5, 141.8, 138.4, 135.2, 130.4,
128.9, 128.6, 127.6, 127.4, 126.2, 125.3, 124.3, 121.4, 117.9, 47.8, 12.5; HRMS (ESI) calcd
for C20H22N, [M + H]+ 276.1747, found 276.1744.
1
4.3.16. N,3-di-p-Tolylnaphthalen-1-amine (3bb). Light yellow solid (131 mg, 81% yield); H
NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.67 (s, 1H),
7.54 (m, 3H), 7.47 (d, J = 7.3 Hz, 1H), 7.43 (d, J = 7.2 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.08
13
(d, J = 8.2 Hz, 2H), 6.98 (d, J = 8.3 Hz, 2H), 6.08 (s, 1H), 2.37 (s, 3H), 2.30 (s, 3H); C
NMR (100 MHz, CDCl3) δ 141.7, 140.1, 138.9, 138.4, 137.3, 135.1, 130.6, 130.1, 129.6,
128.9, 127.3, 126.6, 126.1, 125.5, 121.5, 119.7, 118.7, 113.6, 21.6, 20.8; HRMS (ESI) calcd
for C24H22N, [M + H]+ 324.1747, found 324.1749.
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4.3.17. 3-(4-Methoxyphenyl)-N-(p-tolyl)naphthalen-1-amine (3cb). Light yellow solid (152
mg, 90% yield); 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.1 Hz,
1H), 7.64 (s, 1H), 7.57 (m, 2H), 7.54 (s, 1H), 7.48 (t, J = 7.4 Hz, 1H), 7.45 – 7.39 (m, 1H),
7.09 (d, J = 8.2 Hz, 2H), 6.99 (d, J = 8.3 Hz, 2H), 6.96 (d, J = 8.6 Hz, 2H), 5.95 (s, 1H), 3.83
(s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.3, 141.8, 140.1, 138.6, 135.2, 133.8,
130.7, 130.1, 128.9, 128.5, 126.6, 126.0, 125.4, 121.5, 119.3, 118.7, 114.3, 113.5, 55.5, 20.8;
HRMS (ESI) calcd for C24H22NO, [M + H]+ 340.1696, found 340.1700.
4.3.18. 3-(4-Bromophenyl)-N-(p-tolyl)naphthalen-1-amine (3db). Light yellow solid (154 mg,
82% yield); 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H),
7.61 (s, 1H), 7.56 – 7.41 (m, 7H), 7.09 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.3 Hz, 2H), 5.98 (s,
13
1H), 2.30 (s, 3H); C NMR (100 MHz, CDCl3) δ 141.3, 140.5, 140.2, 137.8, 135.0, 131.9,
131.1, 130.1, 129.0, 126.8, 126.1, 125.9, 121.7, 121.4, 119.7, 119.0, 112.5, 20.8; HRMS (ESI)
calcd for C23H19BrN, [M + H]+ 388.0695, found 388.0700.
4.3.19. 1-(4-(4-(p-Tolylamino)naphthalen-2-yl)phenyl)ethan-1-one (3eb). Light yellow solid
(114 mg, 65% yield); 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.0 Hz, 3H), 7.89 (d, J = 7.9
Hz, 1H), 7.75 – 7.66 (m, 3H), 7.59 – 7.43 (m, 3H), 7.11 (d, J = 8.2 Hz, 2H), 7.02 (d, J = 8.2
Hz, 2H), 6.02 (s, 1H), 2.61 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 197.9, 145.9,
141.3, 140.6, 137.6, 135.9, 134.9, 131.2, 130.2, 129.2, 129.0, 127.5, 126.9, 126.4, 126.2,
121.4, 120.2, 119.1, 112.4, 26.8, 20.9; HRMS (ESI) calcd for C25H22NO, [M + H]+ 352.1696,
found 352.1698.
4.3.20. 3-n-Hexyl-N-(p-tolyl)naphthalen-1-amine (3fb). Light yellow oil (87 mg, 55% yield);
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.3 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.47 – 7.40
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(m, 1H), 7.40 – 7.34 (m, 1H), 7.29 (s, 1H), 7.16 (s, 1H), 7.07 (d, J = 8.2 Hz, 2H), 6.92 (d, J =
8.3 Hz, 2H), 5.83 (s, 1H), 2.80 – 2.55 (m, 2H), 2.30 (s, 3H), 1.64 (m, 2H), 1.44 – 1.15 (m, 6H),
13
0.87 (t, J = 6.9 Hz, 3H); C NMR (100 MHz, CDCl3) δ 142.1, 141.1, 139.1, 135.0, 130.2,
130.0, 128.2, 126.2, 125.8, 124.8, 121.6, 120.9, 118.3, 116.1, 36.4, 31.9, 31.4, 29.2, 22. 8,
20.8, 14.3; HRMS (ESI) calcd for C23H28N, [M + H]+ 318.2216, found 318.2211.
4.3.21. 3-(t-Butyl)-N-(p-tolyl)naphthalen-1-amine (3gb). Light yellow oil (78 mg, 54% yield);
1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.50 – 7.34
(m, 4H), 7.06 (d, J = 8.1 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 5.85 (s, 1H), 2.30 (s, 3H), 1.36 (s,
13
9H); C NMR (100 MHz, CDCl3) δ 149.1, 142.5, 138.7, 134.7, 130.0, 129.8, 128.7, 126.2,
126.0, 125.1, 121.5, 117.9, 117.5, 114.6, 35.1, 31.3, 20.8; HRMS (ESI) calcd for C21H24N, [M
+ H]+ 290.1903, found 290.1904.
4.3.22. 3-(Prop-1-en-2-yl)-N-(p-tolyl)naphthalen-1-amine (3hb). Light yellow oil (71 mg,
52% yield); 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H),
7.58 – 7.37 (m, 4H), 7.08 (d, J = 8.2 Hz, 2H), 6.94 (d, J = 8.2 Hz, 2H), 5.86 (s, 1H), 5.42 (s,
13
1H), 5.14 (s, 1H), 2.31 (s, 3H), 2.22 (s, 3H); C NMR (100 MHz, CDCl3) δ 143.2, 142.1,
139.3, 138.8, 134.8, 130.3, 130.0, 129.0, 126.9, 126.5, 125.6, 121.6, 119.1, 118.2, 113.1,
112.7, 22.0, 20.8; HRMS (ESI) calcd for C20H20N, [M + H]+ 274.1590, found 274.1593.
4.3.23. 6-Fluoro-3-phenyl-N-(p-tolyl)naphthalen-1-amine (3ib). Light yellow solid (113 mg,
1
69% yield); H NMR (400 MHz, CDCl3) δ 7.95 (m, 1H), 7.60 (m, 3H), 7.50 – 7.38 (m, 4H),
7.34 (d, J = 7.3 Hz, 1H), 7.22 – 7.13 (m, 1H), 7.08 (d, J = 8.2 Hz, 2H), 6.96 (d, J = 8.3 Hz,
2H), 5.86 (s, 1H), 2.30 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 161.3 (d, J = 246.4 Hz), 160.1,
141.4, 140.9, 140.5, 140.4, 136.1 (d, J = 9.2 Hz), 131.1, 130.1, 128.9, 127.7, 127.5, 124.3 (d,
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J = 9.1 Hz), 123.2, 119.3 (d, J = 4.7 Hz), 118.9, 115.6 (d, J = 25.2 Hz), 113.0, 111.9 (d, J =
20.3 Hz), 20.8; HRMS (ESI) calcd for C23H19FN, [M + H]+ 328.1496, found 328.1498.
4.3.24. 3-(4-Chlorophenyl)-6-fluoro-N-(p-tolyl)naphthalen-1-amine (3jb). Light yellow solid
(117 mg, 65% yield); 1H NMR (400 MHz, CDCl3) δ 7.97 (m, 1H), 7.52 (m, 3H), 7.46 (m, 1H),
7.42 – 7.35 (m, 3H), 7.24 – 7.17 (m, 1H), 7.11 (d, J = 8.2 Hz, 2H), 6.98 (d, J = 8.3 Hz, 2H),
5.95 (s, 1H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ161.4 (d, J = 246.6 Hz), 141.1,
140.8, 139.4, 139.2, 136.1 (d, J = 9.4 Hz), 133.8, 131.4, 130.2, 129.1, 128.7, 124.2 (d, J = 9.0
Hz), 123.2, 119.1, 119.0 (d, J = 5.3 Hz), 115.8 (d, J = 25.1 Hz), 112.2, 111.9 (d, J = 20.4 Hz),
20.9; HRMS (ESI) calcd for C23H18ClFN, [M + H]+ 362.1106, found 362.1112.
4.3.25. 6-Fluoro-3-(4-methoxyphenyl)-N-(p-tolyl)naphthalen-1-amine (3kb). Light yellow
solid (141 mg, 79% yield); 1H NMR (400 MHz, CDCl3) δ 7.93 (m, 1H), 7.54 (m, 3H), 7.46 –
7.40 (m, 2H), 7.15 (td, J = 9.0, 2.4 Hz, 1H), 7.08 (d, J = 8.1 Hz, 2H), 6.94 (d, J = 8.5 Hz, 4H),
5.86 (s, 1H), 3.81 (s, 3H), 2.30 (s, 3H); 13C NMR (101 MHz, CDCl3) δ161.3 (d, J = 246.1 Hz),
159.5, 141.5, 140.4, 140.0, 136.2 (d, J = 9.2 Hz), 133.4, 130.9, 130.1, 128.5, 124.3 (d, J = 9.0
Hz), 123.0, 118.8, 118.6 (d, J = 4.9 Hz), 115.3 (d, J = 25.1 Hz), 114.4, 112.9, 111.7 (d, J =
20.2 Hz), 55.4, 20.8; HRMS (ESI) calcd for C24H21FNO, [M + H]+ 358.1602, found
358.1603.
4.3.26. 2-Benzyl-3-phenyl-N-(p-tolyl)naphthalen-1-amine (3lb). Light yellow solid (122 mg,
61% yield); 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H),
7.72 (s, 1H), 7.43 (t, J = 7.4 Hz, 1H), 7.39 – 7.26 (m, 6H), 7.19 (t, J = 7.2 Hz, 2H), 7.15 –
7.10 (m, 1H), 6.95 (d, J = 7.5 Hz, 2H), 6.90 (d, J = 8.2 Hz, 2H), 6.36 (d, J = 8.2 Hz, 2H), 5.31
(s, 1H), 4.05 (s, 2H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 144.6, 142.2, 141.9, 140.7,
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137.0, 133.2, 133.0, 131.0, 129.8, 129.4, 128.8, 128.2, 128.2, 128.0, 127.8, 127.3, 127.2,
126.3, 126.2, 126.1, 124.5, 114.1, 35.3, 20.6; HRMS (ESI) calcd for C30H26N, [M + H]+
400.2060, found 400.2063.
4.3.27. 2-n-Pentyl-3-phenyl-N-(p-tolyl)naphthalen-1-amine (3mb). Light yellow liquid (102
mg, 54% yield); 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.2 Hz, 1H), 7.80 (d, J = 7.8 Hz,
1H), 7.62 (s, 1H), 7.51 – 7.33 (m, 7H), 6.95 (d, J = 7.8 Hz, 2H), 6.50 (d, J = 7.4 Hz, 2H),
5.35(s, 1H), 2.81 – 2.61 (m, 2H), 2.24 (s, 3H), 1.34 (m, 2H), 1.06 (d, J = 3.4 Hz, 4H), 0.69 (t,
J = 6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 145.5, 142.3, 141.9, 136.4, 135.3, 132.7,
130.9, 129.8, 129.5, 128.2, 128.1, 127.6, 127.3, 127.1, 126.2, 125.8, 124.2, 114.1, 32.0, 30.2,
29.1, 22.2, 20.6, 13.9; HRMS (ESI) calcd for C28H30N, [M + H]+ 380.2373, found 380.2370.
Acknowledgements
This project was supported by the National Natural Science Foundation of China (21473097,
21273125).
Supplementary data
1
13
The copies of H-NMR, C-NMR charts of all products and the x-ray structural details for
3ai associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tet.xxxx.
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References and notes:
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14. When we finished the experiments, and are preparing manuscript, Wen and co-workers
.
reported a similar Cu(OAc)2 H2O-catalyzed aminobenzannulation of (ortho-alkynyl)-
arylketones with amines: Zhang, M.; Ruan, W.; Zhang, H.-J.; Li, W.; Wen, T.-B. J. Org.
Chem. 2016, 81, 1696−1703.
15. The structures of all the products were identified by their 1H-NMR, 13C-NMR and HRMS
(ESI), 3ai was further confirmed by x-ray crystallography (see Supplementary data). The
supplementary crystallographic data of 3ai, CCDC 1472396, can be obtained free of
charge via www.ccdc.cam.ac.uk.
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