A room-temperature, copper-catalyzed cascade process for diethyl 2-aryl-3,4-dihydro-4-oxo-1,1(2 H)-naphthalenedicarboxylate

Article abstract of DOI:10.1055/s-0030-1257937

A room-temperature cascade process for the formation of diethyl 2-aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylate is described by using a combination of Michael addition and copper-catalyzed -arylation of malonic acid derivatives. The protocol worked well for a variety of 1-(2-iodoaryl)enones and displayed great functional group compatibility. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1257937

PAPER
3289
A Room-Temperature, Copper-Catalyzed Cascade Process for
Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylate
D
iethyl 2-Aryl-
h
e
4-oxo-1,1(
2
n
H
)-naphthal
g
e
nedicarboxy
q
late iu Li,a,b Liangbin Fu,b,c Jiajia Wei,c Chengyong Ha,a Duanqing Pei,c Qian Cai,*c Ke Ding*c
a
Key Laboratory of Cellulose and Lignocellulosics Chemistry, Guangzhou Institute of Chemistry, Chinese Academy of Sciences,
Guangzhou, Guangdong, P. R. of China
b
c
Graduate School of the Chinese Academy of Sciences, Beijing, P. R. of China
Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health,
Chinese Academy of Sciences, No.190, Kaiyuan Avenue, Science Park, Guangzhou 510530, P. R. of China
Fax +86(20)32015299; E-mail: cai_qian@gibh.ac.cn; E-mail: ding_ke@gibh.ac.cn
Received 23 March 2010; revised 22 June 2010
Although no desired product was detected in the absence
of copper salts, we were pleased to find that product 2a
was obtained with 5% yield under the catalysis of 10
mol% CuI at room temperature using sodium hydroxide
Abstract: A room-temperature cascade process for the formation
of diethyl 2-aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarbox-
ylate is described by using a combination of Michael addition and
copper-catalyzed a-arylation of malonic acid derivatives. The pro-
tocol worked well for a variety of 1-(2-iodoaryl)enones and dis- as the necessary base (Table 1, entry 1). Further investiga-
played great functional group compatibility.
tion revealed that supporting ligands, such as picolinic
acid7d and L-proline7c could significantly improve the re-
Key words: Michael addition, copper, catalysis, cascade reactions,
a-arylation
action efficiency (Table 1, entries 2 and 3). When trans-
Table 1 A Copper-Catalyzed Cascade Process for the Formation of
Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxy-
latesa
3-Aryl-3,4-dihydronaphthalen-1(2H)-ones, also known as
g-aryl-a-tetralones, are important intermediates for the
synthesis of the rodenticide flocoumafen and many other
bioactive dihydro- or tetrahydronaphthalenic com-
pounds.1 Intramolecular Friedel–Crafts acylation is the
classical method for synthesizing this class of com-
pounds.1,2 However, this approach is only suitable for a
limited range of precursors and/or gives low yields.
O
O
I
OMe
CuI/ligand
1a
OMe
+
base, solvent
room temperature
CH2(CO2Et)2
EtOOC
COOEt
2a
Copper-catalyzed arylation of malonates and their deriva-
tives represents one of the most efficient methods avail-
able for the construction of C–C bonds. However, the
original protocol shares similar deficiencies to those
found with Ullmann chemistry, in that high temperatures
and stoichiometric amounts of copper complex are re-
quired, and the reactions are sometimes difficult to repro-
duce.3,4 In recent years, great advances have been
achieved in copper-catalyzed Ullmann-type reactions5
and the optimized processes under mild conditions have
been successfully applied to the synthesis of a-aryl mal-
onates.6,7 More significantly, the reaction had been report-
ed to proceed at room temperature.7d
H
N
Ph
Ph
CO2H
COOH
N
H
N
H
N
CO2H
A
B
C
Entry
Ligand
Base
Solvent
DMSO
DMSO
DMSO
DMSO
dioxane
DMF
Yield (%)b
c
1
2
–
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
K2CO3
K3PO4
Cs2CO3
5
A
B
C
C
C
C
C
C
C
50
3
45
4
85
5
75
In this paper, we would like to report a feasible method for
the synthesis of 3-aryl-3,4-dihydronaphthalen-1(2H)-one
derivatives by using a one-pot cascade process that com-
bines a Michael addition reaction8 and room-temperature,
copper-catalyzed C–C bond formation.
6
20
7
toluene
DMSO
DMSO
DMSO
n.d.d
n.d.d
40
8
The study was initiated by an investigation into the poten-
tial cascade reaction of unsaturated ketone 1a with diethyl
malonate under the catalysis of copper(I) iodide (Table 1).
9
10
76
a Reaction conditions: 1 (0.5 mmol), diethyl malonate (0.6 mmol),
CuI (0.05 mmol), ligand (0.1 mmol), base (1.25 mmol), r.t., 3 h.
b Isolated yield.
SYNTHESIS 2010, No. 19, pp 3289–3294
Advanced online publication: 30.07.2010
DOI: 10.1055/s-0030-1257937; Art ID: F05210SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0
c No ligand.
d No desired product was detected.

3290
Z. Li et al.
PAPER
Table 2 Scope of 1-(2-Iodoaryl)enone Substrates for the Formation of Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylatea
Entry Aryl iodide
Product
Yield
(%)b
Entry Aryl iodide
Product
Yield
(%)
O
O
O
O
Cl
Cl
1
68
62
65
82
87
40c
42c
10
50c
87
67
63
68
75
82
N
I
I
N
EtO2C
EtO2C
CO2Et
O
CO2Et
O
2b
2k
1b
1k
O
O
OMe
2
11
S
OMe
S
I
I
EtO2C
EtO2C
CO2Et
O
CO2Et
O
1l
2c
2l
1c
O
O
S
3
12
S
I
I
EtO2C
EtO2C
CO2Et
O
CO2Et
O
2d
1d
2m
1m
O
O
4
13
O
O
I
I
EtO2C
EtO2C
CO2Et
CO2Et
1n
2e
2n
1e
O
O
I
O
O
5
14
I
MeO
MeO
t-Bu
EtO2C
EtO2C
CO2Et
CO2Et
O
t-Bu
2f
2o
1o
1f
O
O
I
O
6
15
I
MeO2C
MeO2C
EtO2C
EtO2C
CO2Et
CO2Et
O
2g
2p
1g
1p
O
O
I
O
OH
7
16
OH
I
MeO2C
MeO2C
OMe
EtO2C
EtO2C
CO2Et
CO2Et
O
OMe
2h
2q
1q
1h
O
O
O
8
75
32
17
18
73
60
I
Cl
I
Cl
Cl
EtO2C
EtO2C
CO2Et
O
CO2Et
O
Cl
2r
2i
1r
1i
O
O
9
I
O2N
I
O2N
CN
EtO2C
EtO2C
CO2Et
CO2Et
CN
2j
2s
1s
1j
a Reaction conditions: 1 (0.5 mmol), diethyl malonate (0.6 mmol), CuI (0.05 mmol), ligand C (0.1 mmol), NaOH (1.25 mmol), r.t., 3 h.
b Isolated yield.
c Reaction time 10 h.
Synthesis 2010, No. 19, 3289–3294 © Thieme Stuttgart · New York

PAPER
Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylate
3291
4,5-diphenylimidazolidine-2-carboxylic acid (ligand C) duced the desired products with excellent or good yields
was used as the supporting ligand, about 85% of the de- (Table 2, entries 14–18).
sired product was isolated when the reaction was per-
It is worth noting that the reactions also performed well
formed at room temperature for three hours (Table 1,
for enones with heteroaryl substituents (Table 2, entries
entry 4). Ligand C was also recognized as an efficient or-
10–13). All the substrates possessing heteroaryl substitu-
ganocatalyst for the Michael addition reaction.9 A screen-
tions produced the desired products with good or moder-
ing of the reaction medium suggested that
ate yields under similar conditions.
dimethylsulfoxide (DMSO) was the optimal solvent for
A mechanism of this copper-catalyzed cascade reaction is
proposed in Scheme 1. 1-(2-Iodoaryl)enones may react
with diethyl malonate to produce the diethyl 2-aryl-3,4-di-
hydro-4-oxo-1,1(2H)-naphthalenedicarboxylate product
the new cascade reaction. Other solvents, such as 1,4-di-
oxane and N,N-dimethylformamide (DMF), gave signifi-
cantly lower isolated yields (Table 1, entries 5 and 6).
When the reaction was carried out in the nonpolar solvent
through two different pathways. One is through copper-
toluene, almost no desired product was detected (Table 1,
catalyzed intermolecular C–C coupling between the di-
entry 7). When a range of bases were also evaluated, it
ethyl malonate and aryl iodides first, followed by an in-
was found that Cs2CO3 was also a suitable base for the
tramolecular Michael addition. The second possibility is
cascade reaction (Table 1, entries 4 and 8–10), however,
that diethyl malonate first reacts with the enone to pro-
duce the Michael addition product B, and subsequent cop-
per-catalyzed intramolecular C–C coupling reaction
sodium hydroxide was chosen as the optimal base for fur-
ther studies because of its economic efficiency.
The scope of this new protocol was further explored by
yields the desired product. Since Michael addition is more
combining diethyl malonate with a variety of 1-(2-iodoar-
favored under mild conditions than the copper-catalyzed
yl)enones under the optimized conditions. As shown in
C–C coupling reactions, we propose that pathway B might
Table 2, almost all the tested combinations successfully
be more reasonable; this hypothesis was confirmed by the
isolation of the intermediate B, which can be obtained ei-
ther under ligand-free conditions as the major product in
produced the desired products with moderate to excellent
isolated yields. However, the substrate bearing a free hy-
droxy group on the phenyl ring delivered the correspond-
our model reaction, or by quenching the CuI/ligand sup-
ing product with significantly lower yield (Table 2, entry
porting system before the reaction had reached comple-
tion. The isolated intermediate B can be further
transformed into the final product under the CuI/ligand
7), which might be due to the acidity of the hydroxy
group. The results indicated that the electronic nature of
the aromatic ring directly linked to the double bond had a
supporting conditions.
clear influence on the cascade reaction. When the aromat-
In summary, we have demonstrated a simple and flexible
cascade process for preparing diethyl 2-aryl-3,4-dihydro-
4-oxo-1,1(2H)-naphthalenedicarboxylates from easily
ic ring carried an electron-donating group, such as methyl,
methoxy or tert-butyl group etc, the desired product was
produced with excellent to good yields (Table 2, entries
available 1-(2-iodoaryl)enones and diethyl malonate. The
1–5). However, when the phenyl ring possessed an elec-
protocol worked well for a variety of 1-(2-iodoar-
tron-withdrawing nitrile group, only 32% of the corre-
yl)enones and displayed great functional group compati-
sponding product was isolated (Table 2, entry 9). The
bility. Our new protocol will greatly facilitate the
steric effect of the aromatic ring directly linked to the dou-
synthesis of g-aryl-a-tetralone-derivatives and should find
many applications in the future.
ble bond also had some influence on the reaction. For in-
stance, substrates with greater steric hindrance (Table 2,
entry 6 and 10) gave significantly lower isolated yield.
The results also showed that the electronic density of the
iodo-substituted phenyl ring had little effect on the cas-
cade process. Almost all of the tested substrates bearing
electron-donating or electron-withdrawing groups pro-
All the 2-iodoaryl enones were made from 2-iodoaryl ketones and
corresponding aryl aldehydes, which were commercially available
from Aldrich, TCI and ACROS. The starting materials and products
were confirmed by NMR and mass spectral analysis.
O
intramolecular
Michael addition
Ar
intermolecular
coupling
CO2Et
CO2Et
path A
O
A
O
O
O
Ar
+
EtO
OEt
Ar
EtO2C
CO2Et
I
O
I
Ar
path B
CO2Et
CO2Et
intermolecular
Michael addition
intramolecular
coupling
B
Scheme 1 The proposed mechanism of the copper-catalyzed cascade reaction
Synthesis 2010, No. 19, 3289–3294 © Thieme Stuttgart · New York

3292
Z. Li et al.
PAPER
Diethyl 4-Oxo-2-m-tolyl-3,4-dihydronaphthalene-1,1(2H)-di-
Synthesis of Substrate 1; General Procedure
2-Iodoaryl acetone (10 mmol), aryl aldehyde (10 mmol), 15%
NaOH (20 mL) and MeOH (20 mL) were added together and stirred
at r.t. for 3 h. After the reaction was complete, EtOAc (20 mL) and
H2O (10 mL) were added. The organic phase was separated, dried
over Na2SO4 and evaporated under vacuum. The substrate 1 was
separated by silica gel column chromatography (EtOAc–PE, 1:50).
carboxylate (2d)
1H NMR (CDCl3, 400 MHz): d = 8.15 (d, J = 7.6 Hz, 1 H), 7.72 (d,
J = 8.0 Hz, 1 H), 7.63 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 1 H),
7.06–6.98 (m, 2 H), 6.91 (s, 1 H), 6.86 (d, J = 7.6 Hz, 1 H), 4.28 (t,
J = 6.0 Hz, 1 H), 4.23–4.12 (m, 2 H), 3.99–3.93 (m, 2 H), 3.53 (dd,
J = 6.0, 17.2 Hz, 1 H), 3.19 (dd, J = 6.0, 17.2 Hz, 1 H), 2.23 (s, 3 H),
1.20 (t, J = 6.8 Hz, 3 H), 1.04 (t, J = 7.2 Hz, 3 H).
Synthesis of 2a–s; General Procedure
13C NMR (CDCl3, 75 MHz): d = 196.0, 169.6, 168.4, 139.7, 137.9,
137.7, 133.2, 132.6, 131.8, 129.7, 128.5, 128.3, 128.2, 126.6, 125.7,
62.4, 62.1, 61.5, 46.6, 42.1, 21.3, 13.7, 13.6.
ESI-MS: m/z = 381.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H25O5: 381.1702; found:
1-(2-Iodoaryl) enone 1 (0.5 mmol), base (1.0 mmol), CuI (0.05
mmol) and solvent (1 mL) were added together into a reacting tube.
Diethyl malonate (0.6 mmol) was slowly added and the mixtures
were stirred at r.t. under the protection of a nitrogen atmosphere.
The reaction was monitored by TLC. Upon completion, EtOAc
(10 mL) and H2O (5 mL) were added to the reaction mixture and the
organic phase was separated, dried over Na2SO4 and evaporated in
vacuum. The residues were loaded onto a silica gel column and pu-
rified (EtOAc–PE, 1:15) to obtain the final products 2.
381.1699.
Diethyl 4-Oxo-2-p-tolyl-3,4-dihydronaphthalene-1,1(2H)-dicar-
boxylate (2e)
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 7.6 Hz, 1 H), 7.73 (d,
J = 8.0 Hz, 1 H), 7.63 (t, J = 7.2 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 1 H),
6.99–6.94 (m, 4 H), 4.29 (t, J = 6.0 Hz, 1 H), 4.23–4.12 (m, 2 H),
4.01–3.92 (m, 2 H), 3.54 (dd, J = 5.6, 17.2 Hz, 1 H), 3.17 (dd, J =
6.4, 17.2 Hz, 1 H), 2.21 (s, 3 H), 1.21 (t, J = 7.2 Hz, 3 H), 1.06 (t,
J = 7.2 Hz, 3 H).
Diethyl 2-(4-Methoxyphenyl)-4-oxo-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2a)
1H NMR (CDCl3, 400 MHz): d = 8.13 (d, J = 8.0 Hz, 1 H), 7.72 (d,
J = 8.0 Hz, 1 H), 7.63 (t, J = 7.6 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 1 H),
7.01 (d, J = 7.6 Hz, 2 H), 6.71 (d, J = 8.4 Hz, 2 H), 4.27 (t, J =
6.0 Hz, 1 H), 4.22–4.10 (m, 2 H), 4.01–3.93 (m, 2 H), 3.92 (s, 3 H),
3.52 (dd, J = 5.6, 17.2 Hz, 1 H), 3.15 (dd, J = 6.0, 17.2 Hz, 1 H),
1.21 (t, J = 6.8 Hz, 3 H), 1.06 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 196.1, 169.6, 168.5, 137.8, 137.2,
136.7, 133.2, 132.7, 131.8, 128.9, 128.6, 128.5, 126.6, 62.5, 62.1,
61.6, 46.3, 42.2, 20.9, 13.7, 13.6.
ESI-MS: m/z = 381.1 [M + H]+.
HR-MS (ESI): m/z [M + H]+ calcd for C23H25O5: 381.1702; found:
13C NMR (CDCl3, 75 MHz): d = 196.1, 169.6, 168.5, 159.0, 137.9,
133.2, 132.6, 131.9, 131.8, 129.9, 128.5, 126.6, 113.7, 62.6, 62.1,
61.6, 55.1, 45.9, 42.4, 13.8, 13.7.
381.1703.
ESI-MS: m/z = 397.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H25O6: 397.1651; found:
397.1650.
Diethyl 2-(4-t-Butylphenyl)-4-oxo-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2f)
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 7.6 Hz, 1 H), 7.72 (d,
J = 8.0 Hz, 1 H), 7.63 (t, J = 8.0 Hz, 1 H), 7.50 (t, J = 7.2 Hz, 1 H),
7.19 (d, J = 8.4 Hz, 2 H), 7.02 (d, J = 8.4 Hz, 2 H), 4.29 (t, J =
5.6 Hz, 1 H), 4.23–4.11 (m, 2 H), 3.96 (q, J = 7.2 Hz, 1 H), 3.53 (dd,
J = 6.0, 17.2 Hz, 1 H), 3.19 (dd, J = 6.4, 17.2 Hz, 1 H), 1.23 (s, 9 H),
1.18 (t, J = 7.2 Hz, 3 H), 0.98 (t, J = 7.2 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 196.2, 169.6, 168.6, 150.4, 137.8,
136.6, 133.2, 132.7, 131.9, 128.5, 128.4, 126.6, 125.2, 62.4, 62.1,
61.6, 46.3, 42.2, 34.3, 14.0, 13.7, 13.5.
Diethyl 4-Oxo-2-phenyl-3,4-dihydronaphthalene-1,1(2H)-di-
carboxylate (2b)
1H NMR (CDCl3, 400 MHz): d = 8.15 (d, J = 8.0 Hz, 1 H), 7.74 (d,
J = 8.0 Hz, 1 H), 7.64 (t, J = 8.4 Hz, 1 H), 7.51 (t, J = 7.6 Hz, 1 H),
7.19–7.16 (m, 3 H), 7.09–7.06 (m, 2 H), 4.32 (t, J = 5.6 Hz, 1 H),
4.23–4.10 (m, 2 H), 3.98–3.92 (m, 2 H), 3.56 (dd, J = 5.6, 17.2 Hz,
1 H), 3.19 (dd, J = 6.4, 17.2 Hz, 1 H), 1.20 (t, J = 7.2 Hz, 3 H), 1.03
(t, J = 7.2 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 196.0, 169.6, 168.5, 139.8, 137.8,
133.3, 132.6, 131.9, 128.8, 128.5, 128.3, 127.6, 126.6, 62.3, 62.2,
61.6, 46.7, 42.2, 13.7, 13.6.
ESI-MS: m/z = 423.1 [M + H]+.
HR-MS (ESI): m/z [M + H]+ calcd for C26H31O5: 423.2171; found:
423.2165.
ESI-MS: m/z = 367.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C22H23O5: 367.1545; found:
367.1540.
Diethyl 4¢-Oxo-3¢,4¢-dihydro-1,2¢-binaphthyl-1¢,1¢(2¢H)-dicar-
boxylate (2g)
1H NMR (CDCl3, 400 MHz): d = 8.19–8.13 (m, 2 H), 7.99 (d, J =
8.0 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 1 H), 7.72–7.64 (m, 2 H), 7.58–
7.48 (m, 3 H), 7.14 (t, J = 8.0 Hz, 1 H), 7.02 (d, J = 7.2 Hz, 1 H),
5.42–5.39 (m, 1 H), 4.24–4.13 (m, 2 H), 3.88 (dd, J = 6.4, 16.8 Hz,
1 H), 3.72–3.63 (m, 2 H), 3.10 (dd, J = 3.2, 16.8 Hz, 1 H), 1.21 (t,
J = 7.2 Hz, 3 H), 0.56 (t, J = 7.2 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 197.9, 171.8, 170.8, 139.1, 138.0,
136.2, 135.4, 134.7, 133.4, 131.3, 130.7, 130.1, 128.8, 128.5, 127.7,
127.3, 127.2, 124.7, 64.6, 63.7, 63.3, 44.5, 41.9, 15.9, 15.2.
Diethyl 2-(3-Methoxyphenyl)-4-oxo-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2c)
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 7.6 Hz, 1 H), 7.74 (d,
J = 8.0 Hz, 1 H), 7.63 (t, J = 7.2 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 1 H),
7.09 (t, J = 8.0 Hz, 1 H), 6.72 (d, J = 8.0 Hz, 1 H), 6.65–6.62 (m,
2 H), 4.29 (t, J = 6.0 Hz, 1 H), 4.23–4.10 (m, 2 H), 4.00–3.94 (m,
2 H), 3.65 (s, 3 H), 3.55 (dd, J = 5.6, 17.2 Hz, 1 H), 3.17 (dd, J =
6.0, 17.2 Hz, 1 H), 1.20 (t, J = 6.8 Hz, 3 H), 1.04 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 195.9, 169.5, 168.4, 159.4, 141.3,
137.7, 133.2, 132.6, 131.9, 129.3, 128.5, 126.6, 121.0, 114.8, 112.9,
62.2, 61.6, 55.0, 46.7, 42.2, 13.7, 13.6.
ESI-MS: m/z = 417.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C26H25O5: 417.1702; found:
417.1706.
ESI-MS: m/z = 397.0 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H25O6: 397.1651; found:
397.1650.
Synthesis 2010, No. 19, 3289–3294 © Thieme Stuttgart · New York

PAPER
Diethyl 2-Aryl-3,4-dihydro-4-oxo-1,1(2H)-naphthalenedicarboxylate
3293
Diethyl 2-(3-Hydroxy-4-methoxyphenyl)-4-oxo-3,4-dihydro-
naphthalene-1,1(2H)-dicarboxylate (2h)
7.14–7.12 (m, 1 H), 6.91 (s, 1 H), 6.79 (d, J = 5.2 Hz, 1 H), 4.48 (t,
J = 6.0 Hz, 1 H), 4.27–4.12 (m, 2 H), 4.04 (q, J = 7.2 Hz, 2 H), 3.51
(dd, J = 5.2, 17.2 Hz, 1 H), 3.14 (dd, J = 5.2, 17.2 Hz, 1 H), 1.22 (t,
J = 6.8 Hz, 1 H), 1.08 (t, J = 6.8 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): d = 195.9, 169.5, 168.4, 139.9, 137.6,
133.3, 132.4, 131.8, 128.6, 128.0, 126.7, 125.3, 123.3, 62.4, 62.2,
61.7, 42.1, 42.0, 13.8, 13.7.
ESI-MS: m/z = 373.0 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C20H21O5S: 373.1110; found:
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 7.6 Hz, 1 H), 7.72 (d,
J = 8.0 Hz, 1 H), 7.63 (t, J = 8.4 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 1 H),
6.69 (s, 1 H), 6.63 (d, J = 8.4 Hz, 1 H), 6.53 (d, J = 8.4 Hz, 1 H),
5.53 (s, 1 H), 4.24–4.11 (m, 3 H), 4.03–3.81 (m, 2 H), 3.80 (s, 3 H),
3.52 (dd, J = 5.6, 17.2 Hz, 1 H), 3.14 (dd, J = 6.0, 17.2 Hz, 1 H),
1.22 (t, J = 7.2 Hz, 3 H), 1.10 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 196.0, 169.6, 168.4, 145.9, 145.3,
137.8, 133.2, 133.0, 132.6, 131.8, 128.5, 126.6, 120.2, 115.5, 110.5,
62.5, 62.1, 61.6, 55.8, 46.1, 42.3, 13.7, 13.6.
373.1108.
ESI-MS: m/z = 413.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H25O7: 413.1600; found:
Diethyl 2-(3-Methylthiophen-2-yl)-4-oxo-3,4-dihydronaphtha-
lene-1,1(2H)-dicarboxylate (2m)
413.1591.
1H NMR (CDCl3, 400 MHz): d = 8.17 (d, J = 8.0 Hz, 1 H), 7.77 (d,
J = 8.4 Hz, 1 H), 7.66 (t, J = 7.6 Hz, 1 H), 7.53 (t, J = 7.6 Hz, 1 H),
6.94 (d, J = 4.8 Hz, 1 H), 6.68 (d, J = 4.8 Hz, 1 H), 4.77 (t, J =
5.2 Hz, 1 H), 4.27–3.95 (m, 4 H), 3.61 (dd, J = 5.6, 17.6 Hz, 1 H),
3.04 (dd, J = 4.4, 17.6 Hz, 1 H), 2.19 (s, 3 H), 1.94 (t, J = 7.2 Hz,
3 H), 1.12 (t, J = 7.2 Hz, 3 H).
Diethyl 2-(4-Chlorophenyl)-4-oxo-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2i)
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 8.0 Hz, 1 H), 7.71 (d,
J = 8.0 Hz, 1 H), 7.65 (t, J = 7.2 Hz, 1 H), 7.52 (t, J = 7.6 Hz, 1 H),
7.17 (d, J = 8.4 Hz, 2 H), 7.05 (d, J = 8.4 Hz, 2 H), 4.29 (t, J =
6.0 Hz, 1 H), 4.22–4.13 (m, 2 H), 4.02–3.94 (m, 2 H), 3.51 (dd, J =
5.6, 17.2 Hz, 1 H), 3.17 (dd, J = 6.4, 17.2 Hz, 1 H), 1.21 (t, J =
7.2 Hz, 3 H), 1.07 (t, J = 7.2 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 195.2, 169.3, 168.4, 136.8, 135.6,
134.9, 133.3, 132.7, 132.4, 128.7, 126.7, 123.8, 62.2, 62.0, 61.8,
42.9, 40.0, 13.8, 13.7, 13.6.
ESI-MS: m/z = 387.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H23O5S: 387.1266; found:
13C NMR (CDCl3, 75 MHz): d = 195.5, 169.4, 168.3, 138.2, 137.7,
133.6, 133.4, 132.5, 131.7, 130.2, 128.6, 128.5, 126.8, 62.3, 62.2,
61.7, 46.2, 41.9, 13.7, 13.6.
387.1267.
ESI-MS: m/z = 401.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C22H22ClO5: 401.1156; found:
Diethyl 2-(Furan-2-yl)-4-oxo-3,4-dihydronaphthalene-1,1(2H)-
dicarboxylate (2n)
401.1150.
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 7.6 Hz, 1 H), 7.62–
7.56 (m, 2 H), 7.48–7.44 (m, 1 H), 7.21 (s, 1 H), 6.21–6.19 (m,
1 H), 6.00 (s, 1 H), 4.47 (t, J = 5.6 Hz, 1 H), 4.33–4.17 (m, 2 H),
4.12 (q, J = 7.2 Hz, 2 H), 3.46 (dd, J = 5.2, 17.6 Hz, 1 H), 3.06 (dd,
J = 6.8, 17.6 Hz, 1 H), 1.27 (t, J = 7.2 Hz, 3 H), 0.97 (t, J = 7.2 Hz,
3 H).
Diethyl 2-(4-Cyanophenyl)-4-oxo-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2j)
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 7.6 Hz, 1 H), 7.70–
7.63 (m, 2 H), 7.54–7.49 (m, 3 H), 7.25–7.24 (m, 2 H), 4.36 (t, J =
6.0 Hz, 1 H), 4.22–4.16 (m, 2 H), 4.01–3.95 (m, 2 H), 3.51 (dd, J =
5.6, 17.2 Hz, 1 H), 3.19 (dd, J = 6.8, 17.2 Hz, 1 H), 1.21 (t, J =
7.2 Hz, 3 H), 1.05 (t, J = 7.2 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 195.1, 169.2, 168.3, 153.0, 141.8,
137.4, 133.2, 132.1, 131.2, 128.5, 126.7, 110.2, 107.8, 62.3, 62.0,
61.9, 40.0, 39.7, 13.8, 13.7.
ESI-MS: m/z = 357.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C20H21O6: 357.1338; found:
13C NMR (CDCl3, 75 MHz): d = 194.9, 169.2, 168.1, 145.0, 137.5,
133.6, 132.3, 131.6, 130.0, 128.9, 126.9, 118.3, 111.8, 62.4, 62.2,
61.9, 46.7, 41.6, 13.7, 13.6.
357.1336.
ESI-MS: m/z = 392.0 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H22NO5: 392.1498; found:
392.1491.
Diethyl 7-Methoxy-4-oxo-2-p-tolyl-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2o)
1H NMR (CDCl3, 400 MHz): d = 8.15 (d, J = 8.8 Hz, 1 H), 7.20 (s,
1 H), 7.03–6.97 (m, 5 H), 4.28–4.15 (m, 3 H), 4.05–3.95 (m, 2 H),
3.91 (s, 3 H), 3.51 (dd, J = 5.6, 17.2 Hz, 1 H), 3.11 (dd, J = 6.0,
17.2 Hz, 1 H), 2.27 (s, 3 H), 1.25 (t, J = 6.8 Hz, 3 H), 1.10 (t, J =
6.8 Hz, 3 H).
Diethyl 2-(2-Chloropyridin-3-yl)-4-oxo-3,4-dihydronaphtha-
lene-1,1(2H)-dicarboxylate (2k)
1H NMR (CDCl3, 400 MHz): d = 8.21 (s, 1 H), 8.10 (d, J = 8.0 Hz,
1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.70 (t, J = 7.6 Hz, 1 H), 7.54 (t, J =
8.0 Hz, 1 H), 7.24 (d, J = 7.6 Hz, 1 H), 6.94–6.91 (m, 1 H), 5.01–
4.99 (m, 1 H), 4.29–3.74 (m, 2 H), 4.01 (q, J = 7.2 Hz, 2 H), 3.74
(dd, J = 5.6, 16.8 Hz, 1 H), 3.02 (dd, J = 2.8, 17.2 Hz, 1 H), 1.09 (t,
J = 7.2 Hz, 3 H), 0.97 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 194.9, 169.5, 168.4, 163.4, 139.8,
137.1, 136.8, 129.0, 128.9, 128.6, 126.4, 116.5, 114.7, 62.6, 62.1,
61.6, 55.5, 46.3, 41.9, 20.9, 13.8, 13.6.
ESI-MS: m/z = 411.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C24H27O6: 411.1808; found:
13C NMR (CDCl3, 75 MHz): d = 194.9, 168.7, 168.4, 151.4, 148.3,
137.5, 136.4, 134.3, 133.5, 132.9, 132.3, 128.9, 126.7, 122.3, 62.6,
62.1, 60.4, 41.9, 41.1, 13.7, 13.5.
411.1804.
ESI-MS: m/z = 402.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H21ClNO5: 402.1108;
1,1-Diethyl 7-Methyl 4-Oxo-2-phenyl-3,4-dihydronaphthalene-
1,1,7(2H)-tricarboxylate (2p)
found: 402.1103.
1H NMR (CDCl3, 400 MHz): d = 8.42 (s, 1 H), 8.20 (d, J = 8.0 Hz,
1 H), 8.14 (d, J = 8.0 Hz, 1 H), 7.18–7.16 (m, 3 H), 7.05–7.03 (m,
2 H), 4.35 (t, J = 5.6 Hz, 1 H), 4.26–4.13 (m, 2 H), 3.99–3.93 (m,
5 H), 3.58 (dd, J = 5.6, 17.2 Hz, 1 H), 3.20 (dd, J = 6.0, 17.2 Hz,
1 H), 1.21 (t, J = 7.2 Hz, 3 H), 1.02 (t, J = 7.2 Hz, 3 H).
Diethyl 4-Oxo-2-(thiophen-2-yl)-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2l)
1H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 8.0 Hz, 1 H), 7.71 (d,
J = 8.0 Hz, 1 H), 7.64 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 1 H),
Synthesis 2010, No. 19, 3289–3294 © Thieme Stuttgart · New York

3294
Z. Li et al.
PAPER
13C NMR (CDCl3, 75 MHz): d = 195.4, 169.2, 168.1, 166.0, 139.4,
137.9, 135.4, 134.2, 133.5, 129.2, 128.7, 128.4, 127.7, 126.7, 62.4,
62.2, 61.8, 52.4, 46.5, 42.3, 13.7, 13.5.
ESI-MS: m/z = 425.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C24H25O7: 425.1600; found:
Acknowledgment
We thank the Knowledge Innovation Program of the Chinese Aca-
demy of Sciences, the 100-talent program of CAS, National Natural
Science Foundation (Grant 90813033), and National Basic Rese-
arch Program of China (Grants 2010CB529706, 2009CB940904)
for their financial support.
425.1602.
1,1-Diethyl 7-Methyl 4-oxo-2-p-tolyl-3,4-dihydronaphthalene-
1,1,7(2H)-tricarboxylate (2q)
References
1H NMR (CDCl3, 400 MHz): d = 8.41 (s, 1 H), 8.19 (d, J = 8.4 Hz,
1 H), 8.12 (d, J = 8.4 Hz, 1 H), 8.98 (d, J = 8.0 Hz, 2 H), 8.93 (d,
J = 8.0 Hz, 2 H), 4.32 (t, J = 6.0 Hz, 1 H), 4.25–4.15 (m, 2 H), 4.02–
3.92 (m, 5 H), 3.56 (dd, J = 5.6, 17.6 Hz, 1 H), 3.17 (dd, J = 6.0,
17.2 Hz, 1 H), 2.24 (s, 3 H), 1.22 (t, J = 7.2 Hz, 3 H), 1.06 (t, J =
6.8 Hz, 3 H).
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ESI-MS: m/z = 439.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C25H27O7: 439.1757; found:
439.1749.
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Diethyl 7-Chloro-4-oxo-2-p-tolyl-3,4-dihydronaphthalene-
1,1(2H)-dicarboxylate (2r)
1H NMR (CDCl3, 400 MHz): d = 8.09 (d, J = 8.4 Hz, 1 H), 7.73 (s,
1 H), 7.47 (d, J = 8.4 Hz, 1 H), 6.99 (d, J = 7.6 Hz, 2 H), 6.93 (d,
J = 7.6 Hz, 2 H), 4.29 (t, J = 6.0 Hz, 1 H), 4.24–4.15 (m, 2 H), 4.03–
3.93 (m, 2 H), 3.54 (dd, J = 6.0, 17.2 Hz, 1 H), 3.12 (dd, J = 6.0,
17.2 Hz, 1 H), 2.25 (s, 3 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.08 (t, J =
7.2 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 194.9, 169.0, 167.9, 139.7, 139.2,
137.4, 136.4, 132.0, 131.1, 129.1, 129.0, 128.5, 128.1, 62.4, 62.2,
61.8, 46.2, 42.1, 20.9, 13.7, 13.6.
ESI-MS: m/z = 415.0 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H24ClO5: 415.1312; found:
415.1307.
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1,1(2H)-dicarboxylate (2s)
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1H NMR (CDCl3, 400 MHz): d = 8.66 (s, 1 H), 8.29 (s, 1 H), 6.98
(d, J = 7.6 Hz, 2 H), 6.87 (d, J = 7.6 Hz, 2 H), 4.37 (t, J = 7.2 Hz,
1 H), 4.28–4.14 (m, 2 H), 4.05–3.95 (m, 2 H), 3.64 (dd, J = 6.0,
17.2 Hz, 1 H), 3.16 (dd, J = 6.0, 17.2 Hz, 1 H), 2.24 (s, 3 H), 1.24
(t, J = 7.2 Hz, 3 H), 1.08 (t, J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 194.5, 168.5, 167.7, 150.4, 139.2,
137.7, 136.5, 135.9, 129.2, 128.4, 127.9, 127.8, 123.1, 62.8, 62.2,
62.1, 45.9, 42.4, 20.8, 13.7, 13.6.
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ESI-MS: m/z = 426.1 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H24NO7: 426.1553; found:
426.1545.
Synthesis 2010, No. 19, 3289–3294 © Thieme Stuttgart · New York