Electronic tuning cyclization of aryl-1,4-enediones: AlCl3-mediated Nazarov-type cyclization to synthesize polysubstituted-1-indanones

Article abstract of DOI:10.1016/j.tet.2014.10.052

An electronic tuning Nazarov-type cyclization protocol was proposed for the synthesis of polysubstituted-1-indanones from the readily available starting materials 1,4-enediones. AlCl₃ was highlighted as the most efficient promoter for this reac

Full text of DOI:10.1016/j.tet.2014.10.052

Tetrahedron 70 (2014) 9536e9544
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Tetrahedron
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Electronic tuning cyclization of aryl-1,4-enediones: AlCl3-mediated
Nazarov-type cyclization to synthesize polysubstituted-1-indanones
Yan-Ping Zhu, Qun Cai, Feng-Cheng Jia, Mei-Cai Liu, Qing-He Gao, Xiang-Gao Meng,
*
An-Xin Wu
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 June 2014
Received in revised form 21 October 2014
Accepted 24 October 2014
Available online 29 October 2014
An electronic tuning Nazarov-type cyclization protocol was proposed for the synthesis of poly-
substituted-1-indanones from the readily available starting materials 1,4-enediones. AlCl3 was high-
lighted as the most efficient promoter for this reaction.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Nazarov cyclization
1,4-Enediones
AlCl3
Polysubstituted-1-indanones
1. Introduction
Indanone derivatives are key structural units that are widely
found in natural products and pharmaceuticals, such as taiwania-
quinol B, pauciflorol F and indacrinone (Scheme 1).1 They can also
often serve as important synthetic precursors for complex chemical
synthesis.2 As a result, many efficient synthetic methods have been
explored for the synthesis of indanone derivatives.3 One such
method that has been relatively utilized is the Nazarov cyclization,
which has proven to be useful in providing stereospecific properties
in the products.
More specifically, Nazarov cyclization is a stereospecific 4
p
electrocyclization method that converts divinyl ketones into
cyclopentenones by activation with a Lewis or Brønsted acid.4 Over
several decades, great efforts have been devoted to the exploitation
of the Nazarov reaction. Many impressive results have been ac-
complished by the groups of Frontier,5 Tius,6 Trauner,7 France,8 and
Ma,9 among others.10 For example, Frontier and co-workers ex-
amined the impact of dienone substitution on Nazarov cyclization
in detail.5d They also developed a series of catalysts such as Cu(II),
Pd(II), Ir(III) and Sc(OTf)3/LiClO4 for Nazarov cyclization reactions
based on a polarizing strategy.5 More recently, Luo and Cheng
proposed an elegant Lewis acid and Brønsted acid combination
Scheme 1. Indanone derivatives in natural products and pharmaceuticals.
ketoesters.11 This strategy led to a dramatic enhancement in the
catalytic activity of the Nazarov reaction.
Despite these achievements, the types of substrates utilized in
the Nazarov reaction primarily consist of divinyl ketones, divinyl
b-
ketoesters and aryl vinyl -ketoesters, among others (Scheme 2).
b
catalyzed strategy for the Nazarov cyclization of aryl vinyl
b-
Moreover, the substituent groups at C-5 are still restricted in
electron-donating groups, such as (hetero)aryl, alkyl and ethenyl
groups. When electron-withdrawing groups, such as aroyl,
ester and conjugated enones, are attached at C-5 position, the
* Corresponding author. Tel./fax: þ86 027 6786 7773; e-mail address: chwuax@
mail.ccnu.edu.cn (A.-X. Wu).
http://dx.doi.org/10.1016/j.tet.2014.10.052
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
9537
Table 1
Optimization of the reaction conditionsa
Scheme 2. The types of substrates for Nazarov cyclization.
Entry
Promoter/equiv
Temp (ꢀC)
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
H2SO4 (1.1)
H3PO4 (1.1)
HCl (1.1)
CF3CO2H (1.1)
CH3SO3H (1.1)
CF3SO3H (1.1)
AlCl3 (1.1)
ZnCl2 (1.1)
FeCl3 (1.1)
TiCl4 (1.1)
SnCl4 (1.1)
InCl3 (1.1)
Cu(OTf)2 (1.1)
AlCl3 (1.1)
AlCl3 (1.1)
AlCl3 (1.1)
AlCl3 (0.5)
AlCl3 (0.3)
AlCl3 (0.5)
AlCl3 (0.5)
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
50
80
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
EtNO2
MeNO2
CHCl3
CH2Cl2
EtNO2
EtNO2
EtNO2
N.R.
N.R.
N.R.
N.R.
Nazarov cyclization reaction can be very difficult to produce. Thus,
further researches into diverse and effective substrates for the
Nazarov cyclization remain desirable.
The 1,4-enedione is an important framework, that is, widely
present in natural products and medicinal compounds. It is well-
known as a versatile precursor in organic synthesis.12 The de-
velopment of an efficient method for the Nazarov cyclization of 1,4-
enediones would therefore be both important and desirable. Based
on the polarizing strategy, we wonder whether increasing the
electronic disposition of C-2 aryl ring or increasing the acid-stage
and amount of promoter might lead to improvements in the re-
activity of aryl-1,4-enediones (Scheme 3). Herein, we reported the
first instance of electronic tuning Nazarov-type cyclization of aryl-
1,4-enediones.
N.R.
N.R.
96% (6:1)c
,
d
N.R.
9
86% (3:1)c
N.R.
10
11
12
13
14
15
16
17
18
19
20
88% (2:1)c
N.R.
N.R.
N.R.
N.R.
N.R.
69 (6:1)c
52 (5:1)c
70 (3:1)c
72 (3:1)c
a
Reaction conditions: 1a (0.5 mmol), promoter (0.55 mmol), solvent (3e5 mL)
under Ar atmosphere at 25 ꢀC.
b
Isolated yield. N.R.¼no reaction.
c
Diastereoselectivities was determined by crude 1H NMR.
d
The optimal conditions for the reaction.
Table 2
The scope of aryl-1,4-enedionesa,b
Scheme 3. Our strategy for Nazarov cyclization of aryl-1,4-enediones.
2. Results and discussion
We initially optimized the experimental conditions using ethyl
4-oxo-4-phenyl-2-(3,4,5-trimethoxybenzoyl)but-2-enoate (1a) as
a model substrate (Table 1). First, a series of Brønsted acids, such as
H2SO4, H3PO4, HCl, CF3CO2H, MeSO3H and CF3SO3H, were screened
for the reaction in EtNO2 at 25 ꢀC (Table 1, entries 1e6). However,
the desired product was not observed. A variety of Lewis acids were
also investigated for the reaction. To our delight, the reaction oc-
curred smoothly to afford the desired product 2a in 96% yield by
using 1.1 equiv of AlCl3 (Table 1, entry 7). When 1.1 equiv of FeCl3 or
SnCl4 were added, the reaction also performed efficiently to furnish
the product 2a in good yield (86% and 88%, entry 9 and 11). How-
ever, other Lewis acids, such as ZnCl2, TiCl4, InCl3 and Cu(OTf)2,
were found not to promote the reaction (entries 8, 10 and 12e13).
Various solvents were also tested, where EtNO2 was found to be the
most efficient solvent for the process (entries 14e16). Yet, further
decreases the amount of AlCl3 (0.3e0.5 equiv) was seen to provide
a moderate yield (entries 17e18). Further investigation found that
changes in temperature had no obvious impact on the reaction
efficiency (entries 19e20). Finally, the optimal reaction conditions
for the reaction were pinpointed as 1a (1.1 mmol) with 1.1 equiv of
AlCl3 at 25 ꢀC in EtNO2 (entry 7).
With the optimal conditions in hand, we initially examined the
impact of the substituent groups at C-6 on the reaction efficiency.13
To our satisfaction, the reaction demonstrated good compatibility
with various substituent groups at the C-6 position (Table 2).
Electron-donating, and electron-withdrawing groups, such as 4-Me,

9538
Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
Table 3
4-OMe, 3,4-O(CH2)2O, 4-Cl, 4-Br, 3,4-Cl2 and 4-NO2, attached to the
phenyl group of C-6 were shown to afford the corresponding
products with excellent yields (2aeh, 85e99% yields, 1:1 to 99:1 dr
ratio). The electronic and steric natures of substituent groups at the
C-6 position were seen to have little influence on the reaction ef-
ficiency. Moreover, the structure of product 2g was further con-
firmed by X-ray crystallography (Fig. 1).14 To our delight, the
heteroaryls, such as 2-furanyl (1i), thiophenyl (1j) and 2-
benzofuranyl (1k), were found suitable for the reaction and pro-
vided the corresponding products 2iek in 90e95% yields (dr:
5:1e99:1). Moreover, the steric hindrance substituent group 1-
naphthyl (1m) was also tolerant to the reaction to yield the corre-
sponding product 2m in 94% yield, respectively (with 2:1 dr ratio).
The scope of 1,4-enediones and aryl vinyl b
-ketoestersa,b
Fig. 1. The X-ray crystal structure illustration for the trans isomer of 2g.
To further access the substituent effects of the C-2 aryl ring on
reaction efficiency, a series of aryl-1,4-enediones 3aef were pre-
pared to explore the scope of the method (Table 3).15 We were
pleased to find that 3,4-dimethoxyl substituted substrates 3aec
were suitable for the reaction and gave the corresponding products
4aec in good yields (88e92%). However, when the aryl at C-2 po-
sition was attached with one methoxyl group, such as 2-OMe, 3-
OMe, or 4-OMe (3def), the reaction could not perform under the
standard conditions. These results suggested that the electronic
disposition of substitutions at C-2 aryl group were very important
to the reaction efficiency. We subsequently examined the sub-
stituent effects of C-5 position on the reactivity. It was found that
conjugated enones (3g) and ester groups (3hei) substituted at C-5
position did not affect the reaction efficiency, and thus the desired
products 4gei were furnished in 85e93% yields. Moreover, the
pattern of the substituent groups at C-4 position was also in-
vestigated. The methylthio group at C-4 in the aryl-1,4-enedione
(3j) was unable to perform to provide the desired product. In ad-
dition, methylsulfinyl (3k) and methylsulfonyl (3l) group did not
perform cyclization. 1,4-Trifluoroacetyl enediones (3men) were
also unable to perform the reaction under the standard conditions.
It is also likely that the improvements in the reactivity were not
obtained even with higher catalyst loading or elevated the reaction
temperature (3jen, with 3 equiv of AlCl3 at 70 ꢀC). These results
demonstrated that the pattern of the substituent groups at C-4
position was critical for aryl-1,4-enediones Nazarov cyclization.
Based on these results, we think that the electronic effect of C-5
position was crucial to the reaction. For further testifying this
product 4o in excellent yield (90% yield, 5:1 dr ratio). When the aryl
at C-5 position was attached with 4-Me or 4-OMe group (3def), the
reaction could also perform under the standard conditions to give
the corresponding products (4p and 4q) in 95% and 96% yields,
respectively (8:1 dr ratio). In addition, the substrates with
methoxyl groups (such as, 4-OMe, 2-OMe, 3,4-OMe2, 2,3,4-OMe3)
at C-2 aryl ring also reacted smoothly to form the desired products
in excellent yields (4reu, 90e94% yields, 2:1 to 15:1 dr ratio). This
time two or three methoxy groups at C-2 aryl ring were not nec-
essary for the reaction.
A possible reaction mechanism was described as follows using
substrate 1a as an example (Scheme 4). Initially, the promoter AlCl3
coordinated with substrate 1a via two-point binding to form the
intermediate A, which was followed by isomerization to afford the
oxyallyl cation B.17 Intermediate B subsequently underwent cycli-
zation to furnish intermediate C. This was followed by
conclusion, a series of aryl vinyl b-ketoesters (3oer) were synthe-
sized (Table 3).16 To our delight, the substrate 3o with a phenyl
group at C-5 position performed smoothly to afford the desired
Scheme 4. The plausible mechanism of the present reaction.

Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
9539
deprotonation to give intermediate D. Finally, the promoter AlCl3
was left to obtain the product 2a.
(925 mg, 2.0 mmol) in CH2Cl2 (25 mL) was stirred at 0 ꢀC for 30 min.
Then 3-chlorobenzoperoxoic acid (1.2 equiv for 3k, 2.5 equiv for 3l)
was dropwise added into the above mixture and stirred for other
3 h, after disappearance of the reactant (monitored by TLC), and
added 150 mL brine to the mixture, then extracted with CH2Cl2
three times (3ꢂ100 mL). The extract was dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (petroleum ether/
EtOAc) to yield the desired product 3k as a yellow solid (yield: 75%).
3. Conclusion
In conclusion, an electronic tuning Nazarov-type cyclization
protocol has been proposed for the synthesis of polysubstituted-1-
indanones in high yields (up to 99%) from the readily available 1,4-
enediones and aryl vinyl b-ketoesters. AlCl3 was highlighted as the
most efficient promoter for this reaction. Further analysis revealed
that the pattern of substituent groups at C-2, C-4 and C-5 positions
were also crucial for the reaction efficiency. When electron-
withdrawing groups were attached at C-5 position (such as aroyls,
esters and conjugated enones), two or more electron-donating
groups at C-2 aryl ring were necessary to promote the reaction.
Further studies on the applications of this strategy will be reported
in due course.
4.1.4. General procedure for synthesis of substrates 1,4-enediones 4h
and 4i. A round flask was charged with ethyl 3-oxo-3-(3,4,5-
trimethoxyphenyl)propanoate 6h (282 mg, 1.0 mmol), ethyl 2-
oxoacetate 7 (1.5 equiv, 75% in toluene solution), CuI (95 mg,
0.5 mmol) and Et3N (1.5 equiv) at room temperature, and then
solvent MeCN (10 mL) was added. The resulting mixture was reflux
for 5e6 h, after disappearance of the reactant (monitored by TLC),
then removed the solvent and added 50 mL water and 30 mL sat-
urated brine solution to the mixture, extracted with EtOAc three
times (3ꢂ50 mL). The extract was dried over anhydrous Na2SO4 and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (petroleum ether/EtOAc) to
yield the desired product 4h as yellow oil (yield: 68%).
4. Experimental
4.1. General
Unless otherwise noted, all aryl methyl ketones, b-keto ester and
other reagents were obtained from commercial suppliers and used
without further purification. TLC analysis was performed using pre-
coated glass plates. Column chromatography was performed using
silica gel (200e300 mesh).
IR spectra were recorded on a PerkineElmer PE-983 infrared
spectrometer as KBr pellets with absorption in cmꢁ1. NMR spectra
were recorded on a Varian Mercury 400 or 600 MHz spectrometer
4.1.5. General procedure for synthesis of 2 and 4 (2a as an exam-
ple). Aryl-1,4-enedione 1a (199 mg, 0.5 mmol) and AlCl3 (73.15 mg,
0.55 mmol) was added to a 20 mL Schlenk tube, and the tube was
protected under Ar atmosphere. Subsequently, solvent EtNO2
(3 mL) was added. The reaction mixture was stirred at 25 ꢀC for
1e10 h, during which it was monitored by TLC. The solution was
diluted with ethyl acetate (30 mL), washed with H2O (3ꢂ10 mL) and
30 mL saturated brine solution, dried over Na2SO4 and concen-
trated under reduced pressure. The residue was purified by column
chromatography on silica gel (petroleum ether/EtOAc) to yield the
desired product 2a as red oil (yield: 96%).
Chemical shifts are reported in parts per million (CDCl3: d 7.26 ppm
for 1H NMR and 77.0 ppm for 13C NMR), relative to the internal
standard of tetramethylsilane (TMS), multiplicities are indicated s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet); coupling
constants (J) are given in Hertz (Hz). HRMS were obtained on
a Bruker Apex-Ultra 7.0T FTMS equipped with an electrospray
source (ESI) or Atmospheric-pressure chemical ionization (APCI).
4.2. Characterization data
4.1.1. General procedure for synthesis of substrates 1aem, 3aeg and
3men (1a as an example). A sealed tube was charged with aceto-
phenone 5a (600 mg, 5 mmol), ethyl 3-oxo-3-(3,4,5-trimethoxy
phenyl)propanoate 6a (1410 mg, 5.0 mmol), iodine (1396 mg,
5.5 mmol) and CuO (440 mg, 5.5 mmol) at room temperature, and
then solvent DMSO (10 mL) was added. The resulting mixture was
stirred at 70 ꢀC for 12 h, after disappearance of the reactant
(monitored by TLC), and added 50 mL water to the mixture, then
extracted with EtOAc three times (3ꢂ50 mL). The extract was
washed with 10% Na2S2O3 solution, dried over anhydrous Na2SO4
and concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel (petroleum ether/EtOAc)
to yield the desired product 1a as a yellow solid (yield: 84%).
4.2.1. Ethyl 4-oxo-4-phenyl-2-(3,4,5-trimethoxybenzoyl)but-2-
enoate (1a). IR (KBr): 3417, 3060, 2960, 2349, 1680, 1579, 1561,
1490, 1450, 1416, 1260, 1180, 1127, 1075, 1025 cmꢁ1 1H NMR
;
(400 MHz, CDCl3):
d
¼8.14 (s, 1H), 7.97 (d, J¼8.0 Hz, 2H), 7.62 (t,
J¼7.68 Hz, 1H), 7.49 (t, J¼8.0 Hz, 2H), 7.15 (s, 2H), 4.31 (q,
J¼7.2 Hz, 2H), 3.91 (s, 3H), 3.85 (s, 6H), 1.26 (t, J¼7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d
¼191.9, 191.1, 190.1, 188.5, 163.6, 153.2,
153.1, 144.2, 143.0, 140.4, 136.1, 134.2, 130.9, 130.7, 128.9, 128.7,
107.1, 107.0, 106.0, 105.8, 62.4, 56.3, 56.1, 56.0, 14.0, 13.8; HRMS
(APCI): m/z [MþH]þ calcd for C22H23O7: 399.1438; found:
399.1439.
4.2.2. Ethyl 4-oxo-4-(p-tolyl)-2-(3,4,5-trimethoxybenzoyl)butanoate
(1b). IR (KBr): 2974, 2943, 2847, 1728, 1656, 1600, 1582, 1451, 1413,
1364, 1326, 1264, 1229, 1185, 1167, 1124, 1089, 1038, 1011 cmꢁ1; 1H
4.1.2. General procedure for synthesis of substrates 1,4-enediones
3j. A solution of 3,4,5-trimethoxyl phenyl acetone 5j (1050 mg,
5.0 mmol), iodine (2538 mg,10 mmol) and CuO (1200 mg,15 mmol)
in DMSO (25 mL) was heated at 65 ꢀC for 18 h. After filtration then
the reaction mixture was then poured into 150 mL brine and the
aqueous layer was extracted with EtOAc (3ꢂ100 mL). The extract
was washed with Na2S2O3 and NaOH solution, dried over anhy-
drous Na2SO4 then the solvent was removed under reduced pres-
sure. The residue was purified by column chromatography on silica
gel with EtOAc/hexane as eluent to give the expected compound 3j
in 82% yield.
NMR (400 MHz, CDCl3):
d
(ppm) 8.13 (s, 1H), 7.87 (d, J¼8.4 Hz, 2H),
7.29 (d, J¼7.6 Hz, 2H), 7.15 (s, 2H), 4.30 (q, J¼7.2 Hz, 2H), 3.91 (s, 3H),
3.85 (s, 6H), 2.42 (s, 3H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3):
d (ppm) 192.1, 188.0, 163.8, 153.2, 148.1, 145.5, 143.9, 143.0,
133.8, 131.0, 129.6, 129.0, 105.9, 62.4, 60.8, 56.1, 21.75, 14.0; HRMS
(ESI): m/z [MþH]þ calcd for C23H24NaO7: 435.1414; found: 435.1407.
4.2.3. Ethyl 4-(4-methoxyphenyl)-4-oxo-2-(3,4,5-trimethoxy
benzoyl)butanoate (1c). IR (KBr): 3433, 2939, 2840, 1704, 1672,
1598, 1504, 1461, 1415, 1379, 1331, 1262, 1176, 1127, 1017 cmꢁ1; IR
(KBr): 3433, 2939, 2840, 1704, 1671, 1656, 1597, 1504, 1460, 1415,
1379, 1331, 1263, 1177, 1127, 1018 cmꢁ1; 1H NMR (400 MHz, CDCl3):
4.1.3. General procedure for synthesis of substrates 1,4-enediones 3k
and 3l. A solution of
a
-methylthio-substituted 1,4-enedione 3j
d
(ppm) 8.14 (s, 1H), 7.96 (d, J¼8.8 Hz, 2H), 7.16 (s, 1H), 6.95 (d,

9540
Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
J¼8.8 Hz, 3H), 4.30 (q, J¼7.2 Hz, 2H), 3.92e3.84 (m, 12H), 1.25 (t,
144.4, 142.9, 132.1, 130.8, 119.9, 113.2, 105.8, 62.4, 60.7, 56.1, 13.9;
HRMS (ESI): m/z [MþH]þ calcd for C20H21O8: 389.1231; found:
389.1231.
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d (ppm) 192.1, 186.6,
164.4, 153.0, 143.4, 133.8, 131.3, 130.9, 129.1, 114.0, 107.2, 105.8, 62.3,
60.7, 56.0, 55.4, 40.4, 13.8; HRMS (ESI): m/z [MþH]þ calcd for
C
23H25O8: 429.1544; found: 429.1544.
4.2.10. Ethyl 4-oxo-4-(thiophen-2-yl)-2-(3,4,5-trimethoxybenzoyl)
butanoate (1j). 1H NMR (400 MHz, CDCl3):
d (ppm) 7.97 (s, 1H), 7.90
4.2.4. Ethyl 4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-oxo-2-(3,4,5-
trimethoxybenzoyl)butanoate (1d). IR (KBr): 3063, 2937, 2837,
1717, 1670,1658, 1581,1504,1459, 1432, 1413,1351,1330, 1291, 1264,
1243, 1200, 1158, 1129, 1065, 1022, 1002 cmꢁ1; 1H NMR (400 MHz,
(s, 1H), 7.77 (d, J¼3.6 Hz, 1H), 7.20 (s, 1H), 7.15 (s, 2H), 4.31 (q,
J¼7.2 Hz, 2H), 3.91 (s, 3H), 3.86 (s, 6H), 1.25 (t, J¼7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d (ppm) 191.75, 180.16, 165.81, 163.58,
153.21, 144.38, 143.90, 136.47, 133.86, 132.82, 130.87, 128.67, 105.86,
CDCl3):
d
(ppm) 8.09 (s, 1H), 7.49 (s, 2H), 7.16 (s, 2H), 6.91 (d,
62.53, 60.79, 56.17, 13.93; HRMS (ESI): m/z [MþH]þ calcd for
J¼8.4 Hz, 1H), 4.33e4.22 (m, 6H), 3.88 (d, J¼8.4 Hz, 9H), 1.26 (t,
C20H21O7S: 405.1003; found: 405.1001.
J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d (ppm) 91.7, 186.2, 163.3,
152.7, 148.9, 143.2, 143.1, 133.3, 130.6, 129.5, 122.8, 117.7, 117.1, 105.4,
4.2.11. Ethyl 4-(benzofuran-2-yl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)
butanoate (1k). IR (KBr): 3433, 2972, 2939, 2839, 2390, 2283, 1728,
1659, 1611, 1583, 1552, 1502, 1459, 1414, 1329, 1279, 1238, 1205,
64.3, 63.5, 61.9, 60.3, 55.7, 13.5; HRMS (ESI): m/z [MþH]þ calcd for
C
24H25O9: 457.1493; found: 457.1492.
1161, 1037 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d (ppm) 8.12 (s, 1H),
4.2.5. Ethyl 4-(4-chlorophenyl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)
butanoate (1e). IR (KBr): 3435, 2977, 2941, 2389, 1729, 1670, 1586,
1503, 1464, 1414, 1361, 1329, 1259, 1227, 1198, 1167, 1127, 1089,
7.74 (d, J¼8.0 Hz, 1H), 7.68 (s, 1H), 7.57 (s, 1H), 7.54 (d, J¼7.2 Hz, 1H),
7.35 (d, J¼7.6 Hz, 1H), 7.17 (s, 2H), 4.33 (q, J¼7.2 Hz, 2H), 3.91 (s, 3H),
3.86 (s, 6H), 1.28 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
1042 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
(ppm) 8.07 (s, 1H), 7.91 (d,
d (ppm) 191.7, 177.7, 163.5, 156.10, 153.3, 153.3, 145.0, 143.0, 132.0,
J¼7.6 Hz, 2H), 7.47 (d, J¼7.2 Hz, 2H), 7.13 (s, 2H), 4.31 (d, J¼7.2 Hz,
130.8, 129.4, 126.9, 124.4, 123.7, 115.6, 112.6, 105.9, 62.5, 60.8, 56.2,
13.9; HRMS (ESI): m/z [MþH]þ calcd for C24H23O8: 439.1387; found:
439.1389.
2H), 3.92 (s, 3H), 3.86 (s, 6H), 1.26 (t, J¼7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3):
d (ppm) 191.8, 187.5, 163.6, 153.2, 144.8, 143.3,
140.9, 134.4, 133.1, 130.8, 130.2, 129.3, 105.9, 62.6, 60.9, 56.2, 14.0;
HRMS (ESI): m/z [MþH]þ calcd for C22H22ClO7: 433.1049; found:
433.1047.
4.2.12. Ethyl 4-(naphthalen-2-yl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)
butanoate (1l). IR (KBr): 3425, 3059, 1724, 1680, 1667, 1619, 1585,
1503, 1465, 1415, 1375, 1362, 1345, 1328, 1284, 1268, 1249, 1195,
4.2.6. Ethyl 4-(4-bromophenyl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)
butanoate (1f). IR (KBr): 3433, 2971, 2942, 2840, 1728, 1712, 1662,
1584, 1502, 1400, 1414, 1365, 1327, 1259, 1236, 1199, 1168, 1125,
1169, 1126, 1045, 1006 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d (ppm)
8.54 (s, 1H), 8.30 (s, 1H), 7.97 (t, J¼8.0 Hz, 2H), 7.86e7.89 (m, 2H),
7.56e7.65 (m, 2H), 7.17 (s, 2H), 4.34 (q, J¼7.2 Hz, 2H), 3.91 (s, 3H),
3.83 (s, 6H), 1.28 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
1093, 1070, 1041, 1005 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d (ppm)
8.06 (s,1H), 7.82 (d, J¼8.0 Hz, 2H), 7.64 (d, J¼8.4 Hz, 2H), 7.12 (s, 2H),
d (ppm) 192.0, 188.4, 163.8, 153.2, 144.2, 143.0, 135.9, 133.8, 133.5,
4.31 (q, J¼7.2 Hz, 2H), 3.92 (s, 3H), 3.86 (s, 6H), 1.26 (t, J¼7.2 Hz, 3H);
132.2, 131.3, 131.0, 129.7, 129.3, 129.0, 127.1, 123.7, 109.8, 105.9, 62.5,
60.8, 56.1, 14.0; HRMS (ESI): m/z [MþH]þ calcd for C26H25O7:
449.1595; found: 449.1593.
13C NMR (100 MHz, CDCl3):
d (ppm) 191.8, 187.7, 163.6, 153.2, 144.8,
143.2, 134.8, 133.0, 132.3, 130.8, 130.3, 129.8, 105.9, 62.6, 60.86, 56.2,
14.0; HRMS (ESI): m/z [MþNa]þ calcd for C22H21BrNaO7: 499.0363;
found: 499.0360.
4.2.13. Ethyl 4-(naphthalen-1-yl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)
butanoate (1m). IR (KBr): 3439, 2939, 2837, 1723, 1666, 1584,
4.2.7. Ethyl
4-(4-nitrophenyl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)
1504, 1461, 1414, 1342, 1241, 1165, 1127, 1003 cmꢁ1 1H NMR
;
butanoate (1g). IR (KBr): 3432, 3120, 2980, 2934, 2840, 1726, 1667,
(400 MHz, CDCl3): d (ppm) 8.45 (s, 1H), 8.09e7.96 (m, 3H), 7.84 (d,
1599,1531,1513,1462,1437,1418,1322,1255,1205,1169,1144,1088,
J¼6.8 Hz, 1H), 7.51e7.48 (m, 3H), 7.09 (s, 2H), 4.31 (q, J¼7.2 Hz,
1013 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
(ppm) 8.33 (d, J¼8.8 Hz,
2H), 3.88 (s, 3H), 3.82 (s, 6H), 1.27 (t, J¼7.2 Hz, 3H); 13C NMR
2H), 8.12 (d, J¼8.4 Hz, 2H), 8.06 (s, 1H), 7.12 (s, 2H), 4.32 (q, J¼7.2 Hz,
(100 MHz, CDCl3): d (ppm) 191.58, 163.58, 152.82, 142.73, 142.41,
2H), 3.92 (s, 3H), 3.86 (s, 6H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR
139.47, 137.30, 134.46, 134.18, 133.39, 133.26, 130.84, 130.2, 129.79,
128.15, 126.50, 125.01, 123.91, 106.79, 105.78, 62.16, 60.44, 55.82,
13.68; HRMS (ESI): m/z [MþH]þ calcd for C26H25O7: 449.1595;
found: 449.1593.
(100 MHz, CDCl3):
d (ppm) 191.46, 187.44, 163.32, 153.27, 151.27,
150.75, 146.06, 143.39, 140.3, 132.31, 130.59, 129.83, 124.05, 105.98,
62.80, 60.87, 56.24, 13.93; HRMS (ESI): m/z [MþH]þ calcd for
C
22H22NO9: 444.1289; found: 444.1283.
4.2.14. Ethyl 2-(3,4-dimethoxybenzoyl)-4-oxo-4-phenylbutanoate
4 . 2 . 8 . E t h yl 4 - ( 3 , 4 - d i c h l o ro p h e nyl ) - 4 - o x o - 2 - ( 3 , 4 , 5 -
(3a). IR (KBr): 3441, 2971, 2389, 2284, 1720, 1666, 1597, 1451,
trimethoxybenzoyl)butanoate (1h). IR (KBr): 3441, 2972, 2901,
1267, 1050 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d (ppm) 8.02 (s, 1H),
1654, 1406, 1393, 1384, 1249, 1076, 1065, 1051 cmꢁ1
;
1H NMR
7.84 (d, J¼7.2 Hz, 2H), 7.47e7.53 (m, 2H), 7.42e7.31 (m, 2H), 7.28 (d,
J¼8.0 Hz, 1H), 6.74 (d, J¼8.0 Hz, 1H), 4.18 (q, J¼7.2 Hz, 2H), 3.81 (s,
3H), 3.79 (s, 3H), 1.13 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
(400 MHz, CDCl3):
d
(ppm) 8.02 (d, J¼7.6 Hz, 2H), 7.79 (d, J¼8.4 Hz,
1H), 7.58 (d, J¼8.4 Hz, 1H), 7.11 (s, 2H), 4.32 (q, J¼7.2 Hz, 2H),
3.74e3.92 (m, 9H), 1.25 (d, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
d
(ppm) 191.6, 188.3, 163.6, 153.6, 149.0, 144.2, 136.0, 133.9,
CDCl3):
d
(ppm) 191.6, 186.7, 167.1, 166.5, 163.5, 153.3, 145.5, 135.6,
133.0, 128.9, 128.6, 128.7, 123.9, 109.9, 109.4, 62.2, 55.8, 55.6, 13.7;
HRMS (ESI): m/z [MþH]þ calcd for C21H21O6: 369.1333; found:
369.1333.
132.5, 131.1, 130.7, 127.8, 116.8, 105.9, 62.7, 60.9, 56.3, 29.6, 14.0;
HRMS (ESI): m/z [MþNa]þ calcd for C22H20ClNaO7: 489.0478;
found: 489.0478.
4.2.15. Ethyl 2-(3,4-dimethoxybenzoyl)-4-(4-methoxyphenyl)-4-
4.2.9. Ethyl 4-(furan-2-yl)-4-oxo-2-(3,4,5-trimethoxybenzoyl)buta-
oxobutanoate (3b). IR (KBr): 3432, 2970, 2938, 2842, 1729, 1666,
noate (1i). 1H NMR (400 MHz, CDCl3):
d
(ppm) 7.99 (d, J¼3.0 Hz,
1594,1513,1463,1420,1367,1350,1267,1207,1168,1140,1017 cmꢁ1
;
1H), 7.69 (s, 1H), 7.37 (s, 1H), 7.16 (d, J¼2.8 Hz, 2H), 4.31 (q, J¼7.2 Hz,
1H NMR (400 MHz, CDCl3):
2H), 7.59 (br s, 2H), 6.83e6.94 (m, 3H), 4.28 (d, J¼6.8 Hz, 2H),
d
(ppm) 8.11 (s, 1H), 7.95 (d, J¼8.0 Hz,
2H), 3.91 (s, 3H), 3.87 (s, 6H), 1.27 (t, J¼7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3):
d (ppm) 191.8, 175.5, 163.4, 153.1, 152.5, 148.0,
3.90e3.93 (m, 6H), 3.85 (s, 3H), 1.23 (t, J¼6.8 Hz, 3H); 13C NMR

Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
9541
(100 MHz, CDCl3):
d
(ppm) 191.0, 187.2, 163.1, 153.7, 150.2, 148.9,
(APCI): m/z [MþH]þ calcd for C22H21O7: 397.1282; found:
145.6, 140.0, 131.7, 129.5, 128.5, 123.9, 123.6, 109.9, 109.2, 77.2, 62.3,
55.6, 55.5, 13.5; HRMS (ESI): m/z [MþH]þ calcd for C22H23O7:
399.1438; found: 399.1437.
397.1279.
4.2.22. Ethyl-4,5,6-trimethoxy-3-(4-methylbenzoyl)-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2b). IR (KBr): 3441, 2940, 1714,
1681, 1605, 1474, 1419, 1384, 1248, 1313, 1253, 1226, 1204, 1183,
4.2.16. Ethyl 2-(3,4-dimethoxybenzoyl)-4-(4-nitrophenyl)-4-oxobut-
2-enoate (3c). IR (KBr): 3431, 3020, 2981, 2949, 1726, 1665, 1599,
1530, 1512, 1462, 1435, 1418, 1437, 1323, 1254, 1205, 1169, 1144, 1117,
1126, 1098, 1012 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d¼8.02 (d,
J¼6.4 Hz, 2H), 7.33 (d, J¼6.4 Hz, 2H), 7.06 (s, 1H), 5.65 (s, 1H), 4.28
1088, 1012 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d (ppm) 8.12 (s, 1H),
(d, J¼6.8 Hz, 2H), 3.92 (s, 6H), 3.72 (s, 1H), 3.68 (s, 3H), 2.46 (s, 3H),
7.93 (d, J¼8.4 Hz, 1H), 7.59 (s, 1H), 7.39 (d, J¼6.8 Hz, 1H), 6.83e6.92
1.30 (t, J¼5.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼198.7, 196.2,
d
(m, 3H), 4.27 (q, J¼6.8 Hz, 1H), 3.80e3.90 (m, 6H), 1.23 (t, J¼7.2 Hz,
191.0, 167.9, 165.7, 155.5, 149.4, 144.9, 140.1, 133.7, 130.6, 129.5,
128.9, 101.3, 62.2, 60.9, 60.1, 58.4, 56.3, 55.2, 45.9, 21.7, 14.2; HRMS
(APCI): m/z [MþH]þ calcd for C23H25O8: 429.1544; found: 429.1524.
3H); 13C NMR (100 MHz, CDCl3):
d (ppm) 191.7, 186.3, 163.6, 153.3,
148.7, 148.5, 143.2, 133.2, 130.9, 128.9, 123.7, 113.7, 109.8, 109.2, 61.9,
55.5, 13.5; HRMS (ESI): m/z [MþNa]þ calcd for C21H19NNaO8:
436.1003; found: 436.1001.
4.2.23. Ethyl-4,5,6-trimethoxy-3-(4-methoxybenzoyl)-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2c). IR (KBr): 3431, 2936, 2842,
1723, 1691, 1599, 1574, 1512, 1473, 1419, 1354, 1317, 1257, 1170, 1129,
4 . 2 .17 . E t h yl 6 - ( 4 - m e t h o x y p h e n y l ) - 4 - o x o - 2 - ( 3 , 4 , 5 -
trimethoxybenzoyl)hexa-2,5-dienoate (3g). IR (KBr): 3445, 2937,
1704, 1668, 1644, 1626, 1583, 1511, 1453, 1412, 1375, 1328, 1301,
1106, 1070, 1024 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼8.12 (d,
J¼8.8 Hz, 2H), 7.27 (s, 1H), 7.02 (d, J¼8.8 Hz, 2H), 5.47 (s, 1H), 3.96 (s,
1262, 1175, 1124, 1024 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
(ppm)
3H), 3.92 (s, 3H), 3.81 (s, 2H), 3.77 (s, 3H), 0.98 (t, J¼7.2 Hz, 3H); 13
C
7.71 (s, 1H), 7.65 (d, J¼16.0 Hz, 1H), 7.50 (d, J¼8.4 Hz, 2H), 7.30 (s,
1H), 7.16 (s, 1H), 6.91 (d, J¼8.4 Hz, 2H), 6.75 (d, J¼16.0 Hz, 1H), 4.30
(q, J¼7.6 Hz, 2H), 3.84e3.91 (m, 12H), 1.26 (t, J¼4.0 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d
¼198.7, 196.2, 168.0, 155.6, 149.5, 144.9,
140.1, 133.7, 130.6, 129.5, 128.9, 101.3, 62.2, 60.9, 60.1, 58.4, 56.3,
45.9, 21.7, 14.2; HRMS (APCI): m/z [MþH]þ calcd for C23H25O8:
429.1544; found: 429.1524.
NMR (100 MHz, CDCl3):
d (ppm) 187.2, 163.7, 162.3, 153.1, 146.4,
142.7, 135.5, 134.5, 131.0, 130.6, 126.5, 123.3, 114.5, 105.8, 62.3, 60.7,
56.1, 55.3, 13.9; HRMS (ESI): m/z [MþH]þ calcd for C25H27O8:
455.1700; found: 455.1695.
4.2.24. Ethyl-3-(2,3-dihydrobenzo[b][1,4]dioxine-6-carbonyl)-4,5,6-
trimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate
(2d). IR
(KBr): 3428, 2981, 2940, 1713, 1675, 1604, 1597, 1507, 1475, 1429,
1349, 1312, 1287, 1259, 1227, 1203, 1162, 1126, 1097, 1065,
4.2.18. Diethyl 2-(3,4,5-trimethoxybenzoyl)but-2-enedioate (3h). IR
(KBr): 3436, 2983, 1723, 1676, 1584, 1503, 1464, 1415, 1370, 1347,
1010 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼7.67 (s, 2H), 7.06 (s, 1H),
1246, 1159, 1127, 1029, 1001 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
6.97 (d, J¼8.8 Hz, 1H), 5.57 (d, J¼4.0 Hz, 1H), 4.35 (d, J¼4.4 Hz, 2H),
d
(ppm) 7.06 (s, 2H), 7.28 (s, 2H), 7.00 (s, 1H), 4.19 (q, J¼7.2 Hz, 2H),
4.29e4.31 (m, 4H), 4.27 (s, 1H), 3.920 (s, 3H), 3.905 (s, 3H), 3.70 (s,
4.03 (q, J¼7.2 Hz, 2H), 3.84 (s, 3H), 3.81 (s, 6H), 1.16 (t, J¼6.8 Hz, 3H),
3H), 1.31 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼197.3,
d
1.06 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
(ppm) 190.8,
196.2, 167.9, 155.5, 149.4, 148.7, 143.5, 140.7, 130.6, 129.9,
122.9, 118.2, 117.4, 101.2, 62.1, 60.8, 60.1, 58.4, 56.2, 45.7, 14.1;
HRMS (APCI): m/z [MþH]þ calcd for C24H25O9: 457.1497; found:
457.1491.
163.6, 163.0, 153.1, 144.8, 143.0, 130.7, 130.4, 105.8, 62.3, 61.6, 60.7,
56.1, 13.8, 13.6; HRMS (ESI): m/z [MþH]þ calcd for C17H21O7:
367.1387; found: 367.1386.
4.2.19. Diethyl 2-(3,4-dimethoxybenzoyl)but-2-enedioate (3i). IR
4.2.25. Ethyl 3-(4-chlorobenzoyl)-4,5,6-trimethoxy-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2e). IR (KBr): 3430, 2938, 1716,
1686, 1584, 1518, 1474, 1420, 1394, 1346, 1313, 1286, 1262, 1219,
(KBr): 2982, 2939, 2842, 1723, 1669, 1595, 1514, 1265, 1420, 1370,
1346, 1271, 1194, 1167, 1144, 1081, 1022 cmꢁ1 1H NMR (400 MHz,
;
CDCl3):
J¼6.8 Hz, 1H), 4.26 (br s, 2H), 4.08 (s, 2H), 3.95 (br s, 6H), 1.18e1.31
(m, 6H); 13C NMR (100 MHz, CDCl3):
(ppm) 190.7, 163.7, 163.2,
d
(ppm) 7.59 (s, 1H), 7.35 (s, 1H), 7.06 (s, 1H), 6.88 (d,
1126, 1072, 1009 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼8.07 (d,
J¼8.4 Hz, 2H), 7.51 (d, J¼8.4 Hz, 2H), 7.06 (s, 1H), 5.62 (d, J¼4.0 Hz,
d
1H), 4.28 (s, 2H), 3.91 (s, 6H), 3.72 (s, 1H), 3.68 (s, 3H), 1.31 (t,
153.8, 149.2, 145.0, 130.2, 128.9, 124.3, 109.3, 62.3, 61.5, 13.8, 13.6;
HRMS (ESI): m/z [MþH]þ calcd for C17H21O7: 337.1282; found:
337.1279.
J¼4.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼167.8, 157.9, 148.4,
d
134.5, 130.6, 130.2, 129.2, 115.7, 115.0, 114.7, 101.3, 100.1, 95.3, 62.3,
60.9, 60.1, 58.3, 56.3, 45.8, 29.6; HRMS (APCI): m/z [MþH]þ calcd for
C22H22ClO7: 433.1049; found: 433.1051.
4.3.20. 2-(Methylsulfinyl)-1,4-bis(3,4,5-trimethoxyphenyl)butane-
1,4-dione (3k). IR (KBr): 3441, 2996, 2941, 2837, 1652, 1580, 1504,
1455, 1414, 1334, 1233, 1203, 1159, 1126, 1070, 1041 cmꢁ1; 1H NMR
4.2.26. Ethyl-3-(4-bromobenzoyl)-4,5,6-trimethoxy-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2f). IR (KBr): 3432, 2937, 1715,
1685, 1619, 1602, 1585, 1518, 1474, 1419, 1394, 1345, 1312, 1286,
1252, 1219, 1126, 1098, 1071, 1009 cmꢁ1; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d (ppm) 7.37 (s, 1H), 7.28 (s, 2H), 7.21 (s, 2H), 3.95
(s, 6H), 3.91 (s, 12H), 3.24 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
(ppm) 190.3, 187.1, 163.9, 153.3, 153.2 144.2, 144.1, 131.0, 130.9,
d
¼7.99 (d, J¼8.0 Hz, 2H),7.66 (d, J¼8.4 Hz, 2H), 7.04 (s, 1H), 5.59 (d,
126.4, 107.6, 106.5, 61.0, 56.4, 42.2; HRMS (ESI): m/z [MþH]þ calcd
J¼4.0 Hz, 1H), 4.27 (q, J¼4.0 Hz, 2H), 3.89 (s, 6H), 3.72 (d, J¼3.6 Hz,
for C23H27O8S: 479.1370; found: 479.1368.
1H), 3.66 (s, 3H), 0.94 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼198.4, 195.7, 167.7, 155.6, 139.4, 135.0, 132.1, 130.8, 130.4, 130.2,
4.2.21. Ethyl-3-benzoyl-4,5,6-trimethoxy-1-oxo-2,3-dihydro-1H-in-
dene-2-carboxylate (2a). IR (KBr): 3431, 2941, 2841, 1714, 1597,
1475, 1448, 1419, 1350, 1314, 1252, 1218, 1127, 1098, 1001 cmꢁ1; 1H
129.2, 128.7, 101.2, 62.2, 60.8, 60.0, 58.2, 56.2, 45.7, 29.6, 19.1, 14.1;
HRMS (APCI): m/z [MþH]þ calcd for C22H22BrO7: 477.0543; found:
477.0546.
NMR (400 MHz, CDCl3):
d
¼8.12 (d, J¼8.0 Hz, 2H), 7.65 (t, J¼7.2 Hz,
1H), 7.54 (t, J¼7.2 Hz, 2H), 7.07 (s, 1H), 5.68 (s, 1H), 4.28 (q,
4.2.27. Ethyl-4,5,6-trimethoxy-3-(4-nitrobenzoyl)-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2g). IR (KBr): 3432, 2940, 1716,
1604, 1528, 1474, 1419, 1348, 1217, 1237, 1213, 1126, 1098, 1073,
J¼7.2 Hz, 2H), 3.92 (s, 3H), 3.90 (s, 3H), 3.74 (s, 1H), 3.68 (s, 3H),
1.30 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼199.1,
196.0, 194.5, 167.8, 155.5, 149.3, 148.4, 139.8, 136.2, 133.8, 130.5,
128.8, 128.7, 101.2, 62.1, 60.8, 60.0, 58.3, 56.2, 45.9, 14.1; HRMS
1011 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼8.39 (d, J¼8.8 Hz, 2H),
8.30 (d, J¼8.8 Hz, 2H), 7.08 (d, J¼8.8 Hz, 1H), 5.68 (d, J¼4.0 Hz, 1H),

9542
Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
4.30 (q, J¼4.0 Hz, 3H), 3.924 (s, 3H), 3.918 (s, 3H), 3.78 (d,
J¼4.0 Hz, 1H), 3.68 (s, 3H), 1.32 (t, J¼6.8 Hz, 3H); 13C NMR
14.0; HRMS (ESI): m/z [MþH]þ calcd for C26H25O7: 449.1595; found:
449.1590.
(100 MHz, CDCl3):
d
¼199.4, 195.1, 167.5, 156.2, 150.5, 150.2, 140.8,
132.1, 129.7, 129.2, 124.1, 123.9, 101.2, 60.9, 60.0, 58.0, 56.2, 46.0,
14.1; HRMS (ESI): m/z [MþH]þ calcd for C22H22NO9: 444.1289;
found: 444.1287.
4.2.33. Ethyl-3-(1-naphthoyl)-4,5,6-trimethoxy-1-oxo-2,3-dihydro-
1H-indene-2-carboxylate (2m). IR (KBr): 3425, 2939, 1712, 1680,
1594, 1573, 1508, 1474, 1419,1349,1314,1234, 1201, 1176, 1126, 1094,
1014 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼8.62 (d, J¼8.0 Hz, 1H),
4.2.28. Ethyl-3-(3,4-dichlorobenzoyl)-4,5,6-trimethoxy-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2h). IR (KBr): 3430, 2936, 1715,
1602, 1583, 1557, 1474, 1419,1388, 1350,1312, 1208, 1127, 1097, 1030,
8.21 (d, J¼7.2 Hz, 1H), 8.04 (d, J¼8.0 Hz, 1H), 7.89 (d, J¼8.0 Hz, 1H),
7.58e7.51 (m, 3H), 7.07 (s, 1H), 5.70 (d, J¼3.6 Hz, 1H), 4.20 (q,
J¼2.8 Hz, 2H), 3.89 (s, 6H), 3.86 (d, J¼3.6 Hz,1H), 3.63 (s, 3H),1.20 (t,
1011 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼8.21 (s, 1H), 7.97 (d,
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼201.7, 196.1, 167.8,
d
J¼6.8 Hz, 1H), 7.62 (d, J¼8.4 Hz, 1H), 7.06 (s, 1H), 5.57 (d, J¼4.0 Hz,
1H), 4.29 (q, J¼7.2 Hz, 2H), 3.913 (s, 3H), 3.918 (s, 3H), 3.84 (d,
J¼10.0 Hz, 1H), 3.71 (s, 3H), 1.32 (t, J¼7.2 Hz, 3H); 13C NMR
155.6, 149.4, 148.2, 134.7, 133.9, 133.6, 130.6, 128.6, 128.4, 128.2,
126.6, 125.7, 124.3, 101.1, 62.0, 60.8, 60.2, 58.2, 56.2, 49.6, 14.0;
HRMS (ESI): m/z [MþH]þ calcd for C26H25O7: 449.1595; found:
449.1590.
(100 MHz, CDCl3):
d
¼197.2, 195.4, 107.6, 155.7, 148.3, 138.9, 138.4,
135.8, 130.9, 130.6, 130.4, 127.7, 101.2, 62.3, 60.9, 58.1, 56.3, 45.8,
29.6, 14.1; HRMS (APCI): m/z [MþH]þ calcd for C22H21Cl2O7:
467.0659; found: 467.0659.
4.2.34. Ethyl-3-benzoyl-4,5-dimethoxy-1-oxo-2,3-dihydro-1H-in-
dene-2-carboxylate (4a). IR (KBr): 3440, 2933, 1724, 1675, 1599,
1557, 1504, 1463, 1416, 1331, 1260, 1171, 1127, 1022 cmꢁ1 1H NMR
;
4.2.29. Ethyl-3-(furan-2-carbonyl)-4,5,6-trimethoxy-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (2i). IR (KBr): 3433, 2941, 1714,
1675, 1601, 1567, 1466, 1419, 1394, 1313, 1259, 1204, 1157, 1127, 1098,
(400 MHz, CDCl3):
d
¼8.09 (d, J¼7.2 Hz, 2H), 7.68 (t, J¼7.2 Hz, 1H),
7.56 (q, J¼8.0 Hz, 2H), 7.21 (s, 1H), 6.67 (s,1H), 5.64 (d, J¼3.6 Hz,1H),
4.28 (q, J¼7.2 Hz, 2H), 4.13 (d, J¼3.6 Hz,1H), 3.91 (s, 3H), 3.78 (s, 3H),
1014 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼7.69 (s, 1H), 7.42 (s, 1H),
1.32 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼197.2, 195.6,
d
7.06 (s, 1H), 6.63 (d, J¼1.6 Hz, 1H), 5.41 (d, J¼2.4 Hz, 1H), 4.28 (q,
J¼7.2 Hz, 2H), 3.92 (s, 3H), 3.91 (s, 3H), 3.81 (s, 1H), 3.75 (s, 3H), 1.31
168.3, 155.8, 152.0, 150.4, 146.4, 139.1, 136.3, 134.0, 129.0, 127.7,
107.3, 105.0, 60.1, 56.9, 56.1, 49.3, 29.6, 14.1; HRMS (ESI): m/z
[MþH]þ calcd for C21H21O6: 369.1333; found: 369.1332.
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼196.0, 186.9, 167.8,
d
155.7, 152.0, 147.5, 138.8, 130.7, 119.1, 112.7, 109.9, 101.4, 62.1, 60.9,
60.3 58.0, 56.3, 46.9, 29.6, 14.2; HRMS (ESI): m/z [MþH]þ calcd for
4.2.35. Ethyl-4,5-dimethoxy-3-(4-methoxybenzoyl)-1-oxo-2,3-
dihydro-1H-indene-2-carboxylate (4b). IR (KBr): 3444, 2939, 1704,
1683, 1600, 1572, 1501, 1460, 1441, 1419, 1346, 1286, 1267, 1221, 1171,
C
20H21O8: 389.1231; found: 389.1231.
4.2.30. Ethyl-4,5,6-trimethoxy-1-oxo-3-(thiophene-2-carbonyl)-2,3-
dihydro-1H-indene-2-carboxylate (2j). IR (KBr): 3427, 3093, 2936,
2851, 1713, 1660, 1517, 1474, 1414, 1349, 1313, 1240, 1205, 1126,
1104, 1019 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d¼8.02 (d, J¼8.8 Hz,
2H), 7.12 (s,1H), 6.95 (d, J¼8.8 Hz,1H), 6.64 (s,1H), 5.52 (d, J¼3.2 Hz,
1H), 4.19 (q, J¼6.8 Hz, 2H), 4.04 (d, J¼3.6 Hz, 1H), 3.83 (s, 3H), 3.82
(s, 3H), 3.72 (s, 3H), 1.24 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
1098, 1013 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼7.89 (d, J¼3.2 Hz,
1H), 7.69 (d, J¼4.8 Hz, 1H), 7.13 (t, J¼4.4 Hz, 1H), 6.99 (s, 1H), 5.40
(d, J¼4.0 Hz, 1H), 4.20 (m, 2H), 3.84 (s, 3H), 3.83 (s, 3H), 3.71 (d,
J¼4.0 Hz, 1H), 3.65 (s, 3H), 1.23 (t, J¼7.2 Hz, 3H); 13C NMR
CDCl3):
d
¼195.8, 195.4, 168.3, 164.1, 155.7, 150.2, 146.8, 131.3, 128.9,
127.6, 114.0, 112.0, 107.1, 104.8, 61.8, 57.0, 55.9, 55.4, 48.7, 41.5, 14.0;
HRMS (ESI): m/z [MþH]þ calcd for C22H23O7: 399.1438; found:
399.1438.
(100 MHz, CDCl3):
d
¼195.8, 191.5, 167.7, 155.6, 148.5, 143.5, 139.1,
135.3, 133.4, 130.5, 128.5, 101.3, 62.1, 60.8, 60.2, 58.3, 56.2, 47.5,
29.6, 14.1; HRMS (ESI): m/z [MþH]þ calcd for C20H21O7S: 405.1003;
found: 405.1001.
4.2.36. Ethyl-4,5-dimethoxy-3-(4-nitrobenzoyl)-1-oxo-2,3-dihydro-
1H-indene-2-carboxylate (4c). IR (KBr): 3448, 2926, 1701, 1590,
1527, 1502, 1465, 1419, 1348, 1301, 1108, 1009 cmꢁ1 1H NMR
;
4.2.31. Ethyl-3-(benzofuran-2-carbonyl)-4,5,6-trimethoxy-1-oxo-
2,3-dihydro-1H-indene-2-carboxylate (2k). IR (KBr): 3427, 2939,
2840, 1714, 1680, 1603, 1554, 1474, 1419, 1348, 1314, 1259, 1229,
(400 MHz, CDCl3):
d
¼8.40 (d, J¼8.8 Hz, 2H), 8.25 (d, J¼8.8 Hz, 2H),
7.30 (s, 1H), 6.69 (s, 1H), 5.66 (d, J¼3.2 Hz, 1H), 4.29 (q, J¼6.8 Hz,
2H), 4.01 (d, J¼3.6 Hz, 1H), 3.92 (s, 3H), 3.84 (s, 3H), 1.32 (t, J¼7.2 Hz,
1202, 1159, 1126, 1096, 1008 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
3H); 13C NMR (100 MHz, CDCl3):
d
¼196.2, 194.6, 181.6, 156.0, 150.7,
d
¼7.77 (d, J¼8.8 Hz, 2H), 7.61 (d, J¼8.0 Hz, 1H), 7.53 (t, J¼4.8 Hz,
145.3, 140.6, 129.9, 129.1, 127.7, 124.1, 123.8, 107.2, 105.1, 62.4, 56.8,
1H), 7.36 (t, J¼4.8 Hz, 1H), 7.08 (s, 1H), 5.57 (s, 1H), 4.30 (q,
J¼3.2 Hz, 2H), 3.92 (s, 6H), 3.83 (d, J¼4.0 Hz, 1H), 3.77 (s, 3H), 1.32
56.1, 54.2, 49.6, 14.1; HRMS (ESI): m/z [MþNa]þ calcd for
C21H19NNaO8: 436.1003; found: 436.1000.
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼195.7, 189.0, 167.8,
d
156.1, 155.8, 151.8, 149.5, 148.5, 138.6, 130.6, 128.9, 126.9, 124.1,
123.6, 115.0, 112.5, 101.3, 62.2, 60.9, 60.4, 58.0, 56.3, 47.1, 14.2;
HRMS (APCI): m/z [MþH]þ calcd for C24H23O8: 439.1387; found:
439.1385.
4.2.37. (E)-Ethyl 4,5,6-trimethoxy-3-(3-(4-methoxyphenyl)acryloyl)-
1-oxo-2,3-dihydro-1H-indene-2-carboxylate (4g). IR (KBr): 3444,
2938, 1705, 1669, 1645, 1627, 1583, 1511, 1453, 1412, 1375, 1328,
1301, 1262, 1175, 1127, 1025 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼7.07 (d, J¼8.8 Hz, 3H), 6.97 (s,1H), 6.74e6.77 (m, 2H), 4.78 (s,1H),
4.2.32. Ethyl-3-(2-naphthoyl)-4,5,6-trimethoxy-1-oxo-2,3-dihydro-
1H-indene-2-carboxylate (2l). IR (KBr): 3424, 3059, 2961, 2937,
2826, 1723, 1667, 1619, 1584, 1502, 1466, 1414, 1362, 1345, 1328,
4.03 (s, 2H), 3.97 (s, 1H), 3.70 (s, 3H), 3.82 (s, 3H), 3.91 (s, 3H), 0.85
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼211.1, 208.5, 198.3,
d
166.3, 158.7, 155.3, 150.7, 149.5, 136.5, 133.0, 129.3, 128.9, 128.6,
113.9, 113.4, 101.6; 72.7, 62.2, 61.9, 61.0, 56.3, 55.2, 52.3, 44.7, 44.0,
14.0; HRMS (ESI): m/z [MþH]þ calcd for C25H27O8: 455.1700; found:
455.1695.
1284, 1266, 1247, 1194, 1168, 1128, 1045, 1008 cmꢁ1 1H NMR
;
(400 MHz, CDCl3):
d
¼8.61 (s, 1H), 8.04 (d, J¼8.4 Hz, 1H), 7.90 (d,
J¼8.0 Hz, 1H), 7.84 (d, J¼8.4 Hz, 1H), 7.79 (d, J¼7.6 Hz, 1H), 7.49 (q,
J¼7.6 Hz, 2H), 6.98 (s, 1H), 5.57 (d, J¼3.6 Hz, 1H), 4.8 (q, J¼3.2 Hz,
2H), 3.80 (s, 3H), 3.78 (s, 3H), 3.72 (d, J¼3.6 Hz, 1H), 3.56 (s, 3H),
4.2.38. Diethyl 5,6,7-trimethoxy-3-oxo-2,3-dihydro-1H-indene-1,2-
0.80 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
¼198.9, 196.0,
dicarboxylate (4h). IR (KBr): 3451, 2941, 1739, 1641, 1602, 1533,
167.9, 155.5, 149.3, 148.3, 135.7, 132.4, 130.7, 130.5, 129.7, 128.8,
128.6, 127.6, 126.8, 124.0, 101.2, 62.1, 60.7, 60.0, 58.4, 56.1, 45.9, 29.5,
1476, 1419, 1349, 1316, 1256, 1179, 1128, 1028 cmꢁ1 1H NMR
;
(400 MHz, CDCl3):
d
¼7.02 (s, 1H), 4.55 (s, 1H), 4.18 (m, 4H),

Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
9543
3.83e3.88 (m, 9H), 3.78 (s, 1H), 1.19e1.27 (m, 6H); 13C NMR
(100 MHz, CDCl3):
101.2, 62.2, 61.6, 61.0, 60.6, 57.9, 56.3, 45.0, 14.1; HRMS (ESI): m/z
[MþH]þ calcd for C17H21O7: 367.1387; found: 367.1387.
1704,1593,1498,1480,1451,1386,1368,1318,1281,1247,1207,1180,
1158, 1083, 1066, 1003 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼196.0, 172.0, 167.6, 155.6, 149.9, 137.8, 130.2,
d
¼7.52 (t,
J¼7.2 Hz, 1H), 7.27e7.32 (m, 2H), 7.14 (d, J¼6.8 Hz, 2H), 6.84 (d,
J¼8.0 Hz, 1H), 6.79 (d, J¼7.2 Hz, 1H), 4.91 (s, 1H), 4.24 (q, J¼6.8 Hz,
2H), 3.98 (s, 3H), 3.66 (s, 1H), 1.30 (t, J¼6.8 Hz, 3H); 13C NMR
4.2.39. Diethyl 6,7-dimethoxy-3-oxo-2,3-dihydro-1H-indene-1,2-
(100 MHz, CDCl3):
d
¼196.0, 168.6, 158.7, 158.2, 141.9, 137.4, 128.9,
dicarboxylate (4i). IR (KBr): 3451, 2981, 1708, 1591, 1503, 1466,
127.9, 127.3, 123.1, 118.3, 109.6, 63.7, 61.7, 55.8, 48.1, 14.2; HRMS
1421, 1369, 1301, 1110, 1022 cmꢁ1
;
1H NMR (600 MHz, CDCl3):
(ESI): m/z [MþH]þ calcd for C19H19O4: 311.1278; found: 311.1278.
d
¼7.18 (d, J¼8.4 Hz, 2H), 4.63 (s, 1H), 4.22e4.31 (m, 4H), 4.18 (s, 1H),
4.00 (s, 3H), 3.92 (s, 3H), 1.34 (t, J¼7.2 Hz, 6H); 13C NMR (100 MHz,
4.2.45. Ethyl
5,6-dimethoxy-1-oxo-3-phenyl-2,3-dihydro-1H-in-
CDCl3):
d
¼195.4, 170.4, 167.9, 155.8, 150.4, 145.1, 127.1, 107.1, 104.6,
dene-2-carboxylate (4t). 205.8 mg, 86% yield; oil; IR (KBr): 3457,
61.9, 61.7, 56.2, 56.0, 47.0, 14.0; HRMS (ESI): m/z [MþH]þ calcd for
2979, 2938, 2838, 1737, 1703, 1677, 1592, 1500, 1465, 1419, 1367,
C
17H21O7: 337.1282; found: 337.1279.
1302, 1257, 1153, 1111, 1022 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼7.55 (t, J¼8.0 Hz, 2H), 7.28e7.35 (m, 4H), 7.22 (s, 1H), 7.16 (d,
4.2.40. Ethyl 1-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-indene-2-
carboxylate (4o). 205.8 mg, 86% yield; mp 79e80 ꢀC; IR (KBr):
3270, 3060, 3027, 2984, 2929, 2871, 1824, 1717, 1654, 1618, 1594,
1476,1453,1415,1375, 1338,1315,1301,1275,1250,1206,1170,1149,
J¼6.8 Hz, 2H), 6.90 (d, J¼7.6 Hz,1H), 6.67 (s,1H), 4.91 (s,1H), 4.26 (q,
J¼6.8 Hz, 2H), 3.84e3.96 (m, 6H), 3.63 (s, 1H), 1.30 (t, J¼7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3):
d¼196.8,190.8,168.4, 167.4, 156.1, 153.5,
151.5, 149.9, 148.8, 141.7, 128.9, 128.7, 127.7, 127.5, 127.1, 123.3, 110.0,
109.8, 107.0, 103.9, 63.5, 61.4, 56.0, 55.8, 55.6, 46.1, 45.3, 13.9, 13.8;
HRMS (ESI): m/z [MþH]þ calcd for C20H21O5: 341.1384; found:
341.1385.
1131, 1092, 1027 cmꢁ1
J¼6.8 Hz, 1H), 7.60 (t, J¼6.8 Hz, 1H), 7.43 (t, J¼6.8 Hz, 1H), 7.26e7.33
(m, 4H), 7.16 (d, J¼6.4 Hz, 2H), 5.01 (s, 1H), 4.26 (t, J¼7.2 Hz, 2H),
3.69 (s, 1H), 1.13 (t, J 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3):
;
1H NMR (400 MHz, CDCl3):
d¼7.82 (d,
d
¼198.5, 168.3, 156.1, 141.7, 135.6, 134.9, 128.9, 128.2, 127.8, 127.7,
4.2.46. Ethyl 4,5,6-trimethoxy-1-oxo-3-phenyl-2,3-dihydro-1H-in-
dene-2-carboxylate (4u). 205.8 mg, 86% yield; oil; IR (KBr): 3437,
2939, 2838, 1738, 1709, 1601, 1472, 1418, 1344, 1313, 1242, 1205,
127.4, 126.6, 124.1, 63.5, 61.7, 48.5, 14.1; HRMS (ESI): m/z [MþNa]þ
calcd for C18H16NaO3: 303.0992; found: 303.0995.
1155, 1127, 1098, 1018 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼7.20 (d,
4.2.41. Ethyl 1-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-indene-2-
carboxylate (4p). 205.8 mg, 86% yield; oil; IR (KBr): 3433, 2981,
2923,1715,1602,1554,1513,1463,1369,1288,1235,1151,1113,1094,
J¼6.4 Hz, 2H), 7.15 (t, J¼7.2 Hz, 1H), 7.04 (t, J¼7.2 Hz, 3H), 4.86 (s,
1H), 4.16 (q, J¼6.8 Hz, 2H), 3.83 (br, 6H), 3.54 (s, 1H), 3.27 (s, 3H),
1.22 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼197.9, 168.3,
d
1043, 1020 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼7.71 (d, J¼6.7 Hz,
155.1,150.2,149.3,143.4,142.7,130.4,128.7,128.5,127.9,127.4,127.0,
100.9, 63.7, 61.8, 60.8, 59.9, 56.2, 46.1, 14.1; HRMS (ESI): m/z
[MþH]þ calcd for C21H23O6: 371.1489; found: 371.1487.
1H), 7.49 (t, J¼7.6 Hz, 1H), 7.33 (d, J¼7.2 Hz, 1H), 7.17 (d, J¼7.6 Hz,
1H), 7.04 (d, J¼7.2 Hz, 2H), 6.95 (d, J¼7.2 Hz, 2H), 4.88 (s, 1H), 4.16 (t,
J¼7.2 Hz, 2H), 3.57 (s, 1H), 2.23 (s, 3H), 1.19 (q, J¼7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d¼198.6, 168.4, 156.4, 138.7, 137.0, 135.6,
Acknowledgements
134.9, 129.6, 129.4, 128.9, 128.1, 127.7, 127.4, 126.7, 126.6, 124.0, 63.6,
61.6, 48.2, 46.8, 20.9, 14.1; HRMS (ESI): m/z [MþNa]þ calcd for
We thank the National Natural Science Foundation of China
(Grant 21032001 and 21272085). We also thank Dr. Chuanqi Zhou,
Hebei University, for analytical support.
C
19H18NaO3: 317.1148; found: 317.1151.
4.2.42. Ethyl 1-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-indene-2-
carboxylate (4q). 205.8 mg, 86% yield; oil; IR (KBr): 3433, 2959,
2935, 2906, 2836, 1713, 1607, 1512, 1463, 1443, 1421, 1369, 1303,
1249, 1177, 1150, 1111, 1093, 1032 cmꢁ1; 1H NMR (400 MHz, CDCl3):
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.10.052.
d
¼7.81 (d, J¼7.2 Hz, 1H), 7.60 (t, J¼7.2 Hz, 1H), 7.43 (t, J¼7.2 Hz, 1H),
7.28 (s, 1H), 7.08 (d, J¼7.6 Hz, 2H), 6.87 (d, J¼7.2 Hz, 2H), 4.96 (s, 1H),
4.26 (q, J¼7.2 Hz, 2H), 3.79 (s, 3H), 3.64 (s, 1H), 1.31 (t, J¼7.2 Hz, 3H);
References and notes
13C NMR (100 MHz, CDCl3):
d¼198.7, 168.4, 158.8, 156.5, 135.6,
1. (a) Dolling, U.-H.; Davis, P.; Grabowski, E. J. J. J. Am. Chem. Soc. 1984, 106, 446; (b)
Banerjee, M.; Makhopadhyay, R.; Achari, B.; Banerjee, A. K. Org. Lett. 2003, 5,
3931; (c) Sugimoto, H.; Iimura, Y.; Yamanishi, Y.; Yamatsu, K. J. Med. Chem. 1995,
38, 4821.
135.0, 134.9,133.7, 128.9,128.5,128.1, 126.7,126.6,124.1,114.3,114.2,
63.7, 61.7, 55.2, 47.9, 46.9, 43.6, 14.1; HRMS (ESI): m/z [MþH]þ calcd
for C19H19O4: 311.1278; found: 311.1278.
2. (a) Scott, J. P.; Ashwood, M. S.; Brands, K. M. J.; Brewer, S. E.; Cowden, C. J.;
Dolling, U.-H.; Emerson, K. M.; Gibb, A. D.; Goodyear, A.; Oliver, S. F.; Stewart, G.
W.; Wallace, D. J. Org. Process Res. Dev. 2008, 12, 723; (b) Sheridan, H.; Walsh, J.
J.; Cogan, C.; Jordan, M.; McCabe, T.; Passante, E.; Frankish, N. H. Bioorg. Med.
Chem. Lett. 2009, 19, 5927.
3. (a) Pletnev, A. A.; Larock, R. C. J. Org. Chem. 2002, 67, 9428; (b) Kerr, D. J.; Metje,
C.; Flynn, B. L. Chem. Commun. 2003, 1380; (c) Wessig, P.; Glombitza, C.; Muller,
G.; Teubner, J. J. Org. Chem. 2004, 69, 7582; (d) Yamabe, H.; Mizuno, A.; Kusama,
H.; Iwasawa, N. J. Am. Chem. Soc. 2005, 127, 3248; (e) Zhu, J.; Zhong, C.; Lu, H.-F.;
Li, G.-Y.; Sun, X. Synlett 2008, 458; (f) Zhong, C.; Zhu, J.; Chang, J.; Sun, X. Tet-
rahedron Lett. 2011, 52, 2815.
4. (a) Di Grandi, M. Org. Biomol. Chem. 2014, 12, 5331; (b) Spencer, W. T., III;
Vaidya, T.; Frontier, A. J. Eur. J. Org. Chem. 2013, 3621; (c) Vaidya, T.; Eisenberg,
R.; Frontier, A. J. ChemCatChem 2011, 3, 1531; (d) Frontier, A. J.; Collison, C.
Tetrahedron 2005, 61, 7577; (e) Tius, M. A. Eur. J. Org. Chem. 2005, 2193; (f)
Pellissier, H. Tetrahedron 2005, 61, 6479.
5. (a) He, W.; Sun, X.; Frontier, A. J. J. Am. Chem. Soc. 2003, 125, 14278; (b) Janka,
M.; He, W.; Frontier, A. J.; Eisenberg, R. J. Am. Chem. Soc. 2004, 126, 6864; (c)
Malona, J. A.; Colbourne, J. M.; Frontier, A. J. Org. Lett. 2006, 8, 5661; (d) He, W.;
Herrick, I. R.; Atesin, T. A.; Caruana, P. A.; Kellenberger, C. A.; Frontier, A. J. J. Am.
Chem. Soc. 2008, 130, 1003; (e) Spencer, W. T.; Levin, M. D.; Frontier, A. J. Org.
Lett. 2011, 13, 414; (f) Lebœuf, D.; Huang, J.; Gandon, V.; Frontier, A. J. Angew.
4.2.43. Ethyl 5-methoxy-1-oxo-3-phenyl-2,3-dihydro-1H-indene-2-
carboxylate (4r). 205.8 mg, 86% yield; oil; IR (KBr): 3434, 3062,
2980, 2939, 2841, 1708, 1664, 1596, 1510, 1490, 1453, 1421, 1368,
1246, 1197, 1167, 1090, 1021 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼7.82 (d, J¼6.4 Hz, 2H), 7.75 (d, J¼8.0 Hz, 1H), 7.31e7.35 (m, 4H),
7.28 (d, J¼6.8 Hz, 1H), 7.24 (t, J¼7.2 Hz, 2H), 7.16 (d, J¼6.4 Hz, 2H),
6.95 (t, J¼7.6 Hz, 2H), 6.89 (d, J¼8.0 Hz,1H), 6.66 (s, 1H), 4.94 (s, 1H),
4.24 (q, J¼6.8 Hz, 2H), 3.78 (s, 3H), 3.66 (s,1H),1.30 (t, J¼7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3):
d¼196.5, 168.6, 166.0, 159.3, 141.9, 141.7,
130.0, 128.9, 128.6, 127.8, 127.3, 116.4, 113.9, 113.8, 109.5, 63.7, 61.6,
61.4, 55.6, 55.3, 48.5, 14.1, 14.0; HRMS (ESI): m/z [MþH]þ calcd for
C
19H19O4: 311.1278; found: 311.1278.
4.2.44. Ethyl 4-methoxy-3-oxo-1-phenyl-2,3-dihydro-1H-indene-2-
carboxylate (4s). 205.8 mg, 86% yield; yellow solid; mp
115e116 ꢀC; IR (KBr): 3422, 3028, 2999, 2959, 2937, 2840, 1729,

9544
Y.-P. Zhu et al. / Tetrahedron 70 (2014) 9536e9544
Chem., Int. Ed. 2011, 50, 10981; (g) Lebœuf, D.; Gandon, V.; Ciesielski, J.; Frontier,
A. J. J. Am. Chem. Soc. 2012, 134, 6296; (h) Lebœuf, D.; Wright, C. M.; Frontier, A. J.
11. Xi, Z.-G.; Zhu, L.; Luo, S.; Cheng, J.-P. J. Org. Chem. 2012, 78, 606.
12. (a) Salva, J.; Faulkner, D. J. J. Org. Chem. 1990, 55, 1941; (b) Eicher, T.; Haupt-
ꢀ
Chem.dEur. J. 2013, 19, 4835; (i) Lebœuf, D.; Theiste, E.; Gandon, V.; Daifuku, S. L.;
Neidig, M. L.;Frontier, A. J. Chem.dEur. J. 2013,19, 4842 and references cited therein.
6. (a) Jolit, A.; Walleser, P. M.; Yap, G. P. A.; Tius, M. A. Angew. Chem., Int. Ed. 2014,
53, 6180; (b) Shimada, N.; Stewart, C.; Bow, W. F.; Jolit, A.; Wong, K.; Zhou, Z.;
Tius, M. A. Angew. Chem., Int. Ed. 2012, 51, 5727; (c) Basak, A. K.; Shimada, N.;
Bow, W. F.; Vicic, D. A.; Tius, M. A. J. Am. Chem. Soc. 2010, 132, 8266; (d) Bow, W.
F.; Basak, A. K.; Jolit, A.; Vicic, D. A.; Tius, M. A. Org. Lett. 2010, 12, 440; (e) Bee,
C.; Leclerc, E.; Tius, M. A. Org. Lett. 2003, 15, 4927.
7. (a) Liang, G.; Xu, Y.; Seiple, I. B.; Trauner, D. J. Am. Chem. Soc. 2006, 128, 11022;
(b) Liang, G.; Trauner, D. J. Am. Chem. Soc. 2004, 126, 9544; (c) Liang, G.; Gradl,
S. N.; Trauner, D. Org. Lett. 2003, 5, 4931.
8. (a) Patil, D. V.; Cavitt, M. A.; France, S. Org. Lett. 2011, 13, 5820; (b) Phun, L. H.;
Patil, D. V.; Cavitt, M. A.; France, S. Org. Lett. 2011, 13, 1952; (c) Patil, D. V.; Phun,
L. H.; France, S. Org. Lett. 2010, 12, 5684.
9. (a) Nie, J.; Zhu, H.-W.; Cui, H.-F.; Hua, M.-Q.; Ma, J.-A. Org. Lett. 2007, 9, 3053; (b)
Cui, H.-F.; Dong, K.-Y.; Nie, J.; Zheng, Y.; Ma, J.-A. Tetrahedron 2010, 51, 2374.
10. (a) Rueping, M.; Ieawsuwan, W.; Antonchick, A. P.; Nachtsheim, B. J. Angew.
Chem., Int. Ed. 2007, 46, 2097; (b) Rueping, M.; Ieawsuwan, W. Adv. Synth. Catal.
2009, 351, 78; (c) Aggarwal, V. K.; Belfield, A. J. Org. Lett. 2003, 5, 5075; (d) Cao,
P.; Deng, C.; Zhou, Y.-Y.; Sun, X.-L.; Zheng, J.-C.; Xie, Z.; Tang, Y. Angew. Chem.,
Int. Ed. 2010, 49, 4463; (e) Shi, F.; Li, X.; Xia, Y.; Zhang, L.; Yu, Z.-X. J. Am. Chem.
Soc. 2007, 129, 15503; (f) Cai, S.; Xiao, Z.; Shi, Y.; Gao, S. Chem.dEur. J. 2014,
http://dx.doi.org/10.1002/chem.201402993
mann, S.; Speicher, A. The Chemistry of Heterocycles; Wiley-VCH: Weinheim,
Germany, 2003; (c) Yin, G. D.; Wang, Z. H.; Chen, A. H.; Gao, M.; Wu, A. X.; Pan,
Y. J. J. Org. Chem. 2008, 73, 3377.
13. (a) Gao, M.; Yang, Y.; Wu, Y.-D.; Deng, C.; Cao, L.-P.; Meng, X.-G.; Wu, A.-X. Org.
Lett. 2010, 12, 1856; (b) Zhu, Y.-P.; Cai, Q.; Gao, Q.-H.; Jia, F.-C.; Liu, M.-C.; Gao,
M.; Wu, A.-X. Tetrahedron 2013, 69, 6392.
14. Crystal data for compound 2g: CCDC 934475. C22H21NO9, formula weight¼443.
ꢁ
ꢁ
ꢁ
ꢁ
40, triclinic, a¼6.868(14) A, b¼9.782(2) A, c¼17.323(4) A,
a
¼98.560(3)ꢀ,
¼100.
b
3
ꢀ
804(4)ꢀ,
g
¼109.566(3) , V¼11,048.5(4) A , T¼298(2) K, space group P-1, Z¼2,
ꢁ
DC¼1.404 Mg/m3,
m
¼0.325 mmꢁ1
,
l
¼0.71073 A, F(000) 464, crystal size 0.
20ꢂ0.10ꢂ0.10 mm3, 3667 independent reflections (Rint¼0.0772), reflections
collected 6317, refinement method full-matrix least-squares on F2, goodness-
of-fit on F2, 1.048, final R indices [I>2s(I)], R1¼0.0640, wR2¼0.1678, largest
diff. peak and hole 0.222 and ꢁ0.249 eꢁ3. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.
uk/data_request/cif.
15. Yin, G.; Zhou, B.; Meng, X.; Wu, A.; Pan, Y. Org. Lett. 2006, 8, 2245.
16. (a) Yang, Y.; Gao, M.; Shu, W.-M.; Wu, L.-M.; Zhang, D.-X.; Wu, A.-X. Org. Biomol.
Chem. 2013, 11, 1226; (b) Desimoni, G.; Faita, G.; Ricci, M.; Righetti, P. Tetrahe-
dron 1998, 54, 9581.
17. Baddeley, G.; Holt, G.; Makar, S. M. J. Chem. Soc. 1952, 3289.