DABCO and Bu3P catalyzed [4 + 2] and [3 + 2] cycloadditions of 3-acyl-2H-chromen-ones and ethyl 2,3-butadienoate

Article abstract of DOI:10.1039/c2ob26300a

DABCO-catalyzed [4 + 2] and Bu₃P-catalyzed [3 + 2] cycloadditions between 3-acyl-2H-chromen-ones and ethyl 2,3-butadienoate were developed for the synthesis of dihydropyran-fused and cyclopenten-fused chromen-2-ones with high regio- and stereo-

Full text of DOI:10.1039/c2ob26300a

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2012, 10, 7739
www.rsc.org/obc
PAPER
DABCO and Bu3P catalyzed [4 + 2] and [3 + 2] cycloadditions of 3-acyl-2H-
chromen-ones and ethyl 2,3-butadienoate†
Ying Wang, Zhi-Hua Yu, Hu-Fei Zheng and De-Qing Shi*
Received 7th July 2012, Accepted 2nd August 2012
DOI: 10.1039/c2ob26300a
DABCO-catalyzed [4 + 2] and Bu3P-catalyzed [3 + 2] cycloadditions between 3-acyl-2H-chromen-ones
and ethyl 2,3-butadienoate were developed for the synthesis of dihydropyran-fused and cyclopenten-fused
chromen-2-ones with high regio- and stereo-selectivities, respectively. The synthetic procedures have the
advantages of mild reaction conditions, convenient handling and good atom economy as well as a wide
substrate scope, which make this method useful for the synthesis of potentially biologically active
dihydropyran-fused and cyclopenten-fused chromen-2-ones derivatives. Possible reaction mechanisms
have also been proposed on the basis of previous literature and our investigation.
further development of the tertiary phosphine and amine cata-
lyzed cycloaddition of allenoates with different α,β-unsaturated
Introduction
Chromen-2-one (coumarin) derivatives have exhibited a wide
range of biological activities and have received more and more
attention. Some of them are used as anti-cancer agents,1a,b anti-
microbial agents,1c,d antiinflammatory agents,1e selective human
dopamine D4 antagonists,1f lipid peroxidation inhibitors,1g
DNA-PK inhibitors,1h aromatase inhibitors,1i inhibitors of mono-
amine oxidases,1j and dual inhibitors of acetylcholinesterase and
monoamine oxidase1k,l etc. Recently, organocatalysts such as ter-
tiary phosphine and tertiary amine have catalyzed cycloadditions
of allenoates, constructing complicated cyclic compounds or
natural product skeletons, and have received more and more
attention by organic chemists.2 Lu et al.’s [3 + 2] cycloaddition
of allenoate catalyzed by tertiary phosphine, in which allenoate
usually acts as the three-carbon unit, sometimes as the two-
carbon one, is well documented.3 On the other hand, [4 + 2]
annulation of allenoates with imine,4 activated olefins5 or tri-
fluoromethyl ketones6 have also been investigated well. In 2003,
Miller and Evans reported the amine-catalyzed Baylis–Hillman
reaction of allenic esters with α,β-unsaturated carbonyls,7
however, the [4 + 2] cycloadditions of allenoates used as the
two-carbon unit with α,β-unsaturated carbonyls were firstly
reported in 2011.8 Despite these prominent works, due to its
divergent reactivity modes, and the regio- and stereo-selectivities
of cycloadditions of allenoates with α,β-unsaturated carbonyls,
carbonyl substrates to obtain novel potentially biologically active
heterocycle skeletons remains in high demand. During the prep-
aration of the manuscript, Shi et al. (ref. 8a, Org. Lett., 2011, 13,
1142) and Wang et al. (ref. 8b, Org. lett., 2011, 13, 1138)
reported the cycloadditions of allenoate and isatin derived elec-
tron deficient olefins (Scheme 1). In Shi’s work, the [4 + 2]
cycloaddition products catalyzed by DMAP are mainly in the
Z-configuration (Z : E = 4 : 1 ∼ only Z), whereas three tautomers
of [4 + 2] cycloadducts are generated when the reaction was cat-
alyzed by DABCO. Secondly, there are two spiro tautomers in
the [3 + 2] cycloadditions catalyzed by Bu3P. Herein, we wish to
report DABCO and Bu3P catalyzed [4 + 2] and [3 + 2] cyclo-
additions of 3-acyl-2H-chromen-ones and ethyl 2,3-butadienoate
to access potentially biologically active dihydropyran-fused and
cyclopenten-fused chromen-2-one derivatives with high regio-
and stereo-selectivity (E-configuration only, Scheme 2).
Key Laboratory of Pesticide and Chemical Biology of Ministry of
Education, College of Chemistry, Central China Normal University,
Wuhan 430079, People’s Republic of China.
E-mail: chshidq@mail.ccnu.edu.cn; Fax: (+86) 27-67862041;
Tel: (+86) 27-67867958
†Electronic supplementary information (ESI) available. CCDC 889494
and 889495. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2ob26300a
Scheme 1 Previous work by Wang8b and Shi.8a
Org. Biomol. Chem., 2012, 10, 7739–7746 | 7739
This journal is © The Royal Society of Chemistry 2012

View Article Online
Table 1 Optimization of conditions
Yieldb (%)
Entrya
Cata.
Solvent
Time/h
2a
3a
1
2
3
4
5
6
7
8
Ph3P
Bu3P
THF
THF
THF
THF
THF
THF
THF
CH2Cl2
CH3OH
CHCl3
MeCN
Toluene
MeCN
CH2Cl2
CH3OH
Toluene
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
24
6
8
8
5
4
24
4
8
6
24
6
12
4
6
6
6
8
4
8
60
85
76
72
Scheme 2 DABCO and Bu3P catalyzed [4 + 2] and [3 + 2] cycloaddi-
tions of 3-acyl-2H-chromen-ones with 2,3-butadienoate.
LBBA1 (Fig. 1)
LBBA2 (Fig. 1)
DMAP
DABCO
DBU
DABCO
DABCO
DABCO
DABCO
DABCO
Bu3P
Bu3P
Bu3P
Bu3P
Bu3P
DABCO
DABCO
Bu3P
75
86
Trace
92
78
80
60
65
9
10
11
12
13
14
15
16
17
18c
19d
20c
21d
65
90
75
72
81
Fig. 1 Structural of bifunctional phosphine catalysts LBBA1 and
LBBA2.
78
80
Results and discussion
82
72
We began the cycloaddition study by utilizing simple substrate
1a and 2,3-butadienoate as the substrates in order to optimize the
reaction conditions. The initial screening was arranged with
20 mol% of tertiary phosphine or amine as the catalyst and THF
(2.5 mL) as the solvent at room temperature with the results sum-
marized in Table 1. To our delight, the reaction proceeded
smoothly and gave [3 + 2] cycloaddition products 3a in 60–85%
yield in the presence of various tertiary phosphines as the cata-
lysts at room temperature (Table 1, entries 1–4); Bu3P was the
most effective catalyst (85% yield, Table 1, entry 2). Whereas
with the tertiary amines as the catalyst, [4 + 2] cycloadduct 2a
was obtained (Table 1, entries 5–7). DABCO was the most effec-
tive catalyst (86% yield, entry 6) and DBU failed to initiate the
reaction (entry 7). Investigations on the effects of various sol-
vents on the reaction indicated that many common solvents were
suitable (Table 1, entries 8–17), among which moderately polar
CH2Cl2 was the best one for both [3 + 2] and [4 + 2] cycloaddi-
tions (entry 8, entry 14). Subsequently, the effects of reaction
temperatures were examined using 20 mol% Bu3P or DABCO in
CH2Cl2 (0.2 M) as a control. The efficiency was weakened
slightly when the reaction was conducted at low temperature
(0 °C, entry 18, entry 20) or under reflux (entry 19 and entry
21). Thus, the optimized reaction conditions were established as
follows: 20 mol% Bu3P or DABCO as the catalysts, with the
ratio of 1 and allenoate as 1 : 1.2, CH2Cl2 (0.2 M) as the solvent
and stirring at room temperature.
Bu3P
4
a All the reactions were carried out on 0.5 mmol scale with the catalyst
(20 mol%) in solvent (0.2 M) at room temperature unless otherwise
noted, with the ratio of 1a : allenoate as 1 : 1.2. b Isolated yields.
c Reaction temperature at 0 °C. d Under reflux.
Table 2 Substrate scope of [4 + 2] cycloadditions of 3-acyl-2H-
chromen-ones with ethyl 2,3-butadienoate catalyzed by DABCO
Yielda,b
(%)
Entry Compd. R1
R2
Time/h M. p./°C
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
C6H5
C6H5
C6H5
C6H5
4
4
4
3
4
3
3
3
4
4
4
3
125.2–126.0 92
151.7–153.3 85
158.8–161.4 79
130.2–132.0 86
6-Br
6-Cl
6-F
6,8-Cl2 C6H5
7-CF3 C6H5
6-CH3 C6H5
7-CH3 C6H5
6-CH3O C6H5
H
H
H
89.2–90.6
80
115.0–116.8 92
144.0–145.4 94
124.0–126.0 95
156.6–158.4 88
110.0–111.2 87
197.0–198.4 86
139.0–140.2 89
With the optimized conditions in hand, we next explored the
scope of the 3-acyl-2H-chromen-one substrates with different
substituents on the benzene rings (Table 2 and Table 3). It was
found that a range of substituents in the 3-acyl-2H-chromen-ones
were accommodated to afford the corresponding cycloadducts in
moderate to excellent yields with high regio- and stereo-selec-
tivities, no matter whether they had electron-withdrawing or
electron-donating substituents on the aromatic ring at different
9
10
11
12
2j
2k
2l
CH3
4-CH3-C6H4
4-Cl-C6H4
1
a Isolated yield of product. b Stereo-configuration was determined by H
NMR and X-ray diffraction analysis of a crystal of 2b (CCDC:
889494†).
7740 | Org. Biomol. Chem., 2012, 10, 7739–7746
This journal is © The Royal Society of Chemistry 2012

View Article Online
Table 3 Substrate scope of [3 + 2] cycloadditions of 3-acyl-2H-
chromen-ones with ethyl 2,3-butadienoate catalyzed by Bu3P
1,2-proton transfer and Bu3P release, producing the [3 + 2]
cycloadduct 3. As for the [4 + 2] cycloaddition pathway cata-
lyzed by DABCO, reaction with 2,3-butadienoate generates
zwitterionic E, in which the γ-position carbanion attacks the
β-carbon of enones 1 to give Z configuration of F, avoiding the
interaction of the ester group with the 3-position acyl one. F con-
verted to the enolate form G, in which the oxygen anion of
enolate G undergoes molecular nucleophilic substitution with
the β-carbon of the α,β-unsaturated ester moiety which is fol-
lowed by the release of DABCO, generating the [4 + 2] cyclo-
adduct 2.
Yield
Entry Compd. R1
R2
Time/h M. p./°C
(%)a,b
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
C6H5
C6H5
C6H5
C6H5
4
4
4
6
6
4
4
4
4
4
123.0–124.4 90
130.1–132.0 91
6-Br
6-Cl
6-F
6,8-Cl2 C6H5
6-CH3
7-CH3
6-CH3O C6H5
H
H
127.0–128.5 94
102.2–104.0 72
128.0–129.8 75
103.0–104.2 85
164.6–166.0 92
118.0–119.0 86
106.0–107.0 86
110.4–111.3 89
Conclusions
C6H5
C6H5
In summary, we have developed novel highly regio- and stereo-
selective [3 + 2] and [4 + 2] cycloadditions of 3-acyl-2H-
chromen-ones with ethyl 2,3-butadienoate catalyzed by Bu3P
and DABCO, respectively, to access potentially biologically
active dihydropyran-fused and cyclopenten-fused chromen-2-one
derivatives in moderate to excellent yields. The synthetic pro-
cedures have the advantages of mild reaction conditions, con-
venient handling and high atom economy as well as wide
substrate scopes. Possible mechanisms have been proposed
based on the reported literature and our investigation.
4-CH3-C6H4
4-Cl-C6H4
10
3j
a Isolated yield of product. b Regio-selectivity was determined by 1H
NMR and X-ray diffraction analysis of a crystal of 3j (CCDC:
889495†).
Experimental
General
All the reactions are conducted under a dry N2 atmosphere. All
the solvents and reagents are commercially available and used as
received with the following exceptions. THF, toluene and
dioxane were distilled from sodium/benzophenone. Dichloro-
methane, chloroform and acetonitrile were distilled from calcium
hydride. Ethanol was distilled form Mg turnings. Substituted
salicylaldehydes and ethyl substituted benzoyl (acetyl) acetates
were prepared according to the literature,9,10 whereas LBBA 1,
LBBA 2 and ethyl 2,3-butadienoate were synthesized according
to the reported methods,11,12 respectively. Melting points were
determined with a WRS-1B digital melting point apparatus, and
the thermometer was uncorrected. 1H and 13C NMR spectra
were recorded on a Varian Mercury PLUS 400 or a Varian
Mercury PLUS 600 spectrometer in chloroform-d. Chemical
shift in parts per million (δ ppm) from an internal standard [tetra-
methylsilane (TMS) or chloroform (CHCl3)], multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, and m = multiplet),
integration, and coupling constant (Hz). 13C NMR chemical
shifts are reported in ppm from CDCl3 (taken as 77.0 ppm). The
mass spectra were obtained on a Finnigan TRACEMS 2000
spectrometer using the EI method or an Applied Biosystems API
2000 LC/MS/MS (ESI-MS) spectrometer. Elemental analyses
were performed with an Elementar Vario EL#xX_CYR_-
HEX_428; CHNSO elemental analyzer. X-ray diffraction analy-
sis was carried out with a Bruker APEX-II CCD X-ray
diffraction instrument.
Scheme 3 Possible mechanisms suggested for the [4 + 2] and [3 + 2]
cycloadditions of 3-acyl-2H-chromen-ones with ethyl 2,3-butadienoate
catalyzed by DABCO and Bu3P, respectively.
positions. Varying the different acyl group in the 3-position (R2
= methyl or substituted phenyl groups) of the 2H-chromen-ones
also gave satisfactory results.
The structures and configurations of the [4 + 2] and [3 + 2]
1
cycloadducts 2 and 3 were assigned via H-NMR, 13C-NMR,
MS, elemental analysis and further confirmed by single crystal
X-ray diffraction analysis (see the ESI†).
Based on our system and the reported literature, possible
mechanisms are suggested as shown in Scheme 3. The reactions
proceed through different cycloaddition modes in the presence
of tertiary phosphine and amine catalysts, respectively. In the
case of the PBu3-catalyzed [3 + 2] cycloaddition reaction, Bu3P
attacks the β-carbon of 2,3-butadienoate to give intermediate A,
which can isomerize to the more stable intermediate B, because
both the phosphonium salt and ester group can stabilize the
β-carbanion of B. So, compound B acts as a 1,3 dipole for the
[3 + 2] cycloaddition with activated olefins 1, which follows by
General procedure for the synthesis of 3-acyl-2H-chromen-
ones 1.13 To a dry 50 mL flask were added substituted salicyl-
aldehyde (8 mmol), ethyl substituted benzoyl (acetyl) acetates
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 7739–7746 | 7741

View Article Online
(8 mmol), piperidine (0.25 mL), several drops of glacial acetic
acid and anhydrous acetonitrile (20 mL). The solution was
stirred under reflux for 0.5–1 h until the reaction completed
(monitored by TLC). The mixture was poured into iced water
(50 mL), filtered and recrystallized with anhydrous ethanol. 1
was obtained as colorless crystals or light yellow solid in
55–82% yield.
7.61 (t, J = 7.2 Hz, 1H), 7.45–7.50 (m, 3H), 7.38 (s, 1H), 7.30
(d, J = 8.4 Hz, 1H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 191.8, 158.6, 154.9, 145.7, 145.5, 136.3, 133.6, 129.5, 128.9,
128.6, 126.2, 125.5, 116.9, 115.7, 22.0.
Preparation of 3-benzoyl-7-methyl-chromen-2-one (1h).13a
1
Light yellow solid, yield 80%, m. p. 157.6–158.8 °C; H NMR
(400 MHz, CDCl3), δ 8.08 (s, 1H), 7.88 (d, J = 8.4 Hz, 2H),
7.67 (t, J = 6.8 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.49 (t, J =
8.0 Hz, 2H), 7.41 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H),
2.17 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 192.0, 158.9,
153.1, 145.7, 136.5, 135.0, 134.0, 129.8, 129.1, 128.8, 127.0,
118.1, 116.8, 21.0.
Preparation of 3-benzoyl-chromen-2-one (1a).13a Yellow
1
solid, yield 85%, m. p. 149.7–151.2 °C; H NMR (600 MHz,
CDCl3), δ 8.09 (s, 1H), 7.89 (d, J = 9.6 Hz, 2H), 7.60–7.67 (m,
3H), 7.49 (t, J = 7.8 Hz, 2H), 7.41 (d, J = 7.8 Hz, 1H), 7.36 (t,
J = 7.2 Hz, 1H);13C NMR (150 MHz, CDCl3): δ 191.6, 158.3,
154.7, 145.3, 136.1, 133.7, 133.6, 129.5, 129.2, 128.5, 126.9,
124.9, 118.1, 116.8.
Preparation of 3-benzoyl-6-methoxy-chromen-2-one (1i).13a
1
Light yellow solid, yield 85%, m. p. 144.0–145.5 °C; H NMR
Preparation of 3-benzoyl-6-bromo-chromen-2-one (1b).13a
Colorless solid, yield 62%, m. p. 171.2–172.1 °C; 1H NMR
(400 MHz, CDCl3), δ 7.99 (s, 1H), 7.88 (d, J = 7.6 Hz, 2H),
7.59–7.65 (m, 3H), 7.50 (t, J = 7.6 Hz, 2H), 7.36 (d, J = 9.2 Hz,
1H);13C NMR (100 MHz, CDCl3): δ 191.0, 157.7, 153.4, 143.7,
136.2, 135.8, 134.0, 131.2, 129.5, 128.6, 128.0, 119.6, 118.6,
117.5.
(400 MHz, CDCl3), δ 8.05 (s, 1H), 7.88 (d, J = 8.0 Hz, 2H),
7.62 (t, J = 8.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 2H), 7.34 (d, J =
8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.01 (s, 1H), 3.87 (s,
3H);13C NMR (100 MHz, CDCl3): δ 191.8, 158.6, 156.4, 149.2,
145.2, 136.2, 133.8, 129.5, 128.6, 127.2, 121.7, 118.4, 117.9,
110.6, 55.9.
Preparation of 3-acetyl-chromen-2-one (1j).13c Light yellow
solid, yield 80%, m. p. 99.7–101.0 °C; 1H NMR (600 MHz,
CDCl3), δ 8.52 (s, 1H), 7.67 (t, J = 4.8 Hz, 2H), 7.34–7.39 (m,
2H), 2.74 (s, 3H), 3.87 (s, 3H);13C NMR (100 MHz, CDCl3): δ
195.4, 159.0, 155.2, 147.4, 134.3, 130.2, 124.9, 124.4, 118.3,
116.6, 30.5.
Preparation of 3-benzoyl-6-chloro-chromen-2-one (1c).13a
White solid, yield 68%, m. p. 161.0–162.0 °C; 1H NMR
(400 MHz, CDCl3), δ 7.99 (s, 1H), 7.88 (d, J = 7.6 Hz, 2H),
7.73 (d, J = 8.0 Hz, 2H), 7.64 (t, J = 8.0 Hz, 1H), 7.50 (t, J =
8.0 Hz, 2H), 7.31 (d, J = 9.2 Hz, 1H);13C NMR (100 MHz,
CDCl3): δ 191.1, 157.7, 153.0, 143.8, 135.8, 134.0, 133.4,
130.2, 129.5, 128.6, 128.2, 119.1, 118.3.
Preparation of 3-(4-methylbenzoyl)-chromen-2-one (1k).13d
1
Light yellow solid, yield 83%, m. p. 170.0–171.0 °C; H NMR
Preparation of 3-benzoyl-6-fluoro-chromen-2-one (1d).13a
White solid, yield 65%, m. p. 157.9–158.3 °C; 1H NMR
(600 MHz, CDCl3), δ 8.00 (s, 1H), 7.88 (d, J = 7.2 Hz, 2H),
7.63 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.37–7.42 (m,
2H), 7.28 (dd, J = 7.2 Hz, J = 2.4 Hz, 1H); 13C NMR
(150 MHz, CDCl3): δ 191.2, 159.9, 157.6 (d, J = 75 Hz), 150.8.7,
144.0, 135.8, 133.9, 129.3, 128.6, 127.9, 121.1, 120.6, 118.2,
114.2 (d, J = 45 Hz).
(400 MHz, CDCl3), δ 8.04 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H),
7.58–7.63 (m, 2H), 7.32–7.40 (m, 2H), 7.27 (d, J = 8.0 Hz, 2H),
2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.1, 158.4,
154.6, 144.9, 144.8, 133.6, 133.4, 129.7, 129.2, 129.1, 127.1,
124.9, 118.1, 116.8, 21.7.
Preparation of 3-(4-chlorobenzoyl)-chromen-2-one (1l). White
1
solid, yield 72%, m. p. 198.0–200.0 °C; H NMR (400 MHz,
CDCl3), δ 8.13 (s, 1H), 7.82 (d, J = 8.0 Hz, 2H), 7.61–7.67 (m,
2H), 7.46 (d, J = 8.0 Hz, 2H), 7.35–7.43 (m, 2H); ESI-MS: m/z
= 285 [M + H]+, 307 [M + Na]+. Anal. calcd for C16H9ClO3: C,
67.50; H, 3.19. Found: C, 67.63; H, 3.27.
Preparation of 3-benzoyl-6,8-dichloro-chromen-2-one (1e).13b
White solid, yield 60%, m. p. 185.4–186.1 °C; 1H NMR
(600 MHz, CDCl3), δ 7.96 (s, 1H), 7.87 (d, J = 7.2 Hz, 2H),
7.69 (s, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 190.6, 156.7, 149.0, 143.3,
135.6, 134.2, 133.3, 130.1, 129.6, 128.9, 128.7, 126.7, 122.9,
120.0.
General procedure for the preparation of 2. To a solution of
3-acyl-2H-chromen-one 1 (0.5 mmol) and ethyl 2,3-butadienoate
(67.2 mg, 0.6 mmol) in CH2Cl2 (2.5 mL) was added DABCO
(11.2 mg, 20 mol %) under a N2 atmosphere. The reaction
mixture was stirred at room temperature for 3–4 h till the reaction
completed (monitored by TLC). After the removal of the
solvent, the residue was subjected to chromatography on a silica
gel (60–120 mesh) column using 10 : 1 petroleum ether–ethyl
acetate solvent mixture as eluent to afford 2 as colorless or light
yellow solid in 79–95% yield.
Preparation of 3-benzoyl-7-(trifluoromethyl)-chromen-2-one
1
(1f). White solid, yield 58%, m. p. 179.9–181.6 °C; H NMR
(400 MHz, CDCl3), δ 8.09 (s, 1H), 7.89 (d, J = 8.0 Hz, 2H),
7.75 (d, J = 8.0 Hz, 1H), 7.60–7.67 (m, 3H), 7.52 (t, J = 7.6 Hz,
2H);13C NMR (100 MHz, CDCl3): δ 190.9, 157.4, 154.2, 143.5,
135.7, 134.6, 134.2, 129.9, 129.6, 129.3, 128.7, 124.3, 121.5,
120.6, 114.3; ESI-MS: m/z = 319 [M + H]+, 341 [M + Na]+.
Anal. calcd for C17H9F3O3: C, 64.16; H, 2.85. Found: C, 64.01;
H, 2.66.
Preparation of (E) ethyl (5-oxo-4-phenyl-1,10b-dihydro-5H-
pyrano[3,4-c]chromen-2-ylidene) acetate (2a). Light yellow
1
solid, yield 92%, m. p. 125.2–126.0 °C; H NMR (600 MHz,
Preparation of 3-benzoyl-6-methyl-chromen-2-one (1g).13a Light
yellow solid, yield 78%, m. p. 157.7–158.9 °C; 1H NMR
(600 MHz, CDCl3), δ 8.03 (s, 1H), 7.88 (d, J = 7.8 Hz, 2H),
CDCl3), δ 7.50 (d, J = 7.8 Hz, 2H), 7.48 (t, J = 7.2 Hz, 1H),
7.42 (t, J = 7.2 Hz, 3H), 7.33 (t, J = 7.2 Hz, 1H), 7.21 (t, J =
7.2 Hz, 1H), 7.10 (d, J = 7.8 Hz, 1H), 5.84 (s, 1H), 4.88 (dd, J =
7742 | Org. Biomol. Chem., 2012, 10, 7739–7746
This journal is © The Royal Society of Chemistry 2012

View Article Online
6.0 Hz, J = 15. 0Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H), 4.01 (dd, J =
5.4 Hz, J = 12.0 Hz, 1H), 2.51 (t, J = 13.2 Hz, 1H), 1.33 (t, J =
7.8 Hz, 3H);13C NMR (100 MHz, CDCl3): δ 166.6, 163.5,
162.2, 161.5, 150.6, 132.9, 130.7, 129.0, 128.8, 128.1, 125.6,
124.8, 122.6, 117.1, 102.3, 101.1, 60.4, 30.1, 25.6, 14.2; EI-MS
(70 eV): m/z = 362 (M+, 10.2), 289 (47.7), 247 (16.5), 221
(26.0), 173 (25.6), 144 (14.7), 129 (13.1), 150 (100), 77 (74.5),
44 (52.0). Anal. calcd for C22H18O5: C, 72.92; H, 5.01. Found:
C, 72.83; H, 4.94.
yellow solid, yield 80%, m. p. 89.2–90.6 °C;1H NMR
(600 MHz, CDCl3), δ 7.53 (s, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.43
(t, J = 7.2 Hz, 3H), 7.32 (s, 1H), 5.88 (s, 1H), 4.82 (dd, J =
6.0 Hz, J = 15.0 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 4.00 (dd, J =
5.4 Hz, J = 12.0 Hz, 1H), 2.54 (t, J = 13.8 Hz, 1H), 1.34
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 166.5,
163.4, 162.5, 159.5, 132.3, 131.0, 129.9, 129.7, 129.5, 128.9,
128.2, 125.7, 124.1, 122.9, 103.0, 99.2, 60.6, 30.6, 25.3, 14.2;
EI-MS (70 eV): m/z = 432 (M + 2, 1.5), 430 (M+, 1.9), 333
(6.2), 331 (11.0), 106 (9.8), 105 (100), 77 (56.1), 51 (9.8), 44
(19.5). Anal. calcd for C22H16Cl2O5: C, 61.27; H, 3.74. Found:
C, 61.08; H, 3.63.
Preparation of (E) ethyl (9-bromo-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2b). Light
yellow solid, yield 85%, m. p. 151.7–153.3 °C;1H NMR
(600 MHz, CDCl3), δ 7.54 (s, 1H), 7.49 (t, J = 7.8 Hz, 3H), 7.42
(dd, J = 7.2 Hz, J = 15.6 Hz, 3H), 6.97 (d, J = 8.4 Hz, 1H), 5.86
(s, 1H), 4.84 (dd, J = 6.0 Hz, J = 14. 4 Hz, 1H), 4.25 (q, J =
7.2 Hz, 2H), 4.00 (dd, J = 5.4 Hz, J = 12.0 Hz, 1H), 2.51 (t, J =
12.6 Hz, 1H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 166.5, 162.9, 160.9, 149.7, 132.7, 132.0, 130.8,
128.8, 128.6, 128.1, 127.4, 124.7, 118.8, 117.4, 102.7, 100.1,
60.5, 30.1, 25.5, 14.2; EI-MS (70 eV): m/z = 441 (M + 1, 3.0),
440 (M+, 3.2), 369 (13.9), 367 (11.8), 341 (10.0), 251 (9.7), 202
(7.0), 189 (10.0), 129 (10.5), 105 (100), 77 (67.5), 44 (16).
Anal. calcd for C22H17BrO5: C, 59.88; H, 3.88. Found: C,
59.64; H,3.97.
Preparation of (E) ethyl (5-oxo-4-phenyl-8-trifluoromethyl-
1,10b-dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2f).
Light yellow solid, yield 92%, m. p. 115.0–116.8 °C;1H NMR
(600 MHz, CDCl3), δ 7.55 (d, J = 7.8 Hz, 1H), 7.47–7.51 (m,
4H), 7.43 (t, J = 7.2 Hz, 2H), 7.35 (s, 1H), 5.87 (s, 1H), 4.90
(dd, J = 6.0 Hz, J = 15.0 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 4.05
(dd, J = 5.4 Hz, J = 12.0 Hz, 1H), 2.55 (t, J = 12.6 Hz, 1H),
1.34 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 166.5,
163.1, 162.7, 160.6, 157.9, 150.8, 132.6, 130.9, 128.8, 128.2,
126.6, 126.4, 125.8, 121.3, 114.4, 102.8, 99.8, 60.5, 30.3, 25.4,
14.2; EI-MS (70 eV): m/z = 430 (M+, 9.3), 357 (20.9), 356
(14.8), 315 (9.8), 289 (11.2), 241 (19.1), 221 (9.5), 212 (11.9),
149 (8.4), 129 (8.5), 106 (10.2), 105 (100), 77 (62.5), 44 (34.8).
Anal. calcd for C23H17F3O5: C, 64.19; H, 3.98. Found: C,
64.33; H, 4.07.
Preparation of (E) ethyl (9-chloro-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2c). Light
yellow solid, yield 79%, m. p. 158.8–160.4 °C;1H NMR
(600 MHz, CDCl3), δ 7.49 (t, J = 7.8 Hz, 3H), 7.42 (t, J =
7.2 Hz, 3H), 7.29 (d, J = 9.0 Hz, 1H), 7.03 (d, J = 7.8 Hz, 1H),
5.86 (s, 1H), 4.85 (dd, J = 5.4 Hz, J = 14. 4 Hz, 1H), 4.25 (q,
J = 7.2 Hz, 2H), 3.99 (dd, J = 5.4 Hz, J = 12.0 Hz, 1H), 2.51 (t,
J = 13.2 Hz, 1H), 1.34 (t, J = 6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 166.5, 162.9, 162.8, 160.9, 149.2, 132.7, 130.8,
130.0, 129.0, 128.8, 128.1, 125.7, 124.3, 118.4, 102.7, 100.1,
60.5, 30.2, 25.5, 14.2; EI-MS (70 eV): m/z = 396 (M+, 7.7), 324
(9.5), 323 (28.7), 322 (12.8), 296 (10.6), 295 (11.4), 281 (8.5),
255 (10.6), 207 (11.5), 178 (10.8), 129 (16.0), 105 (100), 77
(62.2), 44 (38). Anal. calcd for C22H17ClO5: C, 66.59; H, 4.32.
Found: C, 66.70; H, 4.17.
Preparation of (E) ethyl (9-methyl-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2g). Light
yellow solid, yield 94%, m. p. 144.0–145.4 °C;1H NMR
(600 MHz, CDCl3), δ 7.50 (d, J = 7.2 Hz, 2H), 7.46 (d, J = 7.2
Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.21 (s, 1H), 7.12 (d, J = 7.8
Hz, 1H), 6.98 (d, J = 7.2 Hz, 1H), 5.84 (s, 1H), 4.88 (dd, J = 6.0
Hz, J = 15.0 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.97 (dd, J = 6.0
Hz, J = 12.0 Hz, 1H), 2.50 (t, J = 13.2 Hz, 1H), 2.37 (s, 3H),
1.34 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 166.8,
163.7, 162.1, 148.4, 134.5, 133.0, 130.6, 129.5, 128.8, 128.1,
126.0, 125.8, 122.1, 116.7, 102.1, 101.4, 60.4, 30.0, 25.8, 20.8,
14.2; EI-MS (70 eV): m/z = 376 (M+, 7.4), 303 (13.3), 277
(18.7), 249 (6.3), 187 (6.7), 127 (6.7), 105 (100), 77 (56.3), 44
(17.8). Anal. calcd for C23H20O5: C, 73.39; H, 5.36. Found: C,
73.17; H, 5.22.
Preparation of (E) ethyl (9-fluoro-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2d). Light
yellow solid, yield 86%, m. p. 130.2–132.0 °C;1H NMR
(600 MHz, CDCl3), δ 7.47–7.51 (m, 3H), 7.42 (t, J = 7.8 Hz,
2H), 7.15 (d, J = 6.6 Hz, 1H), 7.01–7.08 (m, 2H), 5.86 (s, 1H),
4.81 (dd, J = 6.0 Hz, J = 15.0 Hz, 1H), 4.24 (q, J = 7.8 Hz, 2H),
3.99 (dd, J = 6.0 Hz, J = 12.6 Hz, 1H), 2.51 (t, J = 13.8 Hz,
1H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
166.5, 162.8 (d, J = 25.1 Hz), 160.6, 146.7, 132.7, 130.8, 128.9,
128.1, 124.3, 118.4, 115.8, 115.6, 112.6, 112.3, 102.6, 100.2,
60.5, 30.3, 25.5, 14.2; EI-MS (70 eV): m/z = 380 (M+, 4.5), 303
(45.9), 276 (27.0), 261 (10.4), 221 (9.0), 173 (27.0), 155 (10.6),
144 (19.9), 120 (14.4), 119 (100), 91 (62.0), 65 (12.5), 44
(31.3). Anal. calcd for C22H17FO5: C, 69.47; H, 4.50. Found: C,
69.60; H, 4.67.
Preparation of (E) ethyl (8-methyl-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2h). Light
yellow solid, yield 95%, m. p. 124.0–126.0 °C;1H NMR
(600 MHz, CDCl3), δ 7.49 (d, J = 7.2 Hz, 2H), 7.46 (d, J = 7.2
Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.02
(d, J = 7.8 Hz, 1H), 6.91 (s, 1H), 5.83 (s, 1H), 4.86 (dd, J = 6.0
Hz, J = 15.0 Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H), 3.96 (dd, J = 5.4
Hz, J = 12.0 Hz, 1H), 2.46 (t, J = 13.2 Hz, 1H), 2.37 (s, 3H),
1.33 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 166.7,
163.7, 162.0, 161.7, 150.4, 139.3, 133.0, 130.6, 128.9, 128.1,
125.5, 125.4, 119.5, 117.4, 102.1, 101.5, 60.4, 29.9, 25.9, 21.0,
14.2; EI-MS (70 eV): m/z = 376 (M+, 9.2), 331 (5.9), 304
(12.3), 303 (43.2), 302 (21.6), 277 (12.4), 275 (14.2), 261
(15.3), 235 (14.6), 221 (14.6), 187 (27.5), 185 (7.9), 158 (8.2),
129 (20.0), 115 (11.0), 105 (100), 91 (12.6), 77 (74.6), 44
Preparation of (E) ethyl (7,9-dichloro-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2e). Light
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 7739–7746 | 7743

View Article Online
(41.6). Anal. calcd for C23H20O5: C, 73.39; H, 5.36. Found: C,
73.53; H, 5.31.
102.5, 101.6, 60.4, 30.1, 25.6, 14.2; EI-MS (70 eV): m/z = 396
(M+, 8.2), 351 (5.7), 325 (20.0), 324 (16.2), 323 (55.4), 322
(14.7), 296 (11.9), 295 (9.6), 285 (8.2), 284 (7.9), 281 (10.8),
255 (15.4), 249 (13.1), 221 (13.0), 202 (11.5), 189 (10.2), 173
(41.1), 163 (10.9), 144 (20.5), 141 (37.0), 139 (100), 111 (54.8),
89 (9.8), 75 (13.6), 44 (36.2). Anal. calcd for C22H17ClO5: C,
66.59; H, 4.32. Found: C, 66.47; H, 4.20.
Preparation of (E) ethyl (9-methoxy-5-oxo-4-phenyl-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2i). White
1
solid, yield 88%, m. p. 156.6–158.4 °C; H NMR (600 MHz,
CDCl3), δ 7.50 (d, J = 6.6 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H),
7.41 (t, J = 7.8 Hz, 2H), 7.03 (d, J = 9.0 Hz, 1H), 6.93 (s, 1H),
6.85 (dd, J = 1.8 Hz, J = 8.4 Hz, 1H), 5.84 (s, 1H), 4.81 (dd, J =
6.0 Hz, J = 15.0 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 3.97 (dd, J =
5.4 Hz, J = 12.0 Hz, 1H), 3.84 (s, 3H), 2.53 (t, J = 12.6 Hz,
1H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
166.6, 163.4, 162.0, 161.8, 156.6, 144.5, 132.9, 130.6, 128.9,
128.1, 123.6, 117.8, 114.0, 110.9, 102.3, 101.1, 60.4, 55.8, 30.4,
25.6, 14.2; EI-MS (70 eV): m/z = 392 (M+, 12.7), 319 (36.5),
291 (14.4), 277 (13.7), 251 (7.2), 203 (6.5), 189 (6.5), 129
(12.5), 105 (100), 77 (52.6). Anal. calcd for C23H20O6: C,
70.40; H, 5.14. Found: C, 70.17; H, 5.05.
General procedure for the preparation of 3. To a flame-dried
Schlenk flask equipped with a magnetic bar was added 3-acyl-
2H-chromen-one 1 (0.5 mmol, 1.0 equiv), Bu3P (20.2 mg,
0.1 mmol, 20 mol%) and dry CH2Cl2 (2 mL) under an argon
atmosphere at room temperature. Then 2,3-butadienoate
(67.2 mg, 0.6 mmol) in CH2Cl2 (0.5 mL) was added slowly and
the resulting mixture was stirred at room temperature for 4–6 h
until the reaction completed (monitored by TLC). After the
removal of the solvent, the residue was subjected to chromato-
graphy on
a silica gel (60–120 mesh) column using
4 : 1 hexane–ethyl acetate solvent mixture as eluent to afford 3
as white or light yellow solid in 72–94% yield.
Preparation of (E) ethyl (4-methyl-5-oxo-1,10b-dihydro-5H-
pyrano[3,4-c]chromen-2-ylidene) acetate (2j). Light yellow
solid, yield 87%, m. p. 110.0–111.2 °C; H NMR (600 MHz,
1
Preparation of 3a-benzoyl-1-(ethoxycarbonyl)-3a,9b-dihydro-
CDCl3), δ 7.36 (d, J = 7.8 Hz, 1H), 7.29 (t, J = 7.2 Hz, 1H),
7.16 (t, J = 7.8 Hz, 1H), 7.05 (d, J = 7.8 Hz, 1H), 5.73 (s, 1H),
4.80 (dd, J = 5.4 Hz, J = 15.0 Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H),
3.86 (d, J = 11.4 Hz, 1H), 2.47 (s, 3H), 2.35 (t, J = 15.0 Hz,
1H), 1.33 (t, J = 7.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
167.1, 164.4, 163.8, 161.8, 150.4, 134.5, 128.8, 125.8, 124.6,
121.9, 116.9, 101.1, 51.4, 29.1, 26.3, 19.8, 14.2; EI-MS (70
eV): m/z = 300 (M+, 14.4), 271 (11.5), 255 (14.5), 254 (10.1),
253 (17.0), 228 (16.6), 227 (100), 226 (16.5), 199 (16.2), 189
(24.5), 173 (90.4), 144 (17.0), 128 (13.5), 115 (24.0), 91 (8.5),
89 (16.3), 67 (24.2), 44 (15.1). Anal. calcd for C17H16O5: C,
67.99; H, 5.37. Found: C, 68.16; H, 5.19.
3H-cyclopenta[c]chromen-4-one (3a). White solid, yield 90%,
m. p. 123.0–124.4 °C; H NMR (600 MHz, CDCl3), δ 7.83 (d,
1
J = 7.8 Hz, 2H), 7.63 (d, J = 7.8 Hz, 1H), 7.55 (t, J = 7.2 Hz,
1H), 7.42 (t, J = 7.8 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.19 (t,
J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 6.95 (s, 1H), 4.91 (s,
1H), 4.22 (q, J = 7.2 Hz, 2H), 3.77 (dd, J = 2.4 Hz, J = 18.6 Hz,
1H), 3.14 (d, J = 18.0 Hz, 1H), 1.28 (t, J = 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 192.1, 167.1, 164.2, 149.3, 142.8,
136.8, 133.6, 132.8, 129.6, 129.2, 128.9, 125.6, 119.2, 117.4,
61.1, 48.6, 48.5, 41.1, 14.2; EI-MS (70 eV): m/z = 362 (M+,
5.6), 271 (75.9), 225 (19.9), 198 (17.3), 105 (100), 77 (47.8).
Anal. calcd for C22H18O5: C, 72.92; H, 5.01. Found: C, 73.01;
H, 5.15.
Preparation of (E) ethyl (5-oxo-4-(p-tolyl)-1,10b-dihydro-5H-
pyrano[3,4-c]chromen-2-ylidene) acetate (2k). White solid, yield
Preparation of 3a-benzoyl-8-bromo-1-(ethoxycarbonyl)-3a,9b-
1
86%, m. p. 197.0–198.4 °C; H NMR (400 MHz, CDCl3), δ
dihydro-3H-cyclopenta[c]chromen-4-one (3b). Light yellow
1
7.40 (d, J = 7.6 Hz, 3H), 7.32 (t, J = 7.6 Hz, 1H), 7.21 (d, J =
8.0 Hz, 3H), 7.08 (d, J = 8.0 Hz, 1H), 5.83 (s, 1H), 4.85 (dd, J =
5.2 Hz, J = 11.4 Hz, 1H), 4.23 (q, J = 7.6 Hz, 2H), 3.98 (dd, J =
5.2 Hz, J = 12.0 Hz, 1H), 2.49 (t, J = 14.0 Hz, 1H), 2.41 (s,
3H), 1.32 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
166.6, 163.6, 162.3, 161.7, 150.7, 141.1, 129.9, 128.9, 125.6,
124.7, 122.8, 117.0, 102.1, 100.6, 60.3, 30.2, 25.7, 21.5, 14.3;
EI-MS (70 eV): m/z = 376 (M+, 9.5), 307 (41.0), 279 (13.3),
265 (11.5), 239 (21.8), 237 (9.0), 220 (6.9), 191 (15.8), 162
(16.6), 129 (15.5), 106 (7.4), 105 (100), 77 (64.7), 44 (46.5).
Anal. calcd for C23H20O5: C, 73.39; H, 5.36. Found: C, 73.17;
H, 5.44.
solid, yield 91%, m. p. 130.1–132.0 °C; H NMR (400 MHz,
CDCl3), δ 7.82 (d, J = 6.8 Hz, 3H), 7.56 (t, J = 7.6 Hz, 1H),
7.44 (t, J = 7.6 Hz, 3H), 7.02 (d, J = 8.4 Hz, 1H), 6.97 (s, 1H),
4.88 (s, 1H), 4.24 (q, J = 7.2 Hz, 2H), 3.73 (dd, J = 2.0 Hz, J =
18.4 Hz, 1H), 3.20 (d, J = 18.4 Hz, 1H), 1.32 (t, J = 6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 191.7, 166.5, 163.8,
148.4, 143.1, 136.2, 133.7, 132.7, 132.3, 129.2, 128.9, 127.7,
121.2, 119.0, 118.0, 61.2, 61.1, 48.5, 41.1, 14.1; EI-MS (70 eV):
m/z = 441 (M + 1, 7.8), 422 (6.8), 337 (10.4), 335 (11.9), 270
(10.1), 213 (14.4), 211 (8.4), 126 (6.9), 106 (15.2), 105 (100),
77 (43.5), 65 (7.2), 44 (17.3). Anal. calcd for C22H17BrO5: C,
59.88; H, 3.88. Found: C, 59.97; H, 3.70.
Preparation of (E) ethyl (4-(4-chlorophenyl)-5-oxo-1,10b-
dihydro-5H-pyrano[3,4-c]chromen-2-ylidene) acetate (2l). White
solid, yield 89%, m. p. 139.0–140.2 °C;1H NMR (400 MHz,
CDCl3), δ 7.31–7.46 (m, 6H), 7.21 (t, J = 7.6 Hz, 1H), 7.08 (d,
J = 8.0 Hz, 1H), 5.83 (s, 1H), 4.86 (dd, J = 5.6 Hz, J = 14. 4
Hz, 1H), 4.24 (q, J = 6.8 Hz, 2H), 3.99 (dd, J = 5.6 Hz, J = 12.0
Preparation of 3a-benzoyl-8-chloro-1-(ethoxycarbonyl)-3a,9b-
dihydro-3H-cyclopenta[c]chromen-4-one (3c). Light yellow
1
solid, yield 94%, m. p. 127.0–128.5 °C; H NMR (400 MHz,
CDCl3), δ 7.82 (d, J = 8.0 Hz, 2H), 7.67 (s, 1H), 7.56 (t, J = 7.2
Hz, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.29 (t, J = 8.0 Hz, 1H), 7.08
(d, J = 8.8 Hz, 1H), 6.96 (s, 1H), 4.88 (s, 1H), 4.23 (q, J =
7.2 Hz, 2H), 3.73 (dd, J = 2.8 Hz, J = 17.6 Hz, 1H), 3.20 (d, J =
18.4 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 191.7, 166.6, 163.8, 147.9, 143.1, 136.2, 133.7,
Hz, 1H), 2.51 (t, J = 14.4 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H); 13
C
NMR (100 MHz, CDCl3): δ 166.5, 163.2, 161.3, 160.9, 150.5,
136.8, 131.3, 130.3, 129.0, 128.4, 125.6, 124.8, 122.4, 117.1,
7744 | Org. Biomol. Chem., 2012, 10, 7739–7746
This journal is © The Royal Society of Chemistry 2012

View Article Online
132.7, 130.5, 129.7, 129.3, 129.2, 128.9, 120.8, 118.6, 61.2,
61.0, 48.5, 41.1, 14.1; EI-MS (70 eV): m/z = 397 (M + 1, 10.5),
378 (9.0), 305 (8.7), 293 (11.6), 291 (23.7), 245 (12.1),
203 (9.5), 202 (72.2), 171 (16.0), 170 (13.8), 155 (9.8), 121
(9.9), 115 (28.8), 114 (98.1), 105 (100), 91 (14.2), 77 (57.8).
Anal. calcd for C22H17ClO5: C, 66.59; H, 4.32. Found: C,
66.43; H, 4.25.
1H), 4.86 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 3.77 (dd, J = 2.8 Hz,
J = 18.0 Hz, 1H), 3.11 (d, J = 18.4 Hz, 1H), 2.32 (s, 3H), 1.26
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 192.1,
167.4, 164.2, 142.6, 139.6, 136.9, 133.5, 132.7, 129.1, 128.8,
127.9, 127.5, 126.5, 117.6, 116.0, 61.0, 60.8, 48.4, 41.0, 21.0,
14.1; EI-MS (70 eV): m/z = 376 (M+, 2.3), 257 (65.4), 243
(12.3), 211 (20.7), 184 (14.3), 128 (7.5), 105 (100), 77 (53.2),
44 (9.0). Anal. calcd for C23H20O5: C, 73.39; H, 5.36. Found: C,
73.27; H, 5.50.
Preparation of 3a-benzoyl-8-fluoro-1-(ethoxycarbonyl)-3a,9b-
dihydro-3H-cyclopenta[c]chromen-4-one (3d). Light yellow
1
Preparation of 3a-benzoyl-8-methoxy-1-(ethoxycarbonyl)-
solid, yield 72%, m. p. 102.2–104.0 °C; H NMR (400 MHz,
3a,9b-dihydro-3H-cyclopenta[c]chromen-4-one
(3h). Light
CDCl3), δ 7.82 (d, J = 8.0 Hz, 2H), 7.54 (t, J = 7.2 Hz, 1H),
7.40–7.45 (m, 3H), 7.12 (dd, J = 4.8 Hz, J = 9.2 Hz, 1H), 7.04
(t, J = 8.0 Hz, 1H), 6.97 (s, 1H), 4.87 (s, 1H), 4.22 (q, J =
7.2 Hz, 2H), 3.77 (dd, J = 2.0 Hz, J = 18.4 Hz, 1H), 3.16 (d, J =
18.0 Hz, 1H), 1.30 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 191.7, 166.8, 164.0, 160.7, 158.3, 145.3, 143.1,
136.3, 133.7, 132.7, 129.1 (d, J = 24 Hz), 127.7 (d, J = 37 Hz),
120.8 (d, J = 8 Hz), 118.7 (d, J = 8 Hz), 116.2 (q, J = 16 Hz),
61.2, 60.5, 48.7, 41.1, 14.1; EI-MS (70 eV): m/z = 380 (M+,
4.3), 362 (10.6), 317 (10.9), 289 (13.1), 275 (46.9), 229 (20.9),
202 (9.3), 173 (5.7), 146 (5.6), 105 (100), 91 (8.5), 77 (47.1), 44
(36.8). Anal. calcd for C22H17FO5: C, 69.47; H, 4.50. Found: C,
69.28; H, 4.41.
yellow solid, yield 86%, m. p. 118.0–119.5 °C; 1H NMR
(400 MHz, CDCl3), δ 7.82 (d, J = 7.6 Hz, 2H), 7.54 (t, J =
7.2 Hz, 1H), 7.42 (t, J = 8.0 Hz, 2H), 7.20 (s, 1H), 7.09 (d, J =
8.8 Hz, 1H), 6.96 (s, 1H), 6.88 (dd, J = 3.2 Hz, J = 9.2 Hz, 1H),
4.86 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 3.81 (dd, J = 3.2 Hz, J =
18.4 Hz, 1H), 3.76 (s, 3H), 3.07 (d, J = 18.4 Hz, 1H), 1.29 (t,
J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 192.0, 167.3,
164.3, 156.9, 143.0, 136.7, 133.5, 132.6, 129.2, 128.9, 119.8,
118.3, 115.4, 113.3, 61.1, 60.3, 55.6, 48.8, 41.0, 14.2; EI-MS
(70 eV): m/z = 392 (M+, 2.0), 287 (47.4), 241 (30.4), 213 (11.0),
186 (3.6), 115 (6.6), 105 (100), 77 (50.6), 43 (7.8). Anal. calcd
for C23H20O6: C, 70.40; H, 5.14. Found: C, 70.55; H, 5.23.
Preparation of 3a-(4-methylbenzoyl)-1-(ethoxycarbonyl)-
Preparation of 3a-benzoyl-6,8-dichloro-1-(ethoxycarbonyl)-
3a,9b-dihydro-3H-cyclopenta[c]chromen-4-one (3i). White solid,
3a,9b-dihydro-3H-cyclopenta[c]chromen-4-one
(3e). White
1
1
yield 86%, m. p. 106.0–107.5 °C; H NMR (400 MHz, CDCl3),
solid, yield 75%, m. p. 128.0–129.8 °C; H NMR (400 MHz,
CDCl3), δ 7.84 (d, J = 7.6 Hz, 2H), 7.60 (s, 1H), 7.57 (t, J = 7.2
Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.40 (d, J = 4.0 Hz, 1H), 6.95
(s, 1H), 4.90 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 3.65 (dd, J =
2.8 Hz, J = 17.2 Hz, 1H), 3.36 (d, J = 18.4 Hz, 1H), 1.30 (t, J =
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 191.6, 165.6,
163.7, 144.3, 143.1, 135.9, 133.9, 132.9, 130.1, 129.8, 129.3,
129.0, 128.5, 122.8, 122.3, 61.8, 61.3, 49.0, 41.2, 14.1; EI-MS
(70 eV): m/z = 430 (M+, 1.0), 327 (11.2), 325 (17.9), 281 (4.2),
279 (4.3), 106 (7.8), 105 (100), 77 (35.2), 44 (5.1). Anal. calcd
for C22H16Cl2O5: C, 61.27; H, 3.74. Found: C, 61.39; H, 3.87.
δ 7.73 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.0 Hz, 1H), 7.33 (t, J =
7.6 Hz, 1H), 7.13–7.23 (m, 4H), 6.94 (s, 1H), 4.90 (s, 1H), 4.21
(q, J = 6.8 Hz, 2H), 3.77 (dd, J = 2.0 Hz, J = 18.0 Hz, 1H), 3.12
(d, J = 18.4 Hz, 1H), 2.37 (s, 3H), 1.29 (t, J = 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 191.6, 167.2, 164.2, 149.3, 144.6,
142.8, 136.8, 130.2, 129.6, 129.3, 129.2, 125.5, 119.3, 117.3,
61.0, 60.8, 48.7, 41.0, 21.6, 14.1; EI-MS (70 eV): m/z = 377
(M + 1, 1.8), 257 (67.0), 243 (12.1), 211 (17.3), 184 (12.8), 127
(5.6), 119 (100), 91 (48.5), 77 (12.5), 44 (19.8). Anal. calcd for
C23H20O5: C, 73.39; H, 5.36. Found: C, 73.51; H, 5.20.
Preparation
3a,9b-dihydro-3H-cyclopenta[c]chromen-4-one
of
3a-(4-chlorobenzoyl)-1-(ethoxycarbonyl)-
(3j). White
Preparation of 3a-benzoyl-8-methyl-1-(ethoxycarbonyl)-3a,9b-
dihydro-3H-cyclopenta[c]chromen-4-one (3f). Light yellow
1
solid, yield 89%, m. p. 110.4–111.3 °C; H NMR (400 MHz,
CDCl3), δ 7.70 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 7.6 Hz, 1H),
7.32 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.19 (t, J =
8.0 Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 6.93 (s, 1H), 4.78 (s, 1H),
4.14 (q, J = 7.2 Hz, 2H), 3.65 (dd, J = 2.4 Hz, J = 18.0 Hz, 1H),
3.08 (d, J = 18.4 Hz, 1H), 1.21 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 191.0, 167.0, 164.1, 149.2, 142.6, 140.1,
136.8, 131.2, 130.6, 129.6, 129.3, 129.2, 125.6, 119.0, 117.4,
61.2, 61.1, 48.5, 41.0, 14.1; EI-MS (70 eV): m/z = 396
(M+, 1.2), 257 (79.0), 211 (23.3), 184 (16.8), 155 (7.4), 141
(32.0), 139 (100), 111 (43.6), 77 (4.8), 75 (8.6), 44 (7.5).
Anal. calcd for C22H17ClO5: C, 66.59; H, 4.32. Found: C,
66.48; H, 4.17.
1
solid, yield 85%, m. p. 103.0–104.2 °C; H NMR (400 MHz,
CDCl3), δ 7.83 (d, J = 7.6 Hz, 2H), 7.54 (t, J = 7.6 Hz, 1H),
7.41 (t, J = 8.4 Hz, 3H), 7.13 (d, J = 8.4 Hz, 1H), 7.04 (d, J =
8.4 Hz, 1H), 6.94 (s, 1H), 4.86 (s, 1H), 4.23 (q, J = 6.0 Hz, 2H),
3.77 (dd, J = 2.8 Hz, J = 18.4 Hz, 1H), 3.11 (d, J = 18.0 Hz,
1H), 2.32 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 192.1, 167.3, 164.2, 147.2, 142.8, 136.9,
135.2, 133.5, 132.7, 129.8, 129.6, 129.2, 128.8, 118.7, 117.1,
61.0, 60.8, 48.5, 40.9, 20.9, 14.1; EI-MS (70 eV): m/z = 376
(M+, 4.2), 358 (4.4), 271 (42.0), 257 (15.3), 225 (19.8), 197
(3.8), 141 (5.3), 115 (9.2), 105 (100), 77 (39.8), 44 (9.6). Anal.
calcd for C23H20O5: C, 73.39; H, 5.36. Found: C, 73.53; H,
5.49.
Preparation of 3a-benzoyl-7-methyl-1-(ethoxycarbonyl)-3a,9b-
Acknowledgements
dihydro-3H-cyclopenta[c]chromen-4-one (3g). Light yellow
1
solid, yield 92%, m. p. 164.6–166.0 °C; H NMR (400 MHz,
We thank the Natural Science Foundation of China (20872046)
and the Fundamental Research Funds for the Central Universities
(no. CCNU09A02013) for financial support.
CDCl3), δ 7.82 (d, J = 7.2 Hz, 2H), 7.49–7.56 (m, 2H), 7.42 (t,
J = 7.6 Hz, 2H), 6.99 (d, J = 8.0 Hz, 1H), 6.96 (s, 1H), 6.92 (s,
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 7739–7746 | 7745

View Article Online
and Z. He, Chem.–Eur. J., 2009, 15, 8698; (o) X.-Y. Guan, Y. Wei and
M. Shi, Org. Lett., 2010, 12, 5024; (p) N. Pinto, P. Retailleau,
A. Voituriez and A. Marinetti, Chem. Commun., 2011, 47, 1015;
(q) H. Xiao, Z. Chai, C. W. Zheng, Y. Q. Yang, W. Liu, J. K. Zhang and
G. Zhao, Angew. Chem., Int. Ed., 2010, 49, 4467.
4 (a) X. F. Zhu, J. Lan and O. Kwon, J. Am. Chem. Soc., 2003, 125, 4716;
(b) R. P. Wurz and G. C. Fu, J. Am. Chem. Soc., 2005, 127, 12234;
(c) X. Meng, Y. Huang, H. Zhao, P. Xie, J. Ma and R. Chen, Org. Lett.,
2009, 11, 991; (d) Y. S. Tran and O. Kwon, Org. Lett., 2005, 7, 4289;
(e) Y.-W. Sun, X.-Y. Guan and M. Shi, Org. Lett., 2010, 12, 5664;
(f) Y.-L. Shi and M. Shi, Org. Lett., 2005, 7, 3057.
5 (a) Y. S. Tran and O. Kwon, J. Am. Chem. Soc., 2007, 129, 12632;
(b) S. Castellano, H. D. G. Fiji, S. S. Kinderman, M. Watanabe, P. de
Leon, F. Tamanoi and O. Kwon, J. Am. Chem. Soc., 2007, 129, 5843;
(c) R. P. Wurz and G. C. Fu, J. Am. Chem. Soc., 2005, 127, 12234;
(d) X.-F. Zhu, J. Lan and O. Kwon, J. Am. Chem. Soc., 2003, 125, 4716;
(e) X.-F. Zh, A.-P. Schaffner, R. C. Li and O. Kwon, Org. Lett., 2005, 7,
2977.
Notes and references
1 (a) Z.-Y. Cai, Y. Yang, X.-H. Liu and X.-B. Qi, Lett. Drug Des. Discov-
ery, 2010, 7, 640; (b) Y. Dong, K. Nakagawa-Goto, C.-Y. Lai,
S. L. Morris-Natschke, K. F. Bastow and K.-H. Lee, Bioorg. Med. Chem.
Lett., 2010, 20, 4085; (c) A. M. Vijesh, M. Arun, A. M. Isloor,
V. Prabhu, S. Ahmad and S. Malladi, Eur. J. Med. Chem., 2010, 45,
5460; (d) M. Mladenović, N. Vuković, N. Nićiforović, S. Sukdolak and
S. Slavica Solujić, Molecules, 2009, 14, 1495; (e) C. A. Kontogiorgis
and D. J. Hadjipavlou-Litina, J. Med. Chem., 2005, 48, 6400;
(f) S. R. Kesten, T. G. Heffner, S. J. Johnson, T. A. Pugsley, J. L. Wright
and L. D. Wise, J. Med. Chem., 1999, 42, 3718; (g) T. Symeonidis,
M. Chamilos, D. J. Hadjipavlou-Litina, M. Kallitsakis and K. E. Litinas,
Bioorg. Med. Chem. Lett., 2009, 19, 1139; (h) I. R. Hardcastle,
X. Cockcroft, N. J. Curtin, M. D. El-Murr, J. J. J. Leahy, M. Stockley,
B. T. Golding, L. Rigoreau, C. Richardson, G. C. M. Smith and
R. J. Griffin, J. Med. Chem., 2005, 48, 7829; (i) F. Leonetti, A. Favia,
A. Rao, R. Aliano, A. Paluszcak, R. W. Hartmann and A. Carotti, J. Med.
Chem., 2004, 47, 6792; ( j) C. Gnerre, M. Catto, F. Leonetti, P. Weber,
P.-A. Carrupt, C. Altomare, A. Carotti and B. Testa, J. Med. Chem., 2000,
43, 4747; (k) Q. Shen, Q. Peng, J. Shao, X. Liu, Z. Huang, X. Pu, L. Ma,
Y.-M. Li, A. S. C. Chan and L. Gu, Eur. J. Med. Chem., 2005, 40, 1307;
(l) C. Brühlmann, F. Ooms, P.-A. Carrupt, B. Testa, M. Catto, F. Leonetti,
C. Altomare and A. Carotti, J. Med. Chem., 2001, 44, 3195.
6 T. Wang and S. Ye, Org. Lett., 2010, 12, 4168.
7 C. A. Evans and S. J. Miller, J. Am. Chem. Soc., 2003, 125, 12394.
8 (a) X.-C. Zhang, S.-H. Cao, Y. Wei and M. Shi, Org. Lett., 2011, 13,
1142; (b) X.-Y. Chen, M.-W. Wen, S. Ye and Z.-X. Wang, Org. Lett.,
2011, 13, 1138; (c) X. Wang, T. Fang and X. Tong, Angew. Chem., Int.
Ed., 2011, 50, 5361; (d) K. D. Ashtekar, R. J. Staples and B. Borhan,
Org. Lett., 2011, 13, 5732.
2 For reviews, see: (a) X. Lu, C. Zhang and Z. Xu, Acc. Chem. Res., 2001,
34, 535; (b) B. J. Cowen and J. S. Miller, Chem. Soc. Rev., 2009, 38,
3102; (c) S. Ma, Acc. Chem. Res., 2009, 42, 1679.
9 For synthetic routes to substituted salicylaldehyde, see: S. Bhatt and
S. K. Nayak, Tetrahedron Lett., 2009, 50, 5823.
10 Y. Zhu, X. Zou, F. Hu, C. Yao, B. Liu and H. Yang, J. Agric. Food
Chem., 2005, 53, 9566.
11 X. Meng, Y. Huang and Y. Chen, Org. Lett., 2009, 11, 137.
12 (a) J. C. Anderson, R. j. Cubbon and J. D. Harling, Tetrahedron: Asym-
metry, 2001, 12, 923; (b) H. Jansch, S. Kannenberg and G. Boche,
Eur. J. Org. Chem., 2001, 2923.
13 For the synthesis of 3-acyl-2H-chromen-ones, see: (a) D. Secci,
S. Carradori, A. Bolasco, P. Chimenti, M. Yáñez, F. Ortuso and
S. Alcaro, Eur. J. Med. Chem., 2011, 46, 4846; (b) Y.-J. Jang, S. Syu,
Y.-J. Chen, M.-C. Yang and W. Lin, Org. Biomol. Chem., 2012, 10, 843;
(c) L. V. Frolova, I. Malik, P. Y. Uglinskii, S. Rogelj, A. Kornienko and I.
V. Magedov, Tetrahedron Lett., 2011, 52, 6643; (d) S.-J. Wang,
H.-W. Zheng, M. Zhang and Y.-K. Jing, Chin. J. Med. Chem., 2009, 19,
321.
3 For selected phosphine catalyzed [3 + 2] cycloadditions of allenoates,
see: (a) C. Zhang and X. Lu, J. Org. Chem., 1995, 60, 2906;
(b) Y. S. Du, X. Y. Lu and Y. H. Yu, J. Org. Chem., 2002, 67, 8901;
(c) Y. Du, X. Lu and C. Zhang, Angew. Chem., Int. Ed., 2003, 42, 1035;
(d) Y. Du, J. Feng and X. Lu, Org. Lett., 2005, 7, 1987; (e) M. Yang,
X. Zhang and X. Lu, Org. Lett., 2007, 9, 5131; (f) S. Zheng and X. Lu,
Org. Lett., 2008, 10, 4481; (g) Z. Lu, S. Zheng, X. Zhang and X. Lu,
Org. Lett., 2008, 10, 3267; (h) X. Yu and X. Lu, Org. Lett., 2009, 11,
4366; (i) S. Zheng and X. Lu, Org. Lett., 2009, 11, 3978; ( j) T. Dudding,
O. Kwon and E. Mercier, Org. Lett., 2006, 8, 3643; (k) B. J. Cowen and
S. J. Miller, J. Am. Chem. Soc., 2007, 129, 10988; (l) Y. Z. Xia, Y. Liang,
Y. Y. Chen, M. Wang, L. Jiao, F. Huang, S. Liu, Y. H. Li and Z. X. Yu,
J. Am. Chem. Soc., 2007, 129, 3470; (m) Y. Q. Fang and E. N. Jacobsen,
J. Am. Chem. Soc., 2008, 130, 5660; (n) S. Xu, L. Zhou, R. Ma, H. Song
7746 | Org. Biomol. Chem., 2012, 10, 7739–7746
This journal is © The Royal Society of Chemistry 2012