One-pot synthesis of 2-aryl-3-alkoxycarbonyl chromones through a cascade Lewis acid-catalyzed aldehyde olefination/oxa-Michael addition/oxidation

Article abstract of DOI:10.1016/j.tet.2012.11.008

2-Aryl-3-alkoxycarbonyl chromones were effectively constructed from aryl aldehydes and 3-(2-(methoxymethoxy) phenyl)propiolates via a cascade Lewis acid catalyzed phenol ether deprotection/aldehyde olefination/intramolecular oxa-Michael addition reaction, and a sequential oxidation. This four-step reaction could be conducted in one-pot with high atom efficiency.

Full text of DOI:10.1016/j.tet.2012.11.008

Tetrahedron 69 (2013) 647e652
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot synthesis of 2-aryl-3-alkoxycarbonyl chromones through
a cascade Lewis acid-catalyzed aldehyde olefination/oxa-Michael
addition/oxidation
*
*
Ningning Wang, Shuying Cai, Chao Zhou, Ping Lu , Yanguang Wang
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
2-Aryl-3-alkoxycarbonyl chromones were effectively constructed from aryl aldehydes and 3-(2-(me-
thoxymethoxy)phenyl)propiolates via a cascade Lewis acid catalyzed phenol ether deprotection/alde-
hyde olefination/intramolecular oxa-Michael addition reaction, and a sequential oxidation. This four-step
reaction could be conducted in one-pot with high atom efficiency.
Received 12 September 2012
Received in revised form 18 October 2012
Accepted 2 November 2012
Available online 8 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Chromones
Heterocycles
Cycloadditions
Lewis acid catalysis
Cascade reactions
1. Introduction
of 4H-chromen-4-ones, lots of works had been focused on their
preparations. By disconnecting the pyran ring, severaldisconnections
The olefination of aldehydes with alkynes was initiallyapproached
by photo irradiation.1 Later on, this reactionwas successfullycatalyzed
by various Lewis acid, such as TiCl4,2 BF3$Et2O,3,4 SbF5,5 MgBr2$Et2O,6
In(OTf)3,7 Yb(OTf)3,8 AgSbF6,9 and AuCl3/AgSbF6.10 The reaction un-
dergoes a [2þ2] cycloaddition to form oxetene intermediates, fol-
lowed by a ring-opening. Some stable oxetenes have been indicated by
isolation.11 The reaction stereoselectivity depends upon the ring-
opening, which could be regulated by torquoselectivity.12e14 In some
cases, stereoselectivity was effectively controlled by existing hetero-
atoms.15,16 Alkynes used in aldehyde olefination possessed electron-
rich triple bonds, such as alkyl aryl alkyne, ynol ethers,
ynamines,17e19 siloxyalkynes,20 and lithium ynolate.13,21,22 To the best
of our knowledge, the electron-withdrawing group substituted al-
kynes were seldom reported for aldehyde olefinations.
4H-Chromen-4-one and its derivatives exist in nature and exhibit
various bioactivities, such as inhibitory effect on hepatitis B virus
(HBV) in vitro without apparent cytotoxicity,23 radical-scavenging
activity,24 and strong affinity to heavy metal ions.25 Chromones
were also designed and synthesized as selective adenosine receptor
ligands (AR ligands) for cancer therapy,26 as potent cathepsin V in-
hibitor for the treatment of atherosclerosis.27 Due to the importance
were possible (Scheme 1). Synthesis of 4H-chromen-4-ones based on
these disconnections had been approached. For instance, Lewis acid
induced oxa-Michael addition on alkynones/alkenones provided
chromone skeleton with high efficiency and broad diversity (Scheme
1, route a).27e30 An alternative method to make CeO bond would be
transition-metal-catalyzed O-olefination, which was demonstrated
by the Ni-catalyzed cycloaddition of salicylic acid ketals to alkynes
(Scheme 1, route aþd).31 Cu-catalyzed Ullmann-type intermolecular
O-arylations could also effectively construct chromone skeleton
(Scheme 1, route b).32 As a significant improvement, this strategy was
approached in absence of transition-metal.33 Although Wittig re-
action made the route c in Scheme 1 possible, it was seldom used.34
Finally, a three-component Pd-catalyzed carbonylative annulation
afforded chromones with a rapid increment in molecular complexity
(Scheme 1, route dþe).35e37 Besides of these novel approaches, re-
action between 2,3-allenoic acids and benzynes also produced
chromone derivatives with a broad substrate diversity due to the
substituent-loading in 2,3-allenoic acids (Scheme 1, route bþe).38
Recently, we discovered an iodine mediated reaction between 3-
(2-hydroxy-phenyl)propiolates
and
N,N-dimethylformamide
(DMF), which furnished chromone skeleton with an elimination of
dimethylamine.39 Encouraged by these results, we were interested
in the reaction between 3-(2-hydroxy-phenyl)propiolates with al-
dehydes, leading to the formation of 2-aryl-3-alkoxycarbonyl
chromones. Herein, we would like to report the results of this effort.
* Corresponding authors. Tel./fax: þ86 571 87951512; e-mail addresses: pinglu@
zju.edu.cn (P. Lu), orgwyg@zju.edu.cn (Y. Wang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.008

648
N. Wang et al. / Tetrahedron 69 (2013) 647e652
Fig. 1. Single crystal structure of 3a.
temperature (Table 1, entry 9) and 80 ꢀC (Table 1, entry 10) and
obtained lower yields. Extending reaction time to 15 h or short-
ening to 9 h also led to a decreased yield. Thus, we determined the
optimized reaction conditions to be utilizing BF3$OEt2 as catalyst, in
solvent of DCE and at 50 ꢀC for 12 h (Table 1, entry 1).
Scheme 1. Synthetic strategies leading to 4H-chromen-4-ones.
With the optimal reaction conditions in hand, we examined the
substrate diversity for this transformation. The results are sum-
marized in Table 2. Electronic effect of substituents on the phenyl
ring of aryl aldehyde was observed. The strong electron-donating
group (Table 2, entries 3 and 4) or strong electron-withdrawing
group substituted substrates (Table 2, entry 8) gave relatively
lower yields of the corresponding products than those with mod-
erate electron-donating (Table 2, entry 1) and moderate electron-
withdrawing groups (Table 2, entries 5e7). Compounds 1b (Table
2, entry 9) and 1c (Table 2, entry 10), modified with methyl or
chloro group on the aromatic ring of 3-(2-hydroxyphenyl)propio-
lates, afforded the corresponding 3i and 3j in 58% and 52% yields,
respectively. It should be indicated that the products were isolated
as a mixture of enols 3 and its tautomers 30 in most cases. The
tautomerism made the NMR spectra of 3 more complicated.
2. Results and discussion
We firstly tested the reaction between methyl 3-(2-
hydroxyphenyl)propiolate (1a) and 4-methylbenzaldehyde (2a) in
the presence of BF3$OEt2 (Table 1). Fortunately, methyl 4-hydroxy-
2-p-tolyl-2H-chromene-3-carboxylate (3a) was obtained and its
structure was established by the single crystal analysis (Fig. 1).40
Table 1
Screening the reaction conditions for the formation of 3aa
Table 2
Preparation of 3 from 3-(2-hydroxyphenyl)propiolates 1a
Entry
Catalyst
Solvent
Temp (ꢀC)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
BF3$Et2O
I2
AgOTf
In(OTf)3
BF3$Et2O
BF3$Et2O
BF3$Et2O
BF3$Et2O
BF3$Et2O
BF3$Et2O
DCE
DCE
DCE
DCE
DCM
MeCN
THF
Toluene
DCE
50
50
50
50
50
50
50
50
rt
74
N.R.
N.D.
17
53
Entry
1 (R1)
2 (R2)
3/Yield (%)b
Trace
N.R.
N.D.
64
1
2
3
4
5
6
7
8
9
1a (H)
1a
1a
1a
1a
1a
1a
1a
1b (Me)
1c (Cl)
2a (4-MeC6H4)
2b (C6H5)
3a/74
3b/56
3c/50
3d/46
3e/61
3f/73
3g71
3h/46
3i/58
3j/52
2c (4-MeOC6H4)
2d (4-Me2NC6H4)
2e (4-FC6H4)
2f (4-ClC6H4)
2g (4-BrC6H4)
2h (4-NO2C6H4)
2a
DCE
80
55
a
The reaction was conducted with 1a (1 mmol), 2a (1 mmol), and Lewis acid
(1 mmol) in 10 mL of solvent for 12 h.
b
Isolated yield.
Delighted by this result, we optimized reaction conditions for
this transformation. The results are listed in Table 1. Among all the
catalysts tested in the solvent of DCE at 50 ꢀC for 12 h (Table 1,
entries 1e4), BF3$OEt2 performed the best, with a respective yield
of 3a in 74%. When I2 was utilized as catalyst, there was no signif-
icant change in the amount of starting materials, 1a and 2a. In the
case of AgOTf, we observed a decreased amount of 1a and 2a, while
3a was not detected. When using BF3$OEt2 as the catalyst at 50 ꢀC,
DCE turned out to be the most suitable solvent as compared to
DCM, MeCN, THF, and toluene (Table 1, entries 5e8). In THF envi-
ronment, no reaction was detected between 1a and 2a. When tol-
uene was adapted, the amount of 1a and 2a decreased with un-
traceable 3a present. We also carried out the reaction at room
10
2a
a
The reaction was conducted with 1 (1 mmol), 2 (1 mmol), and BF3$Et2O
(1 mmol) in 10 mL of DCE at 50 ꢀC for 12 h.
b
Isolated yield.
Methyl 3-(2-hydroxyphenyl)propiolates 1 were prepared from
methyl 3-(2-(methoxymethoxy)phenyl)propiolates 4 in the pres-
ence of acid as we previously reported.39 We, therefore, integrated
the Lewis acid-catalyzed conversion from 4 into 1, the Lewis acid-
catalyzed aldehyde olefination, the intramolecular oxa-Michael
addition, and the DDQ oxidation into one-pot to get chromones 5
(Scheme 2). Under the optimized reaction conditions, 4a, 2a, and

N. Wang et al. / Tetrahedron 69 (2013) 647e652
649
Scheme 3. Formation of 5n from 2d or 2n.
Scheme 2. One-pot synthesis of 5 from 4.
BF3$Et2O were mixed in DCE and reacted at 50 ꢀC for 16 h to afford
3a in 70% isolated yield. Without purification, the resulting 3a could
be converted into 5a via a one-pot oxidation with DDQ in 1,4-
dioxane (Table 3, entry 1). In this way, chromones 5aem were
synthesized in 25e52% yields. In some cases, although the oxida-
tions from 3 to 5 were carried out for 48 h, we still observed
unreacted 3 by TLC tracking. The unsubstituted benzaldehyde 2b
furnished 5b in 52% yield (Table 3, entry 2). With electron
withdrawing-group on the phenyl ring of aldehyde, compounds
2eeh afforded the corresponding products 5cef in yields ranging
from 31 to 38% (Table 3, entries 3e6). However, the strong electron-
donating group substituted 2c just afforded 3c in 48% yield al-
though the oxidation step had been applied in refluxing 1,4-
dioxane for 48 h. For the cases of 2d and 2n, both of them pos-
sessing electron-rich aromatic system, the dearomatized product
5n was isolated in 22% and 20%, respectively (Scheme 3). A retro
FriedeleCrafts alkylation might occur during the oxidation process
because the electron-rich aromatic ring was able to be protonated.
Furthermore, when picolinaldehyde (2o) was used, methyl ben-
zofuran-2-carboxylate (6) was obtained in 30% yield (Scheme 4).
Picolinaldehyde did not participate in the reaction and methyl
benzofuran-2-carboxylate came from the Lewis acid catalyzed self-
cyclization of 4a.
Scheme 4. Formation of benzofuran 6.
Table 3
One-pot synthesis of 5 from methyl 3-(2-(methoxymethoxy) phenyl)-propiolates 4a
Entry
4 (R1)
2 (R2)
Yield of 5 (%)b
1c
2c
3
4
5
6
7
8
9
10
11c
12c
13c
4a (H)
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b (Me)
4c (Cl)
2a (4-MeC6H4)
2b (C6H5)
5a/32
5b/52
5c/38
5d/35
5e/31
5f/33
5g/32
5h/30
5i/25
5j/31
5k/30
5l/37
5m/41
2e (4-FC6H4)
2f (4-ClC6H4)
2g (4-ClC6H4)
2h (4-NO2C6H4)
2i (2-ClC6H4)
2j (3-ClC6H4)
2k (4-IC6H4)
2l (2-CF3C6H4)
2m (2-naphthlenyl)
2b
2b
a
Reactions were conducted with 4 (1 mmol), 2 (1 mmol), and BF3$Et2O (1 mmol)
in 10 mL of DCE at 50 ꢀC for 16 h. After removal of DCE, DDQ (1.3 mmol) in 1,4-
dioxane (10 mL) was added and refluxed for 48 h.
b
Isolated yield based on 4.
4 and 2 reacted for 12 h, oxidation of 3 lasted for 36 h.
c
Scheme 5. Possible mechanism for the cascade formation of 5.
Based on above observations, weproposed a possible mechanism
for this cascade process as indicated in Scheme 5. Firstly, phenol
ether 4a undergoes the Lewis acid catalyzed deprotection to yield
phenol 1a. Secondly, the Lewis acid catalyzed formal [2þ2] cyclo-
addition of2 with either 4a or 1agenerates theoxeteneintermediate
DDQ into 5. When the aryl group in 3 is electron-rich, a retro Frie-
deleCrafts alkylation occurs to give 5n as the final product.
3. Conclusions
A or B, which undergoes a ring-opening to form a,b-unsaturated
ketone C or D, respectively. Subsequent intramolecular oxa-Michael
addition of C or D leads to the formation of 3. Finally, 3 is oxidized by
In conclusion, we developed a one-pot cascade method for the
construction of 2-aryl-3-alkoxycarbonyl chromones. The process

650
N. Wang et al. / Tetrahedron 69 (2013) 647e652
involves a Lewis acid catalyzed deprotection of phenol ether,
a Lewis acid catalyzed olefination of aldehyde with alkyne, an
intramolecular oxa-Michael addition, and a DDQ oxidation. The
present four-step reaction could be conducted in one-pot with high
atom efficiency.
nmax 2954, 1745, 1691, 1609, 1465, 1255, 1031, 830; 1H NMR
(500 MHz, CDCl3)
d
12.27 (s, 0.5H), 7.95 (dd, J¼7.9, 1.7 Hz, 1H), 7.68
(dd, J¼7.7, 1.7 Hz, 0.5H), 7.53 (ddd, J¼8.8, 7.2, 1.7 Hz, 1H), 7.44e7.40
(m, 2H), 7.30e7.23 (m, 1.5H), 7.11e7.05 (m, 1H), 7.02 (dd, J¼8.4,
1.0 Hz, 1H), 6.94 (m, 2.5H), 6.81e6.75 (m, 1.5H), 6.20 (s, 0.5H), 5.64
(d, J¼12.4 Hz, 1H), 4.10 (d, J¼12.4 Hz, 1H), 3.83 (s, 3H), 3.75 (s, 3H),
4. Experimental section
3.65 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 188.0, 167.7, 161.3, 160.5,
159.8, 155.8, 136.8, 133.5, 132.3, 128.8, 128.8, 128.7, 127.6, 127.1,
124.5, 122.1, 121.3, 120.0, 118.3, 117.9, 117.4, 114.3, 113.8, 94.5, 81.0,
74.5, 59.8, 55.5, 55.3, 52.6, 52.0; HRMS (EI): calcd for C18H16O5
(Mþ): 312.0998, found 312.0999.
4.1. General
Infrared spectra were obtained on a FTIR spectrometer. Flash
column
chromatography
was
performed
employing
200e300 mesh silica gel. NMR spectra were recorded on 400 MHz
or 500 MHz for 1H NMR and at 100 MHz or 125 MHz for 13C NMR in
CDCl3. Chemical shifts were reported in parts per million with ei-
ther TMS or residual solvent as an internal standard. The following
abbreviations are used to describe peak patterns where appropri-
ate: b¼broad, s¼singlet, d¼doublet, t¼triplet, q¼quartet,
m¼multiplet. Coupling constants are reported in Hertz (Hz). High-
resolution mass spectra (HRMS) were recorded by EI ionization.
Melting points were measured with micro melting point apparatus.
4.2.4. Methyl
2-(4-(dimethylamino)phenyl)-4-hydroxy-2H-chro-
mene-3-carboxylate (3d) and its ketone form 3d0. Compound 3d0/
3d¼1/0.15 in CDCl3; yellow solid, mp 136e137 ꢀC; yield 46%
(0.15 g); IR (cmꢁ1
) nmax 2904, 1738, 1686, 1605, 1145, 989, 816, 777;
1H NMR (500 MHz, CDCl3)
d
12.27 (s, 0.15H), 7.94 (dd, J¼7.9, 1.6 Hz,
1H), 7.68 (dd, J¼7.8, 1.5 Hz, 0.15H), 7.51 (ddd, J¼8.6, 7.3, 1.7 Hz, 1H),
7.36e7.31 (m, 2H), 7.24e7.20 (m, 0.45H), 7.08e7.03 (m, 1H), 7.01 (d,
J¼8.3 Hz, 1H), 6.95e6.90 (m, 0.15H), 6.75 (d, J¼7.7 Hz, 0.15H), 6.71
(t, J¼5.8 Hz, 2H), 6.60 (d, J¼8.8 Hz, 0.30H), 6.17 (s, 0.15H), 5.58 (d,
J¼12.4 Hz, 1H), 4.14 (d, J¼12.4 Hz, 1H), 3.73 (s, 0.45H), 3.64 (s, 3H),
4.2. Typical procedure for the synthesis of 3a
2.97 (s, 6H), 2.90 (s, 0.90H); 13C NMR (125 MHz, CDCl3)
d 188.7,
168.0, 161.7, 156.1, 151.5, 150.8, 136.9, 133.5, 128.7, 127.8, 126.7, 124.6,
123.9, 122.0, 121.3, 120.3, 120.1, 118.5, 118.3, 117.6, 112.5, 112.2, 94.8,
81.6, 75.0, 59.8, 52.7, 52.1, 40.7; HRMS (EI): calcd for C19H19O4N
(Mþ): 325.1314, found 325.1318.
To a solution of 1a (0.22 g, 1 mmol) and 2a (0.12 g, 1 mmol) in
DCE (10 mL) was added dropwise a solution of boron trifluoride
etherate (1 mmol) in DCE (10 mL) at 0 ꢀC under N2 atmosphere. The
reaction mixture was stirred at 50 ꢀC for 12 h. Then, the reaction
was quenched with water (1 mL) and the mixture was washed with
brine solution (10 mL), dried over anhydrous MgSO4, and then
concentrated under vacuum. The crude product was purified by
silica gel column (hexane/ethyl acetate as eluent).
4.2.5. Methyl 2-(4-fluorophenyl)-4-hydroxy-2H-chromene-3-
carboxylate (3e) and its ketone form 3e0. Compound 3e0/3e¼1/1 in
CDCl3; white solid, mp 94e95 ꢀC; yield 61% (0.18 g); IR (cmꢁ1
) nmax
2956, 1682, 1605, 1223, 1151, 1000, 833, 766; 1H NMR (500 MHz,
CDCl3)
d
12.27 (s, 1H), 7.95 (dd, J¼7.9, 1.4 Hz, 1H), 7.68 (dd, J¼7.8,
4.2.1. Methyl 4-hydroxy-2-(p-tolyl)-2H-chromene-3-carboxylate
1.3 Hz, 1H), 7.58e7.51 (m, 1H), 7.49 (dd, J¼8.6, 5.3 Hz, 2H), 7.33 (dd,
J¼8.5, 5.4 Hz, 2H), 7.28 (dd, J¼7.8,1.0 Hz,1H), 7.14e7.07 (m, 3H), 7.03
(d, J¼8.4 Hz, 1H), 6.99e6.92 (m, 3H), 6.78 (d, J¼8.2 Hz, 1H), 6.21 (s,
1H), 5.68 (d, J¼12.3 Hz, 1H), 4.06 (d, J¼12.3 Hz, 1H), 3.76 (d,
(3a) and its ketone form 3a0. Compound 3a0/3a¼1/0.55 in CDCl3;
white solid, mp 111e112 ꢀC; yield 74% (0.22 g); IR (cmꢁ1
) nmax 2920,
2853, 1738, 1691, 1459, 1145, 811, 761; 1H NMR (500 MHz, CDCl3)
d
12.26 (s, 0.55H), 7.95 (d, J¼7.9 Hz, 1H), 7.68 (d, J¼7.7 Hz, 0.55H),
J¼4.3 Hz, 3H), 3.65 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 187.8, 170.8,
7.53 (dd, J¼11.3, 4.3 Hz, 1H), 7.37 (d, J¼7.9 Hz, 2H), 7.26 (s, 1H),
7.24e7.20 (m, 2.75H), 7.07 (dd, J¼7.4, 4.5 Hz, 2H), 7.03 (d, J¼8.4 Hz,
1H), 6.94 (t, J¼7.5 Hz, 0.55H), 6.78 (d, J¼8.2 Hz, 0.55H), 6.21 (s,
0.55H), 5.66 (d, J¼12.2 Hz, 1H), 4.10 (d, J¼12.2 Hz, 1H), 3.75 (s,
1.65H), 3.64 (s, 3H), 2.37 (s, 3H), 2.28 (s, 1.65H); 13C NMR (125 MHz,
167.7, 163.5 (d, J¼247 Hz), 163.4, 163.0 (d, J¼245.5 Hz), 161.3, 155.8,
137.2, 136.2 (J¼3 Hz), 133.8, 132.9 (d, J¼3 Hz), 129.5 (d, J¼8 Hz),
129.3 (d, J¼8 Hz), 127.9, 124.8, 122.5, 121.8, 120.2, 118.4, 118.0, 117.6,
116.2 (d, J¼22 Hz), 115.6 (d, J¼22 Hz), 94.4, 80.8, 74.3, 60.2, 52.8,
52.2; HRMS (EI): calcd for C17H13O4F (Mþ): 300.0798, found
300.0796.
CDCl3)
d 188.2, 167.9, 161.5, 156.1, 139.7, 138.6, 137.5, 137.0, 134.0,
133.7, 129.9, 129.7, 129.4, 127.8, 127.5, 125.8, 124.8, 122.3, 121.5,
120.2, 118.5, 118.2, 117.6, 94.6, 81.4, 74.9, 60.0, 52.7, 52.2, 21.6, 21.5;
HRMS (EI): calcd for C18H16O4 (Mþ): 296.1049, found 296.1055.
4.2.6. Methyl 2-(4-chlorophenyl)-4-hydroxy-2H-chromene-3-
carboxylate (3f) and its ketone form 3f0. Compound 3f0/3f¼0.40/1
in CDCl3; white solid, mp 120e121 ꢀC; yield 73% (0.23 g); IR (cmꢁ1
)
4.2.2. Methyl 4-hydroxy-2-phenyl-2H-chromene-3-carboxylate (3b)
and its ketone form 3b0. Compound 3b0/3b¼1/0.8 in CDCl3; pink
nmax 2953, 1653, 1627, 1439, 1258, 1090, 805, 762; 1H NMR
(500 MHz, CDCl3)
d
12.26 (s, 1H), 7.95 (dd, J¼7.9, 1.6 Hz, 0.4H), 7.68
solid, mp 107e109 ꢀC; yield 56% (0.16 g); IR (cmꢁ1
)
nmax 2920, 1730,
(dd, J¼7.8, 1.5 Hz, 1H), 7.54 (dd, J¼11.3, 4.3 Hz, 0.4H), 7.47e7.35 (m,
2H), 7.29 (dd, J¼7.6, 5.9 Hz, 2.6H), 7.27e7.21 (m, 2H), 7.08 (d,
J¼7.8 Hz, 0.4H), 7.03 (d, J¼8.3 Hz, 0.4H), 6.95 (dd, J¼11.0, 4.1 Hz, 1H),
6.78 (d, J¼8.2 Hz, 1H), 6.20 (s, 1H), 5.68 (d, J¼12.3 Hz, 0.4H), 4.04 (d,
J¼12.2 Hz, 0.4H), 3.76 (s, 3H), 3.66 (s, 1.2H); 13C NMR (125 MHz,
1682, 1645, 1442, 1304, 1030, 762; 1H NMR (500 MHz, CDCl3)
d
12.28 (s, 0.8H), 7.95 (dd, J¼7.9, 1.4 Hz, 1H), 7.68 (dd, J¼7.7, 1.3 Hz,
0.8H), 7.55e7.51 (m, 1H), 7.49 (dd, J¼7.6, 1.5 Hz, 2H), 7.40 (t,
J¼6.2 Hz, 3.2H), 7.36 (dd, J¼7.7, 1.2 Hz, 1.6H), 7.30e7.23 (m, 3H), 7.08
(t, J¼7.5 Hz, 1H), 7.03 (d, J¼8.3 Hz, 1H), 6.94 (t, J¼7.5 Hz, 0.8H), 6.79
(d, J¼8.2 Hz, 0.8H), 6.25 (s, 0.8H), 5.70 (d, J¼12.2 Hz, 1H), 4.10 (d,
J¼12.2 Hz, 1H), 3.75 (s, 2.4H), 3.63 (s, 3H); 13C NMR (125 MHz,
CDCl3)
d 187.6, 170.8, 167.7, 163.5, 161.2, 155.8, 138.9, 137.2, 135.7,
135.5, 134.6, 133.9, 129.4, 129.2, 128.9, 127.9, 127.3, 124.9, 122.6,
121.9, 120.1, 118.4, 118.0, 117.6, 94.2, 80.9, 74.3, 60.0, 52.9, 52.2;
HRMS (EI): calcd for C17H13O4Cl (Mþ): 316.0502, found 316.0499.
CDCl3)
d 188.0, 167.8, 161.4, 156.1, 140.4, 137.1, 136.9, 133.7, 129.8,
129.2, 129.0, 128.7, 128.7, 127.8, 127.5, 127.5, 125.8, 124.8, 122.4,
121.6, 120.2, 118.5, 118.1, 117.5, 94.5, 81.5, 60.1, 52.7, 52.2; HRMS (EI):
calcd for C17H14O4 (Mþ): 282.0892, found 282.0887.
4.2.7. Methyl 2-(4-bromophenyl)-4-hydroxy-2H-chromene-3-
carboxylate (3g) and its ketone form 3g0. Compound 3g0/3g¼0/1 in
CDCl3; pink solid, mp 139e141 ꢀC; yield 71% (0.26 g); IR (cmꢁ1
) nmax
4.2.3. Methyl 4-hydroxy-2-(4-methoxyphenyl)-2H-chromene-3-
2951, 1627, 1438, 1261, 1093, 1004, 804, 762; 1H NMR (500 MHz,
CDCl3)
12.26 (s, 1H), 7.68 (dd, J¼7.7, 1.5 Hz, 1H), 7.44e7.37 (m, 2H),
7.31e7.19 (m, 3H), 6.99e6.93 (m, 1H), 6.79 (d, J¼8.1 Hz, 1H), 6.19 (s,
carboxylate (3c) and its ketone form 3c0. Compound 3c0/3c¼1/0.5
d
in CDCl3; white solid, mp 108e109 ꢀC; yield 50% (0.16 g); IR (cmꢁ1
)

N. Wang et al. / Tetrahedron 69 (2013) 647e652
651
1H), 3.76 (s, 3H); 13C NMR (125 MHz, CDCl3)
139.4, 133.9, 131.9, 129.3, 124.9, 122.8, 121.9, 118.0, 117.6, 94.1, 74.3,
52.3; HRMS (EI): calcd for C17H13O4Br (Mþ): 359.9997, found
359.9998.
d
170.8, 163.5, 155.8,
7.64 (d, J¼8.2 Hz, 2H), 7.51 (d, J¼8.4 Hz, 1H), 7.43 (dd, J¼11.2, 3.9 Hz,
1H), 7.30 (d, J¼8.1 Hz, 2H), 3.81 (s, 3H), 2.43 (s, 3H); 13C NMR
(100 MHz, CDCl3)
d 175.3, 166.2, 163.5, 156.1, 142.7, 134.6, 129.9,
129.3, 128.2, 126.3, 125.9, 123.3, 118.3, 117.9, 53.1, 21.9; HRMS (EI):
calcd for C18H14O4 (Mþ): 294.0892, found 294.0890.
4.2.8. Methyl 4-hydroxy-2-(4-nitrophenyl)-2H-chromene-3-
carboxylate (3h) and its ketone form 3h0. Compound 3h0/3h¼0.38/
4.3.2. Methyl 4-oxo-2-phenyl-4H-chromene-3-carboxylate
1 in CDCl3; white solid, mp 43e44 ꢀC; yield 46% (0.15 g); IR (cmꢁ1
)
(5b). Yellow solid, mp 76e80 ꢀC; yield 52% (146 mg); 1H NMR
nmax 2955, 1744, 1656, 1522, 1346, 1264, 764, 730; 1H NMR
(500 MHz, CDCl3)
(400 MHz, CDCl3)
7.53 (ddd, J¼14.6, 10.0, 4.7 Hz, 4H), 7.46 (t, J¼7.5 Hz, 1H), 3.79 (s,
3H); 13C NMR (100 MHz, CDCl3)
175.3, 165.9, 163.4, 156.1, 134.7,
d
8.27 (dd, J¼7.9, 1.2 Hz, 1H), 7.78e7.69 (m, 3H),
d
12.30 (s, 1H), 8.29 (d, J¼8.7 Hz, 0.76H), 8.14 (d,
J¼8.7 Hz, 2H), 7.97 (dd, J¼8.0, 1.7 Hz, 0.38H), 7.70 (td, J¼5.9, 5.5,
3.1 Hz, 1.76H), 7.58 (ddd, J¼8.7, 7.3, 1.8 Hz, 0.38H), 7.54 (d, J¼8.7 Hz,
2H), 7.35e7.28 (m, 1H), 7.14 (t, J¼7.6 Hz, 0.38H), 7.06 (d, J¼8.3 Hz,
0.38H), 7.00 (t, J¼7.5 Hz,1H), 6.84 (d, J¼8.2 Hz,1H), 6.31 (s, 1H), 5.83
(d, J¼12.2 Hz, 0.38H), 4.04 (d, J¼12.2 Hz, 0.38H), 3.80 (s, 3H), 3.68 (s,
d
132.2, 132.0, 129.1, 128.2, 126.3, 126.0, 123.3, 118.4, 118.3, 53.1;
HRMS (EI): calcd for C17H12O4 (Mþ): 280.0736, found 280.0731.
4.3.3. Methyl 2-(4-fluorophenyl)-4-oxo-4H-chromene-3-carboxylate
(5c). Yellow solid, mp 94e96 ꢀC; yield 38% (113 mg); 1H NMR
1.14H); 13C NMR (125 MHz, CDCl3)
d 186.6, 170.3, 167.2, 163.6, 160.6,
155.4, 148.5, 147.9,147.3, 143.7, 137.2, 134.0, 128.3, 128.1, 127.8, 124.9,
124.2, 123.8, 122.7, 122.1, 119.9, 118.2, 117.6, 117.3, 93.5, 80.1, 73.7,
59.8, 52.9, 52.2; HRMS (EI): calcd for C17H13O6N (Mþ): 327.0743,
found 327.0745.
(400 MHz, CDCl3)
d
8.22 (d, J¼7.9 Hz, 1H), 7.75e7.64 (m, 3H),
7.51e7.40 (m, 4H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
175.2,
165.9, 164.9 (d, J¼254 Hz), 162.3, 156.1, 134.8, 130.7 (d, J¼9 Hz),
128.38, 128.35, 126.4 (d, J¼30 Hz), 123.3, 118.3, 116.6, 116.4, 53.2;
HRMS (EI): calcd for C17H11FO4 (Mþ): 298.0641, found 298.0642.
4.2.9. Methyl 4-hydroxy-6-methyl-2-(p-tolyl)-2H-chromene-3-
carboxylate (3i). White solid, mp 110e112 ꢀC; yield 58% (0.18 g);
4.3.4. Methyl 2-(4-chlorophenyl)-4-oxo-4H-chromene-3-carboxylate
IR (cmꢁ1
)
nmax 2910,1747,1680,1515,1254,1215,1000, 828; 1H NMR
(5d). Yellow solid, mp 99e103 ꢀC; yield 35% (110 mg); 1H NMR
(500 MHz, CDCl3)
d
7.72 (d, J¼1.6 Hz, 1H), 7.36 (d, J¼8.1 Hz, 2H), 7.33
(400 MHz, CDCl3)
J¼8.4 Hz, 1H), 7.46 (t, J¼7.5 Hz, 1H), 7.21 (t, J¼8.6 Hz, 2H), 3.81 (s,
3H); 13C NMR (100 MHz, CDCl3)
174.9, 165.5, 161.9, 155.7, 138.1,
134.6, 130.3, 129.4, 129.3, 128.5, 126.1, 125.9, 123.0, 118.1, 53.0;
HRMS (EI): calcd for C17H11ClO4 (Mþ): 314.0346, found 314.0349.
d
8.26 (d, J¼7.9 Hz,1H), 7.81e7.70 (m, 3H), 7.52 (d,
(d, J¼8.5 Hz, 1H), 7.21 (d, J¼7.9 Hz, 2H), 6.92 (d, J¼8.4 Hz, 1H), 5.62
(d, J¼12.2 Hz, 1H), 4.07 (d, J¼12.2 Hz, 1H), 3.64 (s, 3H), 2.36 (s, 3H),
d
2.33 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
188.1, 167.8, 159.4, 139.4,
137.9, 133.8, 131.6, 129.6, 127.2, 127.1, 119.6, 118.0, 81.2, 59.8, 52.5,
21.4, 20.6; HRMS (EI): calcd for C19H18O4 (Mþ): 310.1205, found
310.1201.
4.3.5. Methyl 2-(4-bromophenyl)-4-oxo-4H-chromene-3-carboxylate
(5e). Yellow solid, mp 121e123 ꢀC; yield 31% (111 mg); 1H NMR
4.2.10. Methyl 6-chloro-4-hydroxy-2-(p-tolyl)-2H-chromene-3-
(400 MHz, CDCl3)
(q, J¼8.5 Hz, 4H), 7.52 (d, J¼8.4 Hz,1H), 7.45 (t, J¼7.6 Hz,1H), 3.81 (s,
3H); 13C NMR (100 MHz, CDCl3)
175.1, 165.7, 162.2, 156.0, 134.8,
132.5, 131.0, 129.8, 126.8, 126.4, 126.2, 123.3, 118.4, 118.3, 53.2;
HRMS (EI): calcd for C17H11BrO4 (Mþ): 357.9841, found 357.9838.
d
8.24 (d, J¼7.9 Hz, 1H), 7.73 (t, J¼7.8 Hz, 1H), 7.63
carboxylate (3j) and its ketone form 3j0. Compound 3j0/3j¼0.85/1
in CDCl3; yellow solid, mp 97e98 ꢀC; yield 52% (0.17 g); IR (cmꢁ1
)
d
nmax 2951,1655,1632,1513,1260, 1107, 859, 814; 1H NMR (500 MHz,
CDCl3)
d
12.21 (s, 1H), 7.89 (d, J¼2.6 Hz, 0.85H), 7.64 (d, J¼2.6 Hz,
1H), 7.46 (dd, J¼8.8, 2.7 Hz, 0.85H), 7.35 (d, J¼8.0 Hz, 1.70H), 7.22 (d,
J¼6.6 Hz, 3.70H), 7.18 (dd, J¼8.7, 2.6 Hz, 1H), 7.09 (d, J¼8.1 Hz, 2H),
6.98 (d, J¼8.8 Hz, 0.85H), 6.71 (d, J¼8.7 Hz, 1H), 6.21 (s, 1H), 5.65 (d,
J¼12.0 Hz, 0.85H), 4.08 (d, J¼12.1 Hz, 0.85H), 3.75 (s, 3H), 3.64 (s,
2.55H), 2.37 (s, 2.55H), 2.29 (s, 3H); 13C NMR (125 MHz, CDCl3)
4.3.6. Methyl 2-(4-nitrophenyl)-4-oxo-4H-chromene-3-carboxylate
(5f). Yellow solid, mp 150e152 ꢀC; yield 33% (107 mg); 1H NMR
(400 MHz, CDCl3)
7.94 (d, J¼8.6 Hz, 2H), 7.78 (t, J¼8.5 Hz, 1H), 7.56 (d, J¼8.4 Hz, 1H),
7.53e7.47 (m, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3)
175.1,
d
8.38 (d, J¼8.7 Hz, 2H), 8.28 (d, J¼9.0 Hz, 1H),
d
186.9, 170.5, 167.3, 161.7, 159.7, 154.3, 139.7, 138.7, 136.7, 136.7,
d
133.3, 133.1, 129.7, 129.3, 127.7, 127.3, 127.2, 126.8, 126.5, 124.2,
120.8, 120.0, 119.1, 118.8, 95.1, 81.4, 74.9, 59.3, 52.7, 52.1, 21.4, 21.3;
HRMS (EI): calcd for C18H15O4Cl (Mþ): 330.0659, found 330.0659.
165.7, 162.2, 156.0, 134.8, 132.5, 131.0, 129.8, 126.8, 126.4, 126.2,
123.3, 118.4, 118.3, 53.2; HRMS (EI): calcd for C17H11NO6 (Mþ):
325.0586, found 325.0590.
4.3. Typical procedure for the synthesis of 5
4.3.7. Methyl 2-(2-chlorophenyl)-4-oxo-4H-chromene-3-carboxylate
(5g). Yellow solid, mp 94e96 ꢀC; yield 32% (100 mg); 1H NMR
To a solution of 4a (0.22 g, 1 mmol) and 2a (0.12 g, 1 mmol) in
DCE (10 mL) was added dropwise a solution of boron trifluoride
etherate (10 mmol) in DCE (10 mL) at 0 ꢀC under N2 atmosphere.
The reaction mixture was stirred at 50 ꢀC for 16 h. After quenched
with water (1 mL), the reaction mixture was washed with brine
solution (10 mL), dried over anhydrous MgSO4, and concentrated
under vacuum. The residue was dissolved in 1,4-dioxane (10 mL).
DDQ (0.30 g,1.3 mmol) was added and the solution was refluxed for
48 h. Water (20 mL) was added and the mixture was extracted with
EtOAc (20 mLꢂ3). The combined organic layer was washed with
water and brine solution, dried over anhydrous MgSO4, and then
concentrated under vacuum. The residue was purified by silica gel
column with hexane/ethyl acetate as eluent.
(500 MHz, CDCl3)
d
8.29 (dd, J¼7.9, 1.1 Hz, 1H), 7.76e7.69 (m, 1H),
7.56e7.45 (m, 5H), 7.39 (td, J¼7.5, 1.1 Hz, 1H), 3.68 (s, 3H); 13C NMR
(125 MHz, CDCl3)
d 174.8, 164.7, 163.6, 156.2, 134.8, 133.5, 132.4,
131.8, 130.7, 130.4, 127.1, 126.6, 126.3, 123.9, 120.0, 118.5, 52.9. HRMS
(EI): calcd for C17H11ClO4 (Mþ): 314.0346, found 314.0339.
4.3.8. Methyl 2-(3-chlorophenyl)-4-oxo-4H-chromene-3-carboxylate
(5h). Yellow solid, mp 90e93 ꢀC; yield 30% (95 mg); 1H NMR
(400 MHz, CDCl3)
J¼7.7 Hz, 1H), 7.54 (d, J¼8.6 Hz, 2H), 7.46 (q, J¼7.5 Hz, 2H), 3.82 (s,
3H); 13C NMR (100 MHz, CDCl3)
175.1, 165.6, 161.7, 156.0, 135.3,
d
8.26 (d, J¼7.9 Hz,1H), 7.78e7.71 (m, 2H), 7.61 (d,
d
134.9, 133.8, 132.0, 130.5, 128.4, 126.5, 126.5, 126.3, 123.4, 118.8,
118.4, 53.2; HRMS (EI): calcd for C17H11ClO4 (Mþ): 314.0346, found
314.0351.
4.3.1. Methyl 4-oxo-2-(p-tolyl)-4H-chromene-3-carboxylate
(5a). Yellow solid, mp 107e111 ꢀC; yield 32% (95 mg); 1H NMR
4.3.9. Methyl 2-(4-iodophenyl)-4-oxo-4H-chromene-3-carboxylate
(400 MHz, CDCl3)
d
8.25 (dd, J¼8.0, 1.5 Hz, 1H), 7.74e7.67 (m, 1H),
(5i). Yellow solid, mp 139e143 ꢀC; yield 25% (102 mg); 1H NMR

652
N. Wang et al. / Tetrahedron 69 (2013) 647e652
(400 MHz, CDCl3)
d
8.26 (d, J¼7.9 Hz,1H), 7.87 (d, J¼8.4 Hz, 2H), 7.74
Supplementary data
(t, J¼7.7 Hz, 1H), 7.52 (d, J¼8.4 Hz, 1H), 7.47 (m, 3H), 3.82 (s, 3H); 13C
NMR (125 MHz, CDCl3)
d
175.2,165.8,162.4,156.1,138.5,134.8,131.7,
The Supplementary data contains copies of 1H and 13C NMR
spectra along with other experimental details. Supplementary data
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2012.11.008.
129.8, 126.6, 126.2, 123.5, 118.6, 118.4, 99.1, 53.3; HRMS (EI): calcd
for C17H11IO4 (Mþ): 405.9702, found 405.9716.
4.3.10. Methyl 4-oxo-2-(2-(trifluoromethyl)phenyl)-4H-chromene-3-
carboxylate (5j). Yellow solid; mp 116e118 ꢀC; yield 31%
References and notes
(108 mg); 1H NMR (400 MHz, CDCl3)
d
8.29 (dd, J¼7.9, 1.2 Hz, 1H),
7.89e7.82 (m, 1H), 7.76e7.65 (m, 3H), 7.64e7.58 (m, 1H), 7.52e7.44
(m, 2H), 3.64 (s, 3H); 13C NMR (125 MHz, CDCl3)
174.4,164.3,163.7,
1. Friedrich, L. E.; Bower, J. D. J. Am. Chem. Soc. 1973, 95, 6869.
2. Kowalski, C. J.; Sakdarat, S. J. Org. Chem. 1990, 55, 1977.
3. Sisko, J.; Balog, A.; Curran, D. P. J. Org. Chem. 1992, 57, 4341.
4. Hsung, R. P.; Zificsak, C. A.; Wei, L.; Douglas, C. J.; Xiong, H.; Mulder, J. A. Org.
Lett. 1999, 1, 1237.
5. Hayashi, A.; Yamaguchi, M.; Hirama, M. Synlett 1995, 195.
6. Oblin, M.; Parrain, J. L.; Rajzmannb, M.; Pons, J. M. Chem. Commun. 1998, 1619.
7. Viswanathan, G. S.; Li, C. J. Tetrahedron Lett. 2002, 43, 1613.
8. Curini, M.; Epifano, F.; Maltese, F.; Rosati, O. Synlett 2003, 552.
9. Rhee, J. U.; Krische, M. J. Org. Lett. 2005, 7, 2493.
d
155.7, 134.6, 131.9, 131.2, 130.6, 130.1 (q, J¼4 Hz), 129.0 (q, J¼32 Hz),
127.1 (q, J¼5 Hz), 126.2, 126.1, 123.5, 123.4 (q, J¼273 Hz), 119.1, 118.2,
52.3; HRMS (EI): calcd for C18H11F3O4 (Mþ): 348.0609, found
348.0612.
4.3.11. Methyl 2-(naphthalen-1-yl)-4-oxo-4H-chromene-3-
10. Jin, T.; Yamamoto, Y. Org. Lett. 2007, 9, 5259.
carboxylate (5k). Yellow solid, mp 164e167 ꢀC; yield 30%
11. Aikawa, K.; Hioki, Y.; Shimizu, N.; Mikami, K. J. Am. Chem. Soc. 2011, 133, 20092.
12. Shindo, M.; Sato, Y.; Yoshikawa, T.; Koretsune, R.; Shishido, K. J. Org. Chem.
2004, 69, 3912.
13. Shindo, M.; Kita, T.; Kumagai, T.; Matsumoto, K.; Shishido, K. J. Am. Chem. Soc.
2006, 128, 1062.
14. Shindo, M.; Morib, S. Synlett 2008, 2231.
15. Shindo, M.; Matsumoto, K.; Mori, S.; Shishido, K. J. Am. Chem. Soc. 2002, 124,
6840.
16. Yoshikawa, T.; Mori, S.; Shindo, M. J. Am. Chem. Soc. 2009, 131, 2092.
17. Kurtz, K. C. M.; Hsung, R. P.; Zhang, Y. Org. Lett. 2006, 8, 231.
18. You, L.; Al-Rashid, Z. F.; Figueroa, R.; Ghosh, S. K.; Li, G.; Lu, T.; Hsung, R. P.
Synlett 2007, 1656.
19. Cheng, D.; Ling, F.; Li, Z.; Yao, W.; Ma, C. Org. Lett. 2012, 14, 3146.
20. Sun, J.; Keller, V. A.; Meyer, S. T.; Kozmina, S. A. Adv. Synth. Catal. 2010, 352, 839.
21. Shindo, M.; Sato, Y.; Shishido, K. Tetrahedron Lett. 1998, 39, 4857.
22. Shindo, M.; Sato, Y.; Shishido, K. J. Org. Chem. 2000, 65, 5443.
23. Sun, Y.; Liu, G.; Huang, H.; Yu, P. Phytochemistry 2012, 75, 169.
24. Fernandes, I. P. G.; Oliveira, S. C. B.; Ghalkhani, M.; Shahrokhian, S.; Oliveira-
Brett, A. M. Electroanalysis 2012, 24, 618.
(99 mg); 1H NMR (400 MHz, CDCl3)
d
8.35 (dd, J¼7.9, 1.2 Hz, 1H),
8.08e8.03 (m, 1H), 7.97e7.93 (m, 1H), 7.91e7.84 (m, 1H), 7.79e7.71
(m, 2H), 7.63e7.44 (m, 5H), 3.64e3.43 (m, 3H); 13C NMR (125 MHz,
CDCl3)
d 175.1, 165.2, 165.1, 156.4, 134.8, 133.8, 131.9, 130.9, 129.9,
128.9, 128.1, 127.8, 127.0, 126.7, 126.3, 125.2, 125.2, 123.9, 120.9,
118.6, 52.8; HRMS (EI): calcd for C21H14O4 (Mþ): 330.0892, found
330.0894.
4.3.12. Methyl 6-methyl-4-oxo-2-phenyl-4H-chromene-3-
carboxylate (5l). Yellow solid, mp 81e84 ꢀC; yield 37% (109 mg);
1H NMR (400 MHz, CDCl3)
d
8.01 (d, J¼15.0 Hz,1H), 7.73 (d, J¼7.1 Hz,
2H), 7.53 (dd, J¼13.2, 7.5 Hz, 4H), 7.42 (d, J¼8.5 Hz, 1H), 3.79 (s, 3H),
2.46 (s, 3H); 13C NMR (100 MHz, CDCl3)
175.4, 166.1, 163.3, 154.4,
d
136.1, 135.9, 132.4, 131.9, 129.1, 128.3, 125.7, 123.1, 118.2, 118.1, 53.1,
21.3; HRMS (EI): calcd for C18H14O4 (Mþ): 294.0892, found
294.0890.
25. Havsteen, B. H. Pharmacol. Ther. 2002, 96, 67.
26. Gaspar, A.; Reis, J.; Kachler, S.; Paoletta, S.; Uriarte, E.; Klotz, K. N.; Moro, S.;
Borges, F. Biochem. Pharmacol. 2012, 84, 21.
27. Alvim, J., Jr.; Severino, R. P.; Marques, E. F.; Martinelli, A. M.; Vieira, P. C.; Fer-
nandes, J. B.; Silva, M. F. G. F.; Correa, A. G. J. Comb. Chem. 2010, 12, 687.
28. McGarry, L. W.; Detty, M. R. J. Org. Chem. 1990, 55, 4349.
29. Zhou, C.; Dubrovsky, A. V.; Larock, R. C. J. Org. Chem. 2006, 71, 1626.
30. Fan, X.; Wang, Y.; Qu, Y.; Xu, H.; He, Y.; Zhang, X.; Wang, J. J. Org. Chem. 2011, 76,
982.
31. Ooguri, A.; Nakai, K.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2009, 131,
13194.
32. Fang, Y.; Li, C. J. Org. Chem. 2006, 71, 6427.
4.3.13. Methyl 6-chloro-4-oxo-2-phenyl-4H-chromene-3-carboxylate
(5m). Yellow solid, mp 102e104 ꢀC; yield 41% (129 mg); 1H NMR
(400 MHz, CDCl3)
d
8.21 (d, J¼2.5 Hz,1H), 7.73 (d, J¼7.6 Hz, 2H), 7.67
(dd, J¼8.9, 2.6 Hz, 1H), 7.59e7.47 (m, 4H), 3.79 (s, 3H); 13C NMR
(100 MHz, CDCl3)
d 174.2, 165.6, 163.8, 154.5, 134.9, 132.3, 132.1,
131.9, 129.2, 128.3, 125.8, 124.4, 120.2, 118.3, 53.2; HRMS (EI): calcd
for C17H11ClO4 (Mþ): 314.0346, found 314.0340.
33. Zhao, J.; Zhao, Y.; Fu, H. Angew. Chem., Int. Ed. 2011, 50, 3769.
34. Kumar, P.; Bodas, M. S. Org. Lett. 2000, 2, 3821.
35. Miao, H.; Yang, Z. Org. Lett. 2000, 2, 1765.
36. Awuah, E.; Capretta, A. Org. Lett. 2009, 11, 3210.
37. Yang, Q.; Alper, H. J. Org. Chem. 2010, 75, 948.
Acknowledgements
38. Chai, G.; Qiu, Y.; Fu, C.; Ma, S. Org. Lett. 2011, 13, 5196.
39. Cai, S.; Shen, Y.; Lu, P.; Wang, Y. Tetrahedron Lett. 2011, 52, 4164.
40. CCDC 892891 contains the supplementary crystallographic data for 3a.
We thank the National Nature Science Foundation of China (No.
21032005) for financial support.