DDQ-mediated tandem synthesis of functionalized pyranocoumarins from 4-hydroxycoumarins and 1,3-diarylallylic compounds

Article abstract of DOI:10.3987/COM-10-11906

A simple and efficient DDQ-mediated oxidative cross-coupling between 4-hydroxycoumarin and 1,3-diarylallylic compounds was developed. The reaction furnished functionalized pyranocoumarins in a single step without using any metal catalyst. The tandem process involves an intermolecular C-C bond formation and an intramolecular C-O bond formation through double oxidative C-H activation.

Full text of DOI:10.3987/COM-10-11906

HETEROCYCLES, Vol. 81, No. 4, 2010
965
HETEROCYCLES, Vol. 81, No. 4, 2010, pp. 965 - 976. © The Japan Institute of Heterocyclic Chemistry
Received, 12th January, 2010, Accepted, 9th February, 2010, Published online, 10th February, 2010
DOI: 10.3987/COM-10-11906
DDQ-MEDIATED TANDEM SYNTHESIS OF FUNCTIONALIZED
PYRANOCOUMARINS
FROM
4-HYDROXYCOUMARINS
AND
1,3-DIARYLALLYLIC COMPOUNDS
Zhenxing He, Xufeng Lin,* Yuanxun Zhu, and Yanguang Wang
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
E-mail: lxfok@zju.edu.cn
Abstract - A simple and efficient DDQ-mediated oxidative cross-coupling
between 4-hydroxycoumarin and 1,3-diarylallylic compounds was developed. The
reaction furnished functionalized pyranocoumarins in a single step without using
any metal catalyst. The tandem process involves an intermolecular C–C bond
formation and an intramolecular C–O bond formation through double oxidative
C–H activation.
There has been great development of various transition-metal-catalyzed coupling reactions in organic
synthesis and related disciplines.1 On the other hand, with the prevalence of “atom economy”2 and “green
chemistry”,3 the direct formations of carbon-carbon bonds4 or carbon-heteroatom bonds5 from C-H bonds
by cross-coupling reactions have attracted great attention recently.
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a well-known powerful oxidant in organic
chemistry,6 particularly useful for dehydrogenation to form aromatic compounds,6a oxidizes activated
methylene6b,6c and hydroxy groups6d to carbonyl compounds. In recent years, there has been enormous
interest in developing DDQ-mediated direct oxidative cross-coupling by C-H activation without using
any metal catalyst.7 Typical examples include the DDQ-mediated cross-dehydrogenative-coupling
reaction between benzyl ethers and simple ketones,7a the DDQ-mediated cyclization reaction of benzylic
and allylic ethers,7b and the oxidative cross-coupling reactions between benzylic substrates and active
methylenic compounds or alcohols.7c-7e To the best of our knowledge, however, there has been no report
on DDQ-mediated tandem double oxidative C-H activation.
Coumarin and its derivatives are one of the important classes of heterocyclic compounds and are known
to possess a wide range of biological activities such as anti-HIV, antimalarial, antibacterial, and cytotoxic.
8
Among the various coumarin derivatives, functionalized pyranocoumarin represents a significant class
of compounds as biologically active compounds.9 As a part of our continuing program on development of

966
HETEROCYCLES, Vol. 81, No. 4, 2010
tandem synthesis of heterocycles,10 we herein reported a tandem approach to functionalized
pyranocoumarins from 1,3-diarylallylic compounds and 4-hydroxycoumarin via the DDQ-mediated
double oxidative C-H activation.
We initially examined the reaction of 4-hydroxycoumarin (1a) with 1,3-diphenyl-1-propene (2a) in the
presence of DDQ (2.0 equiv) using CH2Cl2 as a solvent (Table 1, entry 1). After reacting under ambient
conditions for 1 h, the resulting mixture was filtered to separate a black solid, consisting mainly of
hydroquinone (DDQH2). The filtrate was concentrated and purified by chromatography on a silica gel
column to give pyranocoumarin 3a with 52% yield. The structure of compound 3a was unambiguously
confirmed by single-crystal X-ray analysis (Figure 1).11 Furthermore, we found that the desired product
3a could be obtained in 68% yield with 4 Å MS as an additive (Table 1, entry 2). In order to slow the
reaction, we then set the reaction temperature to 0 oC and this reaction was completed for 3 h. However,
the yield reduced obviously (Table 1, entry 3). When the reaction temperate was increased to reflux, the
yield resulted in a slight decrease (Table 1, entry 4). Then various solvents were screened. The reaction
could proceed in ClCH2CH2Cl with good efficiency (Table 1, entry 5). When MeCN and PhMe were used
as solvents, the yield was remarkably diminished (Table 1, entries 6 and 7). No desired product was
detected when CHCl3, MeNO2 or THF were used as solvents (Table 1, entries 8, 9 and 10). Switching the
ratio of substrates 1a/2a decreased the yield (Table 1, entry 11). The influence of the amount of DDQ was
also evaluated and both increase and decrease the amount of DDQ reduced the yield (Table 1, entries 13
and 14). No product was detected in the absence of DDQ (Table 1, entry 15). Thus, the most suitable
reaction conditions for the formation of 3a were established (Table 1, entry 2).
Table 1. Screening for the Reaction Conditionsa
Ph
OH
O
DDQ
Ph
+
Ph
Ph
4A MS
solvent
1 h
O
1a
O
2a
O
3a
O
Entry
Solvent
Temp.
Yield (%)b
1
2
3
4
5
6
7
8
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
rt
rt
52c
68
48
65
66
35
24
nd
nd
nd
0 oC
reflux
rt
ClCH2CH2Cl
MeCN
rt
rt
rt
rt
PhMe
CHCl3
MeNO2
THF
10
rt

HETEROCYCLES, Vol. 81, No. 4, 2010
967
11
12
13
14
15
CH2Cl2
rt
rt
rt
rt
rt
47d
58e
55f
41g
0h
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
a Conditions: 2a (0.25 mmol), 1a (1.2 equiv.), DDQ (2.0 equiv.), 4 Å MS (0.25 g), solvent (3 mL), 1 h.
b Isolated yield.
c None of 4 Å MS.
d 0.25 mmol of 1a, 1.2 equiv. of 2a, 2.0 equiv. of DDQ.
e 0.25 mmol of 1a, 1.0 equiv. of 2a, 2.0 equiv. of DDQ.
f 3.0 equiv. of DDQ.
g 1.6 equiv. of DDQ.
h In the absence of DDQ.
Figure 1. X-Ray crystal structure of 3a
The scope of the reaction was investigated with a variety of reactants under the optimized reaction
conditions, and the results were presented in Table 2. 4-Hydroxycoumarins 1a-1d and 1,3-diarylallylic
compounds 2a-2e underwent the oxidative cross-coupling process to generate 3a-3l in modest to good
yields (48-72%). The electronic effect of the substituents on aromatic ring of substrates 1 was
observed (Table 2, entries 1-3 and 5-7). The electron-donating group substituted 4-hydroxycoumarin
1b (Table 2, entries 2 and 6) gave higher yields than the electron-withdrawing group substituted
substrates 1c (Table 2, entries 3 and 7). Similarly, reaction of 1,3-diarylallylic compounds 2a and 2b with
4-hydroxy-6-methyl-2-pyrone 1d allows the efficient synthesis of product 3d and 3h in moderate yields
under the optimized conditions, respectively (Table 2, entries 4 and 8). The electronic effect of the
substituents on the aromatic ring of 2 was examined. When the substrates 2 are bearing a halogen group,
the reaction gave good yields in a rapid rate (Table 2, entries 5-8). However, the result was the opposite
when an electron-donating group was introduced (Table 2, entry 9).

968
HETEROCYCLES, Vol. 81, No. 4, 2010
Table 2.
Formation of functionalized pyranocoumarinsa
Ar
OH
O
2.0 equiv. DDQ
4 Å MS
Ar
+
R
Ar
Ar
R
CH2Cl2, rt
O
O
O
O
1
2
3
OH
OH
OH
OH
Cl
O
O
O
O
O
O
O
O
1a
1b
1c
1d
entry
1
2 (Ar)
reaction
time (h)
product
yield (%)b
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1a
1b
1c
1d
1a
2a(C6H5)
1
1
1
3a
3b
3c
3d
3e
3f
3g
3h
3i
68
70
55
63
70
72
64
66
48
2a
2a
2a
1
2b(4-BrC6H4)
0.75
0.75
0.75
0.75
1.5
2b
2b
2b
2c(4-CH3C6H4)
a Reaction conditions: 2 (0.25 mmol), 1 (1.2 equiv.), DDQ (2.0 equiv.), 4 Å MS (0.25 g), CH2Cl2 (3 mL), rt
b Isolated yield
To expand the scope of the substrates, we further examined the mono-substituted 1,3-diarylpropenes 2d
(Scheme 1) and 2e (Scheme 2). In these cases, we obtained a mixture of two isomers 3j+3j (in 65% total
yield), 3k+3k (in 57% total yield) or 3l+3l (in 48% total yield), respectively. The ratios of two isomers
1
3j+3j, 3k+3k and 3l+3l were 4:1, 7:3, and 3:1, respectively, which were determined by H NMR
analysis.
OH
2.0 equiv. DDQ
4 Å MS
R
+
CH2Cl2, rt
45 min
O
O
Cl
2d
1a: R =H
1b:
R=Me
Cl
O
O
O
O
+
R
R
O
Cl
O
3j:
3j':
3k':
R =H
3k:
R =H
65% total yield
R =Me
R =Me 57% total yield
Scheme 1. Synthesis of 3j+3j and 3k+3k

HETEROCYCLES, Vol. 81, No. 4, 2010
969
OH
O
Cl
2.0 equiv. DDQ
4 Å MS
+
CH2Cl2, rt
45 min
O
2e
1b
Cl
O
Cl
O
+
O
O
O
O
3l: R =H
3l': R =H
48% total yield
Scheme 2. Synthesis of 3l+3l
To provide further insight into the mechanism, (E)-3-(1,3-diphenylallyl)-4-hydroxy-2H-chromen-2-one
4a was conducted the oxidative coupling reaction in the presence of 1.1 equiv. DDQ under ambient
conditions in CH2Cl2 (Scheme 3). The expected product 3a was obtained in 86% yield by an
intramolecular oxidation coupling reaction promoted by DDQ. Furthermore, we found that the reaction
did not proceed in the absence of DDQ (Table 1, entry 15).
Ph
OH
Ph
O
1.1 equiv DDQ
Ph
Ph
CH2Cl2, rt
0.5 h
O
O
O
O
4a
3a
86% yiled
Scheme 3. Intramolecular oxidation coupling reaction of 4a
According to the literatures7 and on the basis of our experiments, a tentative mechanism for the coupling
reaction is proposed in Scheme 4. A single electron transfer from alkene 2a to DDQ generates a radical
ion pair 2a-1, which further converts to the ion pair 2a-2 through hydrogen transfer from the allylic
radical cation to DDQ radical anion. Then, a proton transfer from 1a to DDQH anion forms the ion pair
1a-1 and DDQH2. The attack of the enolate anion to the allylic cation in the ion pair 1a-1 generates the
intermediate 4a. A single electron transfer from 4a to DDQ generates another radical ion pair 4a-1, which
is immediately converted to the ion pair 4a-2 through a hydrogen transfer. Further proton transfer from
hydroxyl group to DDQH anion in the ion pair 4a-2 generates the Zwitterion 4a and DDQH2. The ring
closing of 4a and the subsequent 1,3 H-shift afford the desired product 3a. For the mono-substituted

970
HETEROCYCLES, Vol. 81, No. 4, 2010
1,3-diarylallylic compounds 2d and 2e, they could generate two different allylic carbocations, which led
to the formation of two isomer products 3j+3j, 3k+3k and 3l+3l (Scheme 5).
H
DQQ
DDQ
Ph
Ph
Ph
Ph
2a
2a-1
OH
O
DDQH
Ph
Ph
O
2a-2
1a
Ph
OH
O
Ph
Ph
DDQH2
Ph
O
O
O
O
1a-1
4a
DDQ
Ph
Ph
OH
O
DDQH
O
O
Ph
DDQ
Ph
OH
O
DDQH2
Ph
Ph
H
O
O
O
4a'
4a-2
4a-1
Ph
Ph
O
O
O
1, 3 H-shift
Ph
Ph
O
O
O
5
3a
Scheme 4. Tentative mechanism for the tandem reaction
Ar2
OH
Ar1
3j, 3k, or 3l
Ar1
Ar2
(b)
O
O
(a)
(b)
(a)
Ar1
O
O
OH
O
3j', 3k', or 3l'
Ar2
O
O
Scheme 5. Formation of two isomer products 3j+3j, 3k+3k and 3l+3l

HETEROCYCLES, Vol. 81, No. 4, 2010
971
In conclusion, we have demonstrated a DDQ-mediated oxidative cross-coupling reaction between
4-hydroxycoumarin and 1,3-diarylallylic compounds, which furnished biologically interesting
pyranocoumarins under ambient conditions without using any metal catalyst. The process involves a
direct intermolecular C-C bond formation and an intramolecular C-O bond formation. It is the first
example for the DDQ-mediated tandem double oxidative C-H activation and further application of this
method is under investigation.
EXPERIMENTAL
Column chromatography was carried out on silica gel (300-400 mesh) with mixed solvents
(petroleum-EtOAc). CH2Cl2 was distilled from CaH2. Infrared spectra was obtained on a FTIR
1
13
spectrometer. NMR spectra was recorded for H NMR at 400 MHz, for C NMR at 100 MHz at 293 K
unless otherwise noted. Chemical shifts are reported relative to residue peaks of the solvents either CDCl3
(7.26 ppm for 1H and 77.27 ppm for 13C) or DMSO-d6 (2.50 ppm for 1H and 40.00 ppm for 13C). Data are
presented as follows: chemical shift (ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet),
coupling constant, J (Hz) and integration. Low-resolution MS and HRMS were obtained using ESI
ionization.
Starting Materials. 1b and 1c were prepared according to the literature.12 The diarylallylic compounds
were prepared according to the literature.13 4a was prepared according to the literature.14
General Procedure for the Synthesis of 3
A
10 mL round-bottom flask was charged with 4-hydroxycoumarin (1) (1.2 equiv.),
1,3-diphenyl-1-propene (2) (0.25 mmol) and 4 Å MS (0.25 g) in 3 mL of CH2Cl2. Then DDQ (2.0
equiv.) was added in portions during 15 min. The reaction mixture was stirred for the corresponding time,
and then filtered through a Celite plug. Purification was done by column chromatography on silica gel
with petroleum and EtOAc (10:1) as the eluent to give the pure product 3.
1
2,4-Diphenylpyrano[3,2-c]chromen-5(4H)-one (3a)9a: A white solid; mp 168-169 ºC; H NMR (400
MHz, CDCl3) δ 8.02 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz, 1 H), 7.73 (d, J = 7.2 Hz, 2 H), 7.56 (m, 1 H),
13
7.47~7.30 (m, 9 H), 7.23 (m, 1 H), 5.84 (d, J = 4.8 Hz, 1 H), 4.70 (d, J = 4.8 Hz, 1 H), ppm; C NMR
(100 MHz, CDCl3) δ 161.42, 155.69, 152.69, 146.82, 143.49, 132.56, 131.96, 129.21, 128.63, 128.59,
128.43, 127.19, 124.61, 124.12, 122.63, 116.78, 114.50, 103.69, 103.62, 36.57 ppm; IR (KBr) v 3026,
2918, 1720, 1632, 1610, 1492, 1387, 1270, 1169, 1012, 765, 692 cm-1; MS (ESI) m/z 374.8 ([M+Na]+);
HRMS (ESI) calcd for C24H16O3 ([M+Na]+), 375.0992; found, 375.0986.
9-Methyl-2,4-diphenylpyrano[3,2-c]chromen-5(4H)-one (3b): A white solid; mp 212-213 ºC; 1H NMR
(400 MHz, CDCl3) δ 7.67 (s, 1 H), 7.60 (d, J = 6.4 Hz, 2 H), 7.48~7.36 (m, 9 H), 7.23 (d, J = 8.4 Hz, 1 H),
13
6.15 (d, J = 3.6 Hz 1 H), 5.77 (d, J = 4.4 Hz, 1 H), 2.43 (s, 3 H) ppm; C NMR (100 MHz, CDCl3) δ

972
HETEROCYCLES, Vol. 81, No. 4, 2010
161.36, 158.85, 151.79, 138.29, 137.94, 135.32, 133.68, 133.66, 129.23, 128.88, 127.87, 127.79, 127.52,
127.38, 122.82, 120.11, 116.36, 114.80, 102.69, 78.77, 20.86 ppm; IR (KBr) v 3055, 3025, 1717, 1625,
1550, 1493, 1397, 1363, 1280, 1111, 1001, 765, 755, 702, 533 cm-1; MS (ESI) m/z 389.02 ([M+Na]+);
HRMS (ESI) calcd for C25H18O3 ([M+Na]+), 389.1148; found, 389.1141.
9-Chloro-2,4-diphenylpyrano[3,2-c]chromen-5(4H)-one (3c): A light yellow solid; mp 177-178 ºC; 1H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 2.0 Hz 1 H), 7.60 (d, J = 6.8 Hz, 2 H), 7.53~7.46 (m, 4 H),
13
7.42~7.36 (m, 5 H), 7.29 (m, 1 H), 6.20 (d, J = 4.4 Hz, 1 H), 5.82 (d, J =4.4 Hz, 1 H), ppm; C NMR
(100 MHz, CDCl3) δ 160.06, 158.12, 151.89, 137.83, 137.58, 134.93, 132.52, 129.50, 129.47, 129.00,
127.97, 127.94, 127.59, 127.40, 122.70, 120.74, 118.07, 116.07, 116.33, 79.05 ppm; IR (KBr) v 3059,
2925, 1721, 1625, 1544, 1480, 1391, 1156, 1114, 993, 760, 699 cm-1; MS (ESI) m/z 409.2 ([M+Na]+);
HRMS (ESI) calcd for C24H15ClO3 ([M+Na]+), 409.0602; found, 409.0594.
7-Methyl-2,4-diphenylpyrano[4,3-b]pyran-5(4H)-one (3d): A yellow oil; 1H NMR (400 MHz,
CD3SOCD3) δ 7.45 (d, J = 8.0 Hz 2 H), 7.30~7.34 (m, 3 H), 7.25~7.18 (m, 5 H), 6.19 (s, 1 H), 6.10 (d, J
13
= 4.4 Hz, 1 H), 5.67 (d, J = 4.4 Hz, 1 H), 2.14 (s, 3 H) ppm; C NMR (100 MHz, CDCl3) δ 166.64,
164.86, 159.51, 138.86, 138.08, 133.75, 129.36, 129.19, 127.96, 127.75, 127.71, 120.11, 100.16, 99.35,
77.72, 20.01 ppm; IR (film) v 3061, 2925, 1723, 1644, 1542, 1493, 1446, 1409, 1206, 1121, 998, 155,
699 cm-1; MS (ESI) m/z 338.9 ([M+Na]+); HRMS (ESI) calcd for C21H16O3 ([M+Na]+), 339.0992; found,
339.0996.
1
2,4-Bis(4-bromophenyl)pyrano[3,2-c]chromen-5(4H)-one (3e): A white solid; mp 158-159 ºC; H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8 Hz, 1 H), 7.59~7.56 (m, 3 H ), 7.50 (d, J = 7.6 Hz, 2 H), 7.43 (d,
J = 8.0 Hz, 2 H), 7.33 (d, J = 8.4 Hz, 1 H), 7.28 (d, J = 7.6 Hz, 1 H), 7.21 (d, J = 7.6 Hz, 2 H), 6.11 (d, J =
13
4.0 Hz, 1 H), 5.73 (d, J = 4.0 Hz, 1 H) ppm; C NMR (100 MHz, CDCl3) δ 161.33, 158.53, 153.56,
136.86, 136.58, 134.66, 132.98, 132.16, 131.10, 129.12, 129.06, 124.13, 123.60, 123.23, 122.07, 119.79,
116.71, 114.90, 102.34, 77.88 ppm; IR (KBr) v 3053, 1724, 1632, 1608, 1553, 1488, 1404, 1385, 1329,
1265, 1211, 1072, 1023, 999. 812, 756 cm-1; MS (ESI) m/z 530.2 ([M+Na]+); HRMS (ESI) calcd for
C24H14Br2O3 ([M+Na]+), 530.9202; found, 530.9205.
2,4-Bis(4-bromophenyl)-9-methylpyrano[3,2-c]chromen-5(4H)-one (3f): A light yellow solid; mp
187-188 ºC; 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 2
H), 7.42 (d, J = 8.4 Hz, 2 H), 7.36 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1 H), 7.21~7.18 (m, 3 H), 6.07 (d, J = 4.4
13
Hz, 1 H), 5.69 (d, J = 4.4 Hz, 1 H), 2.40 (s, 3 H), ppm; C NMR (100 MHz, CDCl3) δ 161.38, 158.72,
151.78, 136.96, 136.67, 134.76, 134.09, 133.92, 132.16, 131.06, 129.16, 129.05, 123.57, 122.76, 122.02,
119.68, 116.48, 114.52, 102.24, 77.91, 20.90 ppm; IR (KBr) v 3064, 2922, 1724, 1630, 1556, 1489, 1402,
1200, 1118, 1072, 1010, 814, 532 cm-1; MS (ESI) m/z 544.8 ([M+Na]+); HRMS (ESI) calcd for
C25H16Br2O3 ([M+Na]+), 544.9358; found, 544.9345.

HETEROCYCLES, Vol. 81, No. 4, 2010
973
2,4-Bis(4-bromophenyl)-9-chloropyrano[3,2-c]chromen-5(4H)-one (3g): A light yellow solid; mp
185-186 ºC; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 2.4 Hz, 1 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.50 (m, 3
H), 7.41 (d, J = 8.4 Hz, 2 H), 7.27 (s, 1 H), 7.17 (d, J = 8.4 Hz, 2 H), 6.11 (d, J = 3.6 Hz, 1 H), 5.73 (d, J
13
= 4.4 Hz, 1 H) ppm; C NMR (100 MHz, CDCl3) δ 160.06, 157.96, 151.87, 136.48, 136.30, 134.37,
132.88, 132.27, 131.14, 129.72, 129.20, 129.04, 123.82, 122.63, 122.20, 120.32, 118.18, 116.03, 102.88,
77.18 ppm; IR (KBr) v 3064, 2922, 1724, 1630, 1556, 1489, 1402, 1267, 1200, 1117, 1072, 1009, 814,
772 cm-1; MS (ESI) m/z 565.2 ([M+Na]+); HRMS (ESI) calcd for C24H13Br2ClO3 ([M+Na]+), 564.9032;
found, 564.9065.
2,4-Bis(4-bromophenyl)-7-methylpyrano[4,3-b]pyran-5(4H)-one (3h): A white solid; mp 186-187 ºC;
1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2 H), 7.47 (d, J = 8.4 Hz, 2 H), 7.36 (d, J = 8.0 Hz, 2
13
H), 7.18 (d, J = 8.4 Hz, 2 H), 5.91 (m, 2 H), 5.55 (d, J = 4.4 Hz, 1 H), 2.25(s, 3 H) ppm; C NMR (100
MHz, CDCl3) δ 166.40, 164.37, 159.96, 137.06, 136.39, 134.13, 132.07, 130.96, 129.21, 129.11, 123.47,
121.97, 118.55, 100.00, 99.34, 77.70, 20.29 ppm; IR (KBr) v 3097, 2924, 1718, 1641, 1541, 1487, 1406,
1205, 1007, 997, 827, 540cm-1; MS (ESI) m/z 494.9 ([M+Na]+); HRMS (ESI) calcd for C21H14Br2O3
([M+Na]+), 494.9202; found, 494.9199.
1
2,4-Dip-tolylpyrano[3,2-c]chromen-5(4H)-one (3i): A yellow oil; H NMR (400 MHz, CDCl3) δ 7.83
(d, J = 8.0 Hz, 1 H), 7.65 (t, J = 8.0 Hz, 1 H), 7.46 (d, J = 7.6 Hz, 2 H), 7.36 (m, 2 H), 7.22 (m,4 H), 7.13
(d, J = 7.6 Hz, 2 H), 6.31 (d, J = 5.2 Hz, 1 H), 5.88 (d, J = 4.8 Hz, 1 H), 2.31 (s, 3 H), 2.28 (s, 3 H) ppm;
13C NMR (100 MHz, CDCl3) δ 160.94, 158.03, 153.29, 138.99, 137.08, 135.54, 135.37, 134.09, 133.48,
129.75. 128.65, 127.68, 124.81, 123.35, 121.11, 116.72, 115.14, 102.99, 77.81, 21.19, 21.16 ppm; IR
(film) v 3028, 2924, 1731, 1614, 1573, 1493, 1398, 1327, 1266, 1177, 759 cm-1; MS (ESI) m/z 403.1
([M+Na]+); HRMS (ESI) calcd for C26H20O3 ([M+Na]+), 403.1305; found, 403.1320.
2-(4-Chlorophenyl)-4-phenylpyrano[3,2-c]chromen-5(4H)-one (3j+3j): A white solid; mp 185-186
ºC; 1H NMR (400 MHz, CDCl3) (3j/3j = 4:1) δ 7.86-7.81 (m, 1 H), 7.58-7.49 (m, 3 H), 7.44-7.24 (m, 9
H), 6.14 (d, J = 4.0 Hz, 0.8 H), 6.11 (d, J = 4.8 Hz, 0.2 H), 5.74-5.72 (m, 1 H) ppm; 13C NMR (100 MHz,
CDCl3) δ 161.45, 158.61, 153.57, 137.99, 137.64, 136.34, 135.26, 134.16, 133.69, 132.74, 132.70, 129.32,
129.11, 128.93, 128.88, 128.77, 128.07, 127.94, 127.92, 127.38, 127.35, 123.98, 123.29, 123.15, 120.49,
119.51, 116.64, 116.61, 115.06, 102.31, 79.69, 77.85 ppm; IR (KBr) v 3034, 2870, 1719, 1624, 1492,
1106, 1022, 986, 759 cm-1; MS (ESI) m/z 409.3 ([M+Na]+); HRMS (ESI) calcd for C24H15ClO3
([M+Na]+), 409.0602; found, 409.0598.
2-(4-Chlorophenyl)-9-methyl-4-phenylpyrano[3,2-c]chromen-5(4H)-one (3k+3k): A white solid; mp
1
172-173 ºC; H NMR (400 MHz, CDCl3) (3k/3k = 7:3) δ 7.61-7.59 (m, 1 H), 7.55-7.49 (m, 2 H),
7.45-7.38 (m, 3 H), 7.35-7.30 (m, 4 H), 7.28-7.24 (m, 1 H), 7.20-7.18 (m,1 H), 6.11 (d, J = 4.4 Hz, 0.69

974
HETEROCYCLES, Vol. 81, No. 4, 2010
13
H), 6.08 (d, J = 4.4 Hz, 0.31 H), 5.72-5.70 (m,1 H), 2.39 (s, 3 H) ppm; C NMR (100 MHz, CDCl3) δ
161.52, 161.14, 158.82, 158.70, 151.77, 138.09, 137.72, 136.65, 136.41, 135.75, 135.24, 134.27, 133.86,
133.82, 133.76, 133.74, 133.64, 129.31, 129.11, 128.93, 128.76, 128.05, 127.89, 127.43, 127.35, 122.84,
122.71, 120.38, 119.41, 116.41, 116.38, 114.67, 114.65, 102.23, 78.73, 20.83 ppm; IR (KBr) v 3066,
2924, 1721, 1632, 1560, 1492, 1400, 1120, 1007, 812, 727 cm-1; MS (ESI) m/z 422.9 ([M+Na]+); HRMS
(ESI) calcd for C25H17ClO3 ([M+Na]+), 423.0758; found, 423.0751.
2-(2-Chlorophenyl)-9-methyl-4-phenylpyrano[3,2-c]chromen-5(4H)-one (3l+3l): A white solid; mp
1
198-199 ºC; H NMR (400 MHz, CDCl3) (3l/3l = 3:1) δ 7.65-7.63 (m, 2 H), 7.47-7.44 (m, 1 H),
7.36-7.29 (m, 8 H), 7.19 (d, J = 8.4 Hz, 1 H), 6.54 (d, J = 4.0 Hz, 1 H), 5.69 (d, J = 3.6 Hz, 1 H), 2.38 (s,
13
2.25 H), 2.36 (s, 0.75 H) ppm; C NMR (100 MHz, CDCl3) δ 161.42, 158.78, 151.78, 137.75, 135.67,
135.37, 133.80, 133.77, 133.57, 133.51, 133.11, 132.93, 130.29, 130.14, 129.87, 129.29, 128.94, 128.86,
127.87, 127.35, 127.24, 122.92, 122.79, 119.06, 116.36, 114.48, 102.54, 102.43, 75.39, 20.89, 20.83
ppm; IR (KBr) v 3057, 2926, 1723, 1627, 1556, 1493, 1397, 1285, 1202, 1114, 1009, 760, 698 cm-1; MS
(ESI) m/z 422.8 ([M+Na]+); HRMS (ESI) calcd for C25H17ClO3 ([M+Na]+), 423.0753; found, 423.0751.
ACKNOWLEDGEMENTS
This work was supported by the National Natural Science Foundation of China (No. 20702047 and
Jo830413) as well as the Natural Science Foundation of Zhejiang Province (R407106 and Y4090028).
REFERENCES (AND NOTES)
1. F. Diederich and P. J. Stang, Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: New York,
1998.
2. (a) B. M. Trost, Acc. Chem. Res., 2002, 35, 695; (b) B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995,
34, 259; (c) B. M. Trost, Science, 1991, 254, 1471.
3. N. Winterton, Green Chem., 2001, 3, G73.
4. (a) V. Ritleng, C. Sirlin, and M. Pfeffer, Chem. Rev., 2002, 102, 1731; (b) T. Naota, H. Takaya, and
S. I. Murahashi, Chem. Rev., 1998, 98, 2599; (c) N. Chatani, T. Asaumi, S. Yorimitsu, T. Ikeda, F.
Kakiuchi, and S. Murai, J. Am. Chem. Soc., 2001, 123, 10935; (d) L. J. Goossen, Angew. Chem. Int.
Ed., 2002, 41, 3775; (e) B. A. Arndtsen, R. G. Bergman, T. A. Mobley, and T. H. Peterson, Acc.
Chem. Res., 1995, 28, 154; (f) H. Chen, S. Schlecht, T. C. Semple, and J. F. Hartwig, Science, 2000,
287, 1995; (g) A. S. Goldman, Nature, 1993, 366, 514; (h) C. Jia, T. Kitamura, and Y. Fujiwara, Acc.
Chem. Res., 2001, 34, 633.
5. (a) T. Hamada, X. Ye, and S. S. Stahl, J. Am. Chem. Soc., 2008, 130, 833; (b) X. Chen, X.-S. Hao, C.

HETEROCYCLES, Vol. 81, No. 4, 2010
975
E. Goodhue, and J.-Q. Yu, J. Am. Chem. Soc., 2006, 128, 6790; (c) Z. Li, D. Capretto, R. Rahaman,
and C. He, Angew. Chem. Int. Ed., 2007, 46, 5184; (d) S. Reed and M. C. White, J. Am. Chem. Soc.,
2008, 130, 3316; (e) P. S. Aburel, W. Zhuang, R. G. Hazell, and K. A. Jorgensen, Org. Biomol.
Chem., 2005, 3, 2344.
6. (a) L. M. Jackman, Adv. Org. Chem., 1960, 2, 329; (b) H.-D. Becker, The Chemistry of the
Quinonoid Compounds; Wiley: Chichester, 1974; (c) H. Lee and R. G. Harvey, J. Org. Chem. 1988,
53, 4587; (d) J. Iwamura and N. Hirao, Tetraheron Lett., 1973, 14, 2447; (e) D. Walker and J. D.
Hiebert, Chem. Rev., 1966, 66, 133; (f) B.-P. Ying, G. Trogden, D. T. Kohlman, S. X. Liang, and
Y.-C. Xu, Org. Lett., 2004, 6, 1523; (g) Y. Zhang and C.-J. Li, Angew. Chem. Int. Ed., 2006, 45,
1949; (h) B. A. Snider, Chem. Rev., 1996, 96, 339.
7. (a) Y. Zhang and C.-J. Li, J. Am. Chem. Soc., 2006, 128, 4242; (b) W. Tu, L. Liu, and P. E.
Floreancig, Angew. Chem. Int. Ed., 2008, 47, 4184; (c) D.-P. Cheng and W.-L. Bao, Adv. Synth.
Catal., 2008, 350, 1263; (d) D.-P. Cheng and W.-L. Bao, J. Org. Chem., 2008, 73, 6881; (e) Y. Li
and W.-L. Bao, Adv. Synth. Catal., 2009, 351, 865; (f) P. C. Montevecchi and M. L. Navacchia, J.
Org. Chem., 1998, 63, 8035; (g) L. Liu and P. E. Floreancig, Org. Lett., 2009, 11, 3152; (h) W. Tu
and P. E. Floreancig, Angew. Chem. Int. Ed., 2009, 48, 4567.
8. (a) A. D. Patil, A. J. Freyer, D. S. Eggleston, R. C. Haltiwanger, M. F. Bean, P. B. Taylor, M. J.
Caranfa, A. L. Breen, H. R. Bartus, R. K. Johnson, R. P. Hertzberg, and J. W. Westley, J. Med.
Chem., 1993, 36, 4131; (b) L. Verotta, E. Lovaglio, G. Vidari, P. V. Finzi, M. G. Neri, A. Raimondi,
S. Parapini, D. Taramelli, A. Riva, and E. Bombardelli, Phytochemistry, 2004, 65, 2867; (c) R. D. H.
Murray, J. Mendez, and S. A. Brown, The Natural Coumarins; Wiley-Chichester: UK, 1982; (d) J.
W. Hinman, H. Hoeksema, E. L. Caron, and W. G. Jackson, J. Am. Chem. Soc., 1956, 78, 1072.
9. (a) J. Reisch, Arch. Pharm., 1966, 299, 806; (b) Y. Acquot, B. Refouvelet, L. Bermont, G. L. Adessi,
G. Leclercq, and A. Xicluna, Pharmazie, 2002, 57, 233; (c) G. Appendino, G. Cravotto, L. Toma, R.
Annunziata, and G. Palmisano, J. Org. Chem., 1994, 59, 5556.
10. (a) D. Hong, X. F. Lin, Y. Zhu, M. Lei, and Y. Wang, Org. Lett., 2009, 11, 5678; (b) X. F. Lin, X.
Dai, Z. Mao, and Y. Wang, Tetrahedron, 2009, 65, 9233; (c) J. Wang, F. Xu, X. F. Lin, and Y.
Wang, Tetrahedron Lett., 2008, 49, 5208; (d) S. Cui, J. Wang, X. F. Lin, and Y. Wang, J. Org.
Chem., 2007, 72, 7779; (e) X. F. Lin, S. Cui, and Y. Wang, Tetrahedron Lett., 2006, 47, 4509; (f) X.
F. Lin, S. Cui, and Y. Wang, Tetrahedron Lett., 2006, 47, 3127; (g) S. Cui, X. F. Lin, and Y. Wang,
Org. Lett., 2006, 8, 4517; (h) S. Cui, X. F. Lin, and Y. Wang, Eur. J. Org. Chem., 2006, 5174; (i) S.
Cui, X. F. Lin, and Y. Wang, J. Org. Chem., 2005, 70, 2866.
11. CCDC-751023 (for 3a) contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data Centre via

976
HETEROCYCLES, Vol. 81, No. 4, 2010
www.ccdc.cam.ac.uk/data_request/cif.
12. D.-H. Gong, L. Zhang, F. Li, J.-Y. Yuan, and C.-Y. Yuan, Chin. J. Chem., 2004, 22, 925.
13. J.-L. Wang, Z.-X. Zhang, X. Xiang, R.-T. Liu, and X.-G. Zhou, J. Org. Chem., 2009, 74, 3299.
14. C. R. Reddy, B. Srikanth, R. N. Narsimha, and D. S. Shin, Tetrahedron, 2008, 64, 11666.