CDC Reaction and Subsequent Cyclization for the Synthesis of 2-Hydroxy-3-alkyl-1,4-naphthoquinones and Pyranonaphthoquinones

Article abstract of DOI:10.1021/acs.joc.6b02787

The metal-free cross-dehydrogenative coupling (CDC) reaction and subsequent cyclization of 2-hydroxy-1,4-naphthoquinone (lawsone) and 1,3-diarylpropene promoted by DDQ has been developed. 2-Hydroxy-3-alkyl-1,4-naphthoquinones and pyranonaphthoquinones wit

Full text of DOI:10.1021/acs.joc.6b02787

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Article
The CDC Reaction and Subsequent Cyclization for the Synthesis of 2-
Hydroxy-3-alkyl-1,4-naphthoquinones and Pyranonaphthoquinones
Dongping Cheng, Lijun Wu, Huawei Lv, Xiaoliang Xu, and Jizhong Yan
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 30 Dec 2016
Downloaded from http://pubs.acs.org on December 30, 2016
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The CDC Reaction and Subsequent Cyclization for the Synthesis of
2ꢀHydroxyꢀ3ꢀalkylꢀ1,4ꢀnaphthoquinones and Pyranonaphthoquinones
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Dongping Cheng,
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou
310014, P. R. China.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R.
†* Lijun Wu,† Huawei Lv,† Xiaoliang Xu‡ and Jizhong Yan†
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†
‡
China
E-mail: chengdp@zjut.edu.cn
Abstract
The metalꢀfree crossꢀdehydrogenative coupling (CDC) reaction and subsequent
cyclization of 2ꢀhydroxyꢀ1,4ꢀnaphthoquinone (lawsone) and 1,3ꢀdiarylpropene
promoted by DDQ has been developed. 2ꢀHydroxyꢀ3ꢀalkylꢀ1,4ꢀnaphthoquinones and
pyranonaphthoquinones with potential pharmaceutical applications are obtained in
moderate to good yields. The reaction is also compatible for 4ꢀhydroxycoumarins.
Keyword: Coupling reaction; DDQ; 2ꢀHydroxyꢀ3ꢀalkylꢀ1,4ꢀnaphthoquinone;
Pyranonaphthoquinone
Introduction
CDC reaction has become a powerful tool to construct carbonꢀcarbon bond, which
possesses advantages of shorter synthetic step and higher atom economy due to
avoiding prefunctionalization of the substrates.1 To accomplish this transformation,
transition metal is usually required in combination with an oxidant. However, use of
transition metal brings the drawback of metal impurities which could be harmful in
important pharmaceutical intermediates and final products.2 Recently, metalꢀfree
approaches have been developed for the CDC reaction,3 in which
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2,3ꢀdichloroꢀ5,6ꢀdicyanoꢀ1,4ꢀbenzoquinone (DDQ) has proved to be an effective
candidate.1b Among the CDC reaction promoted by DDQ, the couplings of Csp3ꢀH
bonds with Csp2ꢀH bonds are few in comparison to the couplings of Csp3ꢀH bonds
with Csp3ꢀH bonds.4 Moreover, they are mainly limited to Csp3ꢀH bonds adjacent to
heteroatoms. For example, Wang demonstrated an asymmetric oxidative coupling
reaction of tertiary amines with α,βꢀunsaturated γꢀbutyrolactam promoted by DDQ
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and an chiral additive.4e Prabhu reported
a
CDC reaction of Nꢀaryl
tetrahydroisoquinolines and 4ꢀhydroxycoumarins with a catalytic amount of DDQ and
molecular oxygen as a terminal oxidant.4g A careful literature survey reveals that the
DDQꢀmediated CDC reaction of Csp3ꢀH bond not adjacent to heteroatoms with
Csp2ꢀH bond is scare.5
Scheme 1. The structures of lawsone, lapachol, dehydroꢀαꢀlapachone, and dehydroꢀβꢀlapachone
3ꢀAlkylꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinone is an important moiety in organic
chemistry for its broad spectrum of pharmacological effects. The typical example is
lapachol I (Scheme 1) which has the activities of antitumor, antimicrobial, antifungal,
antiviral
etc.6
The
common
method
for
preparing
3ꢀalkylꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinone is the addition of lawsone 1a (Scheme 1) with
electrophilic reagents, such as the Mannich addition with intermediate of aldehyde
and amine,7 the Michael addition with α,βꢀunsaturated carbonyl compound,8 the
Knoevenagel condensation with aldehyde or ketone.9 Another available way to
synthesize 3ꢀalkylꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinone is the radical reaction of lawsone
with carboxylic acid.10 The naturally widely existing pyranonaphthoquinone plays
important biological roles in animals and plants.11 Synthesis of pyranonaphthoquinone
could be achieved through acid or oxidative cyclization of lapachol,12 or by the
domino reaction like the Knoevenagelꢀelectrocyclic reaction13 from lawsone directly.
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9
It was reported that both lapachol and isolapachol could be cyclized to give a mixture
of dehydroꢀαꢀlapachone II and dehydroꢀβꢀlapachone III in the presence of DDQ
(Scheme 1).14 However, the alkylation and cyclization of lawsone with
1,3ꢀdiarylpropene through CꢀH bond oxidation has been not yet developed. In
continuation of our interest in CDC reactions,4aꢀ4b herein, we wish to report a
metalꢀfree DDQ mediated CDC reaction of Csp2ꢀH bond of lawsone and allylic
Csp3ꢀH bond of 1,3ꢀdiarylpropene and subsequent cyclization to synthesize the
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corresponding
products
3ꢀalkylꢀ2ꢀhydroxylꢀ1,4ꢀnaphthoquinones
and
pyranonaphthoquinones.
Results and Discussion
To obtain the optimized reaction conditions, the coupling reaction of lawsone 1a
with 1,3ꢀdiphenylpropene 2a was chosen as a model reaction (Table 1). It was carried
out under MeNO2 in the presence of DDQ (1.2 equiv.). To our delight, the desired
coupling product 3a was obtained with 63% yield after 0.5 hr, accompanied by the
formation of a small amount of cyclized product 4a (entry 1). At first, several solvents
were examined (entries 2ꢀ6). The coupling reaction could proceed in all examined
solvents. The best result was given when 1,2ꢀdichloroethane was used as the solvent
(entry 2). Then the amount of DDQ was surveyed. With decreasing the amount of
DDQ, the yield of coupling product was also decreased (entry 8). However, with
increasing DDQ to a certain amount, the yield of coupling product was decreased and
the yield of cyclized product could be promoted obviously (entries 9ꢀ10).
Table 1: Screening of the coupling reaction conditionsa
Entry
Time (hr)
0.5
Solvent
MeNO2
DDQ (equiv.)
Yield of 3a (%)b
1
2
3
1.2
1.2
1.2
63
87
65
0.5
CH2ClCH2Cl
CH2Cl2
0.5
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0.5
1,4ꢀdioxane
CH3COOC2H5
CHCl3
1.2
11
74
62
86
78
70
21
0.5
0.5
1
1.2
1.2
1.2
1.1
1.5
2.0
6
7
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
CH2ClCH2Cl
8
0.5
0.5
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a 0.2 mmol of 1a, 0.24 mmol of 2a, 2 mL of solvent, r.t. b Isolated yield of 3a.
With the optimized reaction conditions in hand, various 1,3ꢀdiarylpropenes 2
were subjected to the coupling reaction (Table 2). Compound 2b possessing bromo
group on the paraꢀposition of benzene ring gave the coupling product 3b with 96%
yield (entry 2). The corresponding products were obtained with 62ꢀ82% yields when
compounds 2 bearing electronꢀdonating group in benzene ring reacted with lawsone
1a (entries 3ꢀ6). It should be pointed out that a mixture of αꢀ and γꢀ isomers were
given when the unsymmetric 1,3ꢀdiarylpropenes 2bꢀ2h were used as the substrates,
which indicated that the allylic free radical or allylic cation from 1,3ꢀdiarylpropenes
could exist in the procedure. 2ꢀIsopropylaminoꢀnaphthoquinone 1b was also adapted
to the reaction. The coupling product 3h was obtained in 70% yield when the reaction
o
time was prolonged to 1 hr at 40 C (entry 9). However, the reaction system became
complex when 2ꢀpyrrolidineꢀnaphthoquinone 1c reacted with 1,3ꢀdiphenylpropene 2a.
The desired product was obtained with only 16% yield. According to the literature,15
the addition sequence of substrate was changed and the yield could be promoted to 64%
(Table 2, entry 10).
Table 2: The coupling reaction of naphthoquinones and 1,3-diarylpropenesa
Entry
1
R1, R2, 2
3
Yield
(%)b
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H, H, 2a
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1a
1a
1a
4ꢀBr, H, 2b
4ꢀCH3, H,
2c
4ꢀCH3O, H,
2d
5
1a
3ꢀCH3, H,
78
2e
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1a
H, 4ꢀCH3,
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2f
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1a
2ꢀCl, H, 2g
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8
1a
4ꢀBr, 4ꢀCl,
2h
9c
2a
O
NH
O
1b
3h
10d
2a
O
O
N
1c
3i
a 0.2 mmol of 1, 0.24 mmol of 2, 0.24 mmol of DDQ, 2 mL of CH2ClCH2Cl, 0.5 hr. b Isolated
yield. 40 oC, 1 hr. d 0.24 mmol of 2a, 0.24 mmol of DDQ, 2 mL of CH2ClCH2Cl, stir for 5 min,
c
then 0.2 mmol of 1c, 1 hr.
4ꢀHydroxycoumarin derivatives possess a broad range of pharmacological and
physiological activities.16 A considerable number of methods about C3ꢀalkylation of
4ꢀhydroxycoumarin were reported. To provide an alternative for C3ꢀallylation of
4ꢀhydroxycoumarin through CꢀH bonds oxidation, the reaction of 4ꢀhydroxycoumarin
5 and 1,3ꢀdiphenylpropene 2a promoted by DDQ was examined. Under the previous
optimized reaction conditions, the desired coupling products were also obtained in
satisfactory yields (Table 3, entries 1ꢀ4).
Table
3
The
coupling
reaction
with
1,3-diphenylpropene
and
4-hydroxycoumarinsa
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Entry
1
R, 5
Product, 6
Yield (%)b
74
H, 5a
6a
2
3
4
CH3, 5b
76
64
6b
Cl, 5c
6c
OCH3, 5d
67
6d
a 0.2 mmol of 5, 0.24 mmol of 2a, 0.24 mmol of DDQ, 2 mL of CH2ClCH2Cl, 0.5 hr. Isolated
b
yield.
In optimization of the coupling reaction conditions, the cyclization product 4a was
isolated in low yield when lawsone 1a reacted with 1,3ꢀdiphenylpropene 2a. In the
continuation of our research, the cyclization reaction was further investigated. Extra
DDQ (1.0 equiv.) was added to the reaction mixture after the coupling reaction of
lawsone 1a with 1,3ꢀdiphenylpropene 2a. It continued to be stirred for 1 hr at room
temperature and the cyclization product was obtained with 84% yield. Similarly,
various substrates were subjected to the cyclization reaction. The corresponding
pyranonaphthoquinones and pyranocoumarins were given in moderate to good yields
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(Table 4, entries 1ꢀ13).
Table 4: Scope of the cyclization reactiona
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Entry
1
1 or 5
2
Product 4
Yield (%)b
84
1a
2a
2
1a
2b
64
3
4
5
1a
1a
1a
2c
2d
2e
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2g
2h
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9c
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5b
5c
2a
2a
2a
2a
13
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10c
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a 0.2 mmol of 1 or 5, 0.24 mmol of 2, 3 mL of CH2ClCH2Cl, 0.24 mmol of DDQ, 0.5 hr; then 0.2
mmol of DDQ, 1 hr, r.t. b Isolated yield. c 40 oC.
Besides, the reaction of lawsone 1a or 4ꢀhydroxycoumarin 5a with
1,3ꢀdiphenylpropene 2a promoted by a catalytic amount of DDQ was examined
o
(Scheme 2). It was performed under AIBN at 80 C in the presence of oxygen
atmosphere (oxygen balloon). The coupling product 3a or 6a was given within 6 hrs.
Scheme 2. The coupling reaction promoted by DDQ/AIBN/O2 system.
Mechanism
Scheme 3. Some control experiments.
To explore the reaction mechanism, some control experiments were performed
(Scheme 3). The yield of coupling product 3a was decreased from 86% to 10% when
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Ar1
Ar2
O
Cl
Cl
NC
NC
Cl
Cl
H
+
O
Ar1
Ar2
O
SET
H
2
NC
CN
O
9
DDQ
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O
OH
Ar2
OH
Ar1
O
OH
Ar1
OH
Ar1
Ar2
O
O
NC
NC
Cl
Cl
H
O
1a
+
- DDQH2
O
Ar2
O
3
DDQ
O
O
OH
O
Ar1
Ar1
O
Ar2
O
O
Ar2
O
+
- DDQH2
+
O
OH
Ar1
Ar2
Ar2
O
4
O
Ar1
Scheme 4. Possible reaction mechanism
a radical scavenger TEMPO was added to the reaction mixture, which obviously
indicated that the reaction was a singleꢀelectron transfer in the process. The
cyclization of coupling product 3a was examined under CH2ClCH2Cl in the presence
of DDQ (1.2 equiv.). The cyclization product 4a was obtained in 85% yield within 1
hr. The yield was decreased to 41% when TEMPO was added to the system. On the
base of the literatures4d and our experiments, a possible mechanism was proposed as
Scheme 4. In the presence of DDQ, 1,3ꢀdiarylpropene generated an allylic cation
which was attacked by the nucleophilic reagent lawsone to give the coupling product
3. The allylic cation was rearranged between αꢀ and γꢀ positions. In our experiment, a
mixture of αꢀ and γꢀ isomers was obtained when unsymmetric 1,3ꢀdiarylpropene was
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used as the substrate. Similarly, compound 3 could react with DDQ to give the allylic
cation, followed by the intramolecular nucleophilic attack of hydroxyl group to
produce the cyclization product 4.
9
Conclusion
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In conclusion, we have developed a novel Csp3ꢀH and Csp2ꢀH CDC reaction and
subsequent cyclization of lawsones or 4ꢀhydroxycoumarins and 1,3ꢀdiarylpropenes
promoted by DDQ. Various 2ꢀhydroxyꢀ3ꢀalkylꢀ1,4ꢀnaphthoquinones and
pyranonaphthoquinones were obtained in good yields under mild conditions.
Experimental Section
General information. Column chromatography was carried out on silica gel (200ꢀ300 mesh). 1H
NMR spectra were recorded on a 500 MHz spectrometer. 13C NMR spectra were recorded on a
125 MHz spectrometer. Chemical shifts were reported in parts per million (δ) relative to the
internal standard TMS (0 ppm) for CDCl3. The coupling constants, J, were reported in Hertz (Hz).
Highꢀresolution mass spectra (HRMS) were recorded on ESIꢀTOF. The reagents were purchased
from commercial chemical reagent companies and used without further purification unless
otherwise stated.
1. General procedure for the synthesis of 3 or 6: To a solution of lawsone 1 or
4ꢀhydroxycoumarin 5 (0.2 mmol) and 1,3ꢀdiarylpropene 2 (0.24 mmol) in CH2ClCH2Cl (2 mL),
DDQ (0.24 mmol, 0.055 g) was added. The resulting mixture was stirred for 0.5 hr at room
temperature. After the completion of the reaction, the solvent was concentrated under reduced
pressure. Purification was done by column chromatography on silica gel (200ꢀ300 mesh) with
petroleum ether and ethyl acetate (3:1) as the eluent to give the pure product 3 or 6.
(E)-2-(1,3-Diphenylallyl)-3-hydroxynaphthoquinone (3a). Purification by flash chromatography
afforded 3a (0.064 g, 87% yield) as yellow oil. 1H NMR (500 MHz, CDCl3/TMS): δ 8.16ꢀ8.14 (m,
1H), 8.11ꢀ8.09 (m, 1H), 7.79ꢀ7.76 (m, 1H), 7.72ꢀ7.68 (m, 1H), 7.57 (s, 1H), 7.45ꢀ7.44 (m, 4H),
7.34ꢀ7.31 (m, 4H), 7.25ꢀ 7.22 (m, 2H), 7.05, 7.02 (dd, J = 8.9, 15.7 Hz, 1H), 6.64 (d, J = 15.8 Hz,
1H), 5.41 (d, J = 9.0 Hz, 1H). 13C NMR (125 MHz, CDCl3/TMS): δ 183.8, 181.8, 152.8, 141.7,
137.3, 135.2, 133.0, 132.9, 132.5, 129.3, 128.6, 128.5, 128.4, 127.8, 127.5, 127.2, 126.5, 126.4,
126.2, 124.8, 44.1. HRMS (ESI): calcd. for C25H18O3 [M+H+] 367.1329; found 367.1335.
Mixture of (E)-2-(3-(4-bromophenyl)-1-phenylallyl)-3-hydroxynaphthoquinone (3b) and
(E)-2-(1-(4-bromophenyl)-3-phenylallyl)-3-hydroxynaphthoquinone (3b') as 3:2. Purification by
flash chromatography afforded 3b and 3b'(0.085 g, 96% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3/TMS): δ 8.15ꢀ8.13 (m, 1H), 8.11ꢀ8.09 (m, 1H), 7.80ꢀ7.76 (m, 1H), 7.72ꢀ7.68 (m, 1H), 7.60
(s, 1H), 7.44ꢀ7.42 (m, 4H), 7.33ꢀ7.29 (m, 4H), 7.26ꢀ7.22 (m, 1H), 7.05ꢀ6.93 (m, 1H), 6.63, 6.56
(dd, J = 15.8, 15.8 Hz, 1H), 5.39 (d, J = 8.9 Hz, 3/5×1H), 5.34 (d, J = 9.0 Hz, 2/5×1H). 13C NMR
(125 MHz, CDCl3/TMS): δ 183.8, 183.7, 181.8, 181.7, 152.87, 152.86, 141.4, 140.8, 137.0, 136.2,
135.3, 135.2, 133.2, 133.1, 132.9, 132.8, 131.6, 131.4, 131.2, 129.7, 129.6, 129.24, 129.22, 128.6,
128.5, 128.0, 127.9, 127.8, 127.6, 127.2, 126.6, 126.4, 126.24, 126.19, 124.6, 124.3, 121.2, 120.4,
44.1, 43.6. HRMS (ESI): calcd. for C25H16BrO3[MꢀH]ꢀ 443.0288; found 443.0298.
Mixture
of
(E)-2-hydroxy-3-(3-phenyl-1-(p-tolyl)allyl)naphthoquinone
(3c)
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(E)-2-hydroxy-3-(1-phenyl-3-(p-tolyl)allyl)naphthoquinone (3c') as 3:2. Purification by flash
chromatography afforded 3c and 3c' (0.059 g, 77% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3/TMS): δ 8.16 (d, J = 7.7 Hz, 1H), 8.10ꢀ8.09 (m, 1H), 7.79ꢀ7.75 (m, 1H), 7.71ꢀ7.67 (m, 1H),
7.62 (s, 1H), 7.47ꢀ7.45 (m, 2H), 7.37ꢀ7.32 (m, 4H), 7.26ꢀ7.23 (m, 1H), 7.16ꢀ7.13 (m, 2H),
7.08ꢀ6.98 (m, 1H), 6.65, 6.64 (dd, J = 15.8, 15.7 Hz, 1H), 5.43ꢀ5.39 (m, 1H), 2.36 (s, 2/5×3H),
2.35 (s, 3/5×3H). 13C NMR (125 MHz, CDCl3): δ 183.83, 183.81, 181.8, 152.8, 152.7, 141.8,
138.6, 137.3, 137.2, 136.0, 135.1, 134.5, 133.0, 132.8, 132.3, 132.2, 129.2, 129.1, 128.9, 128.5,
128.3, 127.8, 127.7, 127.5, 127.4, 127.1, 126.43, 126.39, 126.30, 126.1, 125.0, 124.9, 44.1, 43.7,
21.2, 21.0. HRMS (ESI): calcd. for C26H19O3 [MꢀH]ꢀ 379.1340; found 379.1322.
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Mixture of (E)-2-hydroxy-3-(1-(4-methoxyphenyl)-3-phenylallyl)naphthoquinone (3d) and
(E)-2-hydroxy-3-(3-(4-methoxyphenyl)-1-phenylallyl)naphthoquinone (3d') as 7:3. Purification by
flash chromatography afforded 3d and 3d' (0.049 g, 62% yield) as yellow oil.1H NMR (500 MHz,
CDCl3/TMS): δ 8.15ꢀ8.13 (m, 1H), 8.10ꢀ8.08 (m, 1H), 7.79ꢀ7.76 (m, 1H), 7.71ꢀ7.68 (m, 1H), 7.58
(s, 7/10×1H), 7.56 (s, 3/10×1H), 7.45ꢀ7.43 (m, 2H), 7.39ꢀ7.35 (m, 2H), 7.33ꢀ7.30 (m, 2H),
7.25ꢀ7.20 (m, 1H), 7.03, 7.00 (dd, J = 8.8, 15.8 Hz, 7/10×1H), 6.91ꢀ6.85 (m, 2H+3/10×1H), 6.61,
6.59 (dd, J = 15.8, 15.7 Hz, 1H), 5.38 (d, J = 9.1 Hz, 3/10×1H), 5.35 (d, J = 8.8 Hz, 7/10×1H),
3.82 (s, 3/10×3H), 3.79 (s, 7/10×3H). 13C NMR (125 MHz, CDCl3/TMS): δ 183.9, 181.9, 159.1,
158.2, 152.8, 152.7, 137.3, 135.1, 133.8, 133.0, 132.9, 132.1, 131.9, 129.2, 129.0, 128.9, 128.5,
128.4, 127.8, 127.6, 127.4, 127.1, 126.4, 126.3, 126.1, 125.0, 114.0, 113.8, 55.3, 55.2, 44.1, 43.4.
HRMS (ESI): calcd. for C26H19O4 [MꢀH]ꢀ 395.1289; found 395.1294.
Mixture
of
(E)-2-hydroxy-3-(3-phenyl-1-(m-tolyl)allyl)naphthoquinone
(3e)
and
(E)-2-hydroxy-3-(1-phenyl-3-(m-tolyl)allyl)naphthoquinone (3e') as 3:2. Purification by flash
chromatography afforded 3e and 3e' (0.059 g, 78% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3/TMS): δ 8.16ꢀ8.14 (m, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.80ꢀ7.76 (m, 1H), 7.72ꢀ7.68 (m, 1H),
7.57 (s, 1H), 7.46ꢀ7.43 (m, 2H), 7.34ꢀ7.31 (m, 2H), 7.25ꢀ7.20 (m, 4H), 7.06ꢀ6.99 (m, 2H), 6.63,
6.61 (dd, J = 15.8, 15.8 Hz, 1H), 5.41 (d, J = 9.1 Hz, 2/5×1H), 5.38 (d, J = 10.0 Hz, 3/5×1H), 2.36
(s, 2/5×3H), 2.34 (s, 3/5×3H). 13C NMR (125 MHz, CDCl3): δ 183.8, 183.7, 181.70, 181.67,
152.83, 152.80, 141.71, 141.65, 141.58, 138.0, 137.9, 137.23, 137.18, 137.11, 135.0, 132.9,
132.73, 132.72, 132.5, 132.3, 132.2, 129.1, 128.8, 128.6, 128.5, 128.4, 128.3, 128.22, 128.17,
127.8, 127.4, 127.3, 127.2, 126.99, 126.96, 126.42, 126.39, 126.35, 126.0, 124.81, 124.76, 124.71,
123.6, 44.1, 44.0, 21.5, 21.3. HRMS (ESI): calcd. for C26H19O3 [MꢀH]ꢀ 379.1340; found 379.1331.
Mixture
of
(E)-2-hydroxy-3-(3-phenyl-1-(p-tolyl)allyl)naphthoquinone
(3c)
and
(E)-2-hydroxy-3-(1-phenyl-3-(p-tolyl)allyl)naphthoquinone (3c') as 3:2. Purification by flash
chromatography afforded 3c and 3c' (0.062 g, 82% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3/TMS): δ 8.15 (d, J = 7.3 Hz, 1H), 8.09 (d, J = 7.7 Hz, 1H), 7.79ꢀ7.75 (m, 1H), 7.71ꢀ7.67
(m, 1H), 7.60 (s, 1H), 7.46ꢀ7.44 (m, 2H), 7.36ꢀ7.31 (m, 4H), 7.25ꢀ7.22 (m, 1H), 7.15ꢀ7.13 (m, 2H),
7.06ꢀ6.96 (m, 1H), 6.64, 6.63 (dd, J = 15.8, 15.8 Hz, 1H), 5.42ꢀ5.38 (m, 1H), 2.35 (s, 2/5×3H),
2.34 (s, 3/5×3H). 13C NMR (125 MHz, CDCl3/TMS): δ 183.84, 183.82, 181.8, 152.79, 152.75,
141.8, 138.7, 137.3, 137.2, 136.0, 135.1, 134.5, 133.0, 132.9, 132.3, 132.2, 129.2, 129.1, 128.9,
128.5, 128.4, 127.8, 127.7, 127.5, 127.4, 127.1, 126.43, 126.39, 126.31, 126.1, 125.0, 124.9, 44.1,
43.7, 21.2, 21.0. HRMS (ESI): calcd. for C26H19O3 [MꢀH]ꢀ 379.1340; found 379.1326.
Mixture of (E)-2-(3-(2-chlorophenyl)-1-phenylallyl)-3-hydroxynaphthoquinone (3f) and
(E)-2-(1-(2-chlorophenyl)-3-phenylallyl)-3-hydroxynaphthoquinone (3f') as 13:12. Purification by
flash chromatography afforded 3f and 3f' (0.060 g, 75% yield) as yellow oil. 1H NMR (500 MHz,
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CDCl3/TMS): δ 8.16ꢀ8.15 (m, 1H), 8.10ꢀ8.08 (m, 1H), 7.79ꢀ7.75 (m, 1H), 7.71ꢀ7.65 (m, 2H), 7.64
(s, 12/25×1H), 7.54 (s, 13/25×1H), 7.48ꢀ7.44 (m, 2H), 7.36ꢀ7.17 (m, 6H), 7.10ꢀ7.01 (m,
12/25×1+12/25×1H), 6.86, 6.83 (dd, J = 8.4, 15.8 Hz, 13/25×1H), 6.64 (d, J = 15.8 Hz,
13/25×1H), 5.64 (d, J = 8.4 Hz, 13/25×1H), 5.47 (d, J = 7.4 Hz, 12/25×1H). 13C NMR (125 MHz,
CDCl3/TMS): δ 183.8, 183.4, 181.8, 181.6, 153.0, 152.9, 141.4, 139.2, 137.1, 135.3, 135.2, 133.7,
133.03, 132.97, 132.95, 132.84, 132.4, 131.7, 130.6, 129.6, 129.4, 129.3, 129.2, 128.53, 128.46,
128.43, 127.9, 127.8, 127.6, 127.2, 127.14, 127.07, 127.04, 126.8, 126.6, 126.5, 126.4, 126.2,
124.6, 123.3, 44.4, 41.9. HRMS (ESI): calcd. for C25H16ClO3 [MꢀH]ꢀ 399.0793; found 399.0798.
Mixture of (E)-2-(1-(4-bromophenyl)-3-(4-chlorophenyl)allyl)-3-hydroxynaphthoquinone (3g)
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and
(E)-2-(3-(4-bromophenyl)-1-(4-chlorophenyl)allyl)-3-hydroxynaphthoquinone
(3g').
Purification by flash chromatography afforded 3g and 3g' (0.073 g, 76% yield) as yellow oil. H
NMR (500 MHz, CDCl3/TMS): δ 8.13 (d, J = 7.7 Hz, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.80ꢀ7.77 (m,
1H), 7.72ꢀ7.69 (m, 1H), 7.63 (s, 1H), 7.44ꢀ7.42 (m, 2H), 7.35 (d, J = 7.6 Hz, 2H), 7.30ꢀ7.27 (m,
4H), 6.97ꢀ6.90 (m, 1H), 6.58, 6.54 (dd, J = 15.8, 15.8 Hz, 1H), 5.34, 5.32 (dd, J = 8.1, 8.2 Hz, 1H).
13C NMR (125 MHz, CDCl3/TMS): δ 183.7, 181.6, 152.9, 140.5, 139.9, 136.0, 135.5, 135.3,
133.2, 132.7, 132.4, 131.7, 131.6, 131.5, 129.6, 129.2, 129.0, 128.7, 128.5, 128.0, 127.6, 127.2,
126.3, 124.1, 124.0, 121.3, 120.5, 43.6, 43.5. HRMS (ESI): calcd. for C25H15BrClO3 [MꢀH]ꢀ
476.9899; found 476.9907.
(E)-2-(1,3-Diphenylallyl)-3-(isopropylamino)naphthoquinone (3h). Purification by flash
chromatography afforded 3h (0.057 g, 70% yield) as orange oil. 1H NMR (500 MHz, CDCl3): δ
8.11ꢀ8.09 (m, 1H), 8.01ꢀ7.99 (m, 1H), 7.70ꢀ7.67 (m, 1H), 7.61ꢀ7.58 (m, 1H), 7.42 (d, J = 7.4 Hz,
2H), 7.37ꢀ7.29 (m, 7H), 7.27ꢀ7.21 (m, 1H), 6.80, 6.76 (dd, J = 7.2, 15.9 Hz, 1H), 6.57 (d, J = 15.8
Hz, 1H), 5.69 (d, J = 7.2 Hz, 1H), 5.12 (d, J = 8.6 Hz, 1H), 4.32ꢀ4.29 (m, 1H), 1.06 (d, J = 6.3 Hz,
3H), 0.90 (d, J = 6.3 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 183.6, 181.8, 146.5, 141.9, 137.1,
134.2, 133.0, 132.6, 131.9, 131.2, 128.7, 128.6, 127.8, 127.5, 127.4, 126.6, 126.4, 126.3, 125.9,
118.1, 47.2, 43.3, 24.24, 24.18. HRMS (ESI): calcd. For C28H26NO2 [M+H+] 408.1958; found
408.1955.
(E)-2-(1,3-Diphenylallyl)-3-(pyrrolidin-1-yl)naphthoquinone (3i). Purification by flash
chromatography afforded 3i (0.054 g, 64% yield) as red oil. 1H NMR (500 MHz, CDCl3/TMS): δ
7.99ꢀ7.98 (m, 1H), 7.91ꢀ7.89 (m, 1H), 7.66ꢀ7.63 (m, 1H), 7.59ꢀ7.56 (m, 1H), 7.46 (d, J = 7.3 Hz,
2H), 7.39 (d, J = 7.6 Hz, 2H), 7.34ꢀ7.29 (m, 4H), 7.25ꢀ7.18 (m, 2H), 7.12, 7.09 (dd, J = 8.4, 16.0
Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 4.98 (d, J = 8.3 Hz, 1H), 3.77 (t, J = 6.4 Hz, 4H), 1.91ꢀ1.87 (m,
4H). 13C NMR (125 MHz, CDCl3): δ 185.5, 182.1, 154.5, 143.6, 137.5, 133.6, 133.3, 132.1, 132.0,
131.6, 128.5, 128.0, 127.6, 127.2, 126.4, 125.8, 125.6, 125.3, 120.1, 54.2, 48.5, 25.8. HRMS (ESI):
calcd. for C29H26NO2 [M+H+] 420.1958; found 420.1955.
(E)-3-(1,3-Diphenylallyl)-4-hydroxy-2H-chromen-2-one (6a).17 Purification by flash
o
chromatography afforded 6a (0.052 g, 74% yield) as white solid, mp 155ꢀ157 C. 1H NMR (500
MHz, CDCl3/TMS): δ 7.83ꢀ7.81 (m, 1H), 7.58ꢀ7.55 (m, 1H), 7.45ꢀ7.39 (m, 6H), 7.35ꢀ7.26 (m,
6H), 7.13 (s, 1H), 6.81, 6.77 (dd, J = 6.3, 16.1 Hz, 1H), 5.57ꢀ6.53 (m, 1H), 5.50 (d, J = 5.8 Hz,
1H). 13C NMR (125 MHz, CDCl3): δ 163.1, 160.9, 152.7, 139.5, 136.1, 134.0, 132.2, 129.4, 128.7,
128.14, 128.09, 127.7, 126.6, 124.0, 123.1, 116.5, 115.9, 106.4, 44.0.
(E)-3-(1,3-Diphenylallyl)-4-hydroxy-6-methyl-2H-chromen-2-one (6b). Purification by flash
o
chromatography afforded 6b (0.056 g, 76% yield) as white solid, mp 87ꢀ89 C. 1H NMR (500
MHz, CDCl3/TMS): δ 7.63 (d, J = 1.2 Hz, 1H), 7.45ꢀ7.37 (m, 7H), 7.35ꢀ7.31 (m, 3H), 7.29ꢀ7.27
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(m, 2H), 7.22 (d, J = 8.5 Hz, 1H), 6.83, 6.80 (dd, J = 6.4, 16.0 Hz, 1H), 6.57ꢀ6.53 (m, 1H), 5.50 (d,
J = 6.1 Hz, 1H), 2.41 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 163.4, 161.0, 150.9, 139.7, 136.2,
133.74, 133.71, 133.2, 129.2, 128.6, 128.3, 128.03, 127.99, 127.6, 126.5, 122.8, 116.3, 115.5,
106.3, 44.0, 20.9. HRMS (ESI): calcd. for C25H19O3 [MꢀH]ꢀ 367.1340; found 367.1341.
(E)-6-Chloro-3-(1,3-diphenylallyl)-4-hydroxy-2H-chromen-2-one (6c).17 Purification by flash
o
chromatography afforded 6c (0.050 g, 64% yield) as white solid, mp 87ꢀ89 C. 1H NMR (500
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MHz, CDCl3/TMS): δ 7.81 (d, J = 2.5 Hz, 1H), 7.50ꢀ7.48 (m, 1H), 7.43ꢀ7.38 (m, 6H), 7.35ꢀ7.32
(m, 3H), 7.29ꢀ7.25 (m, 3H), 6.80, 6.77 (dd, J = 6.5, 16.1 Hz, 1H), 6.57ꢀ6.54 (m, 1H), 5.47 (d, J =
6.3 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 162.7, 159.8, 151.0, 139.3, 136.0, 134.1, 132.1,
129.6, 129.4, 128.7, 128.1, 128.0, 127.8, 127.7, 126.5, 122.8, 118.0, 117.1, 107.4, 44.1.
(E)-3-(1,3-Diphenylallyl)-4-hydroxy-6-methoxy-2H-chromen-2-one (6d). Purification by flash
o
chromatography afforded 6d (0.051 g, 67% yield) as white solid, mp 148ꢀ150 C. 1H NMR (500
MHz, CDCl3/TMS): δ7.44ꢀ7.38 (m, 6H), 7.34ꢀ7.31 (m, 3H), 7.29ꢀ7.25 (m, 4H), 7.15ꢀ7.12 (m, 1H),
6.81, 6.78 (dd, J = 6.3, 16.1 Hz, 1H), 6.56ꢀ6.52 (m, 1H), 5.50 (d, J = 6.2 Hz, 1H), 3.83 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 163.4, 160.7, 155.9, 147.2, 139.6, 136.2, 133.9, 129.3, 128.7, 128.2,
128.1, 127.7, 126.6, 120.5, 117.7, 116.2, 106.6, 104.7, 55.8, 44.0. HRMS (ESI): calcd. for
C25H20NaO4 [M+Na]+ 407.1254; found 407.1238.
2. General procedure for the synthesis of 4: To a solution of lawsone 1 or 4ꢀhydroxycoumarin 5
(0.2 mmol), 1,3ꢀdiarylpropene 2 (0.24 mmol) in CH2ClCH2Cl (3 mL), DDQ (0.24 mmol, 0.055 g)
was added. The resulting mixture was stirred for 0.5 hr at room temperature. Then extra DDQ (0.2
mmol, 0.045 g) was added. The mixture was stirred for another 1 hr at room temperature. After the
completion of the reaction, the solvent was concentrated under reduced pressure. Purification was
done by column chromatography on silica gel (200ꢀ300 mesh) with petroleum ether and ethyl
acetate (5:1) as the eluent to give the pure product 4.
2,4-Diphenyl-2H-benzo[g]chromene-5,10-dione (4a). Purification by flash chromatography
1
afforded 4a (0.061 g, 84% yield) as yellow solid, mp 174ꢀ176 oC. H NMR (500 MHz,
CDCl3/TMS): δ 8.12ꢀ8.10 (m, 1H), 8.01ꢀ7.99 (m, 1H), 7.71ꢀ7.69 (m, 2H), 7.58 (d, J = 6.5 Hz, 2H),
7.44ꢀ7.39 (m, 6H), 7.30ꢀ7.28 (m, 2H), 6.16 (d, J = 4.5 Hz, 1H), 5.98 (d, J = 4.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3): δ 181.3, 179.4, 154.8, 138.6, 137.5, 135.2, 134.3, 133.2, 132.2, 131.1, 129.4,
128.9, 128.1, 127.8, 127.7, 127.4, 126.7, 126.1, 124.2, 121.0, 78.1. HRMS (ESI): calcd. for
C25H17O3 [M+H+] 365.1172; found 365.1175.
Mixture of 2-(4-bromophenyl)-4-phenyl-2H-benzo[g]chromene-5,10-dione
(4b) and
4-(4-bromophenyl)-2-phenyl-2H-benzo[g]chromene-5,10-dione (4b') as 13:12. Purification by
flash chromatography afforded 4b and 4b' (0.057 g, 64% yield) as yellow solid. 1H NMR (500
MHz, CDCl3/TMS): δ 8.11ꢀ8.09 (m, 1H), 8.00ꢀ7.99 (m, 1H), 7.73ꢀ7.68 (m, 2H), 7.56ꢀ7.51 (m,
3H), 7.46ꢀ7.39 (m, 4H), 7.28ꢀ7.26 (m, 1H), 7.17ꢀ7.14 (m, 1H), 6.15 (d, J = 4.5 Hz, 12/25×1H),
6.11 (d, J = 4.6 Hz, 13/25×1H), 5.96 (d, J = 4.6 Hz, 12/25×1H), 5.94 (d, J = 4.6 Hz, 13/25×1H).
13C NMR (125 MHz, CDCl3): δ 181.3, 181.2, 179.33, 179.28, 155.0, 154.6, 138.4, 137.6, 137.4,
136.6, 135.7, 134.4, 133.4, 133.3, 132.2, 132.1, 131.33, 131.28, 131.0, 129.5, 129.3, 129.1, 129.0,
128.2, 128.0, 127.7, 127.4, 126.8, 126.7, 126.2, 126.1, 124.5, 123.7, 123.5, 121.9, 121.1, 120.5,
78.2. HRMS (ESI): calcd. for C25H16BrO3 [M+H+] 443.0277; found 443.0287.
Mixture
of
2-phenyl-4-(p-tolyl)-2H-benzo[g]chromene-5,10-dione
(4c)
and
4-phenyl-2-(p-tolyl)-2H-benzo[g]chromene-5,10-dione (4c') as 13:12. Purification by flash
chromatography afforded 4c and 4c' (0.059 g, 78% yield) as yellow solid. 1H NMR (500 MHz,
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CDCl3): δ 8.11ꢀ8.08 (m, 1H), 8.02ꢀ7.99 (m, 1H), 7.71ꢀ7.67 (m, 2H), 7.59ꢀ7.57 (m, 1H), 7.48ꢀ7.46
(m, 1H), 7.42ꢀ7.39 (m, 3H), 7.30ꢀ7.28 (m, 1H), 7.23ꢀ7.17 (m, 3H), 6.15ꢀ6.13 (m, 1H), 5.97ꢀ5.94
(m, 1H), 2.41 (s, 13/25×3H), 2.37 (s, 12/25×3H). 13C NMR (125 MHz, CDCl3): δ 181.4, 181.3,
179.5, 179.4, 154.81, 154.78, 139.5, 138.7, 137.6, 135.7, 135.1, 135.0, 134.4, 134.3, 134.2, 133.2,
133.1, 132.26, 132.23, 131.1, 129.5, 129.3, 128.9, 128.8, 128.1, 127.83, 127.76, 127.7, 127.4,
127.2, 126.7, 126.6, 126.0, 124.2, 123.7, 121.2, 121.0, 78.1, 78.0, 21.3, 21.2. HRMS (ESI): calcd.
for C26H19O3 [M+H+] 379.1329; found 379.1326.
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Mixture of 4-(4-methoxyphenyl)-2-phenyl-2H-benzo[g]chromene-5,10-dione (4d) and
2-(4-methoxyphenyl)-4-phenyl-2H-benzo[g]chromene-5,10-dione (4d') as 2:1. Purification by
flash chromatography afforded 4d and 4d' (0.051 g, 65% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3): δ8.10ꢀ8.07 (m, 1H), 8.02ꢀ7.99 (m, 1H), 7.71ꢀ7.68 (m, 2H), 7.58 (d, J = 6.9 Hz, 2/3×2H),
7.52 (d, J = 8.5 Hz, 1/3×2H), 7.43ꢀ7.39 (m, 3H), 7.31ꢀ7.29 (m, 2/3×1H), 7.22ꢀ7.21 (m, 1+1/3×1H),
6.93 (d, J = 8.5 Hz, 2H), 6.12 (d, J = 4.2 Hz, 1H), 5.95, 5.93 (dd, J = 4.6, 4.4 Hz, 1H), 3.85 (s,
2/3×3H), 3.81 (s, 1/3×3H). 13C NMR (125 MHz, CDCl3): δ 181.3, 181.2, 179.4, 179.3, 160.5,
159.3, 154.8, 154.7, 138.7, 137.6, 135.0, 134.7, 134.18, 134.15, 133.09, 133.06, 132.3, 132.2,
131.05, 131.02, 130.9, 129.5, 129.3, 129.2, 128.8, 128.5, 128.0, 127.7, 127.6, 127.3, 126.6, 126.5,
125.9, 124.1, 123.3, 121.1, 120.9, 114.2, 113.5, 78.1, 77.9, 55.3, 55.2. HRMS (ESI): calcd. for
C26H19O4 [M+H+] 395.1278; found 395.1294.
Mixture
of
2-phenyl-4-(m-tolyl)-2H-benzo[g]chromene-5,10-dione
(4e)
and
4-phenyl-2-(m-tolyl)-2H-benzo[g]chromene-5,10-dione (4e') as 27:23. Purification by flash
chromatography afforded 4e and 4e' (0.045 g, 60% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3): δ 8.12ꢀ8.10 (m, 1H), 8.01ꢀ7.99 (m, 1H), 7.71ꢀ7.69 (m, 2H), 7.59ꢀ7.57 (m, 1H), 7.42ꢀ7.37
(m, 4H), 7.30ꢀ7.27 (m, 2H), 7.21ꢀ7.20 (m, 23/50×1+23/50×1H), 7.12 (s, 27/50×1H), 7.06 (d, J =
7.7 Hz, 27/50×1H), 6.15 (d, J = 4.6 Hz, 27/50×1H), 6.12 (d, J = 4.5 Hz, 23/50×1H), 5.97ꢀ5.95 (m,
1H), 2.40 (s, 27/50×3H), 2.39 (s, 23/50×3H). 13C NMR (125 MHz, CDCl3): δ 181.30, 181.26,
179.4, 154.9, 154.7, 138.69, 138.67, 138.61, 137.7, 137.6, 137.5, 135.2, 135.0, 134.3, 133.2, 132.3,
131.1, 130.1, 129.3, 128.9, 128.7, 128.6, 128.4, 128.1, 128.0, 127.9, 127.8, 127.7, 127.4, 126.7,
126.0, 124.8, 124.5, 124.3, 124.0, 121.2, 121.0, 78.3, 78.1, 21.50, 21.45. HRMS (ESI): calcd. for
C26H19O3 [M+H+] 379.1329; found 379.1342.
Mixture
of
2-phenyl-4-(p-tolyl)-2H-benzo[g]chromene-5,10-dione
(4c)
and
4-phenyl-2-(p-tolyl)-2H-benzo[g]chromene-5,10-dione (4c') as 1:1. Purification by flash
chromatography afforded 4c and 4c' (0.047 g, 62% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3): δ 8.11ꢀ8.08 (m, 1H), 8.02ꢀ7.99 (m, 1H), 7.71ꢀ7.68 (m, 2H), 7.59ꢀ7.57 (m, 1H), 7.48 (d, J
= 8.1 Hz, 1H), 7.43ꢀ7.39 (m, 3H), 7.30ꢀ7.28 (m, 1H), 7.23ꢀ7.17 (m, 3H), 6.15ꢀ6.13 (m, 1H),
5.97ꢀ5.95 (m, 1H), 2.42 (s, 1/2×3H), 2.37 (s, 1/2×3H). 13C NMR (125 MHz, CDCl3): δ 181.4,
181.3, 179.4, 154.81, 154.78, 139.4, 138.7, 137.58, 137.55, 135.7, 135.1, 135.0, 134.4, 134.24,
134.22, 133.15, 133.13, 132.25, 132.23, 131.0, 129.5, 129.3, 128.84, 128.80, 128.0, 127.8, 127.74,
127.68, 127.4, 127.2, 126.64, 126.61, 126.0, 124.2, 123.7, 121.2, 121.0, 78.1, 78.0, 21.3, 21.2.
HRMS (ESI): calcd. for C26H19O3 [M+H+] 379.1329; found 379.1338.
2-(2-Chlorophenyl)-4-phenyl-2H-benzo[g]chromene-5,10-dione (4f). Purification by flash
chromatography afforded 4f (0.025 g, 31% yield) as yellow solid, mp 158ꢀ160 oC. 1H NMR (500
MHz, CDCl3): δ 8.15ꢀ8.13 (m, 1H), 8.03ꢀ8.02 (m, 1H), 7.74ꢀ7.70 (m, 2H), 7.67ꢀ7.65 (m, 1H),
7.48ꢀ7.45 (m, 1H), 7.39ꢀ7.32 (m, 5H), 7.28ꢀ7.25 (m, 2H), 6.51 (d, J = 4.0 Hz, 1H), 5.87 (d, J = 3.9
Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 181.3, 179.1, 155.2, 138.4, 135.3, 135.2, 134.4, 133.3,
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132.7, 132.2, 131.1, 130.2, 130.1, 128.8, 128.1, 127.9, 127.4, 127.3, 126.7, 126.1, 123.8, 121.0,
75.6. HRMS (ESI): calcd. for C25H16ClO3 [M+H+] 399.0782; found 399.0779.
4-(2-Chlorophenyl)-2-phenyl-2H-benzo[g]chromene-5,10-dione (4f'). Purification by flash
chromatography afforded 4f' (0.016 g, 20% yield) as yellow oil. 1H NMR (500 MHz, CDCl3): δ
8.10ꢀ8.08 (m, 1H), 7.99ꢀ7.97 (m, 1H), 7.69ꢀ7.60 (m, 4H), 7.46ꢀ7.32 (m, 7H), 6.27ꢀ6.16 (m, 1H),
6.00ꢀ5.85 (m, 1H). 13C NMR (125 MHz, DMSO): δ 181.1, 179.2, 138.5, 135.1, 134.2, 131.6,
131.1, 130.6, 129.7, 129.33, 129.25, 128.1, 127.7, 126.4, 126.1, 120.4, 75.1. HRMS (ESI): calcd.
for C25H16ClO3 [M+H+] 399.0782; found 399.0800.
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Mixture of 4-(4-bromophenyl)-2-(4-chlorophenyl)-2H-benzo[g]chromene-5,10-dione (4g) and
2-(4-bromophenyl)-4-(4-chlorophenyl)-2H-benzo[g]chromene-5,10-dione (4g'). Purification by
flash chromatography afforded 4g and 4g' (0.066 g, 69% yield) as yellow oil. 1H NMR (500 MHz,
CDCl3): δ 8.11ꢀ8.09 (m, 1H), 8.00ꢀ7.98 (m, 1H), 7.72ꢀ7.70 (m, 2H), 7.55ꢀ7.49 (m, 3H), 7.44ꢀ7.35
(m, 3H), 7.21ꢀ7.19 (m, 1H), 7.15ꢀ7.13 (m, 1H), 6.11, 6.10 (dd, J = 4.6, 4.7 Hz, 1H), 5.921, 5.917
(dd, J = 4.5, 4.5 Hz, 1H). 13C NMR (125 MHz, DMSO): δ 180.8, 178.7, 154.6, 137.7, 137.32,
137.26, 136.8, 134.5, 133.7, 133.6, 133.0, 132.9, 132.1, 131.75, 131.72, 130.8, 130.7, 129.6, 129.5,
129.3, 129.2, 128.8, 127.7, 126.0, 125.5, 125.08, 125.07, 122.4, 120.6, 120.44, 120.38, 76.32,
76.29. HRMS (ESI): calcd. for C25H15BrClO3 [M+H+] 476.9888; found 476.9866.
1-Isopropyl-2,4-diphenyl-1,10a-dihydrobenzo[g]quinoline-5,10(2H,4aH)-dione
(4h).
Purification by flash chromatography afforded 4h (0.011 g, 13% yield) as purple oil. 1H NMR
(500 MHz, CDCl3): δ 8.06ꢀ8.04 (m, 1H), 7.93ꢀ7.91 (m, 1H), 7.64ꢀ7.62 (m, 2H), 7.37 (d, J = 7.7
Hz, 2H), 7.34ꢀ7.30 (m, 3H), 7.27ꢀ7.18 (m, 5H), 5.93 (d, J = 7.4 Hz, 1H), 5.35 (d, J = 7.4 Hz, 1H),
4.92ꢀ4.89 (m, 1H), 1.49 (d, J = 6.6 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 182.9, 180.2, 146.4, 141.7, 140.8, 136.9, 133.8, 133.1, 132.6, 132.4, 128.4, 127.9, 127.7,
127.4, 127.1, 126.3, 126.1, 125.9, 122.7, 122.4, 53.8, 52.7, 24.3, 21.7. HRMS (ESI): calcd. For
C28H23NO2 [M+H+] 406.1802; found 406.1809.
2,4-Diphenylpyrano[3,2-c]chromen-5(2H)-one (4i). Purification by flash chromatography
afforded 4i (0.048 g, 68% yield) as yellow solid, mp 149ꢀ151 oC . 1H NMR (500 MHz, CDCl3): δ
7.89ꢀ7.87 (m, 1H), 7.60ꢀ7.54 (m, 3H), 7.46ꢀ7.41 (m, 3H), 7.40ꢀ7.35 (m, 5H), 7.32 (d, J = 8.2 Hz,
1H), 7.30ꢀ7.27 (m,1H), 6.17 (d, J = 4.2 Hz, 1H), 5.79 (d, J = 4.2 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 161.4, 158.7, 153.7, 138.3, 137.9, 135.3, 132.6, 129.3, 129.0, 128.0, 127.9, 127.55,
127.47, 124.0, 123.3, 120.3, 116.7, 115.3, 102.9, 78.8. HRMS (ESI): calcd. for C24H17O3 [M+H+]
353.1172; found 353.1180.
9-Methyl-2,4-diphenylpyrano[3,2-c]chromen-5(2H)-one
(4j).
Purification
by
flash
chromatography afforded 4j (0.038 g, 52% yield) as yellow solid, mp 202ꢀ204 C. 1H NMR (500
MHz, CDCl3): δ 7.66 (s, 1H), 7.60 (d, J = 6.9 Hz, 2H), 7.48ꢀ7.36 (m, 9H), 7.23 (d, J = 8.4 Hz, 1H),
6.15 (d, J = 4.1 Hz, 1H), 5.78 (d, J = 4.1 Hz, 1H), 2.42 (s, 3H). 13C NMR (125 MHz, CDCl3): δ
161.4, 158.9, 151.8, 138.3, 137.9, 135.3, 133.69, 133.66, 129.2, 128.9, 127.9, 127.8, 127.5, 127.4,
122.8, 120.1, 116.4, 114.8, 102.7, 78.8, 20.9. HRMS (ESI): calcd. For C25H19O3 [M+H+] 367.1329;
found 367.1317.
o
9-Chloro-2,4-diphenylpyrano[3,2-c]chromen-5(2H)-one
(4k).
Purification
by
flash
chromatography afforded 4k (0.051 g, 66% yield) as yellow solid, mp 203ꢀ205 C.1H NMR (500
MHz, CDCl3): δ 7.82 (d, J = 2.5 Hz, 1H), 7.59ꢀ7.57 (m, 2H), 7.50ꢀ7.44 (m, 4H), 7.40ꢀ7.33 (m, 5H),
7.26 (d, J = 8.8 Hz, 1H), 6.17 (d, J = 4.2 Hz, 1H), 5.80 (d, J = 4.2 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 160.1, 158.1, 151.9, 137.9, 137.6, 135.0, 132.5, 129.53, 129.50, 129.0, 128.00, 127.98,
o
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127.6, 127.4, 122.7, 120.8, 118.1, 116.4, 103.4, 79.1. HRMS (ESI): calcd. For C24H16ClO3 [M+H+]
387.0782; found 387.0794.
9-Methoxy-2,4-diphenyl-4a,10b-dihydropyrano[3,2-c]chromen-5(2H)-one (4l). Purification by
o
flash chromatography afforded 4l (0.042 g, 54% yield) as yellow solid, mp 148ꢀ149 C. 1H NMR
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(500 MHz, CDCl3): δ 7.61ꢀ7.59 (m, 2H), 7.48ꢀ7.43 (m, 3H), 7.42ꢀ7.35 (m, 5H), 7.27ꢀ7.25 (m, 2H),
7.16ꢀ7.13 (m, 1H), 6.16 (d, J = 4.2 Hz, 1H), 5.79 (d, J = 4.2 Hz, 1H), 3.86 (s, 3H). 13C NMR (125
MHz, CDCl3): δ 161.1, 158.8, 155.9, 148.2, 138.2, 137.9, 135.3, 129.2, 128.9, 127.9, 127.8, 127.5,
127.4, 120.9, 120.3, 117.8, 115.4, 104.8, 103.0, 78.8, 55.9. HRMS (ESI): calcd. For C25H19O4
[M+H+] 383.1278; found 383.1272.
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3. General procedure for the coupling reaction catalyzed by DDQ: To a solution of lawsone 1a
or 4ꢀhydroxycoumarin 5a (0.2 mmol) and 1,3ꢀdiphenylpropene 2a (0.24 mmol, 0.047 g) in
MeNO2 (1 mL), DDQ (0.04 mmol, 0.009 g) and AIBN (0.04 mmol, 0.007 g) was added. The
o
resulting mixture was stirred for 6 hrs at 80 C in the presence of oxygen atmosphere (oxygen
balloon). After the completion of the reaction, the solvent was concentrated under reduced
pressure. Purification was done by column chromatography on silica gel (200ꢀ300 mesh) with
petroleum ether and ethyl acetate (3:1) as the eluent to give the pure product 3a or 6a.
Supporting information
Copies of 1H and 13C NMR spectra for all isolated compounds.
Acknowledgements
This work was supported by the Natural Science Foundation of China (21602197), the Natural
Science Foundation of Zhejiang Provincial (LY15B020004) and the Open Research Fund Program
of Collaborative Innovation Center of Membrane Separation and Water Treatment (2016YB07).
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