Stereoselective synthesis of 2,8-dioxabicyclo[3.3.1]nonane derivatives via a sequential Michael addition/bicyclization reaction

Article abstract of DOI:10.1021/jo400081q

A highly efficient and stereoselective synthesis of coumarin-, 1,3-cyclohexanedione-, and 1,4-naphthoquinone-fused 2,8-dioxabicyclo[3.3.1] nonanes is described. This was achieved via a sequential Michael addition/bicyclization reaction from easily accessible 3-(2-hydroxyphenyl)-1- phenylprop-2-en-1-one derivatives. Three chemical bonds (one C-C bond and two C-O bonds), two six-membered cycles, and two stereogenic centers were formed in a one-pot operation.

Full text of DOI:10.1021/jo400081q

Article
pubs.acs.org/joc
Stereoselective Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane
Derivatives via a Sequential Michael Addition/Bicyclization Reaction
Guodong Yin,*,† Tianbing Ren,† Yin Rao,† Yifan Zhou,† Zhexian Li,† Wenming Shu,‡ and Anxin Wu*,‡
†Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, College of Chemistry and Environmental Engineering, Hubei
Normal University, Huangshi 435002, PR China
‡Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, PR
China
S
* Supporting Information
ABSTRACT: A highly efficient and stereoselective synthesis
of coumarin-, 1,3-cyclohexanedione-, and 1,4-naphthoquinone-
fused 2,8-dioxabicyclo[3.3.1]nonanes is described. This was
achieved via a sequential Michael addition/bicyclization
reaction from easily accessible 3-(2-hydroxyphenyl)-1-phenyl-
prop-2-en-1-one derivatives. Three chemical bonds (one C−C
bond and two C−O bonds), two six-membered cycles, and
two stereogenic centers were formed in a one-pot operation.
dioxabicyclo[3.3.1]nonanes is still of significant interest.
Recently, we reported an efficient synthesis of novel function-
alized 2-aryl-4-(indol-3-yl)-4H-chromenes by the reactions of 2-
hydroxychalcones with substituted indoles in the presence of a
catalytic amount of iodine.13 In a continuation of our efforts to
develop new synthetic protocols for building valuable
heterocyclic frameworks,14 we herein describe a highly efficient
and stereoselective synthesis of 1-substituted coumarin-fused
2,8-dioxabicyclo[3.3.1]nonanes from easily available staring
materials 3-(2-hydroxyphenyl)-1-phenylprop-2-en-1-one deriv-
atives (5) and 4-hydroxycoumarin (4) (Scheme 1, Path IV).
Moreover, 5,5-dimethyl-1,3-cyclohexanedione (7a), 1,3-cyclo-
hexanedione (7b) and 2-hydroxy-1,4-naphthoquinone (9) were
also found suitable for the reactions, affording the correspond-
ing 1,3-dione- and 1,4-naphthoquinone-fused 2,8-
dioxabicyclo[3.3.1]nonanes in excellent yields with high
stereoselectivity.
INTRODUCTION
■
Methylene-bridged bicyclic systems, such as Troger’s base1 and
̈
its derivatives have been widely employed as molecular
tweezers,2 ion receptors,3 and high affinity DNA targeting
fluorescent supramolecular scaffolds4 because of their rigid
skeletons. In accordance, a great deal of effort has been devoted
to the synthesis of similar types of molecular framework in
recent years.5−7 2,8-Dioxabicyclo[3.3.1]nonane ring systems,
which can be described as the analogues of Troger’s base, are
̈
interesting and elaborate V-shaped rigid molecules. Meanwhile,
these structural fragments are also embodied in a wide range of
natural products, e.g., biflavonoid derivative (1), dracoflavan C
(2), and dracoflavan D (3) (Figure 1).8
It is well-known that 4-hydroxycoumarin is widely used in
organic synthesis for the preparation of many synthetic drugs
and drug candidates (such as warfarin, phenprocoumon,
brodifacoum, and arisugacin A), all of which have shown
excellent biological and pharmacological activities.9 However,
few routes have thus far been reported for the synthesis of
coumarin-fused 2,8-dioxabicyclo[3.3.1]nonanes. In 1981, Jurd
demonstrated that 1-aryl-substituted 2,8-dioxabicyclo[3.3.1]-
nonanes could be synthesized by the reaction of flavylium
chloride with 4-hydroxycoumarin (4) in warm acetic acid and
hydrochloric acid solution (Scheme 1, Path I).10 Manolov also
illustrated a base-catalyzed condensation reaction between 3-
benzoylcoumarin (or 3-acetylcoumarin) and 4-hydroxycoumar-
in to afford the corresponding 1-phenyl (or 1-methyl) 2,8-
dioxabicyclo[3.3.1]nonanes (Scheme 1, Path II).11 Yang
reported that these kinds of molecules, which had further
potential to act as Vitamin K 2,3-epoxide reductase (VKOR)
inhibitors, could be achieved through the reactions of 2-
phenylchroman-4-ol with 4-hydroxycoumarin in the presence
of aluminum chloride (Scheme 1, Path III).12 Accordingly, the
development of a simple and efficient method toward 2,8-
RESULTS AND DISCUSSION
■
Initially, an attempted reaction of 3-(2-hydroxyphenyl)-1-
phenylprop-2-en-1-one (5a, 0.5 mmol) with 4-hydroxycoumar-
in (4, 0.5 mmol) was carried out under varied conditions. We
were pleased to find that the unexpected product coumarin-
fused 1-phenyl 2,8-dioxabicyclo[3.3.1]nonane (6a) was ob-
tained in excellent yield (94%) in refluxing toluene for 6 h
(Table 1, entry 1). The solution became homogeneous as the
starting materials were completely dissolved. When the reaction
mixture was cooled to room temperature and stood overnight,
the yellow crystals of 6a precipitated and were found to be pure
enough for structural analysis. The structure was identified by
1
means of H NMR, 13C NMR, IR, and HRMS. The steric
Received: January 14, 2013
Published: March 12, 2013
© 2013 American Chemical Society
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Figure 1. Examples of natural products.
Scheme 1. Strategy for the Synthesis of 2,8-Dioxabicyclo[3.3.1]nonanes
configuration. Nevertheless, decreasing the reaction temper-
ature resulted in a low yield in toluene, and 6a was not
observed in THF (Table 1, entries 2−4). This transformation
was also attempted in other different solvents, such as benzene,
MeCN, MeOH, EtOH, t-BuOH, DMF and DMSO, but 6a was
only isolated in 12−38% yield (Table 1, entries 5−8, 10−12). It
should also be noted that when n-PrOH was used as the
solvent, the reaction gave the product 6a in 93% isolated yield
(Table 1, entry 9). Considering ease of workup and
purification, the optimized reaction conditions were identified
as the reaction of 5a with 1.0 equiv of 4 in toluene at reflux
temperature.
With the optimal reaction conditions in hand, we then
examined the reactions of 4-hydroxycoumarin with a variety of
3-(2-hydroxyphenyl)-1-phenylprop-2-en-1-one derivatives (5),
which were synthesized according to the known methods,13,15
to establish the generality of the present transformation. The
results are listed in Scheme 2. The reactions for the substrates
bearing electron-donating substituents (−OMe) on the phenyl
ring of R2 performed smoothly to deliver the corresponding 6b
and 6c in slightly lower yields (80 and 76%). We then expected
to introduce the halogen atom into the target molecules, which
is known to be readily converted into related important
derivatives via classic coupling reactions (Heck, Suzuki,
Sonogashira, Liebeskind−Srogl, et al). It was found that the
substrates bearing electron-withdrawing halogen-atom (−Cl,
−Br and −F) on the phenyl rings delivered the corresponding
products 6d−f in excellent yields (90−93%). Heteroaryl (R2 =
2-furyl, 2-thienyl) and alkyl group (−Me) substituted substrates
were also suitable for the reactions, affording the corresponding
products 6g−i in good yields (75−80%). To our delight, 5-
Table 1. Optimization of Reaction Condition for the
Synthesis of 6a
a
b
entry
solvent
temp (°C)
time (h)
yield (%)
1
toluene
toluene
toluene
THF
reflux
80
6
6
94
30
<5
0
2
3
60
6
4
reflux
reflux
reflux
reflux
reflux
reflux
reflux
110
6
5
benzene
MeCN
MeOH
EtOH
6
38
23
15
24
93
32
12
23
6
10
10
10
10
10
10
10
7
8
9
n-PrOH
t-BuOH
DMF
10
11
12
DMSO
110
a
All reactions were performed with 5a (0.5 mmol) and 4 (0.5 mmol)
b
in solvent (4.0 mL). Isolated yield.
configuration was further clarified by X-ray single-crystal
diffraction analysis, which was in accordance with the reported
literature (see the Supporting Information).11 One of the
dihydropyran rings fused with the benzopyran ring adopted an
e,f-diplanar configuration, while the other displayed a similar
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ab
,
Scheme 2. Synthesis of Coumarin-Fused 2,8-Dioxabicyclo[3.3.1]nonanes
a
b
All reactions were performed with 4 (0.5 mmol) and 5 (0.5 mmol) in toluene (4.0 mL) at reflux. Isolated yield.
chloro-, 3,5-dichloro-, 5-bromo- and 4-methoxy-substituted 3-
(2-hydroxyphenyl)-1-phenylprop-2-en-1-ones (R1) also pro-
vided 6j−q in 72−90% yields.
(see the Supporting Information) and was shown to adopt the
same configuration as the analogous in literatures.16,17
Naphthoquinones and quinones are ubiquitous in nature and
have been found to have a wide range of biological activities,
including cytotoxicity to cancer cells.18 The involvement of
naphthoquinone moieties in Michael-type addition reactions
are widely studied in organic synthesis.19,20 A literature survey
revealed that there are no examples for the preparation of
naphthoquinone-fused 2,8-dioxabicyclo[3.3.1]nonane deriva-
tives. Consequently, 2-hydroxy-1,4-naphthoquinone (9) was
also used to react with 3-(2-hydroxyphenyl)-1-phenylprop-2-
en-1-one derivatives in n-PrOH at reflux. As shown in Scheme
4, the corresponding products 10a−i were isolated in good
yields (68−88%) when R2 was electron-rich/deficient aromatic,
Encouraged by the results achieved above, we hoped that the
substrates of this efficient reaction system could be further
extended. Next, 5,5-dimethylcyclohexane-1,3-dione (7a) and
1,3-cyclohexanedione (7b) were employed to react with 3-(2-
hydroxyphenyl)-1-phenylprop-2-en-1-one derivatives under
standard reaction conditions. As shown in Scheme 3,
electron-rich/deficient aromatic, heterocyclic aromatic and
methyl group substrates also gave the corresponding products
8a−n in good yields (70−87%). In addition, the structure of 8f
was also confirmed by X-ray single-crystal diffraction analysis
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a b
,
Scheme 3. Synthesis of 1,3-Cyclohexanedione-Fused 2,8-Dioxabicyclo[3.3.1]nonanes
a
b
All reactions were performed with 5 (0.5 mmol) and 7 (0.5 mmol) in toluene (4.0 mL) at reflux. Isolated yield
heterocyclic aromatic and methyl substituted groups. Moreover,
chlorine- and bromine-substituted substrates (R1 = Cl, Br) were
also suitable for this reaction, affording the corresponding
products 10j−l in 78−83% yields.
However, when the mixture of 5a and noncyclic pentane-2,4-
dione (11) was heated at reflux for 10 h, the corresponding 2,8-
dioxabicyclo[3.3.1]nonane product was not observed, but 3-(2-
phenyl-4H-chromen-4-yl)pentane-2,4-dione (12) was isolated
in 71% yield (Scheme 5).
Moreover, it was found that no reaction occurred when the
mixture of 4-hydroxycoumarin (4) and 1,3-diphenyl-2-propen-
1-one (chalcone) was heated in refluxing toluene for 16 h,21
which indicated that the reaction was obviously affected by the
hydroxy (−OH), probably because of the acidity of the proton.
Therefore, the present reactions can be regarded as a self-
catalyzed process. Subsequently, a possible reaction mechanism
was proposed as shown in Scheme 6 (using 6a as an example).
First, 4-hydroxycoumarin reacted with 3-(2-hydroxyphenyl)-1-
phenylprop-2-en-1-one (5a) to form intermediate I through a
Michael addition reaction.22 Then intramolecular cyclization of
intermediate I gave two possible hemiketal-form intermediate
II or III,13,20a,23,24 both of which afforded the same target
product 6a via a spontaneous intramolecular cyclization process
after loss of water.10,11
CONCLUSIONS
■
In summary, we have described a highly efficient and
stereoselective construction of coumarin-, 1,3-cyclohexane-
dione- and 1,4-naphthoquinone-fused 2,8-dioxabicyclo[3.3.1]-
nonanes via a sequential Michael addition/bicyclization
reaction from 3-(2-hydroxyphenyl)-1-phenylprop-2-en-1-one
derivatives. Three chemical bonds (one C−C bond and two
C−O bonds), two six-membered cycles, and two stereogenic
centers were formed in a one-pot operation. Easily accessible
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ab
,
Scheme 4. Synthesis of 1,4-Naphthoquinone-Fused 2,8-Dioxabicyclo[3.3.1]nonanes
a
b
All reactions were performed with 5 (0.5 mmol) and 9 (0.5 mmol) in n-PrOH (4.0 mL) at reflux. Isolated yield.
phenylprop-2-en-1-one derivatives (5, 0.5 mmol) was heated at reflux
in anhydrous toluene in a sealed tube (4.0 mL). The solution became
homogeneous as the starting materials were completely dissolved.
After the reactant disappeared (6−12 h, monitored by thin layer
chromatography), the mixture was cooled to room temperature and
stood overnight. Thus the crystals were precipitated, filtrated and
washed with a small amount of anhydrous ethanol, and the target
products 6 were obtained as the yellow solids.
Scheme 5
Compound 6a. Yellow solid: 173 mg, 94% yield; mp 234−235 °C;
IR (KBr, cm−1) 3441, 2358, 1706, 1630, 1486, 1393, 1233, 1117, 1019,
760; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.85 (d, J = 7.6 Hz, 1H),
7.77−7.75 (m, 2H), 7.56−7.45 (m, 5H), 7.31−7.17 (m, 3H), 7.07−
6.96 (m, 2H), 4.39 (s, 1H), 2.46−2.42 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 161.5, 158.2, 152.4, 151.3, 139.7, 131.9, 129.4, 128.6,
128.3, 128.2, 125.6, 125.1, 124.0, 122.7, 122.1, 116.6, 116.3, 115.0,
106.0, 100.2, 32.9, 27.1; ESI-MS m/z 369.17 [M + H]+.
Compound 6b. Yellow solid: 159 mg, 80% yield; mp 188−189 °C;
IR (KBr, cm−1) 3441, 2359, 1716, 1628, 1513, 1390, 1245, 1114, 1029,
760; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.86 (d, J = 7.6 Hz, 1H),
7.68 (d, J = 8.7 Hz, 2H), 7.55−7.48 (m, 2H), 7.31−7.17 (m, 3H),
7.06−6.96 (m, 4H), 4.39 (s, 1H), 3.88 (s, 3H), 2.45−2.42 (m, 2H);
13C NMR (75 MHz, CDCl3) δ (ppm) 161.7, 160.3, 158.4, 152.4,
151.4, 132.0, 131.9, 128.3, 128.2, 127.0, 125.1, 124.0, 122.7, 122.0,
116.7, 116.3, 115.1, 113.9, 106.0, 100.3, 55.4, 32.9, 27.3; ESI-MS m/z
399.15 [M + H]+.
starting materials, a wide scope of substrates, excellent yields
and ease of purification (no column chromatography) were the
main advantages of this reaction.
EXPERIMENTAL SECTION
■
General Experimental Details. All substrates and reagents were
commercially available and used without further purification. IR
spectra were recorded as KBr pellets with absorption in cm−1. 1H and
13C NMR spectra were recorded on 300 MHz spectrometers using
CDCl3 as the solvent. Chemical shifts are reported relative to TMS
(internal standard). High resolution mass spectra were recorded on
TOF-QII (ESI). Mass spectra was recorded on ESI or EI (70 eV).
Melting points were determined using an electrothermal capillary
melting point apparatus and not corrected.
General Procedure for the Synthesis of 6. A mixture of 4-
hydroxycoumarin (4, 81 mg, 0.5 mmol) and 3-(2-hydroxyphenyl)-1-
Compound 6c. Yellow solid: 172 mg, 76% yield; mp 194−195 °C;
IR (KBr, cm−1) 3438, 2943, 1709, 1631, 1517, 1454, 1391, 1267, 1226,
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Scheme 6. Possible Reaction Mechanism
1
1116, 1028, 761; H NMR (300 MHz, CDCl3) δ (ppm) 7.85 (d, J =
128.4, 128.2, 127.1, 126.6, 125.5, 124.8, 124.1, 122.8, 122.3, 116.6,
116.4, 114.8, 105.9, 99.2, 33.0, 27.1; HRMS (ESI) calcd for C22H15O4S
[M + H]+ 375.0686, found 375.0683.
7.7 Hz, 1H), 7.56−7.48 (m, 2H), 7.34−7.17 (m, 5H), 7.07−6.97 (m,
3H), 4.40 (s, 1H), 3.95 (s, 6H), 2.48−2.45 (m, 2H); 13C NMR (75
MHz, CDCl3) δ (ppm) 161.5, 158.2, 152.3, 151.3, 149.8, 148.9, 132.2,
131.9, 128.3, 128.2, 125.1, 124.0, 122.6, 122.1, 118.2, 116.7, 116.3,
115.1, 110.8, 109.0, 106.0, 100.2, 56.04, 55.98, 32.9, 27.2; HRMS
(ESI) calcd for C26H21O6 [M + H]+ 429.1333, found 429.1318.
Compound 6d. Yellow solid: 185 mg, 92% yield; mp 223−224 °C;
IR (KBr, cm−1) 3410, 1715, 1631, 1489, 1390, 1330, 1232, 1118, 1014,
884, 821, 761; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.83 (d, J = 7.9
Hz, 1H), 7.70 (d, J = 8.6 Hz, 2H), 7.56−7.46 (m, 4H), 7.30−7.17 (m,
3H), 7.06−6.97 (m, 2H), 4.40−4.38 (m, 1H), 2.47−2.35 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 161.4, 158.0, 152.3, 151.1, 138.2,
135.4, 132.0, 128.8, 128.4, 128.2, 127.2, 124.9, 124.1, 122.6, 122.2,
116.7, 116.3, 114.9, 106.0, 99.9, 32.8, 27.1; HRMS (ESI) calcd for
C24H16ClO4 [M + H]+ 403.0732, found 403.0712.
Compound 6i. Yellow solid: 115 mg, 75% yield; mp 254−255 °C;
IR (KBr, cm−1) 3445, 1703, 1628, 1487, 1446, 1390, 1142, 1035, 862,
762; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.78 (d, J = 7.8 Hz, 1H),
7.48−7.42 (m, 2H), 7.24−7.19 (m, 2H), 7.15−7.10 (m, 1H), 6.94−
6.86 (m, 2H), 4.30 (s, 1H), 2.34−2.19 (m, 2H), 2.00 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 161.6, 158.0, 152.2, 151.1, 131.8,
128.09, 128.07, 125.0, 123.8, 122.7, 121.6, 116.5, 116.0, 114.9, 105.7,
99.7, 30.7, 26.7, 26.6; ESI-MS m/z 307.17 [M + H]+.
Compound 6j. Yellow solid: 181 mg, 90% yield; mp 194−195 °C;
IR (KBr, cm−1) 3441, 2356, 1705, 1628, 1482, 1391, 1237, 1117, 1012,
883, 826, 758; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.89 (d, J = 7.9
Hz, 1H), 7.87−7.73 (m, 2H), 7.57−7.50 (m, 5H), 7.34−7.26 (m, 2H),
7.17−7.13 (m, 1H), 6.98 (d, J = 8.7 Hz, 1H), 4.36 (t, J = 3.0 Hz, 1H),
2.44 (d, J = 3.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 161.4,
158.3, 152.5, 150.0, 139.3, 132.2, 129.6, 128.7, 128.3, 127.8, 127.0,
126.6, 125.6, 124.2, 122.8, 117.6, 116.8, 114.9, 105.4, 100.3, 32.6, 27.1;
HRMS (ESI) calcd for C24H16ClO4 [M + H]+ 403.0732, found
403.0726.
Compound 6k. Yellow solid: 173 mg, 80% yield; mp 206−207 °C;
IR (KBr, cm−1) 3439, 1711, 1629, 1511, 1481, 1394, 1340, 1249, 1174,
1119, 1030, 880, 825, 763; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.84
(d, J = 7.3 Hz, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.54−7.49 (m, 2H),
7.31−7.23 (m, 2H), 7.15−7.11 (m, 1H), 7.03−6.94 (m, 3H), 4.34−
4.24 (m, 1H), 3.87 (s, 3H), 2.42−2.35 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 161.4, 160.4, 158.3, 152.4, 150.0, 132.1, 131.4, 128.2,
127.7, 126.9, 126.8, 126.7, 124.1, 122.7, 117.6, 116.7, 114.9, 113.9,
105.3, 100.3, 55.4, 32.6, 27.1; HRMS (ESI) calcd for C25H18ClO5 [M
+ H]+ 433.0837, found 433.0838.
Compound 6e. Yellow solid: 208 mg, 93% yield; mp 220−221 °C;
IR (KBr, cm−1) 3440, 1715, 1632, 1488, 1390, 1232, 1116, 1012, 884,
1
819, 760; H NMR (300 MHz, CDCl3) δ (ppm) 7.84 (d, J = 7.8 Hz,
1H), 7.64−7.50 (m, 6H), 7.32−7.18 (m, 3H), 7.06−6.97 (m, 2H),
4.40 (s, 1H), 2.42−2.36 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
(ppm) 161.4, 158.0, 152.3, 151.1, 138.8, 132.0, 131.8, 128.4, 128.2,
127.5, 124.9, 124.1, 123.7, 122.6, 122.3, 116.7, 116.3, 114.9, 106.0,
99.9, 32.7, 27.0; HRMS (ESI) calcd for C24H16BrO4 [M + H]+
447.0226, found 447.0236.
Compound 6f. Yellow solid: 174 mg, 90% yield; mp 222−223 °C;
IR (KBr, cm−1) 3425, 1715, 1631, 1501, 1391, 1332, 1231, 1115, 1021,
885, 826, 761; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.84 (d, J = 7.7
Hz, 1H), 7.77−7.73 (m, 2H), 7.56−7.48 (m, 2H), 7.31−7.16 (m, 5H),
7.06−6.97 (m, 2H), 4.40 (s, 1H), 2.44−2.42 (m, 2H); 13C NMR (75
1
MHz, CDCl3) δ (ppm) 163.3 (d, JCF = 247.2 Hz), 161.5, 158.1,
4
152.4, 151.2, 135.7 (d, JCF = 3.2 Hz), 132.0, 128.4, 128.2, 127.7 (d,
Compound 6l. Yellow solid: 178 mg, 85% yield; mp 203−204 °C;
IR (KBr, cm−1) 3428, 2359, 1721, 1637, 1481, 1392, 1339, 1229, 1148,
1127, 1015, 890, 831, 752; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.83
(d, J = 7.5 Hz, 1H), 7.75−7.71 (m, 2H), 7.57−7.51 (m, 2H), 7.34−
7.13 (m, 5H), 6.97 (d, J = 8.7 Hz, 1H), 4.36 (t, J = 3.0 Hz, 1H), 2.42
(d, J = 3.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 163.3 (d,
3JCF = 8.3 Hz), 125.0, 124.1, 122.6, 122.2, 116.7, 116.3, 115.5 (d, 2JCF
=
21.6 Hz), 115.0, 106.0, 100.0, 33.0, 27.2; HRMS (ESI) calcd for
C24H16FO4 [M + H]+ 387.1027, found 387.1036.
Compound 6g. Yellow solid: 142 mg, 79% yield; mp 204−206 °C;
IR (KBr, cm−1) 3437, 1710, 1633, 1488, 1391, 1222, 1117, 1022, 877,
759; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.81 (d, J = 7.7 Hz, 1H),
7.53−7.45 (m, 3H), 7.28−7.15 (m, 3H), 7.01−6.95 (m, 2H), 6.82 (d, J
= 2.7 Hz, 1H), 6.52 (s, 1H), 4.41 (s, 1H), 2.60−2.57 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 161.4, 157.7, 152.3, 150.8, 150.7,
143.3, 132.0, 128.3, 128.2, 124.9, 124.0, 122.8, 122.2, 116.6, 116.3,
114.8, 110.6, 108.3, 106.0, 96.6, 29.5, 26.3; HRMS (ESI) calcd for
C22H15O5 [M + H]+ 359.0914, found 359.0914.
4
1JCF = 247.3 Hz), 161.3, 158.2, 152.4, 149.8, 135.3 (d, JCF = 3.2 Hz),
3
132.3, 128.4, 127.8, 127.7 (d, JCF = 8.5 Hz), 127.1, 126.5, 124.2,
2
122.7, 117.6, 116.8, 115.6 (d, JCF = 21.8 Hz), 114.8, 105.4, 100.0,
32.6, 27.1; HRMS (ESI) calcd for C24H15ClFO4 [M + H]+ 421.0637,
found 421.0642.
Compound 6m. Yellow solid: 194 mg, 89% yield; mp 229−230 °C;
IR (KBr, cm−1) 3429, 2359, 1718, 1637, 1452, 1393, 1331, 1263, 1116,
1
Compound 6h. Yellow solid: 150 mg, 80% yield; mp 218−219 °C;
1039, 1015, 995, 921, 758; H NMR (300 MHz, CDCl3) δ (ppm)
IR (KBr, cm−1) 3403, 1708, 1633, 1487, 1391, 1330, 1231, 1116, 1030,
7.88−7.78 (m, 3H), 7.57−7.46 (m, 5H), 7.34−7.25 (m, 3H), 4.37 (t, J
= 2.9 Hz, 1H), 2.52 (dd, J1 = 13.8 Hz, J2 = 2.9 Hz, 1H), 2.36 (dd, J1 =
13.8 Hz, J2 = 2.9 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ (ppm)
161.3, 158.3, 152.5, 146.1, 138.7, 132.4, 129.7, 128.74, 128.68, 127.9,
126.9, 126.3, 125.7, 124.2, 122.9, 122.1, 116.8, 114.7, 104.7, 100.6,
1
982, 761; H NMR (300 MHz, CDCl3) δ (ppm) 7.85 (d, J = 7.6 Hz,
1H), 7.55−7.43 (m, 3H), 7.37 (d, J = 3.3 Hz, 1H), 7.30−7.10 (m,
4H), 7.03−6.96 (m, 2H), 4.41 (s, 1H), 2.66−2.53 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ (ppm) 161.6, 158.0, 152.3, 150.9, 142.8, 132.1,
3137
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32.5, 27.3; HRMS (ESI) calcd for C24H15Cl2O4 [M + H]+ 437.0342,
found 437.0345.
32.4, 28.7, 27.8, 25.2; HRMS (ESI) calcd for C24H25O4 [M + H]+
377.1747, found 377.1745.
Compound 6n. Yellow solid: 184 mg, 79% yield; mp 226−227 °C;
IR (KBr, cm−1) 3413, 2966, 1712, 1623, 1451, 1393, 1334, 1249, 1186,
1102, 1032, 921, 758; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.84 (d, J
= 7.9 Hz, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.55−7.51 (m, 1H), 7.45 (d, J
= 2.3 Hz, 1H), 7.33−7.24 (m, 3H), 7.03 (d, J = 8.7 Hz, 2H), 4.37−
4.35 (m, 1H), 3.88 (s, 3H), 2.50 (dd, J1 = 13.8 Hz, J2 = 3.1 Hz, 1H),
2.34 (dd, J1 = 13.8 Hz, J2 = 2.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ (ppm) 161.3, 160.5, 158.4, 152.5, 146.2, 132.3, 130.8, 128.6, 128.0,
127.1, 126.8, 126.3, 124.2, 122.9, 122.1, 116.7, 114.7, 114.0, 104.6,
100.7, 55.4, 32.5, 27.4; HRMS (ESI) calcd for C25H17Cl2O5 [M + H]+
467.0448, found 467.0445.
Compound 8c. Yellow solid: 166 mg, 87% yield; mp 144−145 °C;
IR (KBr, cm−1) 3441, 2950, 1629, 1483, 1329, 1231, 1101, 1023, 884,
835, 756; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.61−7.57 (m, 2H),
7.44−7.37 (m, 3H), 7.17−7.12 (m, 1H), 7.00−6.89 (m, 2H), 4.23−
4.21 (m, 1H), 2.39 (s, 2H), 2.29−2.10 (m, 4H), 1.10 (s, 3H), 0.95 (s,
3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.7, 167.3, 151.2, 138.8,
135.1, 128.6, 128.1, 127.6, 127.1, 126.3, 121.7, 115.9, 115.4, 99.4, 50.4,
41.5, 32.9, 32.4, 28.7, 27.9, 25.1; HRMS (ESI) calcd for C23H22ClO3
[M + H]+ 381.1252, found 381.1254.
Compound 8d. Yellow solid: 154 mg, 85% yield; mp 136−137 °C;
IR (KBr, cm−1) 3441, 2953, 1630, 1511, 1480, 1383, 1331, 1229, 1157,
1
1106, 1034, 884, 841, 756; H NMR (300 MHz, CDCl3) δ (ppm)
Compound 6o. Yellow solid: 202 mg, 89% yield; mp 202−203 °C;
IR (KBr, cm−1) 3441, 1714, 1628, 1503, 1451, 1393, 1334, 1236, 1157,
7.66−7.61 (m, 2H), 7.40−7.37 (m, 1H), 7.16−7.10 (m, 3H), 7.00−
6.89 (m, 2H), 4.22 (s, 1H), 2.39 (s, 2H), 2.29−2.11 (m, 4H), 1.10 (s,
3H), 0.95 (s, 3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.7, 167.3,
1
1101, 1037, 925, 882, 763; H NMR (300 MHz, CDCl3) δ (ppm)
7.86−7.76 (m, 3H), 7.58−7.53 (m, 1H), 7.47 (d, J = 2.4 Hz, 1H),
7.35−7.18 (m, 5H), 4.39−4.37 (m, 1H), 2.51 (dd, J1 = 13.7 Hz, J2 =
3.2 Hz, 1H), 2.35 (dd, J1 = 13.7 Hz, J2 = 2.8 Hz, 1H); 13C NMR (75
1
4
163.1 (d, JCF = 246.6 Hz), 151.3, 136.2 (d, JCF = 3.1 Hz), 128.1,
3
127.7 (d, JCF = 8.2 Hz), 127.6, 126.3, 121.7, 115.9, 115.4, 115.3 (d,
2JCF = 21.6 Hz), 99.5, 50.4, 41.6, 33.1, 32.4, 28.7, 27.8, 25.1; HRMS
(ESI) calcd for C23H22FO3 [M + H]+ 365.1547, found 365.1553.
Compound 8e. Yellow solid: 126 mg, 75% yield; mp 157−158 °C;
IR (KBr, cm−1) 3439, 2962, 1626, 1382, 1230, 1113, 1017, 864, 757;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.48 (s, 1H), 7.36 (d, J = 7.1
Hz, 1H), 7.14−7.09 (m, 1H), 6.97−6.88 (m, 2H), 6.68 (d, J = 2.3 Hz,
1H), 6.45 (s, 1H), 4.24 (s, 1H), 2.50−2.15 (m, 6H), 1.07 (s, 3H), 0.93
(s, 3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.7, 167.0, 151.6,
150.8, 143.0, 128.1, 127.6, 126.3, 121.7, 116.0, 115.4, 110.4, 107.7,
96.2, 50.3, 41.4, 32.3, 29.6, 28.7, 27.8, 24.2; HRMS (ESI) calcd for
C21H21O4 [M + H]+ 337.1434, found 337.1432.
1
MHz, CDCl3) δ (ppm) 163.4 (d, JCF = 247.7 Hz), 161.2, 158.2,
152.5, 146.0, 134.7 (d, 4JCF = 3.2 Hz), 132.5, 128.7, 127.9 (d, 3JCF2= 8.5
Hz), 127.8, 127.1, 126.3, 124.3, 122.8, 122.1, 116.8, 115.8 (d, JCF
=
21.8 Hz), 114.6, 104.7, 100.3, 32.5, 27.3; HRMS (ESI) calcd for
C24H14Cl2FO4 [M + H]+ 455.0248, found 455.0250.
Compound 6p. Yellow solid: 195 mg, 87% yield; mp 212−213 °C;
IR (KBr, cm−1) 3427, 1716, 1634, 1483, 1392, 1337, 1233, 1118, 996,
1
875, 818, 759; H NMR (300 MHz, CDCl3) δ (ppm) 7.88−7.85 (m,
1H), 7.75−7.67 (m, 3H), 7.55−7.50 (m, 4H), 7.33−7.26 (m, 3H),
6.92 (d, J = 8.6 Hz, 1H), 4.37−4.34 (m, 1H), 2.43 (d, J = 3.0 Hz, 2H);
13C NMR (75 MHz, CDCl3) δ (ppm) 161.3, 158.3, 152.4, 150.5,
139.2, 132.2, 131.2, 130.6, 129.6, 127.2, 125.6, 124.1, 122.7, 118.1,
116.8, 114.9, 114.3, 105.4, 100.2, 32.5, 27.0; HRMS (ESI) calcd for
C24H16BrO4 [M + H]+ 447.0226, found 447.0229.
Compound 8f. Yellow solid: 134 mg, 76% yield; mp 163−164 °C;
IR (KBr, cm−1) 3443, 2945, 1630, 1383, 1231, 1105, 1036, 881, 839,
1
762, 718; H NMR (300 MHz, CDCl3) δ (ppm) 7.37 (d, J = 6.0 Hz,
Compound 6q. Yellow solid: 143 mg, 72% yield; mp 177−178 °C;
2H), 7.28−7.26 (m, 1H), 7.16−7.04 (m, 2H), 6.98−6.88 (m, 2H),
4.25−4.15 (m, 1H), 2.45−2.15 (m, 6H), 1.08 (s, 3H), 0.93 (s, 3H);
13C NMR (75 MHz, CDCl3) δ (ppm) 195.7, 167.2, 151.1, 143.6,
128.0, 127.6, 126.8, 126.2, 125.1, 121.7, 116.0, 115.7, 115.4, 98.6, 50.3,
41.5, 33.1, 32.4, 28.7, 27.8, 25.1; HRMS (ESI) calcd for C21H21O3S
[M + H]+ 353.1206, found 353.1212.
1
IR (KBr, cm−1) 3440, 1720, 1621, 1243, 1118, 1034; H NMR (300
MHz, CDCl3) δ (ppm) 7.88 (d, J = 7.9 Hz, 1H), 7.78−7.75 (m, 2H),
7.54−7.42 (m, 5H), 7.32−7.24 (m, 2H), 6.64−6.54 (m, 2H), 4.36−
4.34 (m, 1H), 3.76 (s, 3H), 2.50−2.38 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 161.6, 159.8, 158.0, 152.3, 152.1, 139.7, 131.9, 129.4,
128.6, 128.5, 125.6, 124.0, 122.7, 117.4, 116.7, 115.1, 108.2, 106.5,
101.9, 100.2, 55.4, 33.2, 26.5; MS (EI, 70 eV) m/z (%) 398.16 (100),
279.09 (19), 275.09 (17), 237.08 (43), 224.09 (57), 199.22 (13).
General Procedure for the Synthesis of 8. A mixture of 3-(2-
hydroxyphenyl)-1-phenylprop-2-en-1-one derivatives (5, 0.5 mmol)
and 5,5-dimethylcyclohexane-1,3-dione/cyclohexane-1,3-dione (7, 0.5
mmol) was heated at reflux in anhydrous toluene in a sealed tube (4.0
mL). The solution became homogeneous as the starting materials were
completely dissolved. After the reactant disappeared (6−12 h,
monitored by thin layer chromatography), the mixture was cooled
to room temperature, and toluene was removed under reduced
pressure. Then, the residue was recrystallized from the mixture of
ethanol/hexane to give the target products 8 as the yellow solids.
Compound 8a. Yellow solid: 138 mg, 80% yield; mp 161−162 °C;
IR (KBr, cm−1) 3443, 2951, 1629, 1381, 1236, 1108, 1023, 883, 761;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.67−7.64 (m, 2H), 7.48−7.37
(m, 4H), 7.16−7.12 (m, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.93−6.88 (m,
1H), 4.22 (s, 1H), 2.39 (s, 2H), 2.29−2.13 (m, 4H), 1.10 (s, 3H), 0.95
(s, 3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.7, 167.5, 151.4,
140.2, 129.0, 128.4, 128.0, 127.5, 126.5, 125.5, 121.5, 116.0, 115.4,
99.8, 50.4, 41.6, 33.0, 32.4, 28.8, 27.8, 25.1; HRMS (ESI) calcd for
C23H23O3 [M + H]+ 347.1642, found 347.1643.
Compound 8g. Yellow solid: 104 mg, 73% yield; mp 138−139 °C;
IR (KBr, cm−1) 3440, 2949, 1619, 1476, 1382, 1252, 1139, 1063, 854,
1
832, 754; H NMR (300 MHz, CDCl3) δ (ppm) 7.31 (d, J = 7.1 Hz,
1H), 7.10−7.04 (m, 1H), 6.86−6.81 (m, 2H), 4.13 (s, 1H), 2.26 (s,
2H), 2.16−2.07 (m, 3H), 1.98−1.93 (m, 1H), 1.81 (s, 3H), 1.04 (s,
3H), 0.90 (s, 3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.7, 167.5,
151.2, 128.0, 127.3, 126.4, 121.1, 115.7, 115.2, 99.2, 50.3, 41.6, 32.3,
31.0, 28.7, 27.8, 26.7, 24.7; HRMS (ESI) calcd for C18H21O3 [M + H]+
285.1485, found 285.1485.
Compound 8h. Yellow solid: 170 mg, 82% yield; mp 118−119 °C;
IR (KBr, cm−1) 3425, 2958, 1630, 1454, 1383, 1250, 1109, 1041, 917,
1
869, 761, 689; H NMR (300 MHz, CDCl3) δ (ppm) 7.70−7.67 (m,
2H), 7.50−7.43 (m, 3H), 7.37 (d, J = 2.5 Hz, 1H), 7.22 (d, J = 2.5 Hz,
1H), 4.21−4.19 (m, 1H), 2.41 (s, 2H), 2.31−2.11 (m, 4H), 1.11 (s,
3H), 0.98 (s, 3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.5, 167.7,
146.2, 139.2, 129.34, 129.29, 128.5, 127.9, 126.3, 126.2, 125.6, 121.7,
114.1, 100.2, 50.3, 41.4, 32.5, 32.4, 28.9, 27.7, 25.3; HRMS (ESI) calcd
for C23H21Cl2O3 [M + H]+ 415.0862, found 415.0853.
Compound 8i. Yellow solid: 131 mg, 82% yield; mp 126−127 °C;
IR (KBr, cm−1) 3445, 2946, 1625, 1382, 1237, 1108, 1026, 877, 758;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.68−7.64 (m, 2H), 7.43−7.39
(m, 4H), 7.18−7.12 (m, 1H), 7.00 (d, J = 8.1 Hz, 1H), 6.95−6.89 (m,
1H), 4.24−4.22 (m, 1H), 2.55−2.13 (m, 6H), 2.03−1.93 (m, 2H); 13
C
Compound 8b. Yellow solid: 134 mg, 71% yield; mp 113−114 °C;
IR (KBr, cm−1) 3445, 2951, 1624, 1515, 1472, 1383, 1332, 1243, 1172,
NMR (75 MHz, CDCl3) δ (ppm) 196.0, 169.1, 151.5, 140.2, 129.0,
128.4, 128.2, 127.6, 126.5, 125.6, 121.5, 116.5, 116.0, 99.6, 36.4, 33.0,
27.8, 25.2, 20.7; HRMS (ESI) calcd for C21H19O3 [M + H]+ 319.1329,
found 319.1324.
1
1105, 1033, 883, 836, 755; H NMR (300 MHz, CDCl3) δ (ppm)
7.60−7.55 (m, 2H), 7.38 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H), 7.16−7.10
(m, 1H), 7.00−6.88 (m, 4H), 4.22−4.20 (m, 1H), 3.84 (s, 3H), 2.38
(s, 2H), 2.28−2.12 (m, 4H), 1.09 (s, 3H), 0.94 (s, 3H); 13C NMR (75
MHz, CDCl3) δ (ppm) 195.8, 167.7, 160.1, 151.5, 132.5, 128.0, 127.5,
126.9, 126.5, 121.5, 115.9, 115.3, 113.7, 99.8, 55.3, 50.3, 41.6, 33.0,
Compound 8j. Yellow solid: 132 mg, 76% yield; mp 99−100 °C; IR
(KBr, cm−1) 3452, 2943, 1625, 1383, 1243, 1176, 1107, 1026, 826,
755; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.58 (d, J = 9.0 Hz, 2H),
3138
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7.41−7.38 (m, 1H), 7.17−7.11 (m, 1H), 7.01−6.89 (m, 4H), 4.21 (s,
1H), 3.84 (s, 3H), 2.54−2.31 (m, 4H), 2.26−2.12 (m, 2H), 2.02−1.92
(m, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 196.0, 169.2, 160.1,
151.5, 132.5, 128.1, 127.5, 126.9, 126.6, 121.4, 116.5, 115.9, 113.7,
99.7, 55.3, 36.4, 33.0, 27.8, 25.3, 20.7; HRMS (ESI) calcd for
C22H21O4 [M + H]+ 349.1434, found 349.1431.
Compound 10c. Yellow solid: 156 mg, 71% yield; mp 185−186 °C;
IR (KBr, cm−1) 3441, 1678, 1637, 1595, 1522, 1337, 1243, 1132, 1033,
1
952, 896, 756; H NMR (300 MHz, CDCl3) δ (ppm) 8.10−8.07 (m,
2H), 7.73−7.67 (m, 2H), 7.46 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H),
7.33−7.28 (m, 2H), 7.21−7.16 (m, 1H), 7.06−6.93 (m, 3H), 4.56−
4.54 (m, 1H), 3.95 (s, 3H), 3.93 (s, 3H), 2.48 (dd, J1 = 13.6 Hz, J2 =
2.8 Hz, 1H), 2.29 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ (ppm) 182.7, 178.8, 153.2, 151.8, 149.7, 148.8, 134.0,
133.4, 131.9, 131.7, 130.9, 128.5, 128.4, 126.4, 126.2, 124.7, 124.1,
121.9, 118.4, 116.6, 110.8, 109.1, 100.0, 55.99, 55.97, 32.0, 26.2;
HRMS (ESI) calcd for C27H20O6Na [M + Na]+ 463.1152, found
463.1130.
Compound 8k. Yellow solid: 148 mg, 84% yield; mp 162−163 °C;
1
IR (KBr, cm−1) 3443, 1626, 1384, 1236, 1103, 1024, 835, 758; H
NMR (300 MHz, CDCl3) δ (ppm) 7.60 (d, J = 8.4 Hz, 2H), 7.43−
7.40 (m, 3H), 7.18−7.13 (m, 1H), 7.01−6.90 (m, 2H), 4.22 (s, 1H),
2.52−2.15 (m, 6H), 2.02−1.95 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ (ppm) 195.9, 168.8, 151.3, 138.8, 135.1, 128.6, 128.2, 127.7, 127.1,
126.4, 121.7, 116.6, 115.9, 99.3, 36.4, 32.9, 27.7, 25.1, 20.7; HRMS
(ESI) calcd for C21H18ClO3 [M + H]+ 353.0939, found 353.0941.
Compound 8l. Yellow solid: 122 mg, 79% yield; mp 193−194 °C;
IR (KBr, cm−1) 3444, 1622, 1382, 1339, 1239, 1156, 1109, 1024, 807,
750; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.48−7.47 (m, 1H), 7.39
(dd, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H), 7.16−7.10 (m, 1H), 6.97−6.89 (m,
2H), 6.68 (d, J = 3.3 Hz, 1H), 6.45 (dd, J1 = 3.3 Hz, J2 = 1.8 Hz, 1H),
4.25−4.23 (m, 1H), 2.50−2.30 (m, 6H), 2.00−1.90 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 196.0, 168.6, 151.6, 150.8, 143.0,
128.2, 127.6, 126.3, 121.7, 116.6, 116.0, 110.4, 107.8, 96.0, 36.4, 29.6,
27.7, 24.3, 20.7; HRMS (ESI) calcd for C19H17O4 [M + H]+ 309.1121,
found 309.1123.
Compound 10d. Yellow solid: 170 mg, 82% yield; mp 218−219
°C; IR (KBr, cm−1) 3424, 3066, 1686, 1635, 1591, 1485, 1403, 1336,
1
1242, 1096, 1007, 951, 886, 761; H NMR (300 MHz, CDCl3) δ
(ppm) 8.08 (d, J = 6.8 Hz, 2H), 7.69 (d, J = 8.1 Hz, 4H), 7.48−7.43
(m, 3H), 7.21−7.16 (m, 1H), 7.05−6.94 (m, 2H), 4.55 (s, 1H), 2.45−
2.25 (m, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 182.6, 178.7,
153.0, 151.6, 138.0, 135.4, 134.1, 133.5, 131.6, 130.9, 128.7, 128.5,
127.3, 126.5, 126.2, 124.7, 124.0, 122.1, 116.6, 99.6, 32.0, 26.1; HRMS
(ESI) calcd for C25H15ClO4Na [M + Na]+ 437.0551, found 437.0533.
Compound 10e. Yellow solid: 183 mg, 80% yield; mp 234−235 °C;
IR (KBr, cm−1) 3440, 1684, 1626, 1590, 1482, 1336, 1241, 1098, 1005,
1
951, 886, 760; H NMR (300 MHz, CDCl3) δ (ppm) 8.11−8.07 (m,
Compound 8m. Yellow solid: 126 mg, 78% yield; mp 149−150 °C;
IR (KBr, cm−1) 3443, 1623, 1383, 1227, 1107, 1029, 866, 754, 712; 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.41−7.36 (m, 2H), 7.28−7.25
(m, 1H), 7.17−7.11 (m, 1H), 7.05 (dd, J1 = 4.8 Hz, J2 = 3.3 Hz, 1H),
6.99−6.89 (m, 2H), 4.24 (s, 1H), 2.51−2.27 (m, 6H), 1.99−1.93 (m,
2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 195.9, 168.7, 151.1, 143.6,
128.2, 127.6, 126.8, 126.25, 126.18, 125.1, 121.7, 116.5, 116.0, 98.5,
36.4, 33.1, 27.7, 25.2, 20.6; HRMS (ESI) calcd for C19H17O3S [M +
H]+ 325.0893, found 325.0888.
Compound 8n. Yellow solid: 90 mg, 70% yield; mp 144−146 °C;
IR (KBr, cm−1) 3439, 2946, 1621, 1381, 1255, 1130, 1059, 862, 820,
756; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.33 (d, J = 7.4 Hz, 1H),
7.11−7.05 (m, 1H), 6.87−6.82 (m, 2H), 4.14−4.12 (m, 1H), 2.41−
2.26 (m, 4H), 2.10−2.05 (m, 1H), 1.98−1.86 (m, 3H), 1.81 (s, 3H);
13C NMR (75 MHz, CDCl3) δ (ppm) 196.0, 169.1, 151.3, 128.1,
127.4, 126.5, 121.1, 116.4, 115.7, 99.0, 36.4, 31.0, 27.8, 26.7, 24.8, 20.7;
HRMS (ESI) calcd for C16H17O3 [M + H]+ 257.1172, found 257.1174.
General Procedure for the Synthesis of 10. A mixture of 3-(2-
hydroxyphenyl)-1-phenylprop-2-en-1-one derivatives (5, 0.5 mmol)
and 2-hydroxynaphthalene-1,4-dione (9, 0.5 mmol) was heated at
reflux in anhydrous n-PrOH in a sealed tube (4.0 mL). After the
reactant disappeared (6−12 h, monitored by thin layer chromatog-
raphy), the mixture was cooled to room temperature and stood
overnight. Thus the crystals were precipitated, filtrated and washed
with a small amount of anhydrous ethanol, and the target products 10
were obtained as the yellow solids.
2H), 7.75−7.58 (m, 6H), 7.48−7.45 (m, 1H), 7.22−7.16 (m, 1H),
7.05−6.94 (m, 2H), 4.55 (t, J = 2.9 Hz, 1H), 2.43 (dd, J1 = 13.6 Hz, J2
= 2.8 Hz, 1H), 2.27 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ (ppm) 182.6, 178.7, 152.9, 151.6, 138.5, 134.1, 133.5,
131.7, 131.6, 130.9, 128.50, 128.49, 127.6, 126.5, 126.2, 124.7, 124.0,
123.6, 122.1, 116.6, 99.7, 31.9, 26.1; HRMS (ESI) calcd for
C25H15BrO4Na [M + Na]+ 481.0046, found 481.0021.
Compound 10f. Yellow solid: 169 mg, 85% yield; mp 188−189 °C;
IR (KBr, cm−1) 3439, 1661, 1639, 1623, 1592, 1514, 1335, 1236, 1158,
1
1098, 1021, 947, 832, 758; H NMR (300 MHz, CDCl3) δ (ppm)
8.10−8.08 (m, 2H), 7.76−7.67 (m, 4H), 7.48−7.45 (m, 1H), 7.21−
7.13 (m, 3H), 7.05−6.94 (m, 2H), 4.55 (t, J = 2.7 Hz, 1H), 2.44 (dd,
J1 = 13.6 Hz, J2 = 2.7 Hz, 1H), 2.28 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ (ppm) 182.7, 178.8, 163.2 (d,
4
1JCF = 246.8 Hz), 153.0, 151.7, 135.4 (d, JCF = 3.2 Hz), 134.1, 133.5,
3
131.7, 131.0, 128.5, 128.4, 127.9 (d, JCF = 8.5 Hz), 126.5, 126.2,
2
124.7, 124.0, 122.1, 116.6, 115.5 (d, JCF = 21.6 Hz), 99.7, 32.1, 26.2;
HRMS (ESI) calcd for C25H15FO4Na [M + Na]+ 421.0847, found
421.0868.
Compound 10g. Yellow solid: 133 mg, 72% yield; mp 191−192
°C; IR (KBr, cm−1) 3442, 1662, 1642, 1625, 1591, 1333, 1240, 1161,
1104, 957, 716; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.08−8.05 (m,
2H), 7.69−7.65 (m, 2H), 7.49−7.44 (m, 2H), 7.16−7.13 (m, 1H),
7.01−6.92 (m, 2H), 6.85−6.83 (m, 1H), 6.48 (dd, J1 = 3.3 Hz, J2 = 1.8
Hz, 1H), 4.56 (t, J = 2.9 Hz, 1H), 2.56 (dd, J1 = 13.5 Hz, J2 = 2.8 Hz,
1H), 2.48 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 182.6, 178.5, 152.7, 151.2, 150.5, 143.3, 134.0, 133.4,
131.6, 130.9, 128.5, 128.4, 126.5, 126.2, 124.6, 124.0, 122.1, 116.6,
110.6, 108.7, 96.5, 28.8, 25.3; HRMS (ESI) calcd for C23H14O5Na [M
+ Na]+ 393.0733, found 393.0721.
Compound 10a. Yellow solid: 167 mg, 88% yield; mp 184−185
°C; IR (KBr, cm−1) 3442, 1663, 1642, 1592, 1335, 1241, 1105, 957,
761; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.10−8.07 (m, 2H),
7.77−7.67 (m, 4H), 7.51−7.44 (m, 4H), 7.21−7.16 (m, 1H), 7.06−
6.93 (m, 2H), 4.56 (t, J = 2.8 Hz, 1H), 2.46 (dd, J1 = 13.6 Hz, J2 = 2.8
Hz, 1H), 2.30 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 182.7, 178.8, 153.2, 151.8, 139.4, 134.0, 133.4, 131.7,
131.0, 129.3, 128.54, 128.47, 128.4, 126.5, 126.2, 125.8, 124.7, 124.2,
121.9, 116.6, 100.1, 32.1, 26.2; HRMS (ESI) calcd for C25H16O4Na [M
+ Na]+ 403.0941, found 403.0924.
Compound 10h. Yellow solid: 135 mg, 70% yield; mp 193−194
°C; IR (KBr, cm−1) 3441, 1662, 1623, 1589, 1326, 1235, 1197, 1098,
1
951, 760; H NMR (300 MHz, CDCl3) δ (ppm) 8.08 (d, J = 5.8 Hz,
2H), 7.69 (s, 2H), 7.47−7.39 (m, 3H), 7.19−6.94 (m, 4H), 4.57 (s,
1H), 2.61−2.44 (m, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm)
182.7, 178.5, 152.8, 151.4, 142.4, 134.0, 133.5, 131.6, 130.9, 128.5,
128.4, 127.0, 126.6, 126.5, 126.2, 125.7, 124.6, 123.9, 122.1, 116.7,
99.0, 32.3, 26.2; HRMS (ESI) calcd for C23H14O4SNa [M + Na]+
409.0505, found 409.0492.
Compound 10b. Yellow solid: 152 mg, 74% yield; mp 189−190
°C; IR (KBr, cm−1) 3440, 1684, 1623, 1593, 1512, 1336, 1165, 1097,
1
946, 884, 756; H NMR (300 MHz, CDCl3) δ (ppm) 8.08−8.05 (m,
Compound 10i. Yellow solid: 108 mg, 68% yield; mp 220−221 °C;
2H), 7.71−7.66 (m, 4H), 7.47−7.44 (m, 1H), 7.17−7.14 (m, 1H),
7.04−6.92 (m, 4H), 4.53 (s, 1H), 3.85 (s, 3H), 2.44 (dd, J1 = 13.6 Hz,
J2 = 3.0 Hz, 1H), 2.29 (dd, J1 = 13.6 Hz, J2 = 3.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ (ppm) 182.7, 178.8, 160.2, 153.2, 151.8, 134.0,
133.3, 131.7, 131.6, 130.9, 128.4, 128.3, 127.1, 126.4, 126.1, 124.6,
124.2, 121.8, 116.6, 113.8, 100.1, 55.3, 32.1, 26.2; HRMS (ESI) calcd
for C26H18O5Na [M + Na]+ 433.1046, found 433.1038.
IR (KBr, cm−1) 3441, 1660, 1622, 1588, 1337, 1257, 1213, 1145, 1098,
1
942, 866, 767; H NMR (300 MHz, CDCl3) δ (ppm) 8.06−8.02 (m,
2H), 7.70−7.63 (m, 2H), 7.41−7.38 (m, 1H), 7.14−7.11 (m, 1H),
7.09−6.86 (m, 2H), 4.56 (t, J = 2.8 Hz, 1H), 2.28 (dd, J1 = 13.6 Hz, J2
= 2.8 Hz, 1H), 2.14 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz, 1H), 1.99 (s, 3H);
13C NMR (75 MHz, CDCl3) δ (ppm) 182.7, 179.0, 153.0, 151.6,
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Article
134.0, 133.3, 131.6, 130.9, 128.3, 128.2, 126.4, 126.1, 124.5, 124.1,
121.5, 116.3, 99.7, 30.1, 26.5, 25.8; HRMS (ESI) calcd for
C20H14O4Na [M + Na]+ 341.0784, found 341.0774.
REFERENCES
■
(1) Troger, J. J. Prakt. Chem. 1887, 36, 225.
̈
́
(2) (a) Pardo, C.; Sesmilo, E.; Gutierrez-Puebla, E.; Monge, A.;
Compound 10j. Yellow solid: 170 mg, 82% yield; mp 211−212 °C;
IR (KBr, cm−1) 3439, 1663, 1624, 1590, 1478, 1333, 1243, 1199, 1097,
953, 760; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.11−8.08 (m, 2H),
7.75−7.69 (m, 4H), 7.50−7.45 (m, 4H), 7.15−7.11 (m, 1H), 6.97 (d, J
= 8.7 Hz, 1H), 4.51 (t, J = 2.6 Hz, 1H), 2.43 (dd, J1 = 13.7 Hz, J2 = 2.6
Hz, 1H), 2.30 (dd, J1 = 13.6 Hz, J2 = 3.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 182.5, 178.6, 153.2, 150.4, 138.9, 134.2, 133.5, 131.6,
130.9, 129.4, 128.6, 128.4, 128.1, 126.7, 126.5, 126.3, 125.7, 124.1,
117.9, 100.1, 31.7, 26.0; HRMS (ESI) calcd for C25H15ClO4Na [M +
Na]+ 437.0551, found 437.0537.
Compound 10k. Yellow solid: 186 mg, 83% yield; mp 208−209
°C; IR (KBr, cm−1) 3442, 1639, 1452, 1348, 1252, 1200, 1096, 928,
708; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.13−8.09 (m, 2H),
7.79−7.71 (m, 4H), 7.50−7.26 (m, 5H), 4.51 (t, J = 2.8 Hz, 1H),
2.43−2.31 (m, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 182.4,
178.4, 153.1, 146.6, 138.3, 134.2, 133.7, 131.5, 130.9, 129.6, 128.8,
128.7, 127.1, 126.7, 126.6, 126.5, 126.3, 125.9, 123.3, 122.5, 100.5,
31.7, 26.3; HRMS (ESI) calcd for C25H14Cl2O4Na [M + Na]+
471.0161, found 471.0148.
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Compound 10l. Yellow solid: 179 mg, 78% yield; mp 205−206 °C;
IR (KBr, cm−1) 3440, 1663, 1637, 1589, 1477, 1332, 1243, 1198, 1100,
1
953, 759; H NMR (300 MHz, CDCl3) δ (ppm) 8.09 (d, J = 7.0 Hz,
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2H), 7.73−7.60 (m, 4H), 7.48−7.46 (m 4H), 7.29−7.25 (m, 1H), 6.92
(d, J = 8.7 Hz, 1H), 4.51 (s, 1H), 2.45−2.28 (m, 2H); 13C NMR (75
MHz, CDCl3) δ (ppm) 182.5, 178.6, 153.1, 151.0, 138.9, 134.2, 133.5,
131.6, 131.3, 130.9, 129.4, 128.6, 126.5, 126.3, 126.2, 125.7, 124.1,
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[M + Na]+ 481.0046, found 481.0046.
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dione (12). A mixture of 3-(2-hydroxyphenyl)-1-phenylprop-2-en-1-
one (5a, 224 mg, 1.0 mmol) and pentane-2,4-dione (11, 100 mg, 1.0
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476; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.67−7.64 (m, 2H),
7.42−7.35 (m, 3H), 7.28−7.22 (m, 1H), 7.14−7.03 (m, 3H), 5.61 (d, J
= 5.4 Hz, 1H), 7.05 (dd, J1 = 7.6 Hz, J2 = 5.4 Hz, 1H), 4.10 (d, J = 7.6
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gdyin@hbnu.edu.cn; chwuax@mail.ccnu.edu.cn.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
We gratefully acknowledge support from the National Natural
Science Foundation of China (Grant 21032001 and 21102042)
and the Science and Technology Foundation for Creative
Research Group of HBDE (2013).
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