Efficient synthesis of functionalized 6-arylsalicylates via microwave-promoted Suzuki cross-coupling reaction

Article abstract of DOI:10.1016/j.tet.2013.08.033

Functionalized 6-arylsalicylate substructures occur in a variety of pharmacologically relevant natural products and bioactive compounds. They are also broadly used as important intermediates in organic synthesis. Traditional synthetic methods have suffered from some drawbacks, such as relatively harsh reaction conditions, narrow range of substrates, and poor yields. Utilizing microwave irradiation, the synthesis of functionalized 6-arylsalicylates via a Suzuki cross-coupling has been developed with a wide range of substrates. Almost all the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicated that electronic effects and steric modifications have little effect on this reaction.

Full text of DOI:10.1016/j.tet.2013.08.033

Tetrahedron 69 (2013) 9025e9032
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of functionalized 6-arylsalicylates via microwave-
promoted Suzuki cross-coupling reaction
*
*
Yu-Chao Liu, Zhi-You Huang, Qiong Chen , Guang-Fu Yang
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan,
Hubei 430079, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 June 2013
Received in revised form 27 July 2013
Accepted 15 August 2013
Available online 22 August 2013
Functionalized 6-arylsalicylate substructures occur in a variety of pharmacologically relevant natural
products and bioactive compounds. They are also broadly used as important intermediates in organic
synthesis. Traditional synthetic methods have suffered from some drawbacks, such as relatively harsh
reaction conditions, narrow range of substrates, and poor yields. Utilizing microwave irradiation, the
synthesis of functionalized 6-arylsalicylates via a Suzuki cross-coupling has been developed with a wide
range of substrates. Almost all the reactions proceeded smoothly and afforded moderate to excellent
yields of products, which indicated that electronic effects and steric modifications have little effect on
this reaction.
Keywords:
Functionalized 6-arylsalicylates
Suzuki cross-coupling reactions
Steric effect
Ó 2013 Elsevier Ltd. All rights reserved.
Electronic effect
Microwave irradiation
1. Introduction
an antioxidant,2 while Cyandione B has exhibited significant
in vitro cytotoxic activity and also displayed anti-inflammatory
Functionalized 6-arylsalicylate substructures occur in a variety
of pharmacologically relevant natural products and bioactive
compounds.1e4 For example (Fig. 1), amaroswerin, has been de-
scribed as a novel hepatoprotective glycoside ester.1 Cyandiones A
and B are novel phenolic acetophenones isolated from the rhizome
of Cynanchum taiwanianum.2a,2b Cyandione A has been shown to be
activity.2 Graphislactones and their derivatives represent high an-
titumor-active.3 Dimethoxypyrimidinylsalicylic acid also showed
potent herbicidal activity as a result of the inhibition of acetohy-
droxy acid synthase.4 In addition, numerous important pharma-
ceutical lead structures contain functionalized 6-arylsalicylates,
and they have also been broadly used as important intermediates in
organic synthesis.5
Two traditional methods have been developed for the synthesis
of functionalized 6-arylsalicylates. The first pathway relied on
transition-metal-catalyzed cyclization reactions.
Although this method has been broadly applied, the synthesis of
sterically encumbered 6-arylsalicylates is still very difficult or with
low yield.6 The second method involved formal [3þ3] cyclizations of
1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-trimethylsilyloxy-
2-en-1-ones, which was developed by Chan et al.1a,7 This method
also suffered from some drawbacks, such as relatively harsh reaction
conditions, narrow range of substrates, and poor yields. Thus, the
development of an efficient method to prepare functionalized 6-
arylsalicylates is of great interest.
Microwave irradiation has emerged as a powerful technique for
promoting a variety of chemical reactions.8 Reactions performed
under microwave irradiation conditions benefit from significant
enhancements in rate and higher product yields. In recent years, we
have developed some new methods for efficient synthesis of het-
erocyclic compounds under microwave irradiation.9 Not long ago,
Fig. 1. Pharmacologically active functionalized 6-arylsalicylates and their derivatives.
* Corresponding authors. Tel.: þ86 27 67867800; fax: þ86 27 67867141; e-mail
addresses: qchen@mail.ccnu.edu.cn (Q. Chen), gfyang@ccnu.edu.cn, gfyang@
mail.ccnu.edu.cn (G.-F. Yang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.033

9026
Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
we developed a convenient method for the synthesis of bulky 4-
substituted isatins by using microwave-assisted Suzuki cross-
coupling reactions.9e Herein, as a continuation of our research on
the synthesis of structurally diverse heterocyclic compounds, we
report the synthesis of functionalized 6-arylsalicylates via a Suzuki
cross-coupling under microwave irradiation.
acceptable yields. It should be noted that incorporation of halogen-
substituents at the ortho, meta or para positions in arylboronic acids
did not retard the reaction, demonstrating that steric modification
can be accomplished without compromising the efficiency of the
process (Table 2, 3bed). More importantly, the reaction proved to be
tolerant of valuable but unstable substituents, such as formyl and
acetyl groups (Table 2, compounds 3m and 3n).
2. Result and discussion
Table 2
The aryl iodide (1) was prepared by using a previously reported
synthetic strategy.10 To optimize the conditions for the palladium-
catalyzed Suzuki cross-coupling reaction, we selected the reaction
between aryl iodide (1) and phenylboronic acids (2a) as a model. As
shown in Table 1, microwave irradiation can also dramatically ac-
celerate these reactions and increase the reaction yields. In addi-
tion, during optimization, the concentration, the stoichiometric
ratio of the catalyst, and the temperature proved to be important
parameters for this reaction. The yield was notably increased to 96%
when the reaction was carried out at 110 ꢀC, with 1 mol % of
Pd(PPh3)4, 2 equiv of NaHCO3, protected by N2, under microwave
irradiation. We also noted that the reaction could not take place
without Pd catalysis (entry 3). If the reaction was carried out at
100 ꢀC, with 1% of Pd(PPh3)4, the transformation was incomplete
(Table 1, entry 10). And then, as compared to the microwave irra-
diation, conventional heating methods have longer reaction time
and lower reaction yields (Table 1, entry 11).
The reaction with aryl iodide (1) and various arylboronic acids or alkenyl boronic
acidsa
Table 1
Optimization of the reaction conditionsa
Entry
Temp (ꢀC)
1:2a
Pd(PPh3)4
Base
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
MW:130c
MW:130
MW:130
MW:120
MW:120
MW:120
MW:120
MW:120
MW:110
MW:100
120d
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
5 mol %
5 mol %
0 mol %
5 mol %
2 mol %
1 mol %
0.5 mol %
0.2 mol %
1 mol %
1 mol %
1 mol %
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
0.5
5
5
5
7
70%
49%
0%
a
Unless otherwise noted, all the reactions were carried out at 0.5 mmol scale
in the solution of DME (3 mL) and H2O (0.6 mL) with 1 mol% of Pd(PPh3)4,
2 equiv of NaHCO3, protected by N2.
59%
90%
92%
87%
53%
96%
40%
82%e
7
10
13
7
25
480
Very promisingly, polysubstituted phenylboronic acids, furan-2-
ylboronic acid, thiophen-2-ylboronic acid, dibenzofuran-4-ylboronic
acid, naphthalen-1-ylboronic acid, and benzofuran-2-ylboronic acid
also reacted with aryl iodide (1) very well and gave moderate to
excellent yields of products (Table 2, 3oew).
We also extended the substrates to alkenyl boronic acids. Not
surprisingly, the process showed good functional group compati-
bility for the alkenyl reagents (Table 2, 3x, 3y).
Finally, we removed the protecting groups of functionalized 6-
arylsalicylates (3) successfully to obtain the target compounds 6-
arylsalicylates (4). For almost all the substrates with different
substituents at 3, deprotection proceeded smoothly and afforded
moderate to excellent yields of products (Table 3).
9
10
11
a
Unless otherwise noted, all the reactions were carried out at 0.5 mmol scale in
the solution of DME (3 ml) and H2O (0.6 ml) with 1 mol % of Pd(PPh3)4, 2 equiv of
base, protected by N2.
b
Isolated yields.
Microwave irradiation.
Conventional heating method.
1 mmol scale in the solution of DME (6 ml) and H2O (1.2 ml).
c
d
e
With the optimized conditions defined, we investigated the
scope of substrates by employing a variety of arylboronic acids
substituted with electron-donating and electron-withdrawing
groups. As shown in Table 2, significant structural variations in the
arylboronic acid components were well tolerated and afforded the
corresponding functionalized 6-arylsalicylates (3) in moderate to
good yields. Both electron-rich and electron-poor arylboronic acids
could be successfully utilized in this transformation. Most groups,
such as methyl, methoxy, tert-butyl, nitro, and trifluoromethyl,
showed no significant effects on the transformation and afforded
good yields of products (Table 2, 3gek). Even potentially problem-
atic bromo-substituted arylboronic acid, could get product 3e with
3. Conclusion
In summary, we have developed a convenient method for the
synthesis of functionalized 6-arylsalicylates (4) from aryl iodide (1)
by using microwave-assisted Suzuki cross-coupling reactions. The
reactions are applicable to a wide range of substrates and produce
a variety of densely functionalized 6-arylsalicylates (4) in good to
excellent yields within a very short time.

Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
9027
Table 3
ether/acetone (20/1 to 10/1) as eluent to give the title compound 3a
(122 mg) in 96% yield.
The synthesis of functionalized 6-arylsalicylates(4) from functionalized 6-
arylsalicylates (3)a
4.2.1. 2,2-Dimethyl-5-phenyl-4H-benzo[d][1,3]dioxin-4-one
(3a). White solid, 122 mg, 96% yield; mp: 164e165 ꢀC. 1H NMR
(600 MHz, CDCl3)
7.35e7.30 (m, 2H), 7.01 (d, J¼7.8 Hz, 1H), 6.97 (d, J¼8.4 Hz, 1H), 1.79
(s, 6H). 13C NMR (100 MHz, CDCl3)
159.31, 156.96, 145.82, 140.00,
d
7.52 (t, J¼7.8 Hz, 1H), 7.40 (dt, J¼7.2, 6.0 Hz, 3H),
d
134.89, 128.42, 127.79, 127.47, 125.63, 116.25, 111.80, 105.11, 25.46. IR
(KBr) 3053, 3001, 2938, 1729, 1597, 1574, 1470, 1380, 1320, 1274,
1258, 1207, 1107, 1045, 945, 894, 814, 763, 698 cmꢁ1. EIMS: m/
z¼254.11 (Mþ). Anal. Calcd for (C16H14O3): C, 75.57; H, 5.55. Found:
C, 75.64; H, 5.77.
4.2.2. 5-(4-Chlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
one (3b). Yellow solid, 134 mg, 93% yield; mp: 175e176 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
7.53 (t, J¼7.8 Hz, 1H), 7.37 (d, J¼8.4 Hz, 2H), 7.26
(t, J¼4.2 Hz, 4H), 6.98 (dd, J¼12.6, 7.8 Hz, 2H), 1.79 (s, 6H). 13C NMR
(100 MHz, CDCl3)
d 159.38, 157.07, 144.49, 138.47, 135.13, 133.58,
129.84, 128.04, 125.54, 116.73, 111.64, 105.30, 25.49. IR (KBr) 3094,
3008, 2990, 1726, 1598, 1581, 1468, 1393, 1381, 1326, 1298, 1278,
1203, 1088, 1053, 945, 836, 810, 697 cmꢁ1. EIMS: m/z¼288.11 (Mþ).
Anal. Calcd for (C16H13ClO3): C, 66.56; H, 4.54. Found: C, 66.38; H,
4.79.
4.2.3. 5-(3-Chlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
one (3c). White solid, 134 mg, 93% yield; mp: 157e158 ꢀC. 1H NMR
(600 MHz, CDCl3)
1H), 7.20 (d, J¼7.2 Hz, 1H), 6.99 (dd, J¼14.4, 7.8 Hz, 2H), 1.80 (s, 6H).
13C NMR (100 MHz, CDCl3)
159.18, 156.98, 144.12, 141.77, 135.09,
d
7.53 (d, J¼7.8 Hz, 1H), 7.37e7.32 (m, 2H), 7.31 (s,
d
133.54, 128.99, 128.38, 127.53, 126.85, 125.49, 116.89, 111.63, 105.32,
25.47. IR (KBr) 3086, 3057, 3020, 2994, 2942, 1731, 1597, 1582, 1563,
1467, 1378, 1319, 1275, 1236, 1204, 1117, 1045, 947, 797, 780,
692 cmꢁ1. EIMS: m/z¼288.13 (Mþ). Anal. Calcd for (C16H13ClO3): C,
66.56; H, 4.54. Found: C, 66.60; H, 4.57.
4. Experimental section
4.1. General information
4.2.4. 5-(2-Chlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
Unless otherwise noted, materials were purchased from com-
mercial suppliers and used without further purification. All the
solvents were treated according to general methods. Flash
column chromatography (FC) was performed using 200e300 mesh
silica gel.
one (3d). White solid, 135 mg, 94% yield; mp: 180e181 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
7.57 (t, J¼7.8 Hz, 1H), 7.44e7.41 (m, 1H),
7.38e7.31 (m, 2H), 7.28 (dd, J¼7.2, 2.4 Hz,1H), 7.03 (d, J¼8.4 Hz, 1H),
6.93 (d, J¼7.8 Hz, 1H), 1.78 (s, 3H), 1.77 (s, 3H). 13C NMR (100 MHz,
CDCl3)
d 159.20, 156.34, 142.08, 139.11, 135.12, 132.23, 129.70,
1H NMR spectra were recorded on 400/600 (400/600 MHz)
128.98, 128.87, 126.75, 125.31, 117.12, 113.10, 105.46, 26.81, 24.28. IR
(KBr) 3057, 3016, 2990, 2938, 1732, 1586, 1461, 1384, 1329, 1280,
1200, 1072, 1052, 942, 808, 762, 710 cmꢁ1. EIMS: m/z¼288.14 (Mþ).
Anal. Calcd for (C16H13ClO3): C, 66.56; H, 4.54. Found: C, 66.60; H,
4.43.
spectrophotometers. Chemical shifts (d) are reported in parts per
million from the solvent resonance as the internal standard (CDCl3:
7.26 ppm, DMSO: 2.50 ppm). Data are reported as follows: chemical
shift, multiplicity (s¼singlet, d¼doublet, t¼triplet, m¼multiplet,
q¼quaternary), coupling constants (Hertz) and integration. 13C
NMR spectra were recorded on 400/600 (100/150 MHz) spectro-
photometers (CDCl3: 77.0 ppm, DMSO: 39.5 ppm) with complete
proton decoupling. Mass spectra were measured on a Trace MS
spectrometer. Elemental analysis was determined on an elemen-
tary analysis instrument. Microwave irradiation reactions were
carried out on a Smith synthesizerÔ instrument.
4.2.5. 5-(4-Bromophenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
one (3e). White solid, 50 mg, 30% yield; mp: 191e192 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
7.53 (dd, J¼7.8, 5.4 Hz, 3H), 7.20 (d, J¼8.4 Hz,
2H), 6.98 (dd, J¼16.2, 7.8 Hz, 2H), 1.79 (s, 6H). 13C NMR (100 MHz,
CDCl3) d 159.34,157.09,144.51, 138.97, 135.13,130.99, 130.16, 125.49,
121.87,116.76,111.62,105.32, 25.52. IR (KBr) 3090, 3008, 2998,1725,
1599, 1582, 1392, 1381, 1326, 1298, 1278, 1238, 1203, 1053, 944,
809 cmꢁ1. EIMS: m/z¼333.17 (Mþ). Anal. Calcd for (C16H13BrO3): C,
57.68; H, 3.93. Found: C, 57.70; H, 3.80.
4.2. General procedure for the synthesis of compounds 3aey
Aryl iodide 1 (152 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol) were
dissolved in DME (3 mL) and H2O (0.6 mL) in a microwave vial
under a nitrogen atmosphere. Pd(PPh3)4 (0.005 mmol, 5.78 mg)
and sodium bicarbonate (84 mg, 1 mmol) were added, and the
reaction mixture was irradiated in a microwave apparatus at 110 ꢀC
for 4e10 min. After the reaction mixture was cooled to ambient
temperature, the product was concentrated, and the crude mixture
was purified by silica gel column chromatography using petroleum
4.2.6. 5-(4-Fluorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
one (3f). White solid, 129 mg, 95% yield; mp: 178e179 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.52 (t, J¼8.0 Hz, 1H), 7.32e7.27 (m, 2H), 7.09 (t,
J¼7.6 Hz, 2H), 6.98 (d, J¼8.0 Hz, 2H), 1.79 (d, J¼2.4 Hz, 6H). 13C NMR
(100 MHz, CDCl3)
d 163.58, 161.13, 159.42, 157.07, 144.75, 135.99,
135.04, 130.21, 130.12, 125.67, 116.53, 114.94, 114.72, 111.77, 105.25,
25.50. IR (KBr) 3064, 3032, 2991, 2942, 1728, 1601, 1582, 1512, 1474,
1385, 1329, 1280, 1215, 1199, 1049, 942, 898, 840, 807, 785,

9028
Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
696 cmꢁ1. EIMS: m/z¼272.13 (Mþ). Anal. Calcd for (C16H13FO3): C,
1580, 1470, 1383, 1324, 1300, 1277, 1202, 1102, 1049, 940, 764,
694 cmꢁ1. EIMS: m/z¼330.17 (Mþ). Anal. Calcd for (C22H18O3): C,
79.98; H, 5.49. Found: C, 80.17; H, 5.37.
70.58; H, 4.81. Found: C, 70.60; H, 4.92.
4.2.7. 2,2-Dimethyl-5-(p-tolyl)-4H-benzo[d][1,3]dioxin-4-one
(3g). White solid, 127 mg, 95% yield; mp: 168e169 ꢀC. 1H NMR
4.2.13. 5-(4-Acetylphenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
(400 MHz, CDCl3)
J¼8.0 Hz, 1H), 6.95 (d, J¼8.4 Hz, 1H), 2.40 (s, 3H), 1.80 (d, J¼2.0 Hz,
6H). 13C NMR (100 MHz, CDCl3)
159.45, 157.02, 145.92, 137.27,
d
7.50 (d, J¼8.0 Hz,1H), 7.28e7.22 (m, 4H), 7.00 (d,
one (3m). White solid, 136 mg, 91% yield; mp: 157e158 ꢀC. 1H NMR
(600 MHz, CDCl3)
(d, J¼8.4 Hz, 2H), 7.01 (dd, J¼18.0, 7.8 Hz, 2H), 2.65 (s, 3H), 1.81 (s,
6H). 13C NMR (100 MHz, CDCl3)
197.60, 159.26, 157.07, 144.98,
d
8.01 (d, J¼8.4 Hz, 2H), 7.56 (t, J¼7.8 Hz, 1H), 7.43
d
137.10, 134.87, 128.64, 128.37, 125.66, 116.02, 111.84, 105.09, 25.49,
21.20. IR (KBr) 3050, 3022, 2994, 2935, 2918, 2866,1730, 1599,1584,
1470, 1381, 1324, 1273, 1255, 1200, 1237, 1106, 1044, 942, 801, 781,
695 cmꢁ1. EIMS: m/z¼268.13 (Mþ). Anal. Calcd for (C17H16O3): C,
76.10; H, 6.01. Found: C, 75.95; H, 5.91.
d
144.52, 135.93, 135.16, 128.75, 127.93, 125.35, 117.06, 111.65, 105.40,
26.57, 25.50. IR (KBr) 3079, 3047, 2999, 2945,1734,1676,1598,1585,
1395, 1326, 1273, 1240, 1204, 1045, 942, 808, 776, 696 cmꢁ1. EIMS:
m/z¼296.26 (Mþ). Anal. Calcd for (C18H16O4): C, 72.96; H, 5.44.
Found: C, 72.80; H, 5.49.
4.2.8. 5-(4-Methoxyphenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-
one (3h). White solid, 128 mg, 90% yield; mp: 165e166 ꢀC. 1H NMR
4.2.14. 4-(2,2-Dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-5-yl)-benzal-
(600 MHz, CDCl3)
(d, J¼7.8 Hz, 1H), 6.94 (dd, J¼8.4, 6.0 Hz, 3H), 3.85 (s, 3H), 1.79 (s,
6H). 13C NMR (100 MHz, CDCl3)
159.61, 159.16, 157.09, 145.61,
d
7.50 (t, J¼7.8 Hz, 1H), 7.28 (d, J¼8.4 Hz, 2H), 7.00
dehyde (3n). Yellow solid, 130 mg, 92% yield; mp: 183e184 ꢀC. 1H
NMR (600 MHz, CDCl3)
d
10.07 (s, 1H), 7.93 (d, J¼7.8 Hz, 2H), 7.57 (t,
d
J¼7.8 Hz, 1H), 7.49 (d, J¼7.8 Hz, 2H), 7.04 (d, J¼8.4 Hz, 1H), 7.00 (d,
134.90, 132.29, 129.75, 125.66, 115.85, 113.37, 111.73, 105.08, 55.10,
25.49. IR (KBr) 3079, 3034, 2994, 2938, 2831,1729, 1603,1469,1445,
1322, 1275, 1246, 1200, 1176, 1106, 1043, 942, 841, 804, 778,
694 cmꢁ1. EIMS: m/z¼284.12 (Mþ). Anal. Calcd for (C17H16O4): C,
71.82; H, 5.67. Found: C, 71.95; H, 5.42.
J¼7.8 Hz, 1H), 1.81 (s, 6H). 13C NMR (100 MHz, CDCl3)
d 191.89,
159.26, 157.11, 146.41, 144.30, 135.28, 135.24, 129.28, 129.23, 125.32,
117.28, 111.64, 105.49, 25.52. IR (KBr) 3080, 3001, 2991, 2857, 1730,
1694, 1602, 1585, 1475, 1384, 1325, 1292, 1276, 1209, 1045, 839, 806,
785, 697 cmꢁ1. EIMS: m/z¼282.26 (Mþ). Anal. Calcd for (C17H14O4):
C, 72.33; H, 5.00. Found: C, 72.30; H, 5.15.
4.2.9. 5-(4-(tert-Butyl)phenyl)-2,2-dimethyl-4H-benzo[d][1,3] dioxin-
4-one (3i). White solid, 143 mg, 92% yield; mp: 117e118 ꢀC. 1H NMR
4.2.15. 5-(4-Fluoro-3-methylphenyl)-2,2-dimethyl-4H-benzo[d][1,3]-
(400 MHz, CDCl3)
(dd, J¼9.2, 2.8 Hz, 2H), 7.01 (dd, J¼7.6, 1.0 Hz, 1H), 6.95 (d, J¼8.4 Hz,
1H), 1.79 (s, 6H), 1.6 (s, 9H). 13C NMR (100 MHz, CDCl3)
159.49,
d
7.50 (t, J¼8.0 Hz, 1H), 7.42 (d, J¼8.4 Hz, 2H), 7.27
dioxin-4-one (3o). White solid, 134 mg, 94% yield; mp: 159e160 ꢀC.
1H NMR (600 MHz, CDCl3)
d
7.51 (t, J¼7.8 Hz, 1H), 7.14 (d, J¼7.2 Hz,
1H), 7.10 (s, 1H), 7.03 (t, J¼9.0 Hz, 1H), 7.00e6.94 (m, 2H), 2.31 (s,
3H),1.80 (s, 6H). 13C NMR (100 MHz, CDCl3)
162.22, 159.78, 159.46,
d
157.02, 150.26, 145.90, 137.02, 134.85, 128.18, 125.77, 124.81, 115.99,
111.82, 105.05, 34.45, 31.26, 25.50. IR (KBr) 3005, 2968, 2905, 2864,
1745, 1598, 1583, 1473, 1392, 1381, 1324, 1270, 1201, 1097, 1041, 940,
846, 805, 766, 692, 567 cmꢁ1. EIMS: m/z¼310.20 (Mþ). Anal. Calcd
for (C20H22O3): C, 77.39; H, 7.14. Found: C, 77.24; H, 7.11.
d
157.09, 145.09, 135.76, 134.97, 131.54, 131.49, 127.62, 127.54, 125.72,
124.38, 124.20, 116.37, 114.62, 114.40, 111.85, 105.24, 25.56, 14.60. IR
(KBr) 3087, 2991, 2942, 2923, 2864, 1736, 1722, 1598, 1580, 1503,
1472, 1328, 1276, 1241, 1224, 1199, 1180, 1102, 1049, 923, 809, 760,
698 cmꢁ1. EIMS: m/z¼286.21 (Mþ). Anal. Calcd for (C17H15FO3): C,
71.32; H, 5.28. Found: C, 71.22; H, 5.34.
4.2.10. 2,2-Dimethyl-5-(4-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]
dioxin-4-one (3j). White solid, 144 mg, 89% yield; mp: 177e178 ꢀC.
1H NMR (600 MHz, CDCl3)
d
7.66 (d, J¼7.8 Hz, 2H), 7.56 (t, J¼7.8 Hz,
1H), 7.43 (d, J¼7.8 Hz, 2H), 7.03 (d, J¼8.4 Hz, 1H), 6.98 (d, J¼7.8 Hz,
1H), 1.80 (s, 6H). 13C NMR (100 MHz, CDCl3)
159.34, 157.15, 144.28,
4.2.16. 5-(3,5-Dichlorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-
4-one (3p). Yellow solid, 157 mg, 97% yield; mp: 139e140 ꢀC. 1H
d
NMR (600 MHz, CDCl3)
7.19 (d, J¼1.8 Hz, 2H), 7.03 (d, J¼8.4 Hz, 1H), 6.95 (d, J¼7.8 Hz, 1H),
1.80 (s, 6H). 13C NMR (100 MHz, CDCl3)
159.02, 157.04, 142.93,
d
7.55 (t, J¼7.8 Hz,1H), 7.37 (d, J¼1.8 Hz, 1H),
143.82, 135.25, 129.67, 129.35, 128.90, 125.55, 124.85, 122.84, 117.22,
111.72, 105.50, 25.54. IR (KBr) 3093, 3006, 2944, 2898, 1726, 1708,
1600, 1579, 1475, 1392, 1328, 1276, 1178, 1108, 1052, 944, 854, 811,
699 cmꢁ1. EIMS: m/z¼322.14 (Mþ). Anal. Calcd for (C17H13F3O3): C,
63.36; H, 4.07. Found: C, 63.45; H, 4.24.
d
142.70, 135.26, 134.18, 127.51, 127.02, 125.34, 117.48, 111.54, 105.52,
25.52. IR (KBr) 3085, 3058, 2991, 2934, 1734, 1583, 1562, 1383, 1325,
1280, 1239, 1198, 1130, 1051, 859, 795, 772, 696 cmꢁ1. EIMS: m/
z¼322.17 (Mþ). Anal. Calcd for (C16H12Cl2O3): C, 59.46; H, 3.74.
Found: C, 59.49; H, 3.67.
4.2.11. 2,2-Dimethyl-5-(4-nitrophenyl)-4H-benzo[d][1,3]dioxin-4-
one (3k). Yellow solid, 136 mg, 91% yield; mp: 181e182 ꢀC. 1H NMR
(600 MHz, CDCl3)
(d, J¼8.4 Hz, 2H), 7.07 (d, J¼8.4 Hz, 1H), 6.99 (d, J¼7.8 Hz, 1H), 1.81
(s, 6H). 13C NMR (100 MHz, CDCl3)
159.30, 157.15, 147.09, 146.92,
d
8.27 (d, J¼8.4 Hz, 2H), 7.59 (t, J¼7.8 Hz, 1H), 7.48
4.2.17. 5-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-4H-benzo[d][1,3]-
dioxin-4-one (3q). Yellow solid,150 mg, 98% yield; mp: 154e155 ꢀC.
d
1H NMR (600 MHz, CDCl3)
d
7.54 (t, J¼7.8 Hz,1H), 7.38e7.33 (m,1H),
7.20e7.13 (m, 2H), 7.01 (d, J¼8.4 Hz, 1H), 6.96 (d, J¼7.8 Hz, 1H), 1.79
(s, 6H). 13C NMR (100 MHz, CDCl3)
159.32, 158.90, 157.15, 156.42,
143.17, 135.45, 129.47, 125.21, 123.07, 117.76, 111.46, 105.66, 25.48. IR
(KBr) 3142, 3101, 3001, 2938, 1730, 1596, 1571, 1468, 1383, 1324,
d
1280, 1239, 1205, 1109, 1049, 1008, 855, 805, 749, 786, 697 cmꢁ1
.
143.37, 137.09, 135.23, 130.55, 128.58, 128.51, 125.60, 120.32, 117.14,
116.12, 115.91, 111.70, 105.47, 25.57. IR (KBr) 3077, 3060, 2988, 1726,
1599, 1577, 1503, 1471, 1324, 1279, 1261, 1239, 1200, 1103, 1051, 811,
697 cmꢁ1. EIMS: m/z¼306.04 (Mþ). Anal. Calcd for (C16H12ClFO3): C,
62.65; H, 3.94. Found: C, 62.46; H, 3.98.
EIMS: m/z¼299.17 (Mþ). Anal. Calcd for (C16H13NO5): C, 64.21; H,
4.38; N, 4.68. Found: C, 64.12; H, 4.30; N, 4.79.
4.2.12. 5-([1,10-Biphenyl]-4-yl)-2,2-dimethyl-4H-benzo[d][1,3] dioxin-
4-one (3l). White solid,155 mg, 94% yield; mp: 198e199 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
7.65 (dd, J¼11.4, 4.8 Hz, 4H), 7.55 (t, J¼7.8 Hz,1H),
4.2.18. 2,2-Dimethyl-5-(3,4,5-trimethoxyphenyl)-4H-benzo[d][1,3]-
7.46 (t, J¼7.8 Hz, 2H), 7.42 (d, J¼8.4 Hz, 2H), 7.36 (t, J¼7.2 Hz, 1H),
dioxin-4-one (3r). Yellow solid, 160 mg, 93% yield; mp: 156e157 ꢀC.
7.08e7.05 (m, 1H), 7.00e6.97 (m, 1H), 1.82 (s, 6H). 13C NMR
1H NMR (600 MHz, CDCl3)
d
7.52 (t, J¼7.8 Hz, 1H), 7.03 (d, J¼7.8 Hz,
1H), 6.98 (d, J¼8.4 Hz,1H), 6.52 (s, 2H), 3.91 (s, 3H), 3.87 (s, 6H), 1.80
(s, 6H). 13C NMR (100 MHz, CDCl3)
159.18, 157.00, 152.58, 145.77,
137.52, 135.67, 134.88, 125.69, 116.39, 111.70, 105.95, 105.14, 60.78,
(100 MHz, CDCl3)
135.03, 129.05, 128.68, 127.25, 127.11, 126.69, 125.78, 116.39, 111.88,
105.27, 25.59. IR (KBr) 3074, 3050, 3026, 2993, 2937, 1733, 1596,
d 159.57, 157.17, 145.58, 140.72, 140.39, 139.05,
d

Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
9029
55.97, 25.53. IR (KBr) 3082, 3023, 2993, 2966, 2942, 1740, 1580,
1.74 (s, 6H). 13C NMR (100 MHz, CDCl3)
d
160.37, 156.82, 141.76,
1474, 1448, 1411, 1314, 1277, 1253, 1115, 1046, 1006, 828, 814 cmꢁ1
.
136.95, 135.11, 132.64, 128.56, 128.06, 127.04, 126.63, 120.90, 116.08,
110.83, 105.13, 25.54. IR (KBr) 3082, 3058, 3039, 3023, 2993, 1722,
1595, 1577, 1472, 1451, 1392, 1321, 1288, 1272, 1249, 1078, 1048, 961,
925, 802, 752, 694 cmꢁ1. EIMS: m/z¼280.11 (Mþ). Anal. Calcd for
(C18H16O3): C, 77.12; H, 5.75. Found: C, 77.03; H, 5.66.
EIMS: m/z¼344.17 (Mþ). Anal. Calcd for (C19H20O6): C, 66.27; H,
5.85. Found: C, 66.35; H, 5.80.
4.2.19. 5-(Furan-2-yl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one
(3s). White solid, 105 mg, 86% yield; mp: 103e104 ꢀC. 1H NMR
(600 MHz, CDCl3)
J¼8.4 Hz, 1H), 6.82 (d, J¼3.0 Hz, 1H), 6.52 (dd, J¼3.0, 1.8 Hz, 1H), 1.78
(s, 6H). 13C NMR (100 MHz, CDCl3)
159.02, 157.05, 151.22, 142.89,
135.08, 133.35, 123.73, 116.63, 111.45, 111.00, 110.37, 105.17, 25.35. IR
(KBr) 3090, 3001, 2985, 1726, 1600, 1584, 1381, 1326, 1207, 1177,
1109, 1054, 944, 846, 812, 699 cmꢁ1. EIMS: m/z¼244.24 (Mþ). Anal.
Calcd for (C14H12O4): C, 68.85; H, 4.95. Found: C, 69.02; H, 5.05.
d
7.55e7.50 (m, 2H), 7.32 (d, J¼7.8 Hz,1H), 6.94 (d,
4.2.25. (E)-2,2-Dimethyl-5-(pent-1-en-1-yl)-4H-benzo[d][1,3]di-
oxin-4-one (3y). Yellow oil, 122 mg, 99% yield. 1H NMR (600 MHz,
d
CDCl3)
d
7.50e7.37 (m, 2H), 7.24 (d, J¼7.8 Hz, 1H), 6.82 (d, J¼8.4 Hz,
1H), 6.30e6.18 (m, 1H), 2.26 (q, J¼7.2 Hz, 2H), 1.71 (s, 6H), 1.53 (dd,
J¼15.0, 7.2 Hz, 2H), 0.97 (t, J¼7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
160.34, 156.67, 142.56, 135.42, 134.96, 128.07, 121.18, 115.39,
110.46, 105.00, 35.17, 25.57, 22.30, 13.71. IR (neat) 3083, 2962, 2875,
1736, 1686, 1672, 1595, 1476, 1391, 1321, 1216, 1165, 1118, 1079, 1050,
982, 963, 922, 849 cmꢁ1. EIMS: m/z¼246.08 (Mþ). Anal. Calcd for
(C15H18O3): C, 73.15; H, 7.37. Found: C, 73.22; H, 7.42.
4.2.20. 2,2-Dimethyl-5-(thiophen-2-yl)-4H-benzo[d][1,3]dioxin-4-
one (3t). Yellow solid, 79 mg, 60% yield; mp: 130e131 ꢀC. 1H NMR
(600 MHz, CDCl3)
(d, J¼7.2 Hz, 2H), 7.10e7.06 (m, 1H), 6.97 (d, J¼8.4 Hz, 1H), 1.78 (s,
6H). 13C NMR (100 MHz, CDCl3)
159.03, 157.15, 140.65, 137.88,
d
7.49 (t, J¼7.8 Hz, 1H), 7.40 (d, J¼4.8 Hz, 1H), 7.14
4.3. General procedure for the synthesis of compounds 4aey
d
134.88, 127.22, 126.98, 126.49, 126.26, 116.89, 112.19, 105.17, 25.45.
IR (KBr) 3101, 3066, 3001, 2940, 1728, 1581, 1472, 1382, 1316, 1274,
1232, 1205, 1089, 1046, 939, 844, 808, 784, 706, 698 cmꢁ1. EIMS: m/
z¼260.09 (Mþ). Anal. Calcd for (C14H12O3S): C, 64.60; H, 4.65; S,
12.32. Found: C, 64.57; H, 4.71; S, 12.41.
To a stirred solution of 3a (254 mg, 1 mmol) in MeOH (10 ml)
was added K2CO3 (152 mg, 1.1 mmol) at room temperature. The
resulting mixture was stirred at 40e50 ꢀC for 4e10 h and then
allowed to cool to room temperature. The solvent was evaporated
in vacuo. The mixture was quenched with saturated aqueous NH4Cl
and 1 N aqueous HCl, and extracted with Et2O. The organic layer
was washed with brine, dried over Na2SO4, and concentrated. Pu-
rification of the residue by flash column chromatography (hexane/
acetone¼5/1) gave 4a (212 mg, 0.93 mmol) in 93% yield.
4.2.21. 5-(Benzofuran-2-yl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one
(3u). Yellow solid, 128 mg, 87% yield; mp: 146e147 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
7.62 (d, J¼7.8 Hz, 1H), 7.58 (t, J¼7.8 Hz, 1H), 7.51 (d,
J¼8.4 Hz, 1H), 7.45 (d, J¼7.8 Hz, 1H), 7.34e7.28 (m, 1H), 7.24 (t,
J¼7.8 Hz, 1H), 7.13 (s, 1H), 7.03 (d, J¼7.8 Hz, 1H), 1.82 (s, 6H). 13C NMR
4.3.1. Methyl 3-hydroxy-[1,10-biphenyl]-2-carboxylate (4a). Colorless
(100 MHz, CDCl3)
d
158.82,157.14,155.03,153.52,135.18,133.15,128.69,
oil, 212 mg, 93% yield. 1H NMR (600 MHz, CDCl3)
d 10.64 (s, 1H), 7.42
124.81,124.65,122.73,121.31,117.76,111.76,111.16,106.50,105.41, 25.41.
IR (KBr) 3082, 3060, 3034, 3015, 2991, 2937, 1735, 1572, 1471, 1282,
1201, 1045, 802, 780, 755, 694 cmꢁ1. EIMS: m/z¼294.14 (Mþ). Anal.
Calcd for (C18H14O4): C, 73.46; H, 4.79. Found: C, 73.33; H, 4.76.
(t, J¼8.4 Hz, 1H), 7.36 (t, J¼7.2 Hz, 2H), 7.33 (d, J¼7.2 Hz, 1H), 7.23 (d,
J¼7.2 Hz, 2H), 7.01 (d, J¼8.4 Hz, 1H), 6.81 (d, J¼7.2 Hz, 1H), 3.49 (s,
3H). 13C NMR (100 MHz, CDCl3)
d 171.29, 161.25, 144.78, 142.59,
133.61, 128.03, 127.56, 126.79, 122.53, 116.57, 112.06, 51.65. IR (KBr)
3060, 3023, 2952, 2848, 1667, 1602, 1572, 1439, 1344, 1270, 1220,
1172, 898, 816 cmꢁ1. EIMS: m/z¼228.38 (Mþ). Anal. Calcd for
(C14H12O3): C, 73.67; H, 5.30. Found: C, 73.55; H, 5.40.
4.2.22. 5-(Dibenzo[b,d]furan-4-yl)-2,2-dimethyl-4H-benzo[d][1,3]-di-
oxin-4-one (3v). White solid, 169 mg, 98% yield; mp: 210e211 ꢀC. 1H
NMR (600 MHz, CDCl3) d 8.00e7.93 (m, 2H), 7.65e7.60 (m, 1H), 7.49
(dd, J¼7.2 1.3 Hz, 1H), 7.44 (t, J¼7.8 Hz, 1H), 7.39 (dt, J¼9.0, 4.2 Hz,
4.3.2. Methyl 40-chloro-3-hydroxy-[1,10-biphenyl]-2-carboxylate
2H), 7.34e7.30 (m, 1H), 7.19 (dd, J¼7.8, 1.2 Hz, 1H), 7.07 (dd, J¼8.4,
(4b). Yellow oil, 225 mg, 86% yield. 1H NMR (400 MHz, CDCl3)
1.2 Hz, 1H), 1.91 (s, 6H). 13C NMR (100 MHz, CDCl3)
d
159.55, 156.74,
d
10.73 (s, 1H), 7.40 (t, J¼8.0 Hz, 1H), 7.36e7.30 (m, 2H), 7.18e7.12
(m, 2H), 7.04e6.99 (m, 1H), 6.75 (dd, J¼7.6, 0.8 Hz, 1H), 3.52 (s, 3H).
13C NMR (100 MHz, CDCl3)
171.05, 161.54, 143.45, 141.14, 133.79,
155.87, 153.41, 139.15, 135.19, 126.89, 126.32, 125.71, 124.82, 124.25,
123.83,122.97,122.67,120.74,120.45,116.90,113.53,111.35,105.44. IR
(KBr) 3081, 3002, 2944,1734,1590,1469,1450,1410,1323,1277,1194,
1043, 912, 843, 810, 795, 756, 695 cmꢁ1. EIMS: m/z¼344.15 (Mþ).
Anal. Calcd for (C22H16O4): C, 76.73; H, 4.68. Found: C, 76.65; H, 4.63.
d
132.81, 129.40, 127.74, 122.47, 117.06, 111.75, 51.79. IR (neat) 3170,
3082, 3007, 2950, 2851, 1664, 1603, 1578, 1494, 1448, 1436, 1337,
1278, 1212, 1173, 1125, 1082, 1100, 1069, 898, 840, 811, 709,
688 cmꢁ1. EIMS: m/z¼262.13 (Mþ). Anal. Calcd for (C14H11ClO3): C,
64.01; H, 4.22. Found: C, 64.21; H, 4.21.
4.2.23. 2,2-Dimethyl-5-(naphthalen-2-yl)-4H-benzo[d][1,3]dioxin-4-
one (3w). Yellow solid, 150 mg, 98% yield; mp: 175e176 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
7.86 (dt, J¼15.6, 6.0 Hz, 3H), 7.82 (s, 1H), 7.56 (t,
4.3.3. Methyl 30-chloro-3-hydroxy-[1,10-biphenyl]-2-carboxylate
J¼7.8 Hz, 1H), 7.49 (dd, J¼6.0, 3.0 Hz, 2H), 7.43 (dd, J¼8.4, 1.5 Hz,
(4c). Yellow oil, 249 mg, 95% yield. 1H NMR (400 MHz, CDCl3)
1H), 7.11 (d, J¼7.8 Hz, 1H), 7.01 (d, J¼8.4 Hz, 1H), 1.83 (s, 6H). 13C
d
10.75 (s, 1H), 7.41 (t, J¼8.0 Hz, 1H), 7.28 (dt, J¼10.0, 2.0 Hz, 2H), 7.24
NMR (100 MHz, CDCl3)
d
159.46, 157.07, 145.76, 137.77, 135.05,
(s, 1H), 7.09 (dt, J¼6.8, 2.0 Hz, 1H), 7.02 (d, J¼8.4 Hz, 1H), 6.76 (d,
133.13, 132.63, 128.08, 127.61, 127.33, 127.02, 126.79, 125.98, 116.41,
111.85, 105.23, 25.52. IR (KBr) 3077, 3052, 2993, 1735, 1721, 1597,
1578, 1483, 1460, 1391, 1318, 1273, 1244, 1199, 1095, 1044, 936, 824,
805, 752, 699 cmꢁ1. EIMS: m/z¼304.14 (Mþ). Anal. Calcd for
(C20H16O3): C, 78.93; H, 5.30. Found: C, 78.82; H, 5.44.
J¼7.6 Hz,1H), 3.52 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 170.97, 161.56,
144.38, 143.17, 133.82, 133.38, 128.76, 128.11, 126.88, 126.39, 122.39,
117.24, 111.69, 51.81. IR (neat) 3062, 3004, 2953, 2854, 1736, 1671,
1596, 1576, 1563, 1448, 1409, 1342, 1276, 1255, 1220, 1173, 1125, 1106,
1079, 1066, 965, 921, 882, 837, 817 cmꢁ1. EIMS: m/z¼262.10 (Mþ).
Anal. Calcd for (C14H11ClO3): C, 64.01; H, 4.22. Found: C, 64.06; H, 4.12.
4.2.24. (E)-2,2-Dimethyl-5-styryl-4H-benzo[d][1,3]dioxin-4-one
(3x). White solid, 136 mg, 97% yield; mp: 104e105 ꢀC. 1H NMR
4.3.4. Methyl 20-chloro-3-hydroxy-[1,10-biphenyl]-2-carboxylate
(600 MHz, CDCl3)
d
8.27 (d, J¼16.2 Hz, 1H), 7.59 (d, J¼7.8 Hz, 2H),
(4d). Yellow oil, 249 mg, 95% yield. 1H NMR (600 MHz, CDCl3)
7.50 (t, J¼7.8 Hz, 1H), 7.43 (d, J¼7.8 Hz, 1H), 7.38 (t, J¼7.8 Hz, 2H),
7.30 (d, J¼7.2 Hz, 1H), 7.09 (d, J¼16.2 Hz, 1H), 6.89 (d, J¼8.4 Hz, 1H),
d
11.11 (s, 1H), 7.46 (t, J¼7.8 Hz, 1H), 7.39 (d, J¼8.4 Hz, 1H), 7.31e7.24
(m, 2H), 7.21 (dd, J¼6.6, 1.8 Hz, 1H), 7.06 (d, J¼8.4 Hz, 1H), 6.71 (d,

9030
Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
J¼7.2 Hz, 1H), 3.51 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
170.82,
143.24, 136.06, 133.88, 132.33, 129.12, 128.41, 124.44, 122.32, 118.97,
117.47, 114.41, 111.58, 109.71, 51.72, 51.59. IR (neat) 3071, 3052, 3012,
2961, 1671, 1617, 1603, 1574, 1449, 1325, 1275, 1216, 1167, 1112, 1064,
1017, 851, 814, 712, 664, 607 cmꢁ1. EIMS: m/z¼296.13 (Mþ). Anal.
Calcd for (C15H11F3O3): C, 60.82; H, 3.74. Found: C, 60.72; H, 3.72.
161.68, 141.48, 141.44, 134.07, 132.42, 129.67, 128.50, 128.15, 126.24,
122.36, 117.49, 112.04, 51.97. IR (neat) 3060, 3004, 2952, 2848, 1668,
1604, 1576, 1443, 1343, 1282, 1219, 1173, 1105, 1049, 902, 817, 758,
710, 695 cmꢁ1
(C14H11ClO3): C, 64.01; H, 4.22. Found: C, 63.90; H, 4.34.
.
EIMS: m/z¼262.12 (Mþ). Anal. Calcd for
4.3.11. Methyl 3-hydroxy-40-nitro-[1,10-biphenyl]-2-carboxylate
4.3.5. Methyl 40-bromo-3-hydroxy-[1,10-biphenyl]-2-carboxylate
(4k). Yellow solid, 267 mg, 97% yield; mp: 130e131 ꢀC. 1H NMR
(4e). Yellow oil, 295 mg, 96% yield. 1H NMR (600 MHz, CDCl3)
(600 MHz, CDCl3)
d
10.88 (s, 1H), 8.25 (d, J¼8.4 Hz, 2H), 7.47 (t,
d
10.73 (s, 1H), 7.49 (d, J¼8.4 Hz, 2H), 7.41 (t, J¼7.8 Hz, 1H), 7.10 (d,
J¼8.4 Hz, 2H), 7.02 (d, J¼7.8 Hz, 1H), 6.75 (d, J¼7.2 Hz, 1H), 3.53 (s,
3H). 13C NMR (100 MHz, CDCl3)
170.97, 161.52, 143.39, 141.58,
J¼7.8 Hz, 1H), 7.40 (d, J¼8.4 Hz, 2H), 7.09 (d, J¼8.4 Hz, 1H), 6.76 (d,
J¼7.2 Hz, 1H), 3.51 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 170.43,
d
161.81, 149.53, 146.66, 142.20, 133.99, 128.93, 122.77, 122.06, 117.95,
111.17, 51.84. IR (KBr) 3101, 2964, 2923, 2846, 1664, 1596, 1573, 1518,
1441, 1346, 1276, 1212, 1173, 1124, 1107, 1064, 852, 818, 755, 713,
697 cmꢁ1. EIMS: m/z¼273.13 (Mþ). Anal. Calcd for (C14H11NO5): C,
61.54; H, 4.06; N, 5.13. Found: C, 61.58; H, 3.97; N, 5.21.
133.76, 130.64, 129.71, 122.36, 120.91, 117.05, 111.64, 51.77. IR (neat)
3154, 3079, 3050, 2996, 2950, 2846, 1663, 1601, 1576, 1495, 1446,
1391, 1337, 1276, 1213, 1174, 1124, 1095, 1066, 1007, 963, 897, 838,
810, 790, 709, 671 cmꢁ1. EIMS: m/z¼307.11 (Mþ). Anal. Calcd for
(C14H11BrO3): C, 54.75; H, 3.61. Found: C, 54.83; H, 3.53.
4.3.12. Methyl 3-hydroxy-[1,10:40,100-terphenyl]-2-carboxylate
4.3.6. Methyl 40-fluoro-3-hydroxy-[1,10-biphenyl]-2-carboxylate
(4f). Yellow oil, 234 mg, 95% yield. 1H NMR (400 MHz, CDCl3)
(4l). Yellow solid, 267 mg, 88% yield; mp: 96e97 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
10.65 (s, 1H), 7.66 (d, J¼7.8 Hz, 2H), 7.62 (d,
d
10.70 (s, 1H), 7.44e7.33 (m, 1H), 7.23e7.10 (m, 2H), 7.08e7.02 (m,
2H), 7.02e6.98 (m, 1H), 6.79e6.73 (m, 1H), 3.51 (s, 3H). 13C NMR
(100 MHz, CDCl3) 171.14, 163.15, 161.46, 160.72, 143.66, 138.63,
J¼8.4 Hz, 2H), 7.47 (t, J¼7.8 Hz, 2H), 7.43 (t, J¼7.8 Hz, 1H), 7.37 (t,
J¼7.2 Hz, 1H), 7.31 (d, J¼8.4 Hz, 2H), 7.02 (d, J¼8.4 Hz, 1H), 6.86 (d,
d
J¼7.8 Hz, 1H), 3.52 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 171.26,
133.68, 129.63, 129.55, 122.57, 116.84, 114.57, 114.35, 111.97, 51.73. IR
(neat) 3066, 3044, 3007, 2954, 1736, 1669, 1606, 1574, 1512, 1447,
161.31, 144.32, 141.56, 140.52, 139.47, 133.65, 128.75, 128.53, 127.28,
126.87, 126.17, 122.52, 116.65, 111.97, 51.66. IR (KBr) 3401, 3063,
3026, 2948, 1663, 1599, 1570, 1441, 1348, 1274, 1222, 1176, 1119,
1066, 848, 815, 767, 711, 698 cmꢁ1. EIMS: m/z¼304.23 (Mþ). Anal.
Calcd for (C20H16O3): C, 78.93; H, 5.30. Found: C, 78.82; H, 5.21.
1343, 1310, 1282, 1221, 1173, 1160, 1123, 1094, 901, 842, 813 cmꢁ1
.
EIMS: m/z¼246.12 (Mþ). Anal. Calcd for (C14H11FO3): C, 68.29; H,
4.50. Found: C, 68.02; H, 4.57.
4.3.7. Methyl 3-hydroxy-40-methyl-[1,10-biphenyl]-2-carboxylate
4.3.13. Methyl 40-acetyl-3-hydroxy-[1,10-biphenyl]-2-carboxylate
(4g). Yellow oil, 218 mg, 90% yield. 1H NMR (400 MHz, CDCl3)
(4m). Yellow solid, 262 mg, 97% yield; mp: 98e99 ꢀC. 1H NMR
d
10.55 (s, 1H), 7.38 (dd, J¼12.0, 4.4 Hz, 1H), 7.14 (dd, J¼18.8, 8.0 Hz,
4H), 7.02e6.92 (m, 1H), 6.84e6.72 (m, 1H), 3.50 (s, 3H), 2.39 (s, 3H).
13C NMR (100 MHz, CDCl3)
171.40, 161.14, 144.79, 139.63, 136.44,
(600 MHz, CDCl3)
d
10.77 (s, 1H), 7.97 (d, J¼8.4 Hz, 2H), 7.44 (t,
J¼7.8 Hz, 1H), 7.33 (d, J¼8.4 Hz, 2H), 7.05 (d, J¼7.8 Hz, 1H), 6.78 (d,
d
J¼7.2 Hz, 1H), 3.49 (s, 3H), 2.66 (s, 3H). 13C NMR (100 MHz, CDCl3)
133.56, 128.30, 127.96, 122.63, 116.33, 112.14, 51.66, 21.14. IR (neat)
3047, 3024, 2993, 2952, 2922, 1667, 1602, 1576, 1446, 1343, 1281,
1264, 1172, 1123, 900, 809 cmꢁ1. EIMS: m/z¼242.18 (Mþ). Anal.
Calcd for (C15H14O3): C, 74.36; H, 5.82. Found: C, 74.23; H, 5.79.
d 197.71, 170.74,161.45, 147.58,143.41, 135.39,133.75, 128.26,127.62,
122.15, 117.28, 111.53, 51.70, 26.53. IR (KBr) 3342, 3189, 3015, 2953,
1680, 1600, 1573, 1446, 1355, 1267, 1215, 1170, 1123, 957, 842, 812,
709, 686 cmꢁ1. EIMS: m/z¼270.19 (Mþ). Anal. Calcd for (C16H14O4):
C, 71.10; H, 5.22. Found: C, 71.12; H, 5.14.
4.3.8. Methyl 3-hydroxy-40-methoxy-[1,10-biphenyl]-2-carboxylate
(4h). Yellow oil, 252 mg, 97% yield. 1H NMR (400 MHz, CDCl3)
4.3.14. Methyl 40-formyl-3-hydroxy-[1,10-biphenyl]-2-carboxylate
d
10.56 (s, 1H), 7.38 (t, J¼8.0 Hz, 1H), 7.19e7.13 (m, 2H), 6.97 (d,
J¼8.4 Hz, 1H), 6.90 (t, J¼5.6 Hz, 2H), 6.79 (d, J¼7.6 Hz, 1H), 3.84 (s,
3H), 3.52 (s, 3H). 13C NMR (100 MHz, CDCl3)
171.43, 161.14, 158.62,
(4n). Yellow solid, 77 mg, 30% yield; mp: 101e102 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
10.80 (s, 1H),10.07 (s,1H), 7.90 (d, J¼8.4 Hz, 2H),
d
7.45 (t, J¼7.8 Hz, 1H), 7.40 (d, J¼7.8 Hz, 2H), 7.07 (d, J¼8.4 Hz, 1H),
144.39, 134.98, 133.53, 129.18, 122.63, 116.20, 113.02, 112.16, 55.20,
51.74. IR (neat) 3375, 3042, 3008, 2957, 2931, 2835,1687,1598,1567,
1513, 1447, 1431, 1291, 1240, 1197, 1175, 1162, 1109, 1088, 1028, 1067,
897, 842, 807, 710, 639 cmꢁ1. EIMS: m/z¼258.18 (Mþ). Anal. Calcd
for (C15H14O4): C, 69.76; H, 5.46. Found: C, 69.59; H, 5.38.
6.78 (d, J¼6.6 Hz, 1H), 3.48 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
191.93, 170.71, 161.64, 149.09, 143.27, 134.82, 133.89, 129.03,
128.77, 122.14, 117.56, 111.44, 51.76. IR (KBr) 3439, 2961, 2832, 2733,
1698, 1672, 1599, 1573, 1446, 1307, 1275, 1213, 1170, 1122, 1095, 838,
809, 709 cmꢁ1. EIMS: m/z¼256.16 (Mþ). Anal. Calcd for (C15H12O4):
C, 70.31; H, 4.72. Found: C, 70.22; H, 4.84.4.
4.3.9. Methyl 40-(tert-butyl)-3-hydroxy-[1,10-biphenyl]-2-carboxylate
(4i). Yellow oil, 273 mg, 96% yield. 1H NMR (600 MHz, CDCl3)
4.3.15. Methyl 40-fluoro-3-hydroxy-30-methyl-[1,10-biphenyl]-2-
carboxylate (4o). Yellow oil, 254 mg, 97% yield. 1H NMR (600 MHz,
d
10.55 (s, 1H), 7.39 (dd, J¼15.6, 7.8 Hz, 3H), 7.16 (d, J¼8.4 Hz, 2H),
6.99 (d, J¼8.4 Hz,1H), 6.83 (d, J¼7.8 Hz,1H), 3.48 (s, 3H),1.36 (s, 9H).
13C NMR (100 MHz, CDCl3)
171.40, 161.12, 149.74, 144.78, 139.54,
CDCl3)
7.03e6.96 (m, 3H), 6.77 (dd, J¼7.8, 1.2 Hz, 1H), 3.53 (s, 3H), 2.31 (s,
3H). 13C NMR (100 MHz, CDCl3)
171.21, 161.68, 161.27, 159.26,
d
10.62 (s, 1H), 7.40 (t, J¼7.8 Hz, 1H), 7.05 (d, J¼7.2 Hz, 1H),
d
133.53, 127.75, 124.41, 122.51, 116.30, 112.22, 51.59, 34.46, 31.33. IR
(neat) 3409, 3074, 3034, 2962, 2867, 1681, 1603, 1575, 1442, 1329,
d
143.85, 138.24, 133.58, 130.94, 127.01, 126.93, 123.96, 123.79, 122.54,
116.62,114.17, 113.95, 112.02, 51.68,14.43. IR (neat) 3046, 3001, 2954,
2923, 1737, 1667, 1604, 1574, 1504, 1446, 1344, 1287, 1233, 1180, 1121,
1094, 1065, 942, 852, 813 cmꢁ1. EIMS: m/z¼260.17 (Mþ). Anal. Calcd
for (C15H13FO3): C, 69.22; H, 5.03. Found: C, 69.03; H, 5.13.
1267, 1202, 1163, 1120, 1091, 1063, 902, 840, 808, 713, 593 cmꢁ1
.
EIMS: m/z¼284.20 (Mþ). Anal. Calcd for (C18H20O3): C, 76.03; H,
7.09. Found: C, 76.09; H, 6.99.
4.3.10. Methyl 3-hydroxy-40-(trifluoromethyl)-[1,10-biphenyl]-2-
carboxylate (4j). Yellow oil, 281 mg, 95% yield. 1H NMR (600 MHz,
CDCl3)
7.35 (d, J¼7.8 Hz, 2H), 7.06 (d, J¼8.4 Hz, 1H), 6.76 (d, J¼7.2 Hz, 1H),
3.49 (s, 3H). 13C NMR (100 MHz, CDCl3)
170.83, 161.73, 146.43,
4.3.16. Methyl 30,50-dichloro-3-hydroxy-[1,10-biphenyl]-2-carboxylate
d
10.81 (s, 1H), 7.63 (d, J¼7.8 Hz, 2H), 7.44 (t, J¼7.8 Hz, 1H),
(4p). Yellow solid, 291 mg, 98% yield; mp: 65e66 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
10.85 (s, 1H), 7.43 (t, J¼7.8 Hz, 1H), 7.34 (s, 1H),
d
7.13 (s, 2H), 7.05 (d, J¼8.4 Hz, 1H), 6.74 (d, J¼7.2 Hz, 1H), 3.58 (s, 3H).

Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
9031
13C NMR (100 MHz, CDCl3)
d
170.58, 161.78, 145.44, 141.66, 133.93,
(m, 1H), 7.51 (dd, J¼12.0, 6.6 Hz, 2H), 7.43 (t, J¼7.8 Hz, 1H), 7.39 (d,
J¼3.0 Hz, 2H), 7.35 (t, J¼7.2 Hz, 1H), 7.11 (d, J¼8.4 Hz, 1H), 6.98 (d,
131.97, 126.80, 126.63, 122.16, 117.82, 111.36, 51.94. IR (KBr) 3077,
2991, 2948, 2899, 2843, 1662, 1595, 1579, 1557, 1441, 1407, 1337,
J¼7.2 Hz, 1H), 3.21 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 171.15,
1273, 1219, 1176, 1117, 1098, 1060, 848, 816, 795, 709, 685 cmꢁ1
.
161.52, 155.98, 153.27, 138.43, 134.16, 127.12, 127.02, 126.73, 124.06,
123.46, 123.09, 122.76, 122.68, 120.61, 119.63, 117.54, 112.71, 111.64,
51.73. IR (KBr) 3439, 3221, 3063, 3039, 2996, 2950, 2848, 1669,
1600, 1570, 1448, 1407, 1342, 1307, 1262, 1221, 1188, 1117, 1103, 1063,
929, 816, 762, 744, 706 cmꢁ1. EIMS: m/z¼318.23 (Mþ). Anal. Calcd
for (C20H14O4): C, 75.46; H, 4.43. Found: C, 75.62; H, 4.30.
EIMS: m/z¼297.16 (Mþ). Anal. Calcd for (C14H10Cl2O3): C, 56.59; H,
3.39. Found: C, 56.62; H, 3.26.
4.3.17. Methyl 30-chloro-40-fluoro-3-hydroxy-[1,10-biphenyl]-2-
carboxylate (4q). Yellow solid, 241 mg, 86% yield; mp: 64e65 ꢀC.
1H NMR (600 MHz, CDCl3)
d
10.80 (s, 1H), 7.42 (t, J¼7.8 Hz, 1H),
7.30e7.27 (m, 1H), 7.13 (t, J¼8.4 Hz, 1H), 7.11e7.06 (m, 1H), 7.04 (d,
4.3.23. Methyl 2-hydroxy-6-(naphthalen-2-yl)benzoate (4w). Yellow
J¼8.4 Hz,1H), 6.75 (d, J¼7.2 Hz,1H), 3.56 (s, 3H). 13C NMR (100 MHz,
oil, 272 mg, 98% yield. 1H NMR (600 MHz, CDCl3)
d 10.74 (s, 1H),
CDCl3)
d
170.80, 161.66, 158.33, 155.87, 142.19, 139.65, 133.82,
7.90e7.84 (m, 2H), 7.81 (d, J¼8.4 Hz, 1H), 7.73 (s, 1H), 7.53e7.49 (m,
2H), 7.47e7.43 (m, 1H), 7.34 (dd, J¼8.4, 1.8 Hz, 1H), 7.05 (dd, J¼8.4,
1.2 Hz, 1H), 6.90 (dd, J¼7.2, 0.6 Hz, 1H), 3.42 (s, 3H). 13C NMR
130.03, 127.94, 127.86, 122.44, 119.87, 117.40, 115.70, 115.49, 112.36,
111.61, 51.86. IR (KBr) 3082, 3060, 3045, 2957, 1665, 1605, 1578,
1505, 1448, 1350, 1283, 1262, 1234, 1218, 1177, 1124, 1100, 1060, 816,
733 cmꢁ1. EIMS: m/z¼280.13 (Mþ). Anal. Calcd for (C14H10ClFO3): C,
59.91; H, 3.59. Found: C, 59.79; H, 3.68.
(100 MHz, CDCl3)
d 171.21, 161.38, 144.57, 140.16, 133.67, 133.00,
132.15, 128.54, 127.86, 127.50, 127.14, 126.62, 126.04, 125.76, 122.88,
116.69, 111.97, 51.57. IR (neat) 3047, 3020, 2953, 1666, 1598, 1571,
1446, 1338, 1277, 1238, 1213, 1191, 1171, 1119, 1084, 1065, 909, 863,
813, 748, 713 cmꢁ1. EIMS: m/z¼278.16 (Mþ). Anal. Calcd for
(C18H14O3): C, 77.68; H, 5.07. Found: C, 77.58; H, 5.17.
4.3.18. Methyl 3-hydroxy-30,40,50-trimethoxy-[1,10-biphenyl]-2-
carboxylate (4r). Yellow solid, 295 mg, 93% yield; mp:
103e104 ꢀC. 1H NMR (600 MHz, CDCl3)
d 10.52 (s, 1H), 7.41 (t,
J¼7.8 Hz, 1H), 7.01 (d, J¼8.4 Hz, 1H), 6.84 (d, J¼7.2 Hz, 1H), 6.45 (s,
4.3.24. (E)-Methyl 2-hydroxy-6-styrylbenzoate (4x). Yellow oil,
2H), 3.90 (s, 3H), 3.85 (s, 6H), 3.56 (s, 3H). 13C NMR (100 MHz,
238 mg, 93% yield. 1H NMR (600 MHz, CDCl3)
d 11.20 (s, 1H), 7.70 (d,
CDCl3)
d
170.97, 160.67, 152.34, 144.23, 138.04, 136.74, 133.25,
J¼16.2 Hz, 1H), 7.50 (d, J¼7.8 Hz, 2H), 7.39 (dt, J¼15.6, 7.8 Hz, 3H),
7.30 (d, J¼7.2 Hz, 1H), 7.09 (d, J¼7.8 Hz, 1H), 6.95 (d, J¼8.4 Hz, 1H),
6.83 (d, J¼16.2 Hz, 1H), 3.99 (s, 3H). 13C NMR (100 MHz, CDCl3)
122.01, 116.35, 112.21, 105.22, 60.65, 55.87, 51.66. IR (KBr) 3427,
3045, 2968, 2946, 2842, 2831, 1660, 1587, 1507, 1468, 1442, 1417,
1351, 1259, 1244, 1209, 1121, 1005, 844, 817, 748, 720, 669 cmꢁ1
.
d 171.51,162.26,141.00,137.35,134.34,130.81,129.50,128.65,127.71,
EIMS: m/z¼318.24 (Mþ). Anal. Calcd for (C17H18O6): C, 64.14; H,
126.53, 119.55, 116.91, 110.74, 52.43. IR (neat) 3436, 3085, 3055,
3023, 3007, 2948, 1664, 1594, 1569, 1448, 1434, 1332, 1315, 1258,
1214, 1199,1170,1113,1064, 997, 966, 804, 757, 727, 702 cmꢁ1. EIMS:
m/z¼254.16 (Mþ). Anal. Calcd for (C16H14O3): C, 75.57; H, 5.55.
Found: C, 75.55; H, 5.45.
5.70. Found: C, 64.21; H, 5.73.
4.3.19. Methyl 2-(furan-2-yl)-6-hydroxybenzoate (4s). Yellow solid,
207 mg, 95% yield; mp: 117e118 ꢀC. 1H NMR (600 MHz, CDCl3)
d
10.24 (s, 1H), 7.47 (s, 1H), 7.41 (t, J¼7.8 Hz, 1H), 7.00 (dd, J¼13.2,
7.8 Hz, 2H), 6.47 (d, J¼3.0 Hz,1H), 6.43 (d, J¼3.0 Hz,1H), 3.73 (s, 3H).
13C NMR (100 MHz, CDCl3)
170.68, 160.46, 153.62, 142.24, 133.56,
4.3.25. (E)-Methyl2-hydroxy-6-(pent-1-en-1-yl)benzoate(4y). Yellow
d
oil,198 mg, 90% yield. 1H NMR (600 MHz, CDCl3)
d 11.11 (s,1H), 7.33 (t,
132.47, 121.57, 117.53, 111.97, 111.12, 107.27, 52.38. IR (KBr) 3334,
3146, 3071, 3028, 3004, 2950, 2843, 1704, 1605, 1588, 1572, 1502,
1451, 1439, 1336, 1305, 1277, 1248, 1170, 1124, 1107, 1067, 1032, 943,
886, 868, 792, 751, 738, 764, 642 cmꢁ1. EIMS: m/z¼218.10 (Mþ). Anal.
Calcd for (C12H10O4): C, 66.05; H, 4.62. Found: C, 66.14; H, 4.64.
J¼7.8 Hz,1H), 6.94e6.86 (m, 3H), 6.05e5.79 (m,1H), 3.95 (s, 3H), 2.20
(d, J¼7.2 Hz, 2H), 1.51 (dd, J¼14.4, 7.2 Hz, 2H), 0.97 (t, J¼7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3)
d 171.57, 161.94, 141.72, 134.02, 132.70,
130.80,119.69,116.00,110.40, 51.93, 34.90, 22.14,13.47. IR (neat) 3054,
2999, 2957, 2923, 2872, 1733, 1664, 1602, 1572, 1448, 1344, 1275,
1256, 1216, 1168, 1118, 1068, 966, 948, 823, 808 cmꢁ1. EIMS: m/
z¼220.20 (Mþ). Anal. Calcd for (C13H16O3): C, 70.89; H, 7.32. Found: C,
70.91; H, 7.29.
4.3.20. Methyl 2-hydroxy-6-(thiophen-2-yl)benzoate (4t). Yellow
oil, 227 mg, 97% yield. 1H NMR (600 MHz, CDCl3)
d 10.48 (s,1H), 7.39
(s, 1H), 7.32 (d, J¼5.4 Hz, 1H), 7.02 (dd, J¼8.4, 4.2 Hz, 2H), 6.93 (dd,
J¼14.4, 5.4 Hz, 2H), 3.62 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 170.92,
Acknowledgements
160.98, 143.33, 136.51, 133.40, 126.55, 125.79, 125.19, 123.54, 117.41,
113.01, 51.99. IR (neat) 3371, 3105, 3012, 2957, 2923, 2849, 1699,
1579, 1464, 1435, 1326, 1291, 1225, 1163, 1121, 1089, 1067, 1032, 794,
767, 712 cmꢁ1. EIMS: m/z¼234.08 (Mþ). Anal. Calcd for (C12H10O3S):
C, 61.52; H, 4.30; S, 13.69. Found: C, 61.45; H, 4.43; S, 13.66.
The research was supported in part by the National Basic Re-
search Program of China (No. 2010CB126103), the NSFC (No.
20902034, 20925206 and 21172091), and the National Key Tech-
nologies R&D Program (2011BAE06B05).
4.3.21. Methyl 2-(benzofuran-2-yl)-6-hydroxybenzoate (4u). Yellow
solid, 257 mg, 96% yield; mp: 69e70 ꢀC. 1H NMR (600 MHz, CDCl3)
References and notes
d
10.39 (s, 1H), 7.62 (d, J¼7.8 Hz, 1H), 7.50e7.44 (m, 2H), 7.30 (t,
J¼7.2 Hz, 1H), 7.28e7.23 (m, 1H), 7.10 (dd, J¼12.0, 7.8 Hz, 2H), 6.81
(s, 1H), 3.63 (s, 3H). 13C NMR (100 MHz, CDCl3)
170.56, 160.90,
1. (a) Gerson, M.; Helmut, R.; Peter, L. Synlett 2008, 963e966; (b) Kawahara, N.;
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Kanamori, H.; Sakamoto, I.; Mizuta, M.; Tanaka, O. Chem. Pharm. Bull. 1986, 34,
1663e1666; (d) Lacaille, D. M.; Galle, K.; Wagner, H. Planta Med. 1996, 62,
365e367; (e) Inouye, H.; Nakamura, Y. Tetrahedron 1971, 27, 1951e1966; (f) Li, J.
C.; Feng, L.; Sun, B. H.; Ikeda, T.; Nohara, T. Biol. Pharm. Bull. 2005, 28, 534e537.
2. (a) Lin, Y. L.; Wu, Y. M.; Kuo, Y. H. Phytochemistry 1997, 45, 1057e1061; (b) Lin,
C. N.; Huang, P. L.; Lu, C. M.; Yen, M. H.; Wu, R. R. Phytochemistry 1997, 44,
1359e1363; (c) Lee, M. K.; Yeo, H.; Kim, J.; Markelonis, G. J.; Oh, T. H.; Kim, Y. C.
J. Neurosci. Res. 2000, 59, 259e264; (d) Lee, M. K.; Yeo, H.; Kim, J.; Kim, Y. C. J.
Pharm. Pharmacol. 2000, 52, 341e345; (e) Huang, P. L.; Won, S. J.; Day, S. H.; Lin,
C. N. Helv. Chim. Acta 1999, 82, 1716e1720; (f) Lin, C. N.; Huang, P. L.; Wang, J. J.;
Day, S. H.; Lin, H. C.; Wang, J. P.; Ko, Y. L.; Teng, C. M. Biochim. Biophys. Acta 1998,
1380, 115e122; (g) Hong, L. P. T.; White, J. M.; Donner, C. D. Aust. J. Chem. 2012,
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d
156.20, 155.02, 133.81, 132.23, 128.73, 124.25, 122.79, 122.45, 121.01,
118.63, 112.18, 110.82, 103.86, 52.45. IR (KBr) 3434, 3068, 3028,
3001, 2950, 1679, 1571, 1451, 1431, 1338, 1279, 1221, 1202, 1160, 1118,
1106, 814, 799, 745, 705 cmꢁ1. EIMS: m/z¼268.13 (Mþ). Anal. Calcd
for (C16H12O4): C, 71.64; H, 4.51. Found: C, 71.56; H, 4.42.
4.3.22. Methyl 2-(dibenzo[b,d]furan-4-yl)-6-hydroxybenzoate
(4v). Yellow solid, 296 mg, 93% yield; mp: 105e106 ꢀC. 1H NMR
(600 MHz, CDCl3)
d
10.88 (s, 1H), 7.97 (d, J¼7.8 Hz, 1H), 7.96e7.90

9032
Y.-C. Liu et al. / Tetrahedron 69 (2013) 9025e9032
ꢀ
3. (a) Holker, J. S. E.; O’Brien, E.; Simpson, T. J. J. Chem. Soc. 1983, 1, 1365e1368; (b)
Stinson, E. E.; Moreau, R. A. Phytochemistry 1986, 25, 2721e2724; (c) Abe, H.;
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