Synthesis of polyphenyls

Article abstract of DOI:10.1016/j.tet.2012.10.039

A facile synthetic route toward functionalized 3-aryl-, 3,3′-diaryl-, 3,3′,5-triaryl-4,4′-dimethoxybiphenyls (polyphenyls) 3-5 with the terphenyl, quaterphenyl, quinquephenyl, and sexiphenyl skeleton starting from biphenyl-4,4′-diol (1) in modest total yield is described. The route has been carried by the two transformations of the regioselective NBS (N-bromosuccinimide)-mediated bromination of 2 in MeCN at reflux and Suzuki-Miyaura cross-coupling reaction of the resulting bromides with arylboronic acids 6 in DME at reflux.

Full text of DOI:10.1016/j.tet.2012.10.039

Tetrahedron 69 (2013) 228e234
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of polyphenyls
*
Meng-Yang Chang , Tein-Wei Lee, Shin-Ying Lin
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
a r t i c l e i n f o
a b s t r a c t
A facile synthetic route toward functionalized 3-aryl-, 3,30-diaryl-, 3,30,5-triaryl-4,40-dimethoxybiphenyls
(polyphenyls) 3e5 with the terphenyl, quaterphenyl, quinquephenyl, and sexiphenyl skeleton starting
from biphenyl-4,40-diol (1) in modest total yield is described. The route has been carried by the two
transformations of the regioselective NBS (N-bromosuccinimide)-mediated bromination of 2 in MeCN at
reflux and SuzukieMiyaura cross-coupling reaction of the resulting bromides with arylboronic acids 6 in
DME at reflux.
Article history:
Received 16 August 2012
Received in revised form 5 October 2012
Accepted 12 October 2012
Available online 23 October 2012
Keywords:
Biphenyl-4,40-diol
Ó 2012 Elsevier Ltd. All rights reserved.
Polyphenyls
SuzukieMiyaura cross-coupling reaction
NBS-mediated bromination
Arylboronic acids
1. Introduction
many approaches that have been reported for the construction of
polyphenyls, including the transition-metal mediated coupling
A number of cross-coupling reactions of polyhalogenated ben-
zofused heterocycles have been reported over the last few years.1,2
Due to the particular electronic reasons and steric parameters
concerning the specific site-selective pattern, some synthetic
methods for preparing site-selective aryl-functionalized heterocy-
cles have been developed.2 For the site-selective SuzukieMiyaura
cross-coupling reactions, the adopted polyhalogenated substrates
include benzenes,2a benzoquinones,2b benzofurans,2c thiophenes,2d
pyrroles,2e indenes,2f pyrazoles,2g naphthalenes,2h xanthones,2i
pyrene,2j and coumarins.2k In continuation of our investigation
into the synthetic applications of biphenyl-4,40-diol (1),3 a syn-
thetic route is employed to create the skeletons of 3-aryl-, 3,30-
diaryl- and 3,30,5-triaryl-4,40-dimethoxy-biphenyls (polyphenyls)
3e5, via two transformations of NBS-mediated bromination of 2 in
MeCN at reflux and SuzukieMiyaura cross-coupling reaction of the
resulting bromide with arylboronic acids 6 in DME at reflux (Fig. 1).
Polyphenyls have received considerable attention in the past
decades due to their presence as the structural motifs in natural
products, biological pharmaceuticals, and functionalized mate-
rials.4 Synthetic polyphenyls are often exploited in the synthetic
material fields, such as organic electronics, chemical biosensors,
and photovoltaic batteries because of their excellent photo-physical
applications.5 For the related biological activities, substituted pol-
yphenyls also possess potential therapeutic values.6 There are
reactions or cycloadditions.7,8 Although some useful routes are
valuable protocols for the synthesis of polyphenyls derivatives,9 it is
still of great importance to develop a simple and efficient route for
the construction of functionalized polyphenyls, especially those
with flexible substitution patterns.
2. Results and discussion
The starting material, 4,40-dimethoxy-biphenyl (2), was provided
by the double O-methylation of the commercially available biphenyl-
4,40-diol (1) with K2CO3 and MeI in the quantitative yield. Next, the
synthesis of functionalized polyphenyls 3e5 was examined. Treat-
ment of 2 reacted with 1.2 equiv of NBS in MeCN at reflux for 5 h to
yield 3-bromo-4,40-dimethoxybiphenyl (7, 84%) and 3,30-dibromo-
MeO
MeO
MeO
MeO
4
Ar
Ar / Ph
Ar / Ph
(a)-(b)
Ar
(a)-(b)
5
3
(a)-(b)
3'
Ar / Ph
Ar
4'
MeO
5
MeO
MeO
MeO
2
4
3
(a) NBS, MeCN, reflux; (b) Pd(PPh3)4, arylB(OH)2 6, Na2CO3, DME, reflux
Ar = a, Ph; b, 4-CF3-Ph; c, 4-MeO-Ph; d, 4-pyridinyl; e, 3,4-(MeO)2-Ph;
f, 4-CHO-Ph; g, 2-Ph-Ph
* Corresponding author. Tel.: þ886 7 3121101x2220; e-mail addresses: mychang@
kmu.edu.tw, mychang624@yahoo.com.tw (M.-Y. Chang).
Fig. 1. Retrosynthetic route toward skeletons 3e5.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.039

M.-Y. Chang et al. / Tetrahedron 69 (2013) 228e234
229
4,40-dimethoxybiphenyl (8, w7%). To examine the SuzukieMiyaura
cross-coupling reaction conditions, we found that Pd(PPh3)4-medi-
ated coupling reaction of substrate 7 provided a yield of 82%, which
was better than Pd(MeCN)2Cl2 (65%) or Pd(OAc)2 (55%). Adjusting the
solvent for the DMF or 1,4-dioxane, the isolated yield (75% or 80%)
was not noticeably enhanced. Furthermore, after screening seven
arylboronic acids 6aeg with different electron-donating or electron-
withdrawing groups (Ar¼a, Ph; b, 4-CF3ePh; c, 4-MeOePh; d, 4-
pyridinyl; e, 3,4-(MeO)2ePh; f, 4-CHOePh; g, 2-PhePh), seven ter-
phenyls 3aeg were isolated with 70%e82% yields via the Pd(PPh3)4-
mediated cross-coupling of mono-bromide 7 as shown in Scheme 1.
Changing the equivalent of NBS (2.2 equiv), major 3,30-dibromide 8
was isolated with a 90% yield.10 Then, by the double SuzukieMiyaura
cross-coupling reaction of 8 with seven arylboronic acids 6aeg, seven
quaterphenyls 4aeg were isolated with 64e76% yields. The structural
frameworks of 4e and 4g were determined using single-crystal X-ray
analysis (Figs. 2 and 3).11
Fig. 3. X-ray structure of 4g.
Table 1
Crystal data for 4e and 4g
CCDC number
Crystal system
Space group
887702 (4e)
Monoclinic
P 1 21/c 1
15.9092(8)
6.7774(3)
11.7769(6)
90
94.4430(10)
90
1266.00(11)/4
296(2)
887701 (4g)
Monoclinic
P 1 21/c 1
8.6547(3)
20.2740(8)
8.8027(4)
90
117.4240(10)
90
1370.99(10)/4
296(2)
MeO
MeO
MeO
ꢀ
Br
Br
a (A)
ꢀ
b (A)
ꢀ
NBS, MeCN
reflux
Pd(PPh3)4, ArB(OH)2 6a-6g
c (A)
(ꢀ)
(ꢀ)
(ꢀ)
+
a
b
g
Na2CO3, DME
Br
3
ꢀ
Volume (A )/Z
Temperature (K)
Dcalcd (Mg/m3)
MeO
MeO
MeO
NBS (1.2 eq): 7 (84%) 8 (~7%)
NBS (2.2 eq): 7 (trace) 8 (90%)
1.276
0.088
1.256
0.076
2
Absorption coefficient (mmꢁ1
)
Crystal size (mm)
q
0.30ꢂ0.30ꢂ0.10
1.28e26.44
10,119
2603 (Rint¼0.0207)
0.0558, 0.1212
0.0413, 0.1101
1.050
0.30ꢂ0.20ꢂ0.17
2.65e26.40
10,763
2788 (Rint¼0.0249)
0.0635, 0.1274
0.0461, 0.1170
1.040
Range for data collection (ꢀ)
MeO
MeO
Reflections collected
Independent reflections
RF, Rw (F2) (all data)a
Ar = (for 7)
Ar = (for 8)
Ar
Ar
Ar
3a, Ph (82%);
4a, Ph (76%);
3b, 4-CF3-Ph (70%);
3c, 4-MeO-Ph (80%);
3d, 4-pyridinyl (75%);
3e, 3,4-(MeO)2-Ph (74%);
3f, 4-CHO-Ph (78%);
3g, 2-Ph-Ph (70%)
4b, 4-CF3-Ph (72%);
4c, 4-MeO-Ph (64%);
4d, 4-pyridinyl (67%);
4e, 3,4-(MeO)2-Ph (70%);
4f, 4-CHO-Ph (72%);
4g, 2-Ph-Ph (69%)
RF, Rw (F2) (I>2 (I))a
s
GOF
a
RF¼SjFoꢁFcj/SjFoj; RW (F2)¼[SWjF2oꢁF2cj2/SW F4o]1/2
.
MeO
MeO
Scheme 1. Synthesis of skeletons 3 and 4.
studied, as shown in Scheme 2, by the above-mentioned protocol;
treatment of model substrate 3a with 1.2 equiv of NBS in MeCN at
reflux yielded 3-phenyl-5-bromo-4,40-dimethoxybiphenyl 9 with
70% yield via a regioselective bromination reaction. However, by
controlling the equivalent of NBS, 3-phenyl-30-bromo-4,40-dime-
thoxybiphenyl 10 had been not detected due to the steric hindrance
of the 3-phenyl group affecting the bromination. Pd(PPh3)4-medi-
ated SuzukieMiyaura cross-coupling of 9 with seven arylboronic
acids 6aeg were isolated 4a and 4hem with 72e85% yields. For the
formation of compounds 3aeg and 4aem with different electron-
MeO
MeO
NBS (1.2 eq)
MeCN, reflux
Pd(PPh3)4, ArB(OH)2 6a-6g
Na2CO3, DME
Br
Fig. 2. X-ray structure of 4e.
MeO
MeO
3a
9 (70%)
The crystal structures of both quaterphenyl 4e and sexiphenyl
4g belong to a monoclinic crystal system and P 1 21/c 1 space group,
and possess the unique serrate helix shape (see Table 1). Single-
crystal X-ray diffraction analysis was employed to prove the con-
stitution and relative configuration of the isolated product. The
ORTEP plot clearly shows that the configuration of a benzene ring of
3,4-dimethoxyphenyl or 2-biphenyl moiety in the 3,30-position of
the 4,40-dimethoxy-biphenyl skeletons are parallel to each other.
Furthermore, synthesis of the quinquephenyl skeleton 4 with the
unsymmetrical 3,30-diaryl-4,40-dimethoxybiphenyl skeleton was
MeO
MeO
Br
Ar =,
4a, Ph (83%);
4h, 4-CF3-Ph (85%);
4i, 4-MeO-Ph (76%);
4j, 4-pyridinyl (81%);
4k, 3,4-(MeO)2-Ph (78%);
4l, Ar1 = 4-CHO-Ph (72%);
4m, Ar1 = 2-Ph-Ph (79%)
Ar
10
(no detected)
MeO
MeO
Scheme 2. Synthesis of unsymmetrical skeleton 4.

230
M.-Y. Chang et al. / Tetrahedron 69 (2013) 228e234
donating aryl groups and electron-withdrawing aryl groups, the
useful combination of the NBS-mediated bromination of 2 or 3a
followed by SuzukieMiyaura cross-coupling of the resulting bro-
mide 7, 8 or 9 with arylboronic acids 6aeg provided different an-
gular and curved skeletons of six terphenyls (3aef), twelve
quaterphenyls (3g, 4aef, 4hel), one quinquephenyl (4m) and one
sexiphenyl (4g) with good to acceptable yields.
Based on the results, the skeleton of dendritic quinquephenyls 5
was examined next, as shown in Scheme 3. First, treatment of the
starting material 4a with NBS (1.2 equiv) provided 11 (36%) and 4a
(50%). To increase the equivalent of NBS, the yield of 11 provided
88% (3.2 equiv) and 93% (5.8 equiv). However, dibromide 12 was
observed by the treatment of 4a with excess NBS. Screening the
conditions (equivalent, reaction time and temperature) in an at-
tempt to provide 12 were unsuccessful. From the phenomenon, we
envisioned that 5-bromo and 3,30-diphenyl group of 11 should
produce the more bulky steric hindrance to decrease the possibility
of a second bromination on the 50-position for the formation of 12.
For the excess NBS-mediated reaction of 4b or 4c in MeCN at reflux
for 5 h, several bromide isomers were isolated from the complex
MeO
MeO
5
2
1) NBS (1.2 eq), HOAc, reflux
5a (30%)
+
2) Pd(PPh3)4, 6a, Na2CO3, DME
(yield of two-step)
3'
MeO
MeO
5h (48%)
4a
Scheme 4. Synthesis of 5h.
reaction products in
a different product ratio. Then, Suzu-
kieMiyaura cross-coupling of the resulting bromide 11 with aryl-
boronic acids 6aeg afforded six quinquephenyls 5aef and one
sexiphenyl 5g with 65e80% yields.
MeO
MeO
MeO
Br
NBS, MeCN
reflux
Pd(PPh3)4, ArB(OH)2 6a-6g
Na2CO3, DME
Fig. 4. X-ray structure of 5h.
MeO
NBS (1.2 eq), 11 (36%) + 4a (50%)
NBS (3.2 eq), 11 (88%) + 4a (~10%)
NBS (5.8 eq), 11 (93%)
4a
3. Conclusion
In summary, we have successfully presented a synthetic route
for the synthesis of polyphenyls (terphenyl, quaterphenyl, quin-
quephenyl, sexiphenyl) with good to acceptable yields via the or-
dinal sequence combination of the regioselective bromination and
SuzukieMiyaura coupling reaction. This synthesis starts from
simple starting material and reagents, and provides a potential
methodology for chemical biology or material science research. The
Scholl oxidative annulation of 3g, 4g, 5g and 5h will be
investigated.
MeO
MeO
Ar
Br
Ar = Ph
5a, Ar = Ph (76%);
5b, Ar = 4-CF3-Ph (65%);
5c, Ar = 4-MeO-Ph (74%);
5d, Ar = 4-pyridinyl (70%);
5e, Ar = 3,4-(MeO)2-Ph (62%)
5f, Ar = 4-CHO-Ph (72%)
5g, Ar = 2-Ph-Ph (80%)
Br
MeO
MeO
12 (no detected)
Scheme 3. Synthesis of skeleton 5.
4. Experimental section
4.1. General
From the synthetic route of 5a, the combination of the regio-
selective bromination and coupling reaction provided an ordinal
sequence to introduce a bromo atom into the C3 (7)/C30 (9)/C5
(11) position followed by the involvement of phenyl group at the
same C3 (3a)/C30 (4a)/C5 (5a) position for the construction of
the skeleton of polyphenyls from the compound 2. We have suc-
cessfully presented an easy and efficient synthetic methodology for
the preparation of polyphenyls. To the best of our knowledge, there
are no reports in the literature considering the preparation of
skeleton 5, with a novel dendritic polyphenyls structural frame-
work (Scheme 4).
THF was distilled prior to use. All other reagents and solvents
were obtained from commercial sources and used without further
purification. Reactions were routinely carried out under an atmo-
sphere of dry nitrogen with magnetic stirring. Products in organic
solvents were dried with anhydrous magnesium sulfate before
concentration in vacuo. Melting points were determined with
a SMP3 melting apparatus. 1H and 13C NMR spectra were recorded
on a Varian INOVA-400 spectrometer operating at 400 and at
100 MHz, respectively. Chemical shifts (d) are reported in parts per
It deserves to be mentioned that when the reaction solvent was
changed to acetic acid for the two steps of 4a via the bromination
reaction/SuzukieMiyaura cross-coupling reaction, 5h with 2,30,5-
triphenyl groups was formed as the major isomer and another
3,30,5-triphenyl isomer 5a was isolated in a 30% yield. And, quin-
quephenyl 5h was determined by single-crystal X-ray crystallog-
raphy. Structure 5h was shown in Fig. 4.11
million (ppm) and the coupling constants (J) are given in Hertz.
High resolution mass spectra (HRMS) were measured with a mass
spectrometer Finnigan/Thermo Quest MAT 95XL. X-ray crystal
structures were obtained with an Enraf-Nonius FR-590 diffrac-
tometer (CAD4, Kappa CCD). Elemental analyses were carried out
with Heraeus Vario III-NCSH, Heraeus CHNeOS-Rapid Analyzer or
Elementar Vario EL III.

M.-Y. Chang et al. / Tetrahedron 69 (2013) 228e234
231
4.2. A representative synthetic procedure of compounds 7
and 8 is as follows
7.01e6.97 (m, 4H), 3.87 (s, 3H), 3.86 (s, 6H); 13C NMR (100 MHz,
CDCl3):
129.12, 127.75 (2ꢂ), 126.20, 114.23, 114.15 (2ꢂ), 113.51 (2ꢂ), 111.51,
55.71, 55.31, 55.25; Anal. Calcd for C21H20O3: C, 78.73; H, 6.29.
Found: C, 78.91; H, 6.51.
d
158.73, 158.72, 155.59, 133.55, 133.37, 130.85, 130.60 (2ꢂ),
NBS (for 7, 428 mg, 2.4 mmol; for 8, 783 mg, 4.4 mmol) was
added to a solution of compound 2 (430 mg, 2.0 mmol) in MeCN
(10 mL) at rt. The reaction mixture was stirred at reflux for 5 h. The
reaction mixture was concentrated to yield the residue. The residue
was extracted with EtOAc (3ꢂ30 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated to afford
crude product. Purification on silica gel (hexanes/EtOAc¼10/1e6/1)
afforded compound 7 or 8.
4.3.4. Compound (3d). Yield 75% (109 mg); colorless solid;
mp¼163e165 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C19H18NO2 292.1338, found 292.1346; 1H NMR
(400 MHz, CDCl3):
d
8.64 (d, J¼8.8 Hz, 2H), 7.56 (dd, J¼2.0, 8.4 Hz,
1H), 7.52e7.49 (m, 5H), 7.06 (d, J¼8.4 Hz, 1H), 6.98 (d, J¼8.8 Hz, 2H),
3.86 (s, 3H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
158.93,
4.2.1. Compound (7). Yield 84% (491 mg); colorless solid;
mp¼116e118 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C14H14Br2O2 293.0177, found 293.0182; 1H
155.56, 149.47 (2ꢂ), 146.28, 133.88, 132.78, 128.79, 128.08, 127.89,
127.72 (2ꢂ), 124.29 (2ꢂ), 114.23, 114.21, 111.76, 55.69, 55.30; Anal.
Calcd for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 78.50; H,
6.12; N, 5.02. Single-crystal X-ray diagram: crystal of compound 3d
was grown by slow diffusion of EtOAc into a solution of compound
3d in CH2Cl2 to yield colorless prism. The compound crystallizes in
NMR (400 MHz, CDCl3):
d
7.74 (d, J¼2.0 Hz, 1H), 7.47e7.43 (m, 3H),
6.98e6.93 (m, 3H), 3.93 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
159.05, 154.80, 134.88, 132.00, 131.46, 127.74 (2ꢂ), 126.55,
114.24 (2ꢂ), 112.09, 111.96, 56.31, 55.33; Anal. Calcd for
the orthorhombic crystal system, space group P b c a,
3
ꢀ
ꢀ
ꢀ
ꢀ
C14H13Br2O2: C, 57.36; H, 4.47. Found: C, 57.55; H, 4.80.
a¼13.8183(12) A, b¼6.7898(6) A, c¼31.286(3) A, V¼2935.4(4) A ,
Z¼8, Dcalcd¼1.318 g/cm3, F(000)¼1232, 2
q
range 1.30e26.41ꢀ, R
4.2.2. Compound (8). Yield 90% (664 mg); colorless solid;
mp¼164e166 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C14H13Br2O2 370.9282, found 370.9287; 1H
indices (all data) R1¼0.0450, wR2¼0.0909.
4.3.5. Compound (3e). Yield 74% (130 mg); colorless solid; mp¼
156e158 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C22H23O4 351.1596, found 351.1600; 1H NMR
NMR (400 MHz, CDCl3):
d
7.71 (d, J¼2.4 Hz, 2H), 7.42 (dd, J¼2.4,
8.8 Hz, 2H), 6.95 (d, J¼8.8 Hz, 2H), 3.93 (s, 6H); 13C NMR (100 MHz,
CDCl3):
d
155.22 (2ꢂ), 133.43 (4ꢂ), 131.50 (2ꢂ), 126.64 (2ꢂ), 112.11
(400 MHz, CDCl3):
d
7.56e7.52 (m, 3H), 7.50 (dd, J¼2.4, 8.4 Hz, 1H),
(2ꢂ), 56.35 (2ꢂ). Compound 8 is a known compound and the an-
7.16e7.14 (m, 2H), 7.04 (d, J¼8.4 Hz, 1H), 7.00e6.95 (m, 3H), 3.94 (s,
alytical data are consistent with those in the literature.10a,b
3H), 3.93 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
158.75, 155.52, 148.38, 148.20, 133.57, 133.28, 131.16, 130.66, 129.12,
4.3. A representative synthetic procedure of compounds 3aeg
is as follows
127.74 (2ꢂ), 126.32, 121.81, 114.15 (2ꢂ), 113.06, 111.58, 110.89, 55.88,
55.86, 55.74, 55.28; Anal. Calcd for C22H22O4: C, 75.41; H, 6.33. Found:
C, 75.60; H, 6.49.
Pd(PPh3)4 (100 mg) and Na2CO3 (106 mg, 1.0 mmol) were added
to a solution of compound 7 (150 mg, 0.5 mmol) in DME (10 mL) at
rt. Then, ArB(OH)2 6aeg (1.0 mmol) was added to the stirred re-
action mixture at rt. The reaction mixture was stirred at reflux for
5 h. The reaction mixture was concentrated to yield the residue. The
residue was extracted with CH2Cl2 (3ꢂ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc¼10/1e6/1) afforded compounds 3aeg.
4.3.6. Compound (3f). Yield 78% (124 mg); colorless solid; mp¼
118e120 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C21H19O3 319.1334, found 319.1341; 1H NMR
(400 MHz, CDCl3):
d
10.06 (s, 1H), 7.94 (d, J¼8.8 Hz, 2H), 7.76 (d,
J¼8.0 Hz, 2H), 7.56 (dd, J¼2.4, 8.4 Hz, 1H), 7.53 (s, 1H), 7.52 (d,
J¼8.8 Hz, 2H), 7.07 (d, J¼8.4 Hz, 1H), 6.98 (d, J¼8.8 Hz, 2H), 3.87 (s,
3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 192.05, 158.92, 155.55,
145.02, 134.92, 133.84, 132.93, 130.21 (2ꢂ), 129.50, 129.46 (2ꢂ),
129.12, 127.77 (2ꢂ), 127.72, 114.25 (2ꢂ), 111.74, 55.75, 55.34.
4.3.1. Compound (3a). Yield 82% (119 mg); colorless solid;
mp¼100e102 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C20H19O2 291.1385, found 291.1395; 1H NMR
4.3.7. Compound (3g). Yield 70% (128 mg); colorless solid; mp¼
114e115 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C26H23O2 367.1698, found 367.1700; 1H NMR
(400 MHz, CDCl3):
d 7.65e7.62 (m, 2H), 7.59e7.54 (m, 4H),
7.51e7.46 (m, 2H), 7.42e7.37 (m, 1H), 7.08 (d, J¼8.4 Hz, 1H),
(400 MHz, CDCl3): d 7.48e7.38 (m, 8H), 7.21e7.16 (m, 5H), 6.96e6.93
7.03e7.00 (m, 2H), 3.88 (s, 6H); 13C NMR (100 MHz, CDCl3):
(m, 2H), 6.76 (d, J¼8.4 Hz, 1H), 3.84 (s, 3H), 3.39 (s, 3H); 13C NMR
d
158.74, 155.56, 138.49, 133.53, 133.25, 130.90, 129.53 (2ꢂ), 129.28,
(100 MHz, CDCl3): d 158.67, 155.40, 142.17, 141.74, 137.16, 133.28,
127.99 (2ꢂ), 127.73 (2ꢂ), 126.99, 126.61, 114.17, 114.15, 111.54, 55.68,
132.96,130.96, 130.80, 130.07, 129.74,129.01 (2ꢂ),127.64,127.61 (2ꢂ),
55.27.
127.49 (2ꢂ), 127.17, 126.50, 126.23, 114.11 (2ꢂ), 111.04, 55.34, 55.09.
4.3.2. Compound (3b). Yield 70% (125 mg); colorless solid;
mp¼88e90 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C21H18F3O2 359.1259, found 359.1264; 1H NMR
4.4. A representative synthetic procedure of compounds 4aeg
is as follows
(400 MHz, CDCl3):
d 7.69 (br s, 4H), 7.57e7.44 (m, 4H), 7.06 (d,
J¼8.8 Hz, 1H), 7.00e6.94 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H); 13C NMR
Pd(PPh3)4 (100 mg) and Na2CO3 (106 mg, 1.0 mmol) were added
to a solution of compound 8 (185 mg, 0.5 mmol) in DME (10 mL) at
rt. Then, ArB(OH)2 6aeg (2.0 mmol) was added to the stirred re-
action mixture at rt. The reaction mixture was stirred at reflux for
5 h. The reaction mixture was concentrated to yield the residue. The
residue was extracted with CH2Cl2 (3ꢂ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc¼10/1e6/1) afforded compounds 4aeg.
(100 MHz, CDCl3):
d 158.92, 155.50, 142.20, 133.82, 133.00, 131.50,
129.87 (2ꢂ), 129.17, 127.77 (2ꢂ), 127.71, 127.49, 126.57, 124.94,
124.90, 114.27 (2ꢂ), 111.69, 55.75, 55.34.
4.3.3. Compound (3c). Yield 80% (128 mg); colorless solid;
mp¼110e112 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C21H21O3 321.1491, found 321.1492; 1H NMR
(400 MHz, CDCl3):
d
7.55e7.48 (m, 6H), 7.04 (d, J¼8.4 Hz, 1H),

232
M.-Y. Chang et al. / Tetrahedron 69 (2013) 228e234
4.4.1. Compound (4a). Yield 76% (139 mg); colorless solid; mp¼
112e114 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C26H23O2 367.1698, found 367.1703; 1H NMR
(400 MHz, CDCl3): d 7.50e7.39 (m, 14H), 7.36e7.24 (m, 6H), 6.99 (d,
J¼8.0 Hz, 2H), 7.72 (d, J¼8.4 Hz, 2H), 3.36 (s, 6H). Single-crystal X-ray
diagram: crystal of compound 4g was grown by slow diffusion of
EtOAc into a solution of compound 4g in CH2Cl2 to yield colorless
prism. The compound crystallizes in the monoclinic crystal system,
(400 MHz, CDCl3):
d 7.59e7.51 (m, 8H), 7.45e7.41 (m, 4H),
7.37e7.32 (m, 2H), 7.05 (d, J¼9.2 Hz, 2H), 3.85 (s, 6H); 13C NMR
ꢀ
ꢀ
(100 MHz, CDCl3):
d
155.68 (2ꢂ), 138.48 (2ꢂ), 133.40 (2ꢂ), 130.99
space group
P
1
21/c 1, a¼8.6547(3) A, b¼20.2740(8) A,
3
ꢀ
c¼8.8027(4) A, V¼1370.99(10) A , Z¼4, Dcalcd¼1.256 g/cm3, F(000)¼
ꢀ
(2ꢂ), 129.56 (4ꢂ), 129.38 (2ꢂ), 128.02 (4ꢂ), 127.04 (2ꢂ), 126.68
(2ꢂ), 111.57 (2ꢂ), 55.75 (2ꢂ). Compound 4a is a known compound
and the analytical data are consistent with those in the literature.12
548,
2q
range 2.65e26.40ꢀ,
R
indices (all data) R1¼0.0635,
wR2¼0.1274.
4.4.2. Compound (4b). Yield 72% (181 mg); colorless solid; mp¼
177e178 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C28H21F6O2 504.1524, found 504.1531; 1H NMR
4.5. A representative synthetic procedure of compound 9 is as
follows
(400 MHz, CDCl3):
d
7.62 (br s, 8H), 7.52 (dd, J¼2.4, 8.4 Hz, 2H), 7.46
NBS (85 mg, 0.48 mmol) was added to a solution of compound
3a (115 mg, 0.4 mmol) in MeCN (10 mL) at rt. The reaction mixture
was stirred at reflux for 5 h. The reaction mixture was concentrated
to yield the residue. The residue was extracted with EtOAc
(3ꢂ30 mL). The combined organic layers were washed with brine,
dried, filtered, and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc¼10/1e6/1) afforded compound 9.
(d, J¼2.4 Hz, 2H), 7.01 (d, J¼8.4 Hz, 2H), 3.80 (s, 6H); 13C NMR
(100 MHz, CDCl3):
(2ꢂ), 129.87 (8ꢂ), 129.62 (2ꢂ), 127.55 (2ꢂ), 126.63 (2ꢂ), 124.95 (q,
J¼3.8 Hz, 2ꢂ), 111.73 (2ꢂ), 55.76 (2ꢂ).
d
155.72 (2ꢂ), 142.09 (2ꢂ), 133.33 (2ꢂ), 131.53
4.4.3. Compound (4c). Yield 64% (136 mg); colorless solid; mp¼131
e133 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1)
calcd for C28H27O4 427.1909, found 427.1908; 1H NMR (400 MHz,
4.5.1. Compound (9). Yield 70% (103 mg); colorless oil; HRMS (ESI,
Mþþ1) calcd for C20H18BrO2 369.0490, found 369.0492; 1H NMR
CDCl3):
d
7.56e7.51 (m, 8H), 7.04 (d, J¼8.4 Hz, 2H), 7.01e6.97 (m, 4H),
3.87 (s, 6H), 3.86 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
158.72 (2ꢂ),
(400 MHz, CDCl3):
d
7.78 (d, J¼2.4 Hz, 1H), 7.58e7.55 (m, 2H),
155.64 (2ꢂ), 133.45 (2ꢂ), 130.81 (2ꢂ), 130.60 (6ꢂ), 130.56 (2ꢂ),
126.24 (2ꢂ), 113.51 (4ꢂ), 111.51 (2ꢂ), 55.70 (2ꢂ), 55.25 (2ꢂ); Anal.
Calcd for C28H26O4: C, 78.85; H, 6.14. Found: C, 79.03; H, 6.31.
7.50e7.41 (m, 5H), 7.37e7.33 (m, 1H), 7.04 (d, J¼9.2 Hz, 1H), 6.95 (d,
J¼8.4 Hz, 1H), 3.93 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
155.99, 154.92, 138.30, 134.75, 132.13, 131.53, 131.14, 129.53 (2ꢂ),
129.31, 128.05 (2ꢂ), 127.14, 126.67, 126.61, 112.14, 112.03, 111.61,
4.4.4. Compound (4d). Yield 67% (123 mg); colorless solid; mp
>245 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C24H21N2O2 369.1603, found 369.1611; 1H NMR
56.35, 55.76.
4.6. A representative synthetic procedure of compounds
4hem is as follows
(400 MHz, CDCl3):
d
8.64 (dd, J¼2.0, 4.8 Hz, 4H), 7.59 (dd, J¼2.0,
8.4 Hz, 2H), 7.54e7.50 (m, 6H), 7.07 (d, J¼8.8 Hz, 2H), 3.87 (s, 6H);
13C NMR (100 MHz, CDCl3):
d
155.83 (2ꢂ), 150.64 (2ꢂ), 149.50 (2ꢂ),
Pd(PPh3)4 (100 mg) and Na2CO3 (64 mg, 0.6 mmol) were added
to a solution of compound 9 (110 mg, 0.3 mmol) in DME (10 mL) at
rt. Then, ArB(OH)2 6beg (0.6 mmol) was added to the stirred re-
action mixture at rt. The reaction mixture was stirred at reflux for
5 h. The reaction mixture was concentrated to yield the residue. The
residue was extracted with CH2Cl2 (3ꢂ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc¼10/1e6/1) afforded compounds 4hem.
146.13 (2ꢂ), 133.27 (2ꢂ), 128.81 (2ꢂ), 128.16 (2ꢂ), 128.08 (2ꢂ),
124.28 (2ꢂ), 121.35 (2ꢂ), 111.82 (2ꢂ), 55.73 (2ꢂ).
4.4.5. Compound (4e). Yield 70% (170 mg); colorless solid; mp¼176
e177 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1)
calcd for C30H31O6 487.2121, found 487.2123; 1H NMR (400 MHz,
CDCl3):
(m, 4H), 7.05 (d, J¼8.4 Hz, 2H), 6.95 (d, J¼8.4 Hz, 2H), 3.93 (s, 6H), 3.92
(s, 6H), 3.87 (s, 6H); 13C NMR (100 MHz, CDCl3):
155.63 (2ꢂ),148.38
d
7.56 (d, J¼2.4 Hz, 2H), 7.53 (dd, J¼2.4, 8.4 Hz, 2H), 7.15e7.12
d
(2ꢂ), 148.23 (2ꢂ), 133.47 (2ꢂ), 131.10 (2ꢂ), 130.74 (2ꢂ), 129.20 (2ꢂ),
126.44 (2ꢂ), 121.82 (2ꢂ), 113.04 (2ꢂ), 111.60 (2ꢂ), 110.88 (2ꢂ), 55.90
(2ꢂ), 55.87 (2ꢂ), 55.77 (2ꢂ); Anal. Calcd for C30H30O6: C, 74.06; H,
6.21. Found: C, 74.38; H, 6.58. Single-crystal X-ray diagram: crystal of
compound 4e was grown by slow diffusion of EtOAc into a solution of
compound 4e in CH2Cl2 to yield colorless prism. The compound
crystallizes in the monoclinic crystal system, space group P 1 21/c 1,
4.6.1. Compound (4h). Yield 85% (111 mg); colorless solid; mp¼72
e74 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1)
calcd for C27H22F3O2 435.1572, found 435.1576; 1H NMR (400 MHz,
CDCl3):
7.47e7.43 (m, 2H), 7.39e7.34 (m, 1H), 7.10e7.06 (m, 2H), 3.87 (s,
3H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3):
155.82, 155.57,
d 7.70 (br s, 4H), 7.62e7.58 (m, 2H), 7.58e7.53 (m, 4H),
d
142.17, 138.40, 133.64, 133.32, 133.08, 131.09, 129.87 (2ꢂ), 129.54
(2ꢂ), 129.50, 129.35, 129.20, 128.84, 128.04 (2ꢂ), 127.54, 127.10,
126.69, 124.94, 124.91, 111.68, 111.61, 55.74 (2ꢂ).
3
ꢀ
ꢀ
ꢀ
ꢀ
a¼15.9092(8) A, b¼6.7774(3) A, c¼11.7769(6) A, V¼1266.00(11) A ,
Z¼4, Dcalcd¼1.276 g/cm3, F(000)¼516, 2
q
range 1.28e26.44ꢀ, R indices
(all data) R1¼0.0558, wR2¼0.1212.
4.6.2. Compound (4i). Yield 76% (90 mg); colorless gum; HRMS
(ESI, Mþþ1) calcd for C27H25O3 397.1804, found 397.1810; 1H NMR
4.4.6. Compound (4f). Yield 72% (152 mg); colorless solid; mp¼176
e178 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1)
calcd for C28H23O4 423.1596, found 423.1602; 1H NMR (400 MHz,
(400 MHz, CDCl3):
d 7.59e7.50 (m, 8H), 7.45e7.41 (m, 2H),
7.37e7.32 (m, 1H), 7.06e7.02 (m, 2H), 6.97 (d, J¼8.8 Hz, 2H), 3.85 (s,
CDCl3):
(dd, J¼2.4, 8.8 Hz, 2H), 7.55 (d, J¼2.4 Hz, 2H), 7.08 (d, J¼8.8 Hz, 2H),
3.87 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
10.06(s,2H),7.94(d, J¼8.0Hz, 4H),7.75(d, J¼8.0Hz, 4H),7.59
3H), 3.85 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
158.75, 155.70 (2ꢂ),
138.51, 133.50, 133.42, 130.99,130.84 (2ꢂ), 130.63 (2ꢂ), 129.57 (2ꢂ),
129.39, 129.18, 128.02 (2ꢂ), 127.03, 126.69, 126.27, 113.55 (2ꢂ),
111.60, 111.56, 55.75 (2ꢂ), 55.28; Anal. Calcd for C27H24O3: C, 81.79;
H, 6.10. Found: C, 81.98; H, 6.48.
d
192.05 (2ꢂ), 155.79 (2ꢂ),
144.89 (2ꢂ),134.98(2ꢂ),133.34 (2ꢂ),130.22(4ꢂ),129.67 (4ꢂ),129.49
(2ꢂ), 129.15 (2ꢂ), 127.81 (2ꢂ), 111.79 (2ꢂ), 55.79 (2ꢂ).
4.4.7. Compound (4g). Yield 69% (180 mg); colorless solid; mp¼235
e236 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C38H31O2 519.2324, found 519.2326; 1H NMR
4.6.3. Compound (4j). Yield 81% (89 mg); colorless solid; mp¼150
e152 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C25H22NO2 368.1651, found 368.1654; 1H NMR

M.-Y. Chang et al. / Tetrahedron 69 (2013) 228e234
233
(400 MHz, CDCl3):
d
8.66 (dd, J¼2.0, 4.8 Hz, 2H), 7.63e7.52 (m, 8H),
(2ꢂ), 129.36 (2ꢂ), 128.62, 128.13, 128.10 (2ꢂ), 127.98 (2ꢂ), 127.36,
7.47e7.43 (m, 2H), 7.39e7.34 (m, 1H), 7.08 (d, J¼8.8 Hz, 1H), 7.07
127.00, 121.80, 115.93, 110.62, 56.00, 55.62.
(dd, J¼0.4, 8.4 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
155.84, 155.65, 149.48 (2ꢂ), 146.24, 138.33, 133.72, 132.89,
4.8. A representative synthetic procedure of compounds 5aeg
is as follows
131.09, 129.50 (2ꢂ), 129.28, 128.83, 128.14, 128.02 (2ꢂ), 127.95,
127.08, 126.66, 124.30 (2ꢂ), 111.78, 111.60, 55.71 (2ꢂ).
Pd(PPh3)4 (100 mg) and Na2CO3 (64 mg, 0.6 mmol) were added
to a solution of compound 11 (135 mg, 0.3 mmol) in DME (10 mL) at
rt. Then, ArB(OH)2 6aeg (0.6 mmol) was added to the stirred re-
action mixture at rt. The reaction mixture was stirred at reflux for
5 h. The reaction mixture was concentrated to yield the residue. The
residue was extracted with CH2Cl2 (3ꢂ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc¼10/1e6/1) afforded compounds 5aeg.
4.6.4. Compound (4k). Yield 78% (100 mg); colorless solid; mp
¼137e138 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C28H27O4 427.1909, found 427.1911; 1H NMR
(400 MHz, CDCl3):
d 7.60e7.52 (m, 6H), 7.46e7.41 (m, 2H),
7.37e7.33 (m, 1H), 7.15e7.12 (m, 2H), 7.07e7.04 (m, 2H), 6.95 (d,
J¼8.8 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H); 13C
NMR (100 MHz, CDCl3):
d 155.69, 155.64, 148.41, 148.24, 138.45,
133.44 (2ꢂ), 131.15, 131.00, 130.76, 129.55 (2ꢂ), 129.39, 129.20,
128.02 (2ꢂ), 127.05, 126.71, 126.42, 121.84, 113.07, 111.59 (2ꢂ),
110.91, 55.92, 55.90, 55.78, 55.75; Anal. Calcd for C28H26O4: C,
78.85; H, 6.14. Found: C, 79.05; H, 6.29. Single-crystal X-ray dia-
gram: crystal of compound 4k was grown by slow diffusion of
EtOAc into a solution of compound 4k in CH2Cl2 to yield colorless
prism. The compound crystallizes in the monoclinic crystal system,
4.8.1. Compound (5a). Yield 76% (101 mg); colorless solid;
mp¼72e74 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C32H27O2 443.2011, found 443.2018; 1H
NMR (400 MHz, CDCl3):
d 7.62e7.60 (m, 2H), 7.45 (s, 1H),
7.45e7.40 (m, 2H), 7.35e7.23 (m, 11H), 7.13 (dd, J¼2.4, 8.4 Hz, 1H),
ꢀ
ꢀ
space group
P
1
21/c 1, a¼28.750(3) A, b¼6.7540(7) A,
3
ꢀ
7.06 (d, J¼2.4 Hz, 1H), 7.03 (s, 1H), 6.83 (d, J¼8.4 Hz, 1H), 3.87 (s,
c¼11.4864(12) A, V¼2225.0(4) A , Z¼4, Dcalcd¼1.273 g/cm3, F(000)¼
3H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 155.47, 154.98,
ꢀ
904,
2
q
range 0.71e26.44ꢀ,
R
indices (all data) R1¼0.0864,
141.83, 140.64, 138.31, 138.02, 133.29, 132.88, 132.78, 132.57,
129.91 (2ꢂ), 129.84, 129.83, 129.70, 129.55 (2ꢂ), 129.48 (2ꢂ),
128.13 (2ꢂ), 128.05 (2ꢂ), 127.78 (2ꢂ), 127.05, 126.74, 126.62,
113.52, 110.75, 55.81, 55.52; Anal. Calcd for C32H26O2: C, 86.85; H,
5.92. Found: C, 86.98; H, 6.11.
wR2¼0.1252.
4.6.5. Compound (4l). Yield 72% (85 mg); colorless solid; mp¼104
e106 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C27H23O3 395.1647, found 395.1655; 1H NMR
(400 MHz, CDCl3):
d
10.06 (s, 1H), 7.94 (d, J¼8.4 Hz, 2H), 7.75 (d,
4.8.2. Compound (5b). Yield 65% (99 mg); colorless solid; mp¼150
e152 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C33H26F3O2 511.1885, found 511.1891; 1H NMR
J¼8.4 Hz, 2H), 7.61e7.52 (m, 6H), 7.45e7.41 (m, 2H), 7.37e7.33 (m,
1H), 7.07 (dd, J¼6.4, 8.4 Hz, 2H), 3.87 (s, 3H), 3.86 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d
192.08, 155.84, 155.64, 144.99, 138.40, 134.94,
(400 MHz, CDCl3): d 7.64e7.57 (m, 5H), 7.49 (s, 1H), 7.47e7.25 (m,
133.70, 133.06, 131.11, 130.23 (2ꢂ), 129.54 (2ꢂ), 129.48 (2ꢂ), 129.36,
129.17, 128.05 (2ꢂ), 127.79, 127.11, 126.70, 113.98, 111.76, 111.63,
55.76 (2ꢂ).
7H), 7.18e7.15 (m, 3H), 7.02 (s, 1H), 6.97 (d, J¼2.0 Hz, 1H), 6.87 (d,
J¼8.4 Hz, 1H), 3.89 (s, 3H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
155.62, 155.19, 145.65, 139.02, 138.08, 137.75, 133.03, 132.80,
132.53, 130.65, 130.27 (2ꢂ), 129.65 (2ꢂ), 129.56 (2ꢂ), 129.52 (2ꢂ),
129.39 (2ꢂ), 128.11 (2ꢂ), 128.02, 127.83 (2ꢂ), 127.25, 126.89, 126.68,
125.11, 113.23, 110.91, 55.85, 55.52.
4.6.6. Compound (4m). Yield 79% (105 mg); viscous gum; HRMS
(ESI, Mþþ1) calcd for C32H27O2 443.2011, found 443.2019; 1H NMR
(400 MHz, CDCl3):
d 7.59e7.57 (m, 2H), 7.50e7.43 (m, 10H),
7.38e7.36 (m, 1H), 7.20e7.16 (m, 5H), 7.02 (d, J¼8.4 Hz, 1H), 6.78 (d,
4.8.3. Compound (5c). Yield 74% (105 mg); colorless solid; mp¼144
e146 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C33H29O3 473.2117, found 473.2122; 1H NMR
J¼8.4 Hz, 1H), 3.85 (s, 3H), 3.41 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
155.58, 155.49, 142.14, 141.73, 138.47, 137.08, 133.35, 132.77,
130.96, 130.92, 130.16, 130.06, 129.74, 129.58 (2ꢂ), 129.24, 129.02
(2ꢂ), 127.98 (2ꢂ), 127.64, 127.51 (2ꢂ), 127.15, 127.02, 126.52, 126.49,
126.24, 111.54, 111.07, 55.74, 55.10.
(400 MHz, CDCl3): d 7.63e7.61 (m, 2H), 7.45e7.41 (m, 2H), 7.44 (s,
1H), 7.36e7.27 (m, 6H), 7.20 (d, J¼8.8 Hz, 2H), 7.14e7.10 (m, 2H),
7.02 (s, 1H), 6.87 (d, J¼8.8 Hz, 2H), 6.85 (d, J¼8.4 Hz, 1H), 3.88 (s,
3H), 3.84 (s, 3H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 158.55,
155.47, 154.93, 140.27, 138.35, 138.07, 134.18, 133.49, 132.89, 132.67,
132.53, 130.96 (2ꢂ), 129.87, 129.78, 129.55 (2ꢂ), 129.52 (2ꢂ), 128.03
(2ꢂ), 127.80 (2ꢂ), 127.00, 126.76 (2ꢂ), 113.63 (2ꢂ), 113.43, 110.76,
55.80, 55.53, 55.32.
4.7. A representative synthetic procedure of compound 11 is
as follows
NBS (206 mg, 1.16 mmol) was added to a solution of compound
4a (73 mg, 0.2 mmol) in MeCN (10 mL) at rt. The reaction mixture
was stirred at reflux for 5 h. The reaction mixture was concentrated
to yield the residue. The residue was extracted with EtOAc
(3ꢂ30 mL). The combined organic layers were washed with brine,
dried, filtered, and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc¼10/1e6/1) afforded compound 11.
4.8.4. Compound (5d). Yield 70% (93 mg); viscous gum; HRMS (ESI,
Mþþ1) calcd for C31H26NO2 444.1964, found 444.1970; 1H NMR
(200 MHz, CDCl3):
d 8.68e8.65 (m, 2H), 7.65e7.52 (m, 12H),
7.47e7.43 (m, 3H), 7.13 (dd, J¼2.4, 8.4 Hz, 1H), 7.06 (d, J¼2.4 Hz, 1H),
3.97 (s, 3H), 3.77 (s, 3H).
4.8.5. Compound (5e). Yield 62% (93 mg); colorless solid; mp¼183
e185 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C34H31O4 503.2222, found 503.2225; 1H NMR
4.7.1. Compound (11). Yield 93% (83 mg); colorless solid; mp¼
99e101 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C26H22BrO2 445.0803, found 445.0814; 1H NMR
(400 MHz, CDCl3):
d
7.62 (d, J¼7.2 Hz, 2H), 7.45 (s, 1H), 7.43 (d,
(400 MHz, CDCl3):
d
7.52e7.49 (m, 2H), 7.47e7.42 (m, 3H),
J¼7.6 Hz, 2H), 7.38e7.33 (m, 4H), 7.31e7.27 (m, 1H), 7.19 (d,
J¼2.4 Hz, 2H), 7.09 (dd, J¼2.4, 8.4 Hz, 1H), 7.02 (s, 1H), 6.94 (dd,
J¼2.0, 8.4 Hz, 1H), 6.88 (d, J¼8.0 Hz, 1H), 6.84 (d, J¼8.8 Hz, 1H), 6.69
(d, J¼1.6 Hz, 1H), 3.92 (s, 3H), 3.90 (s, 3H), 3.79 (s, 3H), 3.62 (s, 3H);
7.35e7.30 (m, 6H), 7.28e7.23 (m, 2H), 7.19 (s, 1H), 6.96e6.94 (m,
1H), 3.78 (s, 3H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3):
155.70,
138.24, 134.54, 133.08, 132.20, 131.26, 131.13, 130.09, 129.61, 129.59
d

234
M.-Y. Chang et al. / Tetrahedron 69 (2013) 228e234
Ali, A.; Rafique, H.; Hussain, M.; Tatar, J.; Saeed, A.; Villinger, A.; Langer, P. Tetrahe-
13C NMR (100 MHz, CDCl3):
d
155.51, 154.98, 148.29, 147.96, 140.31,
dron 2011, 67, 5244; (h) Hassan, Z.; Hussain, M.; Villinger, A.; Langer, P. Tetrahedron
2012, 68, 6305; (i)Akrawi, O.A.;Mohammed, H.H.; Patonay, T.;Villinger, A.;Langer,
P. Tetrahedron2012, 68, 6298;(j)Machuy, M.M.;Wutele,C.;Schreiner, P. R.Synthesis
2012, 44, 1405; (k) Akrawi, O. A.; Nagy, G. Z.; Patonay, T.; Villinger, A.; Langer, P.
Tetrahedron Lett. 2012, 53, 3206.
138.29, 127.98, 134.31, 133.66, 132.87, 132.61, 132.45, 130.07, 129.86,
129.62, 129.52 (2ꢂ), 129.43 (2ꢂ), 128.04 (2ꢂ), 127.88 (2ꢂ), 127.03,
126.83, 121.80, 113.77, 113.15, 110.99, 110.80, 55.93, 55.81, 55.66,
55.59.
3. (a) Chang, M.-Y.; Lee, T.-W.; Wu, M.-H. Org. Lett. 2012, 14, 2198; (b) Chang, M.-Y.;
Lee, T.-W.; Wu, M.-H. Heterocycles 2012, 85, 1607.
4. For a review on the synthesis of natural terphenyls, see: (a) Liu, J.-K. Chem. Rev.
2006, 106, 2209 For a review on the syntheses of perylenequinones, see: (b)
Mulrooney, C. A.; O’Brien, E. M.; Morgan, B. J.; Kozlowski, M. C. Eur. J. Org. Chem.
2012, 3887.
5. (a) Mullen, K.; Wegner, G. Electronic Materials: The Oligomer Approach; Wiley-
VCH: Weinhein, Germany, 1988; (b) Chen, B.; Baumeister, U.; Pelzl, G.; Das, M.
K.; Zeng, X.; Ungar, G.; Tschierske, C. J. Am. Chem. Soc. 2005, 127, 16578; (c)
Wright, R. S. Tetrahedron Lett. 2003, 44, 7129; (d) Udayakumar, B. S.; Schuster,
G. B. J. Org. Chem. 1992, 57, 348.
6. (a) Ohkanda, J.; Lockman, J. W.; Kothare, M. A.; Qian, Y.; Blaskovich, M. A.; Sebti,
S. M.; Hamilton, A. D. J. Med. Chem. 2002, 45, 177; (b) Roberti, M.; Pizzirani, D.;
Recanatini, M.; Simoni, D.; Grimaudo, S.; Di Cristina, A.; Abbadessa, V.; Gebbia,
N.; Tolomeo, M. J. Med. Chem. 2006, 49, 3012; (c) Guo, H.; Hu, H.; Liu, S.; Liu, X.;
Zhou, Y.; Che, Y. J. Nat. Prod. 2007, 70, 1519; (d) Zhang, C.; Ondeyka, J. G.; Herath,
K. B.; Guan, Z.; Collado, J.; Pelaez, F.; Leavitt, P. S.; Gurnett, A.; Nare, B.; Liberator,
P.; Singh, S. B. J. Nat. Prod. 2006, 69, 710; (e) Lin, J. M.; Gowda, A. S. P.; Sharma,
A. K.; Amin, S. Bioorg. Med. Chem. 2012, 20, 3202.
4.8.6. Compound (5f). Yield 72% (102 mg); colorless solid;
mp¼193e194 ꢀC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C33H27O3 471.1960, found 471.1969;
1H NMR (400 MHz, CDCl3):
d
10.02 (s, 1H), 7.83 (d, J¼8.4 Hz,
2H), 7.62e7.60 (m, 2H), 7.47 (s, 1H), 7.46e7.42 (m, 4H),
7.37e7.24 (m, 6H), 7.08 (s, 1H), 7.07 (dd, J¼2.4, 10.0 Hz, 1H), 7.03
(s, 1H), 6.82 (d, J¼8.4 Hz, 1H), 3.89 (s, 3H), 3.77 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d 191.93, 155.65, 155.26, 148.37, 139.13,
138.08, 137.69, 134.63, 133.16, 132.78, 132.72, 132.56, 130.79,
130.60 (2ꢂ), 130.20, 129.83, 129.55 (2ꢂ), 129.52 (2ꢂ), 129.38
(2ꢂ), 128.11 (2ꢂ), 127.87 (2ꢂ), 127.27, 126.91, 113.17, 110.88,
55.87, 55.53.
7. For a review, see: Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 1359.
4.8.7. Compound (5g). Yield 80% (124 mg); viscous gum; HRMS
(ESI, Mþþ1) calcd for C38H31O2 519.2324, found 519.2332; 1H NMR
8. (a) Cho, C. H.; Kim, I. S.; Park, K. Tetrahedron 2004, 60, 4589; (b) Miguez, J. M. A.;
Sousa-Pedrares, L. A. A.; Vila, J. M.; Hii, K. K. J. Org. Chem. 2007, 72, 7771; (c)
Todd, M. H.; Balasubramanian, S.; Abell, C. Tetrahedron Lett. 1997, 38, 6781; (d)
Shimizu, H.; Manabe, K. Tetrahedron Lett. 2006, 47, 5927; (e) Taylor, R. H.; Felpin,
F.-X. Org. Lett. 2007, 9, 2911; (f) Zhang, L.; Liang, F.; Cheng, X.; Liu, Q. J. Org.
Chem. 2009, 74, 899.
(200 MHz, CDCl3):
d 7.58e7.21 (m, 17H), 7.21e7.01 (m, 3H),
6.85e6.77 (m, 2H), 6.64e6.62 (m, 2H), 3.80 (s, 3H), 3.77 (s, 3H).
Acknowledgements
9. (a) Perato, S.; Voisin-Chiret, A. S.; Santos, J. S. O.; Legay, R.; Oulyadi, H.; Rault, S.
Tetrahedron 2012, 68, 1910; (b) Guillen, E.; Hierrezuelo, J.; Martínez-Mallorquin,
R.; Lopez-Romero, J. M.; Rico, R. Tetrahedron 2011, 67, 2555; (c) De Giorgi, M.;
Voisin-Chiret, A. S.; Santos, J. S. O.; Corbo, F.; Franchini, C.; Rault, S. Tetrahedron
2011, 67, 6145; (d) Zhang, X.; Xie, W.; Chen, W. Tetrahedron 2010, 66, 1188; (e)
Voisin-Chiret, A. S.; Muraglia, M.; Burzicki, G.; Perato, S.; Corbo, F.; Santos, J. S.
O.; Franchini, C.; Rault, S. Tetrahedron 2010, 66, 8000; (f) Rajca, A.; Wang, H.;
Bolshov, P.; Rajca, S. Tetrahedron 2001, 57, 3725; (g) King, B. T.; Kroulik, J.;
Robertson, C. R.; Rempala, P.; Hilton, C. L.; Korinek, J. D.; Gortari, L. M. J. Org.
Chem. 2007, 72, 2279; (h) Goto, H.; Katagiri, H.; Furusho, Y.; Yashima, E. J. Am.
Chem. Soc. 2006, 128, 7176; (i) Goto, H.; Furusho, Y.; Miwa, K.; Yashima, E. J. Am.
Chem. Soc. 2009, 131, 4710; (j) Ormsby, J. L.; Black, T. D.; Hilton, C. L.; Bharat;
King, B. T. Tetrahedron 2008, 64, 11370; (k) Mitchell, P. S. R.; Sengul, I. F.; Kan-
demir, H.; Nugent, S. J.; Chen, R.; Bowyer, P. K.; Kumar, N.; Black, D. S. Tetra-
hedron 2012, 68, 8163; (l) Kikuchi, H.; Matsuo, Y.; Katou, Y.; Kubohara, Y.;
Oshima, Y. Tetrahedron 2012, 68, 8884; (m) Dohi, T.; Kamitanaka, T.; Watanabe,
S.; Hu, Y.; Washimi, N.; Kita, Y. Chem.dEur. J. 2012, 18, 13614.
10. (a) Bovicelli, P.; Antonioletti, R.; Onori, A.; Delogu, G.; Fabbri, D.; Dettori, M. A.
Tetrahedron 2006, 62, 635; (b) Tohma, H.; Morioka, H.; Takizawa, S.; Arisawa, M.;
Kita, Y. Tetrahedron 2001, 57, 345; (c) Pansay, S.; Prachumrak, N.; Jungsuttiwong,
S.; Keawin, T.; Sudyoadsuk, T.; Promarak, V. Tetrahedron Lett. 2012, 53, 4568.
11. CCDC 894027 (3d), 887702 (4e), 887701 (4g), 896139 (4k), and 894046 (5h)
contain the supplementary crystallographic data for this paper. This data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: 44-1223-336033;
e-mail: deposit@ccdc.cam.ac.uk).
The authors would like to thank the National Science Council of
the Republic of China for its financial support (NSC 99-2113-M-037-
006-MY3).
Supplementary data
Scanned photocopies of 1H and 13C NMR spectral data were
supported. Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.tet.2012.10.039.
References and notes
1. For reviews on the syntheses of cross-coupling reactions of polyhalogenated
heterocycles, see: (a) Schroter, S.; Stock, C.; Bach, T. Tetrahedron 2005, 61, 2245;
(b) Schnurch, M.; Flasik, R.; Khan, A. F.; Spina, M.; Mihovilovic, M. D.; Stanetty, P.
Eur. J. Org. Chem. 2006, 3283; (c) Wang, R.; Manabe, K. Synthesis 2009, 1405.
2. (a) Sharif, M.; Zeeshan, M.; Reimann, S.; Villinger, A.; Langer, P. Tetrahedron Lett.
2010, 51, 2810; (b) Ullah, I.; Khera, R. A.; Hussain, M.; Villinger, A.; Langer, P. Tet-
rahedron Lett. 2009, 50, 4651; (c) Hung, N. T.; Hussain, M.; Malik, I.; Villinger, A.;
Langer, P. Tetrahedron Lett. 2010, 51, 2420; (d) Dang, T. T.; Rasool, N.; Dang, T. T.;
Reinke, H.; Langer, P. Tetrahedron Lett. 2007, 48, 845; (e) Toguem, S.-M. T.; Fatunsin,
O.; Villinger, A.; Langer, P. Tetrahedron Lett. 2011, 52, 3732; (f) Hussain, M.; Hung, N.
T.;Khera, R. A.;Villinger, A.;Langer, P. Tetrahedron Lett. 2011, 52,184;(g)Khera, R. A.;
12. Mirk, D.; Wibbeling, B.; Froehlich, R.; Waldvogel, S. R. Synlett 2004, 1970.