One-pot synthesis of functionalized p-terphenyl derivatives

Article abstract of DOI:10.1016/j.tet.2013.07.023

A one-pot synthetic route for preparing functionalized p-terphenyl derivatives 1 and 4 is developed. The route is easily carried from the treatment of cinnamyl aldehydes 2 with substituted allylsulfones 3 in good yields via the tandem intermolecular aldol condensation/intramolecular electrocyclization/ oxidative dehydrogenation.

Full text of DOI:10.1016/j.tet.2013.07.023

Tetrahedron 69 (2013) 7916e7924
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot synthesis of functionalized p-terphenyl derivatives
*
Meng-Yang Chang , Chieh-Kai Chan, Ming-Hao Wu
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
Article history:
A one-pot synthetic route for preparing functionalized p-terphenyl derivatives 1 and 4 is developed. The
route is easily carried from the treatment of cinnamyl aldehydes 2 with substituted allylsulfones 3 in
good yields via the tandem intermolecular aldol condensation/intramolecular electrocyclization/oxida-
tive dehydrogenation.
Received 30 May 2013
Received in revised form 3 July 2013
Accepted 8 July 2013
Available online 12 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Sulfonyl p-terphenyl
Cinnamaldehydes
Allylsulfones
Aldol condensation
Electrocyclization
1. Introduction
O
O
Z
Y
Z
Y
S
S
O
O
oxidative
electrocyclization
Functionalized terphenyls have received attention due to their
presence as the structural motifs in natural products,1 organic
electronics, chemical biosensors,2 and biological pharmaceuticals.3
There are a number of synthetic approaches available to investigate
the skeleton of terphenyl, including major transition-metal medi-
ated SuzukieMiyaura coupling reactions.4 Although some useful
routes are valuable protocols for preparing multi-substituted ter-
phenyl derivatives,5 it is still of great importance to develop
a simple and efficient one-pot domino route for the construction of
functionalized terphenyls, especially those with flexible sub-
stitution patterns. Core structures with biaryl and sulfonyl sub-
stituents have been used as nonsteroidal anti-inflammatory drugs,
such as DuP-697, SC-58125, and MK 966.3a,6 In this paper, we
present a novel one-pot expeditious cascade-type for establishing
the skeleton of sulfonyl p-terphenyls 1 via the NaH-mediated
treatment of substituted cinnamaldehydes 2 with substituted
allylsulfones 3.7
dehydrogenation
X
X
1
O
Z
Y
O
Z
Y
S
S
O
O
3
aldol
+
X
condensation
CHO
2
X
Scheme 1. One-pot route of sulfonyl p-terphenyls 1.
constructing diversified frameworks; it has been successfully ap-
plied to variously synthetic fields.9
2. Results and discussion
The one-pot convergent C3þC3 synthetic route of an o-terphenyl
skeleton
1 includes the regioselective aldol condensation of
Cinnamyl sulfones 3 were easily prepared in good yields via
a one-pot chlorination of commercially available cinnamyl alcohols
with TsCl and Et3N followed by nucleophilic substitution of the
resulting cinnamyl chlorides with Z-SO2Na (Z¼Me, Ph, Tol) in
refluxing aqueous dioxane.10 PCC-mediated oxidation of cinnamyl
alcohols afforded cinnamaldehydes 2 in good yields. With two
starting materials 2 and 3 in hand, p-terphenyls 1aead with the
configuration of 1,4-diaryl-2-sulfonylbenzene was obtained in
65e85% yields via the NaH-mediated tandem procedure, as shown
substituted cinnamaldehydes 2 with substituted allylsulfones 3,
intramolecular 1,6-6
p
-electrocyclization,8 and oxidative de-
hydrogenation, as shown in Scheme 1. The one-pot expeditious
cascade-type ring closure forms a six-membered core structure.
The one-pot domino reaction is a useful synthetic tool for
* Corresponding author. Tel.: þ886 7 3121101x2220; e-mail addresses: mychang@
kmu.edu.tw, mychang624@yahoo.com.tw (M.-Y. Chang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.023

M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
7917
in Scheme 2. The structures of compounds 1b and 1h were de-
compound 1b exhibited one doublet at
d
8.64 for H-30 protons. Two
termined by single-crystal X-ray crystallography, as shown in
Fig. 1.11 The formation of compounds 1aead was confirmed
through spectral analysis. For example, the 1H NMR spectrum of
CH protons appeared as doublets of doublets of H-50 (
d 7.78) and H-
60 (
d 7.22). The structure of compound 1b was also confirmed by
HRMS, which showed a peak at m/z 533.2166 [Mþþ1].
Changing the base to DBU, t-BuOK, DMAP or LDA (from rt to
reflux) with different equivalents in THF, we found that model
substrate 1a (X¼Y¼H, Z¼Tol) was obtained at a yield range of
35e76% via a tandem process (see Table 1). Under different con-
ditions (entries 1e7), the dehydrated skeleton of diarylhexatriene
was not observed.12 According to the experimental results, we
envision that NaH is an optimal base for increasing the product
yield under boiling THF conditions for 3 h.
O
Z
Y
S
O
Y = H
Z = Tol
3a, Z = Tol 3d, Y = 4-OMe
3b, Z = Ph 3e, Y = 4-F
3c, Z = Me 3f, Y = 3,4-O CH
H
3'
O
Z
Y
S
4'
2
2
NaH
THF
1''
O
+
1
1'
H
5'
CHO
X
H
6'
Table 1
X
Reaction of compounds 2a and 3aa
1a-1ad
(30 examples)
2a, X = H
2d, X = 3,4-O CH
Base (equiv), temp (ꢀC), time (h)
1a, yield (%)b
35c
76
2
2
Entry
2b, X = 4-OMe
2c, X = 4-F
2e, X = 4-NMe
2
1
2
3
4
5
6
7
NaH (4), rt, 20
NaH (4), reflux, 3
NaH(10), reflux, 6
DBU (4), reflux, 6
t-BuOK (4), reflux, 6
DMAP (2), reflux, 10
LDA (1.0 M, 4), reflux, 6
68
Y = H, Z = Tol
1a, X = H (76%)
Y = 4-OMe, Z = Tol
55d,e
43d,e
40d,e
64
1p, X = H (80%)
1b, X = 4-OMe (70%) X-Ray 1q, X = 4-OMe (82%)
1c, X = 4-F (78%)
1r, X = 4-F (78%)
1d, X = 3,4-O CH (74%)
1s, X = 3,4-O CH (84%)
2
2
2 2
1e, X = 4-NMe (65%)
1t, X = 4-NMe (76%)
2
2
a
Y = H, Z = Ph
Y = 4-F, Z = Tol
The reactions were run on a 0.5 mmol scale with 2a and 3a in THF (10 mL).
The product was >95% pure as determined by 1H NMR analysis.
The starting material 3a (32%) was recovered.
b
c
1f, X = H (79%)
1u, X = H (85%)
1g, X = 4-OMe (73%)
1h, X = 4-F (80%) X-Ray
1i, X = 3,4-O CH (70%)
1v, X = 4-OMe (74%)
1w, X = 4-F (75%)
1x, X = 3,4-O CH (80%)
d
e
No starting material was recovered.
2
2
2
2
Unknown products or complex mixture with different yields was isolated (for
1j, X = 4-NMe (68%)
Y = H, Z = Me
1y, X = 4-NMe (74%)
2
Y = 3,4-O CH , Z = Tol
2 2
2
entry 4, 20%; entry 5, 28%; entry 6, 44%).
1k, X = H (75%)
1l, X = 4-OMe (70%)
1m, X = 4-F (75%)
1z, X = H (78%)
1aa, X = 4-OMe (80%)
1ab, X = 4-F (76%)
With the successful results in hand, the one-pot NaH-mediated
reaction of compounds 2fek and 3a was examined under the above
conditions, as shown in Scheme 3. Compared with the moderate
yields of skeleton 1, skeleton 4 with 4-biphenyl (4a), bicyclic 1-
naphthalene (4b), 2-quinoline (4f), tricyclic 9-anthracene (4c), or
heterocyclic 2-furan (4d), and 2-thiphene (4e) was isolated with
the lower yields (60e82%). Qinquephenyl 4g was prepared from the
reaction of aldehyde 2l with the p-terphenyl group and compound
3a via the (3þ3) route. During the tandem reaction procedure, the
plausible reasons should be summarized as: (1) the intramolecular
1n, X = 3,4-O CH (78%)
1ac, X = 3,4-O CH (75%)
2 2
1ad, X = 4-NMe (72%)
2
2
2
1o, X = 4-NMe (66%)
2
Scheme 2. One-pot synthesis of sulfonyl p-terphenyls 1.
O
Tol
S
Ph
NaH
THF
O
CHO
3a
+
Ar
1
Ar
1
2f, Ar = 4-Ph-Ph
2i, Ar = 2-furan
1
1
4a-4h
2g, Ar = 1-naphthene 2j, Ar = 2-thiophene
1
1
1
2h, Ar = 9-anthracene 2k, Ar = 2-naphthalene
1
Tol
O
S
O
O
Tol
Tol
Ph
S
Ph
S
Ph
O
O
O
4a (73%)
4b (67%)
4c (60%)
O
O
O
Tol
Tol
Tol
S
Ph
S
Ph
S
Ph
O
O
O
N
O
S
4e (82%)
4f (62%)
O
4d (79%)
Tol
S
Ph
O
CHO
3a, NaH
THF
4g (58%)
Ph
2l
Ph
Scheme 3. Synthesis of p-terphenyl derivatives 4.
Fig. 1. X-ray Structures of compounds 1b and 1h.

7918
M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
steric hindrance repulsion of the bicyclic or tricyclic aromatic ring
affected the ring closure and (2) the electronic effect of the het-
erocyclic ring increased the barrier of electrocyclization.
thermodynamic conditions. For the intermediate A1 (P¼Me), the
formed -carbanion of compound 3g was more stable than the g-
position such that it was easy to trigger the occurrence of aldol
condensation. At another stage of intermediate A2, when the P
group was a Ph substituent, the delocalized carbanion of compound
a
Furthermore, when the substituent of skeleton 3 was changed
from an aryl to a methyl group under the above mentioned con-
ditions, five biphenyls 5aee with 1-aryl-2-methyl-4-sulfonylben
zene skeleton were provided in 62e78% yields via the one-pot
domino reaction of compounds 2aee and 3g (see Scheme 4). This
is a novel, high-yield, and one-pot cascade route to the framework
of functionalized biphenyls. The structure of compound 5b was
determined by single-crystal X-ray crystallography (Fig. 2).11
3a preferred to choose the
than the stable intermediate. Next, the intermolecular nucleophilic
addition of cinnamaldehydes 2a with intermediate A1 (SN2,
carbanion of compound 3g) or A2 (SN20,
-carbanion of compound
g-position with less steric hindrance
a
-
g
3a) afforded intermediate B1 or B2. After the intramolecular proton
exchange of intermediate B1 or B2 followed by dehydration, the
preferred intermediate D1 or D2 with a fully (E,E,E)-conjugated
configuration was formed. Intermediate C1 or C2, with an (E,Z,E)-
triene motif exhibited a stronger repulsion with steric hindrance
than did intermediate D1 or D2. For intermediate D1 or D2, the
orientation of the o-styryl group and the sulfonyl or phenyl group
on the central alkene was trans-configured from one to another (E-
orientation). Next, compound 1a or 5a was generated by the 1,6-
electrocyclic disrotatory ring closure of intermediate D1 or D2
followed by oxidative dehydrogenation of the resulting in-
termediate E1 or E2.
O
O
Tol
Me
S
Me
S
Tol
O
O
NaH
THF
3g
+
2a~2e
X
5a, X = H (78%)
5b, X = 4-OMe (70%) X-Ray
5c, X = 4-F (62%)
5d, X = 3,4-O CH Ph (69%)
2
2
5e, X = 4-NMe (64%)
2
In the next work, desulfonation of skeletons 1, 4, and 5 was
further studied. With treatment of compounds 1x, 1ac, 4b, 4def,
and 5aec with sodium amalgam in MeOH, desulfonative com-
pounds 6aei could be obtained in 70e90% yields, as shown in
Scheme 6. The structure of compound 6e was determined by
single-crystal X-ray crystallography (Fig. 3).11 Therefore, the de-
rivatives of three biphenyls 6aec and six p-terphenyls 6dei were
formed by desulfonation. To extend this one-pot domino protocol
for the application of cinnamyl azide (3h) or cinnamyl nitrile (3i),
we found that a complex mixture was observed for the reaction of
compounds 1a and 3h or 3i. From the observation, we envisioned
that the sulfonyl group should be the key substituent affecting aldol
condensation.
Scheme 4. One-pot synthesis of skeleton 5.
Fig. 2. X-ray structure of compound 5b.
O
Tol
Me
S
Me
O
As shown in Scheme 5, a reasonable explanation for the rapid
synthesis of compounds 5a and 1a should be that the resonance
between intermediates A1 and A2 was first generated via NaH-
mediated deprotonation of compounds 3g and 3a under
6a, X = H (84%)
6b, X = 4-OMe (78%)
6c, X = 4-F (88%)
5a-5c
+
X
X
O
+
O
O
O
Tol
S
O
O
O
O
Na(Hg)
Tol
Tol
α
Me
Ph
S
P
S
O
O
MeOH
6d, X = 4-F (72%)
6e, X = 3,4-O CH (70%) X-Ray
+
1x, 1ac
O
A1
X
X
Tol
O
2
2
P = Me (for 3g)
S
P
B1
2a
NaH
(a)
+
O
O
Tol
+
3g, P = Me
3a, P = Ph
(b)
S
Ph
Ph
O
6f, Ar = 2-furan (73%)
O
O
Tol
Tol
S
Ph
O
6g, Ar = 2-thiophene (83%)
6h, Ar = 1-naphthalene (74%)
6i, Ar = 2-quinoline (73%)
γ
S
P
(a) deprotonation
Ar
Ar
O
O
(b) nucleophilic substitution
(c) dehydration
4b, 4d-4f
A2
Ph
P = Ph (for 3a)
B2
(d) 1,6-electrocyclization
Scheme 6. Synthesis of skeleton 6.
(e) oxidative dehydrogenation
(c)
O
O
O
Tol
Tol
Tol
Me
Ph
S
Me
Ph
S
Me
S
O
O
O
E1
D1
C1
Ph
5a
+
Z-orientation with
+
stronger repulsion
+
+
(e)
(d)
1a
O
O
O
Tol
Tol
Tol
S
Ph
S
Ph
S
Ph
O
O
O
E2
D2
C2
Ph
Ph
Ph
Scheme 5. A possible mechanism to compound 1a or 5a.
Fig. 3. X-ray structure of compound 6e.

M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
7919
3. Conclusion
to the reaction mixture at 0 ꢀC. The solvent was concentrated under
reduced pressure. The residue was diluted with water (10 mL) and
the mixture was extracted with EtOAc (3ꢁ20 mL). The combined
organic layers were washed with brine, dried, filtered, and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc¼10/1w6/1) afforded compounds 1aead.
In summary, we have successfully presented a synthetic meth-
odology for p-terphenyl 1, p-terphenyl derivatives 4, and biphenyl
5, which involves the tandem site-selective aldol condensation of
aryl cinnamaldehydes 2 with substituted allylsulfones 3, the
intramolecular 1,6-electrocyclic disrotatory ring closure followed
by oxidative dehydrogenation. The one-pot synthesis of function-
alized p-terphenyl and biphenyl via various reaction conditions was
investigated well. The structures of key products were confirmed
by X-ray crystal analysis. The one-pot transition metal-free syn-
thetic approach begins with simple starting materials and reagents,
and provides a potential methodology for the synthetic research of
p-terphenyl derivatives with the sulfonyl substituent. Further in-
vestigation regarding one-pot synthesis of multi-functionalized
polyphenyls will be conducted and published in due course.
4.3.1. 20-(Toluene-4-sulfonyl)[1,10;40,100]terphenyl
(1a). Yield¼76%
(146 mg); White solid; mp¼155e156 ꢀC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C25H21O2S 385.1262,
found 385.1266; 1H NMR (400 MHz, CDCl3):
d
8.67 (d, J¼2.0 Hz, 1H),
7.80 (dd, J¼2.0, 8.0 Hz, 1H), 7.73e7.71 (m, 2H), 7.54e7.50 (m, 2H),
7.46e7.42 (m, 1H), 7.34e7.30 (m, 1H), 7.28e7.20 (m, 3H), 7.16e7.13
(m, 2H), 7.04e6.98 (m, 4H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
143.4, 140.8, 140.7, 140.4, 139.0, 138.0, 137.9, 133.2, 131.0, 130.1
(2ꢁ), 129.1 (2ꢁ), 128.9 (2ꢁ), 128.2, 127.8 (2ꢁ), 127.6, 127.2 (2ꢁ),
127.2 (2ꢁ), 126.9, 21.5; Anal. Calcd for C25H20O2S: C, 78.09; H, 5.24.
Found: C, 78.23; H, 5.40.
4. Experimental section
4.1. General
4.3.2. 4-Methoxy-20-(toluene-4-sulfonyl)[1,10;40,100]terphenyl
(1b). Yield¼70% (145 mg); White solid; mp¼159e160 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C26H23O3S 415.1368, found 415.1364; 1H NMR (400 MHz, CDCl3):
All other reagents and solvents were obtained from commercial
sources and used without further purification. Reactions were
routinely carried out under an atmosphere of dry nitrogen with
magnetic stirring. Products in organic solvents were dried with
anhydrous MgSO4 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 oper-
d
8.64 (d, J¼2.0 Hz,1H), 7.78 (dd, J¼2.0, 8.0 Hz, 1H), 7.70 (d, J¼8.0 Hz,
2H), 7.52e7.49 (m, 2H), 7.44e7.41 (m, 1H), 7.25 (d, J¼8.0 Hz,1H), 7.16
(d, J¼8.4 Hz, 2H), 7.01 (d, J¼8.4 Hz, 2H), 6.95 (d, J¼8.4 Hz, 2H), 6.76 (d,
J¼8.8 Hz, 2H), 3.86 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
159.3, 143.3, 140.62, 140.61, 140.5, 139.0, 138.0, 133.5, 131.3 (2ꢁ),
ating at 200/400 and at 100 MHz, respectively. Chemical shifts (
d
)
131.0, 130.3, 129.0 (2ꢁ), 128.9 (2ꢁ), 128.2, 127.8 (2ꢁ), 127.2 (2ꢁ),
127.0, 112.7 (2ꢁ), 55.3, 21.5; Anal. Calcd for C26H22O3S: C, 75.34; H,
5.35. Found: C, 75.59; H, 5.54. Single-crystal X-ray diagram: crystal of
compound 1bwas grown byslow diffusion of EtOAc into a solution of
compound 1b in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group Pꢂ1,
are reported in parts per 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 EnrafeNonius
FR-590 diffractometer (CAD4, Kappa CCD). Elemental analyses were
carried out with Heraeus Vario III-NCSH, Heraeus CHN-OS-Rapid
Analyzer or Elementar Vario EL III.
3
ꢀ
ꢀ
ꢀ
ꢀ
a¼6.4366(5) A, b¼9.7802(8) A, c¼17.0284(16) A, V¼1019.48(15) A ,
Z¼2, dcalcd¼1.350 g/cm3, F(000)¼436, 2
q
range 1.25e26.40ꢀ, R in-
dices (all data) R1¼0.0841, wR2¼0.1732.
4.2. A representative synthetic procedure of skeleton 3 is as
follows
4.3.3. 4-Fluoro-20-(toluene-4-sulfonyl)[1,10;40,100 ]terphenyl (1c). Yield¼78%
(157 mg); White solid; mp¼185e186 ꢀC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C25H20FO2S 403.1168,
Triethylamine (Et3N, 250 mg, 2.5 mmol) was added to a solution
of commercially available cinnamyl alcohols (2.0 mmol) in CH2Cl2
(15 mL) at rt. p-Toluenesulfonyl chloride (TsCl, 420 mg, 2.2 mmol)
was slowly added to the reaction mixture at rt. The reaction mix-
ture was stirred at reflux for 4 h. The reaction mixture was cooled to
rt. Substituted sulfinic sodium salt (3.0 mmol) was added to a so-
lution of the resulting cinnamyl chlorides at rt. A co-solvent of
water (5 mL) and 1,4-dioxane (10 mL) was added to the reaction
mixture at rt. The reaction mixture was stirred at reflux for 6 h. The
reaction mixture was cooled to rt. The solvent was concentrated
under reduced pressure. The residue was diluted with water
(10 mL) and the mixture was extracted with EtOAc (3ꢁ30 mL). The
combined organic layers were washed with brine, dried, filtered,
and evaporated to afford crude product. Purification on silica gel
found 403.1174; 1H NMR (400 MHz, CDCl3):
7.80 (dd, J¼2.0, 8.0 Hz, 1H), 7.72e7.70 (m, 2H), 7.54e7.50 (m, 2H),
7.46e7.42 (m, 1H), 7.25 (d, J¼8.0 Hz, 1H), 7.17 (d, J¼8.4 Hz, 2H),
7.05e6.98 (m, 4H), 6.94e6.89 (m, 2H), 2.35 (s, 3H); 13C NMR
d
8.64 (d, J¼2.0 Hz, 1H),
(100 MHz, CDCl3):
d
162.5 (d, J¼245.6 Hz), 143.6, 141.0, 140.5, 139.7,
138.9, 137.9, 133.8 (d, J¼3.8 Hz), 133.2, 131.9 (d, J¼8.3 Hz, 2ꢁ), 131.0,
129.1 (2ꢁ), 129.0 (2ꢁ), 128.3, 127.7 (2ꢁ), 127.2 (2ꢁ), 127.1, 114.2 (d,
J¼22.0 Hz, 2ꢁ), 21.5; Anal. Calcd for C25H19FO2S: C, 74.60; H, 4.76.
Found: C, 74.89; H, 5.02.
4.3.4. 3,4-Methylenedioxy-20-(toluene-4-sulfonyl)[1,10; 40,100]terphenyl
(1d). Yield¼74% (158 mg); White solid; mp¼151e152 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C26H21O4S 429.1161, found 429.1162; 1H NMR (400 MHz, CDCl3):
(hexanes/EtOAc¼6/1w2/1) afforded skeleton 3. Skeleton
3 is
known and the analytical data are consistent with those in the
d
8.64 (d, J¼2.0 Hz, 1H), 7.78 (dd, J¼2.0, 8.0 Hz, 1H), 7.71e7.69 (m,
literature.10
2H), 7.53e7.49 (m, 2H), 7.45e7.41 (m,1H), 7.26e7.24 (m, 3H), 7.06 (d,
J¼8.0 Hz, 2H), 6.68 (d, J¼8.0 Hz, 1H), 6.51 (d, J¼1.6, 8.0 Hz, 1H), 6.40
(d, J¼1.6 Hz, 1H), 5.98 (s, 2H), 2.35 (s, 3H); 13C NMR (100 MHz,
4.3. A representative synthetic procedure of compounds
1aead is as follows
CDCl3):
d
147.13, 146.66, 143.51, 140.75, 140.20 (2ꢁ), 138.97, 137.98,
133.25, 131.51, 130.97, 129.05 (2ꢁ), 128.87 (2ꢁ), 128.22, 127.83 (2ꢁ),
127.17 (2ꢁ), 126.90, 123.90, 110.57, 107.21, 101.01, 21.48; Anal. Calcd
for C26H20O4S: C, 72.88; H, 4.70. Found: C, 72.61; H, 4.93.
Sodium hydride (NaH, 60% in oil, 80 mg, 2.0 mmol) was added to
a solution of compounds 3aef (0.5 mmol) in THF (8 mL). A solution
of compounds 2aee (0.5 mmol) in the THF (2 mL) was added to the
reaction mixture at rt. The reaction mixture was stirred at reflux for
3 h. The reaction mixture was cooled to rt. Water (1 mL) was added
4.3.5. 4-Dimethylamino-20-(toluene-4-sulfonyl)[1,10;40,100]terphenyl
(1e). Yield¼65% (139 mg); White solid; mp¼194e195 ꢀC

7920
M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
124.0, 110.6, 107.3, 101.0; Anal. Calcd for C25H18O4S: C, 72.45; H,
4.38. Found: C, 72.58; H, 4.22.
for C27H26NO2S 428.1684, found 428.1688; 1H NMR (400 MHz,
CDCl3):
d
8.64 (d, J¼2.0 Hz, 1H), 7.77 (dd, J¼2.0, 8.0 Hz, 1H),
7.72e7.69 (m, 2H), 7.52e7.48 (m, 2H), 7.44e7.40 (m, 1H), 7.27 (d,
J¼8.0 Hz, 1H), 7.18 (d, J¼8.4 Hz, 2H), 6.99 (d, J¼8.8 Hz, 2H), 6.92 (d,
J¼8.0 Hz, 2H), 6.59 (d, J¼8.8 Hz, 2H), 3.00 (s, 6H), 2.32 (s, 3H); 13C
4.3.10. 20-Benzenesulfonyl-4-dimethylamino[1,10;40,100]terphenyl
(1j). Yield¼68% (140 mg); White solid; mp¼128e129 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C26H24NO2S 414.1528, found 414.1530; 1H NMR (400 MHz,
NMR (100 MHz, CDCl3):
d
150.0,143.0,141.4 (2ꢁ),140.7,140.0,139.2,
138.1, 133.6, 130.9 (2ꢁ), 130.9 (2ꢁ), 129.0 (2ꢁ), 128.8 (2ꢁ), 128.0,
127.8 (2ꢁ), 127.1 (2ꢁ), 126.9, 111.3, 40.6 (2ꢁ), 21.5; Anal. Calcd
for C27H25NO2S: C, 75.85; H, 5.89; N, 3.28. Found: C, 75.74; H, 6.09;
N, 3.55.
CDCl3):
d
8.66 (d, J¼2.0 Hz, 1H), 7.79 (dd, J¼2.0, 8.0 Hz, 1H),
7.73e7.70 (m, 2H), 7.53e7.49 (m, 2H), 7.44e7.34 (m, 2H),
7.31e7.28 (m, 3H), 7.22e7.18 (m, 2H), 6.90 (d, J¼8.8 Hz, 2H), 6.58 (d,
J¼8.8 Hz, 2H), 2.99 (s, 6H); 13C NMR (100 MHz, CDCl3):
d 150.1,
144.2, 141.5, 140.9, 140.4, 140.0, 139.1, 133.7, 131.3, 131.1, 130.9 (2ꢁ),
129.0 (2ꢁ), 128.1 (2ꢁ), 128.0, 127.7 (2ꢁ), 127.1 (2ꢁ), 127.0, 111.4
(2ꢁ), 40.6 (2ꢁ).
4.3.6. 20-Benzenesulfonyl[1,10;40,100]terphenyl (1f). Yield¼79% (146
mg); White solid; mp¼148e149 ꢀC (recrystallized from hexanes
and EtOAc); HRMS (ESI, Mþþ1) calcd for C24H19O2S 371.1106, found
371.1108; 1H NMR (400 MHz, CDCl3):
d
8.69 (d, J¼2.0 Hz, 1H), 7.82
4.3.11. 20-Methanesulfonyl[1,10;40,100]terphenyl (1k). Yield¼75% (116
mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C19H17O2S
(dd, J¼2.0, 8.0 Hz, 1H), 7.74e7.71 (m, 2H), 7.55e7.53 (m, 2H),
7.52e7.50 (m, 2H), 7.46e7.37 (m, 2H), 7.34e7.28 (m, 3H), 7.27e7.17
309.0949, found 309.0950; 1H NMR (400 MHz, CDCl3):
d 8.47 (d,
(m, 3H), 7.02e6.99 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
140.8,
J¼2.0 Hz, 1H), 7.87 (dd, J¼2.0, 8.0 Hz, 1H), 7.69e7.67 (m, 2H),
140.8, 140.7, 140.1, 138.9, 137.8, 133.2, 132.5, 131.2, 130.1 (2ꢁ), 129.1
(2ꢁ), 128.3 (2ꢁ), 128.3, 127.7 (2ꢁ), 127.6, 127.3 (2ꢁ), 127.2 (2ꢁ),
127.0; Anal. Calcd for C24H18O2S: C, 77.81; H, 4.90. Found: C, 78.03;
H, 5.12.
7.58e7.41 (m, 9H), 2.66 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
141.1,
134.0, 139.7, 138.8, 138.2, 133.2, 131.3, 130.2 (2ꢁ), 129.1 (2ꢁ), 128.5,
128.3, 128.1 (2ꢁ), 127.2 (2ꢁ), 126.8, 43.3; Anal. Calcd for C19H16O2S:
C, 74.00; H, 5.23. Found: C, 74.11; H, 5.41.
4.3.7. 20-Benzenesulfonyl-4-methoxy[1,10;40,100]terphenyl (1g). Yield¼73%
(146 mg); White solid; mp¼169e170 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C25H21O3S
4.3.12. 20-Methanesulfonyl-4-methoxy[1,10;40,100 ]terphenyl (1l). Yield¼70%
(118 mg); White solid; mp¼180e181 ꢀC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C20H19O3S
401.1212, found 401.1218; 1H NMR (400 MHz, CDCl3):
d
8.67
339.1055, found 339.1052; 1H NMR (400 MHz, CDCl3):
d 8.46 (d,
(d, J¼2.0 Hz, 1H), 7.80 (dd, J¼2.0, 8.0 Hz, 1H), 7.73e7.70 (m, 2H),
7.54e7.50 (m, 2H), 7.45e7.38 (m, 2H), 7.30e7.20 (m, 5H), 6.93
(d, J¼8.8 Hz, 2H), 6.75 (d, J¼8.8 Hz, 2H), 3.85 (s, 3H); 13C
J¼2.0 Hz, 1H), 7.85 (dd, J¼2.0, 8.0 Hz, 1H), 7.68e7.66 (m, 2H),
7.51e7.40 (m, 6H), 7.02e6.98 (m, 2H), 3.88 (s, 3H), 2.66 (s, 3H); 13C
NMR (100 MHz, CDCl3):
d 159.8, 140.8, 139.9, 139.8, 138.9, 133.8,
NMR (100 MHz, CDCl3):
d
159.3, 140.9, 140.7, 140.6, 140.3,
131.5 (2ꢁ), 131.3, 130.2, 129.1 (2ꢁ), 128.2, 127.1 (2ꢁ), 126.8, 113.5
139.0, 133.5, 132.5, 131.3 (2ꢁ), 131.1, 130.1, 129.1 (2ꢁ), 128.3
(2ꢁ), 128.2, 127.7 (2ꢁ), 127.2 (2ꢁ), 127.0, 112.8 (2ꢁ), 55.3;
Anal. Calcd for C25H20O3S: C, 74.97; H, 5.03. Found: C, 75.14; H,
5.32.
(2ꢁ), 55.3, 43.1.
4.3.13. 4-Fluoro-20-methanesulfonyl[1,10;40,100]terphenyl (1m). Yield¼75%
(122 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C19H16FO2S
327.0855, found 327.0859; 1H NMR (400 MHz, CDCl3):
d 8.46 (d,
4.3.8. 20-Benzenesulfonyl-4-fluoro[1,10;40,100]terphenyl (1h). Yield¼80%
(155 mg); White solid; mp¼135e136 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C24H18FO2S
J¼2.0 Hz, 1H), 7.87 (dd, J¼2.0, 8.0 Hz, 1H), 7.69e7.66 (m, 2H),
7.53e7.48 (m, 4H), 7.47e7.41 (m, 2H), 7.18e7.15 (m, 2H), 2.69 (s,
3H); 13C NMR (100 MHz, CDCl3):
d
162.8 (d, J¼246.4 Hz), 141.4,
389.1012, found 389.1013; 1H NMR (400 MHz, CDCl3):
d
8.68 (d,
139.8, 139.0, 138.7, 134.0, 133.4, 132.0 (d, J¼8.4 Hz, 2ꢁ), 131.4, 129.1
J¼2.0 Hz, 1H), 7.82 (dd, J¼2.0, 8.0 Hz, 1H), 7.73e7.70 (m, 2H),
7.54e7.50 (m, 2H), 7.47e7.41 (m, 2H), 7.30e7.23 (m,
5H), 6.99e6.95 (m, 2H), 6.93e6.87 (m, 2H); 13C NMR (100 MHz,
(2ꢁ), 128.4, 127.2 (2ꢁ), 127.0, 115.1 (d, J¼21.2 Hz, 2ꢁ), 43.4.
4.3.14. 3,4-Methylenedioxy-20-methanesulfonyl[1,10; 40,100]terphenyl
(1n). Yield¼78% (137 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C20H17O4S 353.0848, found 353.0852; 1H NMR (400 MHz,
CDCl3):
d
162.5 (d, J¼246.4 Hz), 141.1, 140.8, 140.2, 139.7, 138.8,
133.7 (d, J¼3.0 Hz), 133.3, 132.7, 131.9 (d, J¼7.6 Hz, 2ꢁ),
131.2, 129.1 (2ꢁ), 128.4 (2ꢁ), 128.4, 127.6 (2ꢁ), 127.2 (2ꢁ),
127.1, 114.3 (d, J¼21.3 Hz, 2ꢁ); Anal. Calcd for C24H17FO2S: C,
74.21; H, 4.41. Found: C, 74.40; H, 4.66. Single-crystal X-ray
diagram: crystal of compound 1h was grown by slow diffusion of
EtOAc into a solution of compound 1h in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the monoclinic crystal
CDCl3):
d
8.45 (d, J¼2.0 Hz, 1H), 7.84 (dd, J¼2.0, 8.0 Hz, 1H),
7.68e7.65 (m, 2H), 7.51e7.47 (m, 2H), 7.44e7.40 (m, 2H), 7.02 (d,
J¼2.0 Hz, 1H), 6.97 (dd, J¼2.0, 8.0 Hz, 1H), 6.90 (d, J¼8.0 Hz, 1H),
6.05 (s, 2H), 2.75 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 147.9, 147.3,
141.1, 139.8, 139.6, 138.8, 133.5, 131.7, 131.3, 129.1 (2ꢁ), 128.3, 127.1
(2ꢁ), 126.9, 123.8, 111.0, 107.9, 101.4, 43.3.
ꢀ
ꢀ
system, space group P 1 21/n 1, a¼9.3403(3) A, b¼9.9796(3) A,
c¼20.1774(5) A, V¼1855.26(9) A , Z¼4, dcalcd¼1.391 g/cm3,
4.3.15. 4-Dimethylamino-20-methanesulfonyl[1,10;40,100]terphenyl
(1o). Yield¼66% (116 mg); White solid; mp¼158e159 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C21H22NO2S 352.1371, found 352.1733; 1H NMR (400 MHz, CDCl3):
3
ꢀ
ꢀ
F(000)¼808,
2
q
range 2.05e26.42ꢀ,
R
indices (all data)
R1¼0.0600, wR2¼0.1640.
4.3.9. 20-Benzenesulfonyl-3,4-methylenedioxy[1,10;40,100]terphenyl
(1i). Yield¼70% (145 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C25H19O4S 415.1004, found 415.1005; 1H NMR (400 MHz, CDCl3):
d
8.46 (d, J¼2.0 Hz, 1H), 7.83 (dd, J¼2.0, 8.0 Hz, 1H), 7.68e7.65 (m,
2H), 7.51e7.39 (m, 6H), 6.80 (d, J¼8.8 Hz, 2H), 3.03 (s, 6H), 2.67 (s,
3H); 13C NMR (100 MHz, CDCl3):
150.1, 140.5, 140.2, 139.9, 139.1,
d
d
8.66 (d, J¼2.0 Hz, 1H), 7.80 (dd, J¼2.0, 8.0 Hz, 1H), 7.72e7.70 (m,
133.6, 131.2, 131.1 (2ꢁ), 130.5, 129.1 (2ꢁ), 128.1, 127.1 (2ꢁ), 126.6,
2H), 7.54e7.50 (m, 2H), 7.46e7.42 (m, 2H), 7.39e7.37 (m, 2H),
7.30e7.25 (m, 3H), 6.66 (d, J¼8.0 Hz, 1H), 6.48 (d, J¼1.6, 8.0 Hz, 1H),
6.42 (d, J¼1.6 Hz, 1H), 5.98 (s, 2H); 13C NMR (100 MHz, CDCl3):
111.6 (2ꢁ), 42.8, 40.3 (2ꢁ).
4.3.16. 400-Methoxy-20-(toluene-4-sulfonyl)[1,10;40,100]terphenyl
(1p). Yield¼80% (166 mg); White solid; mp¼168e169 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
d
147.2, 146.6, 140.9, 140.8, 140.4, 140.3, 138.9, 133.3, 132.6, 131.3
(2ꢁ), 131.2, 129.1 (2ꢁ), 128.3 (2ꢁ), 127.7 (2ꢁ), 127.2 (2ꢁ), 127.0,

M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
7921
C26H23O3S 415.1368, found 415.1366; 1H NMR (400 MHz, CDCl3):
2H), 7.34e7.18 (m, 6H), 7.13 (d, J¼8.4 Hz, 2H), 7.03e6.97 (m, 4H),
2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
143.4, 141.8, 140.5, 139.7, 137.8, 137.7, 135.2 (d, J¼3.8 Hz), 133.2,
130.8, 130.1 (2ꢁ), 128.9 (2ꢁ), 128.8, 127.8 (2ꢁ), 127.6, 127.3 (2ꢁ),
126.7 (2ꢁ), 116.0 (d, J¼21.3 Hz, 2ꢁ), 21.5; Anal. Calcd for
C25H19FO2S: C, 74.60; H, 4.76. Found: C, 74.79; H, 4.89.
d
8.62 (d, J¼2.0 Hz,1H), 7.75 (dd, J¼2.0, 8.0 Hz,1H), 7.66 (d, J¼8.8 Hz,
d
163.0 (d, J¼246.4 Hz),
2H), 7.33e7.29 (m, 1H), 7.26e7.19 (m, 3H), 7.14 (d, J¼8.0 Hz, 2H),
7.06e6.97 (m, 6H), 3.89 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d 159.9, 143.3, 140.4, 140.3, 140.1, 138.1, 138.0, 133.1, 131.4,
130.4, 130.1 (2ꢁ), 128.9 (2ꢁ), 128.3 (2ꢁ), 127.8 (2ꢁ), 127.5, 127.2
(2ꢁ), 126.4, 114.5 (2ꢁ), 55.4, 21.5; Anal. Calcd for C26H22O3S: C,
75.34; H, 5.35. Found: C, 75.68; H, 5.54.
4.3.22. 400-Fluoro-4-methoxy-20-(toluene-4-sulfonyl)[1,10;40,100]ter-
phenyl (1v). Yield¼74% (160 mg); White solid; mp¼183e184 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C26H22FO3S 433.1274, found 433.1275; 1H NMR (400 MHz,
4.3.17. 4,400-Dimethoxy-20-(toluene-4-sulfonyl)[1,10; 40,100]terphenyl
(1q). Yield¼82% (182 mg); White solid; mp¼171e172 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C27H25O4S 445.1474, found 445.1477; 1H NMR (400 MHz, CDCl3):
CDCl3):
d
8.59 (d, J¼2.0 Hz, 1H), 7.73 (dd, J¼2.0, 8.0 Hz, 1H),
7.69e7.64 (m, 2H), 7.26e7.15 (m, 5H), 7.01 (d, J¼8.0 Hz, 2H), 6.95 (d,
d
8.60 (d, J¼2.0 Hz,1H), 7.73 (dd, J¼2.0, 8.0 Hz,1H), 7.65 (d, J¼8.0 Hz,
J¼8.8 Hz, 2H), 6.76 (d, J¼8.8 Hz, 2H), 3.86 (s, 3H), 2.33 (s, 3H); 13C
2H), 7.22 (d, J¼8.0 Hz, 1H), 7.17 (d, J¼8.0 Hz, 2H), 7.03 (d, J¼8.8 Hz,
2H), 7.00 (d, J¼8.0 Hz, 2H), 6.94 (d, J¼8.8 Hz, 2H), 6.75 (d, J¼8.8 Hz,
2H), 3.88 (s, 3H), 3.85 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz,
NMR (100 MHz, CDCl3):
d
162.9 (d, J¼247.2 Hz), 159.3, 143.4, 140.7,
140.6, 139.5, 137.9,135.2 (d, J¼3.0 Hz),133.5, 131.3 (2ꢁ),130.8, 130.2,
128.9 (2ꢁ), 128.8 (d, J¼8.7 Hz, 2ꢁ), 127.8 (2ꢁ), 126.8, 116.0 (d,
J¼21.2 Hz, 2ꢁ), 112.7 (2ꢁ), 55.3, 21.5; Anal. Calcd for C26H21FO3S: C,
72.20; H, 4.89. Found: C, 72.39; H, 5.02.
CDCl3):
d 159.8, 159.2, 143.3, 140.5, 140.1, 139.9, 138.0, 133.4, 131.5,
131.3 (2ꢁ), 130.4, 130.4, 128.8 (2ꢁ), 128.2 (2ꢁ), 127.7 (2ꢁ), 126.4,
114.5 (2ꢁ), 112.7 (2ꢁ), 55.4, 55.3, 21.5.
4.3.23. 4,400-Difluoro-20-(toluene-4-sulfonyl)[1,10;
40,100]terphenyl
4.3.18. 4-Fluoro-400-methoxy-20-(toluene-4-sulfonyl)[1,10;40,100]ter-
phenyl (1r). Yield¼78% (168 mg); White solid; mp¼160-161 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C26H22FO3S 433.1274, found 433.1273; 1H NMR (400 MHz,
(1w). Yield¼75% (157 mg); White solid; mp¼175e176 ꢀC (recry
stallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C25H19F2O2S 421.1074, found 421.1075; 1H NMR (400 MHz, CDCl3):
d
8.61 (d, J¼2.0 Hz, 1H), 7.75 (dd, J¼2.0, 8.0 Hz, 1H), 7.69e7.65 (m,
CDCl3):
d
8.61 (d, J¼2.0 Hz, 1H), 7.75 (dd, J¼2.0, 8.0 Hz, 1H), 7.65 (d,
2H), 7.25e7.14 (m, 5H), 7.04 (d, J¼8.0 Hz, 2H), 7.00e6.97 (m, 2H),
J¼8.8 Hz, 2H), 7.21 (d, J¼8.0 Hz, 1H), 7.16 (d, J¼8.0 Hz, 2H),
6.93e6.89 (m, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3):
7.06e7.02 (m, 4H), 7.00e6.96 (m, 2H), 6.93e6.88 (m, 2H), 3.89 (s,
d
163.0 (d, J¼246.3 Hz), 162.5 (d, J¼246.3 Hz), 143.7, 140.6, 140.0,
3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
162.4 (d,
139.7, 137.7, 135.0 (d, J¼3.1 Hz), 133.7 (d, J¼3.8 Hz), 131.8 (d,
J¼8.3 Hz, 2ꢁ), 130.9, 129.0 (2ꢁ), 128.9 (d, J¼8.3 Hz, 2ꢁ), 127.7 (2ꢁ),
127.4, 126.8, 116.1 (d, J¼21.2 Hz, 2ꢁ), 114.2 (d, J¼21.2 Hz, 2ꢁ), 21.5.
J¼245.6 Hz), 159.9, 143.6, 140.6, 140.4, 138.9, 137.9, 133.9 (d,
J¼3.0 Hz), 133.2, 131.9 (d, J¼8.3 Hz, 2ꢁ), 131.3, 130.5, 129.0 (2ꢁ),
128.3 (2ꢁ), 127.7 (2ꢁ), 126.5, 114.5 (2ꢁ), 114.1 (d, J¼21.2 Hz, 2ꢁ),
55.4, 21.5; Anal. Calcd for C26H21FO3S: C, 72.20; H, 4.89. Found: C,
72.43; H, 5.03.
4.3.24. 400-Fluoro-3,4-methylenedioxy-20-(toluene-4-sulfonyl)
[1,10;40,100]terphenyl (1x). Yield¼80% (178 mg); White solid;
mp¼184e185 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C26H20FO4S 447.1066, found 447.1059; 1H
4.3.19. 3,4-Methylenedioxy-400-methoxy-20-(toluene-4-sulfonyl)[1,10;
40,100]terphenyl (1s). Yield¼84% (192 mg); White solid; mp¼
140e141 ꢀC (recrystallized from hexanes and EtOAc); HRMS (ESI,
Mþþ1) calcd for C27H23O5S 459.1266, found 459.1270; 1H NMR
NMR (400 MHz, CDCl3):
d
8.58 (d, J¼2.0 Hz, 1H), 7.72 (dd, J¼2.0,
8.0 Hz, 1H), 7.68e7.64 (m, 2H), 7.26e7.17 (m, 5H), 7.06 (d, J¼8.0 Hz,
2H), 6.67 (d, J¼8.0 Hz, 1H), 6.50 (dd, J¼2.0, 8.0 Hz, 1H), 6.39 (d,
J¼2.0 Hz, 1H), 5.98 (s, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3):
(400 MHz, CDCl3):
d
8.56 (d, J¼2.0 Hz, 1H), 7.73 (dd, J¼2.0, 8.0 Hz,
1H), 7.64 (d, J¼8.8 Hz, 2H), 7.25 (d, J¼8.4 Hz, 2H), 7.21 (d, J¼8.0 Hz,
1H), 7.07e7.00 (m, 4H), 7.02 (d, J¼2.0 Hz, 1H), 6.50 (dd, J¼2.0,
8.0 Hz, 1H), 6.39 (d, J¼2.0 Hz, 1H), 5.97 (s, 2H), 3.88 (s, 3H), 2.35 (s,
d
163.0 (d, J¼246.2 Hz), 147.2, 146.7, 143.6, 140.8, 140.2, 139.8, 137.9,
135.1 (d, J¼3.1 Hz), 133.3, 131.4, 130.8, 128.9 (2ꢁ), 128.8 (d, J¼8.3 Hz,
2ꢁ), 127.8 (2ꢁ), 126.7, 123.9, 116.0 (d, J¼22.0 Hz, 2ꢁ), 110.5, 107.2,
101.0, 21.5; Anal. Calcd for C26H19FO4S: C, 69.94; H, 4.29. Found: C,
70.16; H, 4.42.
3H); 13C NMR (100 MHz, CDCl3):
d 159.9, 147.1, 146.6, 143.5, 140.6,
140.3, 139.5, 138.0, 133.2, 131.6, 131.4, 130.4, 128.8 (2ꢁ), 128.2 (2ꢁ),
127.8 (2ꢁ), 126.3, 123.9, 114.5 (2ꢁ), 110.6, 107.2, 101.0, 55.4, 21.5.
4.3.25. 400-Fluoro-4-dimethylamino-20-(toluene-4-sulfonyl)[1,10;40,100]
terphenyl (1y). Yield¼74% (165 mg); White solid; mp¼174e175 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C27H25FNO2S 446.1590, found 446.1595; 1H NMR (400 MHz,
4.3.20. 4-Dimethylamino-400-methoxy-20-(toluene-4-sulfonyl)
[1,10;40,100]terphenyl (1t). Yield¼76% (174 mg); White solid;
mp¼145e146 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C28H28NO3S 458.1790, found 458.1785; 1H
CDCl3):
d
8.58 (d, J¼2.0 Hz, 1H), 7.71 (dd, J¼2.0, 8.0 Hz, 1H),
NMR (400 MHz, CDCl3):
d
8.58 (d, J¼2.0 Hz, 1H), 7.72 (dd, J¼2.0,
7.68e7.64 (m, 2H), 7.26 (d, J¼7.6 Hz, 2H), 7.22e7.16 (m, 3H), 6.99
(d, J¼8.0 Hz, 2H), 6.91 (d, J¼8.8 Hz, 2H), 6.00 (br s, 2H), 3.00 (s,
8.0 Hz, 1H), 7.64 (d, J¼8.8 Hz, 2H), 7.23 (d, J¼8.0 Hz, 1H), 7.17 (d,
J¼8.0 Hz, 2H), 7.03 (d, J¼8.4 Hz, 2H), 6.98 (d, J¼8.0 Hz, 2H), 6.91 (d,
J¼8.4 Hz, 2H), 6.60 (br s, 2H), 3.88 (s, 3H), 3.00 (s, 6H), 2.32 (s, 3H);
6H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 162.9 (d,
J¼245.6 Hz), 143.1, 140.8, 139.1, 138.0, 135.3 (d, J¼3.0 Hz), 133.7,
130.9 (2ꢁ), 130.8, 128.8 (d, J¼8.4 Hz, 2ꢁ), 128.7 (2ꢁ), 128.5, 128.4,
127.8 (2ꢁ), 127.2, 126.8, 116.0 (d, J¼22.0 Hz, 2ꢁ), 111.4 (2ꢁ), 40.7
(2ꢁ), 21.5.
13C NMR (100 MHz, CDCl3):
d
159.7, 150.0, 143.0, 140.6 (2ꢁ), 139.7,
138.1 (2ꢁ), 133.5, 131.7, 130.9 (2ꢁ), 130.4, 128.8 (2ꢁ), 128.2 (2ꢁ),
127.8 (2ꢁ), 126.4, 114.5 (2ꢁ), 111.4 (2ꢁ), 55.4, 40.7 (2ꢁ), 21.5; Anal.
Calcd for C28H27NO3S: C, 73.49; H, 5.95; N, 3.06. Found: C, 73.62; H,
6.11; N, 3.22.
4.3.26. 300,400-Methylenedioxy-20-(toluene-4-sulfonyl)[1,10;40,100]ter-
phenyl (1z). Yield¼78% (167 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C26H21O4S 429.1161, found 429.1163; 1H NMR
4.3.21. 400-Fluoro-20-(toluene-4-sulfonyl)[1,10;40,100]terphenyl
(1u). Yield¼85% (171 mg); White solid; mp¼162e163 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C25H20FO2S 403.1168, found 403.1168; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d
8.58 (d, J¼2.0 Hz, 1H), 7.71 (dd, J¼2.0, 8.0 Hz,
1H), 7.34e7.29 (m, 1H), 7.24e7.18 (m, 6H), 7.13 (d, J¼8.0 Hz, 2H),
7.02e6.93 (m, 4H), 6.05 (s, 2H), 2.33 (s, 3H); 13C NMR (100 MHz,
d
8.61 (d, J¼2.0 Hz, 1H), 7.75 (dd, J¼2.0, 8.0 Hz, 1H), 7.69e7.66 (m,
CDCl3): d 148.5, 147.9, 143.4, 140.5, 140.4, 140.3, 138.0, 137.9, 133.1,

7922
M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
130.6, 130.1 (2ꢁ), 128.9 (2ꢁ), 128.0, 127.8 (2ꢁ), 127.6, 127.2 (2ꢁ),
filtered, and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc¼10/1w6/1) afforded compounds
4aeg.
126.6, 121.0, 108.8, 107.6, 101.4, 21.5.
4.3.27. 300,400-Methylenedioxy-4-methoxy-20-(toluene-4-sulfonyl)
[1,10;40,100]terphenyl (1aa). Yield¼80% (183 mg); White solid;
mp¼168e169 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C27H23O5S 459.1266, found 459.1268; 1H NMR
4.4.1. 20-(Toluene-4-sulfonyl)[1,40;10,100;400,1000]quaterphenyl
(4a). Yield¼73% (168 mg); White solid; mp¼145e146 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C31H25O2S 461.1575, found 461.1577; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d
8.55 (d, J¼2.0 Hz, 1H), 7.69 (dd, J¼2.0, 8.0 Hz,
1H), 7.21 (d, J¼8.0 Hz, 1H), 7.19e7.15 (m, 4H), 7.01 (d, J¼8.4 Hz, 2H),
6.96e6.93 (m, 3H), 6.75 (d, J¼8.8 Hz, 2H), 6.05 (s, 2H), 3.85 (s, 3H),
d
8.69 (d, J¼2.0 Hz, 1H), 7.83 (dd, J¼2.0, 8.0 Hz, 1H), 7.75e7.73 (m,
2H), 7.72e7.62 (m, 2H), 7.55e7.43 (m, 7H), 7.32 (d, J¼8.0 Hz, 2H),
7.19 (d, J¼8.4 Hz, 2H), 7.11 (d, J¼8.4 Hz, 2H), 6.98 (d, J¼8.8 Hz, 2H),
2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 159.2, 148.4, 147.8, 143.3,
140.5, 140.2, 138.0, 133.4, 133.3, 131.3 (2ꢁ), 130.6, 130.3, 129.2,
128.9 (2ꢁ), 127.8 (2ꢁ), 126.6, 121.0, 112.7 (2ꢁ), 108.8, 107.5, 101.4,
55.3, 21.5.
2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 143.4, 140.8, 140.7, 140.6,
140.5, 140.4, 139.0, 137.9, 137.0, 133.1, 131.0, 130.6 (2ꢁ), 130.1, 129.1
(2ꢁ), 128.9 (4ꢁ), 128.3, 127.9 (2ꢁ), 127.5, 127.3 (2ꢁ), 127.2 (2ꢁ),
127.1, 125.9, 21.5.
4.3.28. 4-Fluoro-300,400-methylenedioxy-20-(toluene-4-sulfonyl)
[1,10;40,100]terphenyl (1ab). Yield¼76% (169 mg); White solid;
mp¼165e166 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C26H20FO4S 447.1066, found 447.1070; 1H
4.4.2. 1-[3-(Toluene-4-sulfonyl)biphenyl-4-yl]naphthalene (4b). Yield¼67%
(145 mg); White solid; mp¼135e136 ꢀC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C29H23O2S 435.1419,
NMR (400 MHz, CDCl3):
d
8.55 (d, J¼2.0 Hz, 1H), 7.71 (dd, J¼2.0,
found 435.1421; 1H NMR (400 MHz, CDCl3):
d
8.81 (d, J¼2.0 Hz, 1H),
8.0 Hz, 1H), 7.21 (d, J¼8.0 Hz, 1H), 7.19e7.15 (m, 4H), 7.03 (d,
7.87 (d, J¼8.0 Hz, 1H), 7.86 (d, J¼8.0 Hz, 1H), 7.80e7.77 (m, 2H), 7.75
(d, J¼8.0 Hz, 1H), 7.57e7.43 (m, 5H), 7.34 (d, J¼8.0 Hz,
1H), 7.33e7.29 (m, 1H), 7.00 (dt, J¼1.2, 6.8 Hz, 1H), 6.89 (d, J¼8.0 Hz,
2H), 6.74 (d, J¼8.0 Hz, 1H), 6.56 (d, J¼8.0 Hz, 2H), 2.04 (s, 3H); 13C
J¼8.0 Hz, 2H), 7.00e6.88 (m, 5H), 6.05 (s, 2H), 2.34 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d
162.5 (d, J¼245.6 Hz), 148.5, 148.0, 143.6, 140.7,
140.5, 139.2, 137.9, 133.8 (d, J¼3.8 Hz), 133.2, 133.1, 131.9, 131.8,
130.7, 129.0 (2ꢁ), 127.7 (2ꢁ), 126.7, 121.0, 114.2 (d, J¼21.2 Hz, 2ꢁ),
108.9, 107.5, 101.4, 21.5; Anal. Calcd for C26H19FO4S: C, 69.94; H,
4.29. Found: C, 70.12; H, 4.51.
NMR (100 MHz, CDCl3):
d 143.0, 141.7, 141.1, 139.0, 138.3,
136.0, 134.3, 133.9, 133.0, 131.9, 130.7, 129.4, 129.1 (2ꢁ), 128.5 (2ꢁ),
128.4, 128.3, 127.7, 127.6 (2ꢁ), 127.2 (2ꢁ), 126.8, 125.5 (2ꢁ), 125.1,
124.6, 21.1.
4.3.29. 300,400-Methylenedioxy-3,4-methylenedioxy-20-(toluene-4-
sulfonyl)[1,10;40,100]terphenyl (1ac). Yield¼75% (177 mg); White
solid; mp¼170e171 ꢀC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C27H21O6S 473.1059, found 473.1062;
4.4.3. 9-[3-(Toluene-4-sulfonyl)biphenyl-4-yl]anthracene (4c). Yield¼60%
(145 mg); White solid; mp¼220e221 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C33H25O2S
1H NMR (400 MHz, CDCl3):
d
8.54 (d, J¼2.0 Hz, 1H), 7.69 (dd,
485.1575, found 485.1572; 1H NMR (400 MHz, CDCl3):
d 8.38 (s, 1H),
J¼2.0, 8.0 Hz, 1H), 7.25e7.16 (m, 5H), 7.06 (d, J¼8.4 Hz, 2H), 6.94
(dd, J¼1.6, 7.2 Hz, 1H), 6.67 (d, J¼8.0 Hz, 1H), 6.49 (dd, J¼2.0,
8.0 Hz, 1H), 6.38 (d, J¼1.6 Hz, 1H), 6.05 (s, 2H), 5.97 (s, 2H), 2.35 (s,
8.19 (d, J¼2.0 Hz,1H), 8.07 (dd, J¼2.0, 8.0 Hz,1H), 8.01e7.99 (m, 2H),
7.95 (d, J¼8.4 Hz, 2H), 7.54e7.28 (m, 10H), 6.94e6.81 (m, 4H), 2.47
(s, 3H).
3H); 13C NMR (100 MHz, CDCl3):
d 148.5, 147.9, 147.1, 146.7, 143.5,
140.7, 140.5, 139.8, 138.0, 133.2, 131.5, 130.6, 128.9 (2ꢁ), 127.8
(2ꢁ), 126.6, 123.9, 121.0, 114.3, 110.6, 108.8, 107.5, 107.2, 101.4,
101.0, 21.5.
4.4.4. 2-[3-(Toluene-4-sulfonyl)biphenyl-4-yl]furan (4d). Yield¼79%
(148 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C23H19O3S
375.1055, found 375.1056; 1H NMR (400 MHz, CDCl3):
d 8.62 (d,
J¼2.0 Hz,1H), 7.83 (dd, J¼2.0, 8.0 Hz,1H), 7.70e7.67 (m, 2H), 7.61 (d,
J¼8.0 Hz, 1H), 7.54e7.48 (m, 4H), 7.45e7.41 (m, 1H), 7.38 (dd, J¼0.8,
2.0 Hz, 1H), 7.16 (d, J¼8.0 Hz, 2H), 6.88 (dd, J¼0.8, 3.6 Hz, 1H), 6.45
(dd, J¼2.0, 3.6 Hz, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3):
4.3.30. 4-Dimethylamino-300,400-methylenedioxy-20-(toluene-4-
sulfonyl)[1,10;40,100]terphenyl (1ad). Yield¼72% (169 mg); White
solid; mp¼163e164 ꢀC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C28H26NO4S 472.1583, found 472.1588;
d
148.9, 143.7, 142.9, 141.3, 139.3, 138.7, 137.8, 132.2, 131.1, 129.4,
1H NMR (400 MHz, CDCl3):
d
8.54 (d, J¼2.0 Hz, 1H), 7.68 (dd, J¼2.0,
129.2 (2ꢁ), 129.1 (2ꢁ), 128.4, 128.1, 127.7 (2ꢁ), 127.2 (2ꢁ), 113.1,
8.0 Hz, 1H), 7.22 (d, J¼8.0 Hz, 1H), 7.19e7.15 (m, 4H), 6.98 (d,
111.4, 21.5.
J¼8.0 Hz, 2H), 6.94e6.89 (m, 3H), 6.58 (d, J¼8.0 Hz, 2H), 6.04 (s, 2H),
2.99 (s, 3H), 2.32 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
148.4 (2ꢁ),
4.4.5. 2-[3-(Toluene-4-sulfonyl)biphenyl-4-yl]thiophene (4e). Yield¼82%
(160 mg); White solid; mp¼171e172 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C23H19O2S2
147.7, 143.0, 142.0, 140.6, 139.7, 138.1 (2ꢁ), 133.6, 133.5, 130.9 (2ꢁ),
130.6, 128.8 (2ꢁ), 127.8 (2ꢁ), 126.6, 120.9, 111.3 (2ꢁ), 108.8, 107.5,
101.4, 40.6 (2ꢁ), 21.5.
391.0827, found 391.0832; 1H NMR (400 MHz, CDCl3):
d 8.69
(d, J¼2.0 Hz, 1H), 7.78 (dd, J¼2.0, 8.0 Hz, 1H), 7.77e7.69 (m,
2H), 7.54e7.50 (m, 2H), 7.45e7.41 (m, 2H), 7.29e7.25 (m, 3H), 7.22
(dd, J¼1.2, 3.6 Hz, 1H), 7.05 (d, J¼8.0 Hz, 2H), 7.02 (dd, J¼3.6,
4.4. A representative synthetic procedure of compounds 4aeg
is as follows
5.2 Hz, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 143.5,
Sodium hydride (NaH, 60% in oil, 80 mg, 2.0 mmol) was added
to a solution of compound 3a (136 mg, 0.5 mmol) in THF (8 mL).
A solution of compounds 2fek (0.5 mmol) or compound 2l
(47 mg, 0.25 mmol) in the THF (2 mL) was added to the reaction
mixture at rt. The reaction mixture was stirred at reflux for 3 h.
The reaction mixture was cooled to rt. Water (1 mL) was added
to the reaction mixture at 0 ꢀC. The solvent was concentrated
under reduced pressure. The residue was diluted with water
(10 mL) and the mixture was extracted with EtOAc (3ꢁ20 mL).
The combined organic layers were washed with brine, dried,
141.4, 141.3, 138.8, 137.4, 137.3, 134.5, 132.9, 130.9, 130.8, 129.1
(2ꢁ), 129.0 (2ꢁ), 128.4, 127.7 (2ꢁ), 127.5, 127.2 (2ꢁ), 127.0,
126.6, 21.5.
4.4.6. 2-[3-(Toluene-4-sulfonyl)biphenyl-4-yl]quinoline (4f). Yield¼62%
(135 mg); White solid; mp¼245e246 ꢀC (recrystallized from hexanes
and EtOAc); HRMS (ESI, Mþþ1) calcd for C28H22NO2S 436.1371, found
436.1377; 1H NMR (400 MHz, CDCl3):
1H), 7.93 (d, J¼8.4 Hz, 1H), 7.89 (dd, J¼2.0, 8.0 Hz, 1H), 7.56e7.69 (m,
5H), 7.64e7.60 (m, 1H), 7.54e7.43 (m, 2H), 7.51 (d, J¼8.0 Hz, 2H), 7.28 (d,
d
8.58 (br s, 1H), 8.26 (d, J¼8.0 Hz,

M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
7923
J¼8.0 Hz, 2H), 6.92 (d, J¼8.4 Hz, 2H), 2.23 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
7.87 (d, J¼8.8 Hz, 2H), 7.82 (d, J¼2.0 Hz, 1H), 7.77 (dd,
CDCl3):
d
157.1, 153.45, 151.1, 143.8, 140.4, 139.0, 138.1, 135.7, 132.3, 131.5,
J¼2.0, 8.0 Hz, 1H), 7.33e7.31 (m, 3H), 7.24e7.19 (m, 2H), 7.13e7.09
129.2 (2ꢁ), 129.1 (2ꢁ), 128.4, 127.8 (2ꢁ), 127.7 (2ꢁ), 127.6 (2ꢁ), 127.3
(m, 2H), 2.41 (s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3):
(2ꢁ), 127.2, 127.1, 123.8, 114.3, 21.4.
d
162.3 (d, J¼245.6 Hz), 145.8, 144.1, 140.7, 138.8, 137.1, 136.0 (d,
J¼3.8 Hz), 130.6, 130.5, 130.4, 129.9 (2ꢁ), 129.1, 127.7 (2ꢁ), 124.9,
115.4 (d, J¼21.2 Hz, 2ꢁ), 21.6, 20.5.
4.4.7. 20-(Toluene-4-sulfonyl)[1,40;10,100;400,1000;4000,10000]quinquephenyl
(4g). Yield¼58% (155 mg); White solid; mp¼225e226 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C37H29O2S 537.1888, found 537.1886; 1H NMR (400 MHz,
4.5.4. 30,40-Methylenedioxy-2-methyl-4-(toluene-4-sulfonyl)biphenyl
(5d). Yield¼69% (126 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C21H19O4S 367.1004, found 341.1015; 1H NMR (200 MHz, CDCl3):
CDCl3):
d
8.69 (d, J¼2.0 Hz, 1H), 7.83 (dd, J¼2.0, 8.0 Hz, 1H),
7.76e7.68 (m, 8H), 7.55e7.37 (m, 7H), 7.33 (d, J¼8.0 Hz, 1H),
7.46e7.42 (m, 1H), 7.20 (d, J¼8.4 Hz, 2H), 7.12 (d, J¼8.4 Hz, 2H),
7.00 (d, J¼8.0 Hz, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
7.88 (d, J¼8.4 Hz, 2H), 7.81 (d, J¼2.0 Hz,1H), 7.76 (dd, J¼2.0, 8.0 Hz,
1H), 7.33 (d, J¼8.4 Hz, 2H), 7.22 (d, J¼8.0 Hz,1H), 7.00e6.88 (m, 3H),
6.02 (s, 2H), 2.39 (s, 3H), 2.30 (s, 3H).
d
143.5, 140.9, 140.6, 140.5, 140.4, 140.3, 140.0, 139.6, 139.0, 137.9,
137.1, 133.1, 131.1, 130.6 (2ꢁ), 129.1 (2ꢁ), 128.9 (2ꢁ), 128.8 (2ꢁ),
128.3, 127.9 (2ꢁ), 127.6 (2ꢁ), 127.5, 127.4 (2ꢁ), 127.2 (2ꢁ), 127.1
(2ꢁ), 127.0, 125.8 (2ꢁ), 21.6.
4.5.5. 40-Dimethylamino-2-methyl-4-(toluene-4-sulfonyl)biphenyl
(5e). Yield¼64% (117 mg); White solid; mp¼241e242 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C22H24NO2S 366.1528, found 366.1531; 1H NMR (400 MHz, CDCl3):
4.5. A representative synthetic procedure of compounds 5aee
is as follows
d
7.86 (d, J¼8.4 Hz, 1H), 7.79 (d, J¼2.0 Hz, 1H), 7.74 (dd, J¼2.0, 8.0 Hz,
1H), 7.33e7.30 (m, 4H), 7.17 (d, J¼8.8 Hz, 2H), 6.78 (br d, J¼8.0 Hz,
2H), 3.00 (s, 6H), 2.40 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz,
Sodium hydride (NaH, 60% in oil, 80 mg, 2.0 mmol) was added to
a solution of compound 3g (105 mg, 0.5 mmol) in THF (8 mL). A
solution of compounds 2aee (0.5 mmol) in the THF (2 mL) was
added to the reaction mixture at rt. The reaction mixture was
stirred at reflux for 3 h. The reaction mixture was cooled to rt.
Water (1 mL) was added to the reaction mixture at 0 ꢀC. The solvent
was concentrated under reduced pressure. The residue was
diluted with water (10 mL) and the mixture was extracted with
EtOAc (3ꢁ20 mL). The combined organic layers were washed with
brine, dried, filtered, and evaporated to afford crude product. Pu-
rification on silica gel (hexanes/EtOAc¼10/1w6/1) afforded com-
pounds 5aee.
CDCl3):
d
147.0, 143.9, 139.4, 139.1, 136.9 (2ꢁ), 130.6, 129.9 (2ꢁ),
129.8 (2ꢁ), 129.1, 127.6 (2ꢁ), 124.9 (2ꢁ), 112.0 (2ꢁ), 40.5 (2ꢁ), 21.5,
20.8; Anal. Calcd for C22H23NO2S: C, 72.30; H, 6.34; N, 3.83. Found:
C, 72.49; H, 6.51; N, 3.98.
4.6. A representative synthetic procedure of compounds 6aei
is as follows
A freshly prepared Na(Hg) (100 mg) was added to a solution of
compounds 1x, 1ac, 4b, 4def, and 5aec (0.3 mmol) in anhydrous
MeOH (10 mL) at rt. After 5 min, the reaction mixture was stirred at
reflux for 2 h, then cooled to rt. Saturated NaHCO3(aq) (2 mL) was
added to the reaction mixture and the solvent was evaporated
under reduced pressure. The residue was extracted with DCM
(3ꢁ30 mL). The combined organic layers were washed with brine,
dried, filtered, and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc¼200/1w60/1) afforded compounds
6aei.
4.5.1. 2-Methyl-4-(toluene-4-sulfonyl)biphenyl (5a). Yield¼78% (126 mg);
White solid; mp¼98e99 ꢀC (recrystallized from hexanes and
EtOAc); HRMS (ESI, Mþþ1) calcd for C20H19O2S 323.1106, found
323.1108; 1H NMR (400 MHz, CDCl3):
d
7.88 (d, J¼8.4 Hz, 2H), 7.82
(d, J¼2.0 Hz, 1H), 7.78 (dd, J¼2.0, 8.0 Hz, 1H), 7.44e7.37 (m, 3H), 7.33
(d, J¼8.4 Hz, 2H), 7.26e7.23 (m, 3H), 2.41 (s, 3H), 2.29 (s, 3H); 13C
NMR (100 MHz, CDCl3):
d
146.8, 144.1, 140.4, 140.1, 138.9, 137.0,
4.6.1. 2-Methylbiphenyl (6a).13a Yield¼84% (42 mg); HRMS
(ESI, Mþþ1) calcd for C13H13 169.1017, found 169.1022; 1H NMR
130.6, 129.9 (2ꢁ), 129.1, 128.7 (2ꢁ), 128.3 (2ꢁ), 127.7 (2ꢁ), 127.6, 124.9,
21.6, 20.6.
(400 MHz, CDCl3):
d
7.59 (d, J¼8.0 Hz, 2H), 7.51 (d, J¼8.0 Hz,
2H), 7.46e7.41 (m, 2H), 7.36e7.31 (m, 1H), 7.28e7.24 (m, 2H), 2.41
(s, 3H).
4.5.2. 40-Methoxy-2-methyl-4-(toluene-4-sulfonyl)biphenyl
(5b). Yield¼70% (123 mg); White solid; mp¼165e166 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1)
calcd for C21H21O3S 353.1212, found 353.1213; 1H NMR
4.6.2. 40-Methoxy-2-methylbiphenyl (6b).13b Yield¼78% (46 mg);
HRMS (ESI, Mþþ1) calcd for C14H15O 199.1123, found 199.1126; 1H
(400 MHz, CDCl3):
d
7.86 (d, J¼8.4 Hz, 2H), 7.80 (d, J¼2.0 Hz, 1H),
NMR (400 MHz, CDCl3):
d
7.53 (d, J¼8.8 Hz, 2H), 7.47 (d, J¼8.8 Hz,
7.76 (dd, J¼2.0, 8.0 Hz, 1H), 7.23e7.30 (m, 3H), 7.18 (d, J¼8.8 Hz,
2H), 6.95 (d, J¼8.8 Hz, 2H), 3.85 (s, 3H), 2.41 (s, 3H), 2.30 (s, 3H);
2H), 7.25 (d, J¼8.8 Hz, 2H), 6.99 (d, J¼8.8 Hz, 2H), 3.86 (s, 3H), 2.41
(s, 3H); 13C NMR (100 MHz, CDCl3):
d
158.9, 137.9, 136.3, 130.2, 129.4
13C NMR (100 MHz, CDCl3):
d
159.2, 146.5, 144.0, 140.1, 138.9,
(2ꢁ), 127.9 (2ꢁ), 126.6 (2ꢁ), 114.1 (2ꢁ), 55.3, 21.0.
137.1, 132.4, 130.7, 130.0 (2ꢁ), 129.9 (2ꢁ), 129.1, 127.7 (2ꢁ),
124.9, 113.7 (2ꢁ), 55.3, 21.6, 20.7; Anal. Calcd for C21H20O3S: C,
71.56; H, 5.72. Found: C, 71.81; H, 5.92. Single-crystal X-ray
diagram: crystal of compound 5b was grown by slow diffusion
of EtOAc into a solution of compound 5b in CH2Cl2 to yield
colorless prisms. The compound crystallizes in the triclinic
4.6.3. 40-Methoxy-2-methylbiphenyl (6c).13c Yield¼88% (49 mg);
HRMS (ESI, Mþþ1) calcd for C13H12F 187.0923, found 187.0924; 1H
NMR (400 MHz, CDCl3):
d
7.56e7.51 (m, 2H), 7.45 (d, J¼8.0 Hz, 2H),
7.27e7.24 (m, 2H), 7.14e7.08 (m, 2H), 2.40 (s, 3H).
crystal system, space group Pꢂ1, a¼8.5706(9) A, b¼9.9688(12) A,
4.6.4. 4-Fluoro-300,400-methylenedioxy[1,10;40,100]terphenyl
(6d). Yield¼72% (63 mg); White solid; mp¼171e172 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C19H14FO2 293.0978, found 293.0979; 1H NMR (400 MHz, CDCl3):
ꢀ
ꢀ
c¼11.1452(12) A, V¼879.52(17) A , Z¼2, dcalcd¼1.331 g/cm3,
3
ꢀ
ꢀ
F(000)¼372,
2
q
range 1.94e26.45ꢀ,
R
indices (all data)
R1¼0.0579, wR2¼0.1608.
d
7.61e7.56 (m, 6H), 7.18e7.10 (m, 4H), 6.91 (d, J¼8.8 Hz, 1H), 6.02
4.5.3. 40-Fluoro-2-methyl-4-(toluene-4-sulfonyl)biphenyl
(5c). Yield¼62% (105 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C20H18FO2S 341.1012, found 341.1015; 1H NMR (400 MHz,
(s, 2H); 13C NMR (100 MHz, CDCl3):
d
162.5 (d, J¼244.9 Hz), 148.2,
147.2, 139.8, 138.8, 136.8, 134.9, 128.5 (d, J¼8.4 Hz, 2ꢁ), 127.3 (2ꢁ),
127.2 (2ꢁ), 120.5, 115.7 (d, J¼21.2 Hz, 2ꢁ), 108.6, 107.5, 101.2;

7924
M.-Y. Chang et al. / Tetrahedron 69 (2013) 7916e7924
Anal. Calcd for C19H13FO2: C, 78.07; H, 4.48. Found: C, 78.31;
H, 4.62.
Supplementary data
Scanned photocopies of 1H and 13C NMR spectral data were
supported. Supplementary data associated with this article can
be found in the online version, at http://dx.doi.org/10.1016/
j.tet.2013.07.023.
4.6.5. 3,4-Methylenedioxy-300,400-methylenedioxy[1,10; 40,100]terphenyl
(6e). Yield¼70% (67 mg); White solid; mp¼240e241 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C20H15O4 319.0970, found 319.0977; 1H NMR (400 MHz, CDCl3):
d
7.56 (s, 4H), 7.11 (s, 2H), 7.10 (dd, J¼1.6, 7.2 Hz, 2H), 6.89 (dd, J¼1.6,
References and notes
7.2 Hz, 2H), 6.01 (s, 4H); 13C NMR (100 MHz, CDCl3):
d
148.2 (2ꢁ),
1. (a) Liu, J.-K. Chem. Rev. 2006, 106, 2209; (b) Guo, H.; Hu, H.; Liu, S.; Liu, X.; Zhou, Y.;
Che, Y. J. Nat. Prod. 2007, 70, 1519; (c) 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.
2. (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.
3. (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) Lin, J. M.; Gowda, A. S. P.; Sharma,
A. K.; Amin, S. Bioorg. Med. Chem. 2012, 20, 3202.
4. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b) Jana, R.; Pathak, T. P.;
Sigman, M. S. Chem. Rev. 2011, 111, 1417; (c) Heravi, M. M.; Hashemi, E. Tetra-
hedron 2012, 68, 9145; (d) Miguez, J. M. A.; Sousa-Pedrares, L. A. A.; Vila, J. M.;
Hii, K. K. J. Org. Chem. 2007, 72, 7771; (e) Taylor, R. H.; Felpin, F.-X. Org. Lett.
2007, 9, 2911.
5. (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) Mitchell, P. S. R.; Sengul, I.
F.; Kandemir, H.; Nugent, S. J.; Chen, R.; Bowyer, P. K.; Kumar, N.; Black, D. S.
Tetrahedron 2012, 68, 8163; (g) Kikuchi, H.; Matsuo, Y.; Katou, Y.; Kubohara, Y.;
Oshima, Y. Tetrahedron 2012, 68, 8884; (h) Dohi, T.; Kamitanaka, T.; Watanabe, S.;
Hu, Y.; Washimi, N.; Kita, Y. Chem.dEur. J. 2012, 18, 13614.
6. (a) Miyamae, T.; Hashizume, H.; Ogawa, T.; Okayama, T.; Nukui, E.; Oshima, K.;
Morikawa, T.; Hagiwara, M. Arzneim.-Forsch. 1997, 47, 13; (b) Chakraborty, S.;
Sengupta, C.; Roy, K. Bioorg. Med. Chem. Lett. 2004, 14, 4665; (c) Pinto, D. J. P.;
Batt, D. G.; Pitts, W. J.; Petraitis, J. J.; Orwat, M. J.; Wang, S.; Jetter, J. W.; Sherk, S. R.;
Houghton, G. C.; Copeland, R. A.; Covington, M. B.; Trzaskos, J. M.; Magolda, R. L.
Bioorg. Med. Chem. Lett. 1999, 9, 919.
147.1 (2ꢁ), 139.5 (2ꢁ), 135.1 (2ꢁ), 127.2 (4ꢁ), 120.2 (2ꢁ), 108.6 (2ꢁ),
107.5 (2ꢁ), 101.2 (2ꢁ); Anal. Calcd for C20H14O4: C, 75.46; H, 4.43.
Found: C, 75.92; H, 4.71. Single-crystal X-ray diagram: crystal of
compound 6e was grown by slow diffusion of EtOAc into a solution
of compound 6e in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the orthorhombic crystal system, space group Pbca,
3
ꢀ
ꢀ
ꢀ
ꢀ
a¼8.6151(5) A, b¼7.8419(4) A, c¼21.2292(11) A, V¼1434.22(13) A ,
Z¼4, dcalcd¼1.474 g/cm3, F(000)¼664, 2
q
range 1.92e26.36ꢀ, R in-
dices (all data) R1¼0.0437, wR2¼0.0814.
4.6.6. 2-Biphenyl-4-yl-furan (6f).13d Yield¼73% (48 mg); HRMS
(ESI, Mþþ1) calcd for C16H13O 221.0966, found 221.0968; 1H NMR
(400 MHz, CDCl3): d 7.78e7.76 (m, 2H), 7.66e7.63 (m, 4H), 7.51 (dd,
J¼0.8, 2.0 Hz, 1H), 7.49e7.45 (m, 2H), 7.39e7.35 (m, 1H), 6.71 (dd,
J¼0.8, 3.6 Hz, 1H), 6.51 (dd, J¼2.0, 3.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3):
d
151.7, 142.1, 140.6, 140.0, 128.8 (2ꢁ), 127.3 (4ꢁ), 126.9 (2ꢁ),
124.2 (2ꢁ), 111.7, 105.1.
4.6.7. 2-Biphenyl-4-yl-thiophene (6g).13e Yield¼83% (59 mg);
HRMS (ESI, Mþþ1) calcd for C16H13S 237.0738, found 237.0735; 1H
NMR (400 MHz, CDCl3):
d 7.73e7.69 (m, 2H), 7.65e7.62 (m, 4H),
7.49e7.45 (m, 2H), 7.40e7.35 (m, 2H), 7.31 (dd, J¼1.2, 5.2 Hz, 1H),
7.12 (dd, J¼3.6, 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 144.0,
140.5, 140.2, 133.4, 128.8 (2ꢁ), 128.1, 127.5 (2ꢁ), 127.4, 126.9 (2ꢁ),
126.3 (2ꢁ), 124.9, 123.1.
4.6.8. 1-Biphenyl-4-yl-naphthalene (6h).13f Yield¼74% (62 mg);
HRMS (ESI, Mþþ1) calcd for C22H17 281.1330, found 281.1335; 1H
7. Zhang, L.; Liang, F.; Cheng, X.; Liu, Q. J. Org. Chem. 2009, 74, 899 and references
cited therein.
8. (a) Brandange, S.; Leijonmarck, H. Chem. Commun. 2004, 292; (b) Yu, T.-Q.; Fu, Y.;
Liu, L.; Guo, Q.-X. J. Org. Chem. 2006, 71, 6157; (c) Magomedov, N. A.; Ruggiero,
P. L.; Tang, Y. Org. Lett. 2004, 6, 3373.
NMR (400 MHz, CDCl3):
d
8.02 (dq, J¼0.8, 8.4 Hz, 1H), 7.95 (dd,
J¼0.8, 8.4 Hz, 1H), 7.91 (d, J¼8.4 Hz, 1H), 7.77e7.71 (m, 4H),
7.63e7.39 (m, 9H); 13C NMR (100 MHz, CDCl3):
d
140.8, 140.1, 139.8,
139.7, 133.8, 131.6, 130.5 (2ꢁ), 128.8 (2ꢁ), 128.3, 127.7, 127.4, 127.1
(2ꢁ), 127.0 (2ꢁ), 126.9, 126.1, 126.0, 125.8, 125.4.
9. (a) Tietze, L. F. Chem. Rev. 1996, 96, 115; (b) Parsons, P. J.; Penkett, C. S.; Shell, A. J.
Chem. Rev. 1996, 96, 195; (c) Wasilke, J. C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C.
Chem. Rev. 2005, 105, 1001; (d) Posner, G. H. Chem. Rev. 1986, 86, 831; (e) Bunce,
R. A. Tetrahedron 1995, 48, 13103.
10. Chang, M.-Y.; Wu, M.-H.; Chen, Y.-L. Org. Lett. 2013, 15, 2822.
11. CCDC 936691 (1b), 936541 (1h), 936536 (5b), and 943826 (6e) 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: þ44 1223 336033; e-mail: de-
posit@ccdc.cam.ac.uk).
12. (a) Mesganaw, T.; Im, G.-Y. J.; Garg, N. K. J. Org. Chem. 2013, 78, 3391; (b)
Crousse, B.; Maladenova, M.; Ducept, P.; Alami, M.; Linstrumelle, G. Tetrahedron
1999, 55, 4353; (c) Mitsudo, T.-A.; Fischetti, W.; Heck, R. F. J. Org. Chem. 1984, 49,
1640.
13. (a) Qiu, Y.; Liu, Y.; Yang, K.; Hong, W.; Jiang, S.; Yao, Z.; Wang, Z.; Li, Z. Org. Lett.
2011, 13, 3556; (b) Mao, S.-L.; Sun, Y.; Yu, G.-A.; Zhao, C.; Yuan, J.; Zhu, X.; Liu, S.-H.;
Han, Z.-J.; Yang, Q. Org. Biomol. Chem. 2012, 9410; (c) Wang, Z.-Y.; Chen, G.-Q.;
Shao, L.-X. J. Org. Chem. 2012, 77, 6608; (d) Haner, J.; Jack, K.; Nagireddy, J.;
Raheem, M. A.; Durham, R.; Tam, W. Synthesis 2011, 731; (e) Hotta, S.
J. Heterocycl. Chem. 2001, 38, 923; (f) Lima, C. F. R. A. C.; Rodriguez-Borges, J. E.;
Santos, L. M. N. B. F. Tetrahedron 2011, 67, 689; (g) Berman, A. M.; Bergman, R. G.;
Ellman, J. A. J. Org. Chem. 2010, 75, 7863.
4.6.9. 2-Biphenyl-4-yl-quinoline (6i).13g Yield¼73% (62 mg); HRMS
(ESI, Mþþ1) calcd for C21H16N 282.1283, found 282.1287; 1H NMR
(400 MHz, CDCl3):
d
8.27 (d, J¼8.4 Hz, 2H), 8.24 (d, J¼8.8 Hz, 1H),
8.20 (d, J¼8.4 Hz, 1H), 7.93 (d, J¼8.4 Hz, 1H), 7.84 (d, J¼8.0 Hz, 1H),
7.78 (d, J¼8.0 Hz, 2H), 7.75e7.68 (m, 3H), 7.56e7.47 (m, 3H),
7.41e7.37 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 156.9, 148.3, 142.1,
140.6, 138.5, 136.8, 129.7, 129.6, 128.8 (2ꢁ), 128.0 (2ꢁ), 127.6 (2ꢁ),
127.5 (2ꢁ), 127.4, 127.2, 127.1, 126.3, 118.9.
Acknowledgements
The authors would like to thank the National Science Council of
the Republic of China for its financial support (NSC 102-2113-M-
037-005-MY2).