Facile and controllable synthesis of multiply substituted benzenes via a formal [3+3] cycloaddition approach

Article abstract of DOI:10.1016/j.tet.2012.10.028

A facile direct [3+3] approach for the conversion of α,β- unsaturated carbonyls to multi-substituted benzenes using allylic phosphonium ylide reagents has been developed. The substituents and their positions on the benzene ring are controllable and predictable by the choice of an appropriate combination of α,β-unsaturated carbonyl compounds and ylides.

Full text of DOI:10.1016/j.tet.2012.10.028

Tetrahedron 69 (2013) 284e292
Contents lists available at SciVerse ScienceDirect
Tetrahedron
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Facile and controllable synthesis of multiply substituted benzenes
via a formal [3þ3] cycloaddition approach
Zhen-Cao Shu, Jian-Bo Zhu, Saihu Liao, Xiu-Li Sun, Yong Tang
*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, 345 Lingling Lu, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 August 2012
Received in revised form 21 September 2012
Accepted 9 October 2012
Available online 16 October 2012
A facile direct [3þ3] approach for the conversion of
a,b-unsaturated carbonyls to multi-substituted
benzenes using allylic phosphonium ylide reagents has been developed. The substituents and their
positions on the benzene ring are controllable and predictable by the choice of an appropriate combi-
nation of
a,
b
-unsaturated carbonyl compounds and ylides.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Multi-substituted benzenes
a,b-Unsaturated ketones
Formal [3þ3] cycloaddition
Aromatization
1. Introduction
2. Results and discussion
Multiply substituted benzenes are important building blocks in
organic synthesis, and also the key structures of many natural
products, bioactive molecules, and functional materials.1 Modifi-
cation of benzenes and ring synthesis are the two major approaches
accessing multi-substituted benzene derivatives. Conventionally,
aromatic substitution and coupling are widely employed methods
to modify benzenes, but they require the pre-introduction of po-
sitioning or directing groups to achieve a precise installation.2 Al-
though a number of methods, such as transition metal-catalyzed
[2þ2þ2] and [4þ2] approaches have been reported for the con-
struction of substituted benzenes, the control of both the sub-
stituents and their positions on the benzene ring at will remains
quite a challenging task.3e7 In the past decade, we focused on the
development of ylide-initiated Michael addition-cyclization re-
actions (YIMACs) and their relevant synthetic applications.8,9 Very
During the course of the reaction optimization of enone 1a with
phosphonium salt 2a in our previous study,11 when DBU was
employed as the base and air was introduced, besides the antici-
pated cyclohexadiene compound 4a, cycloaromatization product
3a was also obtained in 23% yield, which was supposed to form via
a conjugate addition/intramolecular Wittig reaction/aromatization
reaction sequence (Table 1, entry 1). We thus envisioned that this
tandem reaction might be a potential facile approach for the con-
struction of multi-substituted benzenes from a,b-unsaturated car-
bonyl compounds. To improve the yield of benzene product 3a, we
first examined the effect of solvent and base. As shown in Table 1,
toluene, 1,2-dichloroethane (DCE), t-BuOH, and THF afforded high
total yields of 3a and 4a, but the aerial oxidation of cyclohexadiene
was sluggish (entries 1e4), giving low 3a/4a ratios. In contrast,
acetone and ethyl acetate gave better ratios, but the total yields
were only moderate (entries 5e6). To our delight, acetonitrile was
found to be fairly efficient for this transformation, affording 3a in
86% isolated yield, and no cyclohexadiene was detected by 1H NMR
analysis (entry 7). Consequently, acetonitrile was employed as the
solvent for the investigation of base effect. Organic bases like
DABCO, DMAP, and DIPEA gave poor 3a-selectivity (entries 8e10).
Inorganic bases, such as NaOH and t-BuOK were inefficient in this
reaction (entries 11e12). K2CO3 provided a moderate selectivity for
3a over 4a (entry 13), whereas Cs2CO3 furnished complete con-
version of cyclohexadiene to benzene derivative, yet the yield of 3a
was lower in comparison with DBU (entry 7 vs 14).12 Moreover,
reaction at 60 ꢀC proved to be critical, as either elevating or
recently, we found that the reactions of a,b-unsaturated ketones
with crotonate-derived phosphonium ylides can yield multi-
substituted benzenes efficiently in a formal [3þ3]10 cycloaddition
manner. Remarkably, the substituents and their positions on the
benzene ring can be well controlled by the choice of enone and
ylide components. In this communication, we wish to report the
preliminary results.
* Corresponding author. Tel.: þ86 21 5492 5156; fax: þ86 21 5492 5078; e-mail
address: tangy@sioc.ac.cn (Y. Tang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.028

Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
285
Table 1
Solvent and base effect on the reaction of enone 1a with phosphonium salt 2a
Table 2
Syntheses of tri-substituted benzene derivativesa
Entry
1
Product/yield (%)b
Entry
11
Product/yield (%)b
Entrya
Base
Solvent
Yield [%] 3aþ4ab
3a/4ac
Yield [%] 3ab
1
2
3
4
5
6
7
8
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DABCO
DMAP
DIPEA
t-BuOK
NaOH
K2CO3
Cs2CO3
DBU
Toluene
DCE
t-BuOH
THF
88
92
95
84
67
60
86
72
88
96
<5
16
86
74
77
70
86
26/74
7/93
23
14
18
48
33
42
86
11
27
12
<5
11
39
74
77
70
86
19/81
35/65
49/51
38/62
>99/1
9/91
7/93
1/99
d
Acetone
EtOAc
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
2
3
12
13
9
10
11
12
13
14
15d
16e
17f
69/31
45/55
>99/1
>99/1
>99/1
>99/1
4
14
DBU
DBU
a
Scale: 0.25 mmol, 1a/2a/base¼1/1.8/3.4, 48 h.
Isolated yield.
5
15
b
c
d
e
f
Determined by 1H NMR.
At 80 ꢀC.
At 40 ꢀC.
1a/2a/base¼1/1.4/3.4.
6
16d
17d,e
18
lowering the temperature decreased the yield (entry 7 vs 15, 16).
The loading of the phosphonium salt 2a can be further reduced to
1.4 equiv without loss in yield (entry 17).13
7c
8
Having established the optimal reaction conditions, we next
examined a series of aryl and alkyl substituted
a,b-unsaturated
ketones. As revealed in Table 2, the reaction proceeded well with
a broad range of chalcone-type substrates, regardless of the elec-
tronic nature (entries 1e7) of the aryl group and the position of the
substituents (entries 8e9), providing the corresponding 2,4-diaryl
substituted benzoate products 3aei in high yields (entries 1e9).
Furyl, thiophenyl, and pyridyl all were well tolerated in this re-
action, which may provide potential application for materials sci-
ence (entries 10e13).1d Functionalities like ester, amide can also be
introduced into the multi-substituted benzene products by using
9
19
20
10
a
Scale: 0.25 mmol, 1/2/DBU¼1/1.4e1.8/3.4, 48 h.
b
c
the corresponding
14e15). Moreover, alkyl substituted
b
,
g
-unsaturated
a
-keto ester or amide (entries
-unsaturated ketones are
Isolated yield.
24 h.
a,b
d
e
72 h.
also suitable substrates (entries 16e17). On the other hand, varia-
tion on the ester group of the phosphonium 2 did not affect the
results (entries 18e20). It is worth noting that this [3þ3] annula-
tion reaction could be a direct and useful method for the trans-
formation of an enone linker in a molecule to a benzene ring as
exemplified by chalcone (see the scheme in Table 2).
Pure ylide was used.14
also accessible using this method (entries 9e12). Therefore, the [3þ3]
annulation reactions of -unsaturated carbonyl compounds with
a,b
crotonate-derived phosphoniumylides canprovide avarietyof di-, tri-,
tetra-, and penta-substituted benzenes, and notably the substituents
and their positions on the benzene ring can be controlled by the se-
lection of an appropriate combination of the substituted enones with
ylides.
To further examine the generality of this [3þ3] approach,
a,b-un-
saturated aldehyde, -substituted -unsaturated ketones, as well as
a
a,b
3-substituted crotonate-derived phosphonium salts were tested un-
der the standard conditions. As shown in Table 3, all these substrates
worked quite well, delivering the corresponding di-, tetra-, and penta-
substituted benzenes in good to high yields. Cinnamaldehyde reacted
with phosphonium salt 2a giving di-substituted benzene 5a (entry 1).
Reactions of a-substituted a,b-unsaturated ketones with phospho-
nium 2a afforded 1,2,3,4-tetra-substituted benzenes (6aec) in good
yields (entries 2e4). Accordingly, 1,2,4,6-tetra-substituted benzenes
Interestingly, when an additional carbonecarbon double bond is
present in the a,b-unsaturated ketone substrates (8a and 9a, Scheme
1), apart from the desired alkenylated benzene derivatives 10a and
12a, the corresponding double bond-saturated compounds 11a and
13a were also observed as a major product under the standard re-
action conditions. These results may suggest the existence of another
aromatization approach via proton transfer, which would compete
with the aromatization via the aerial oxidation and lead to product
11a and 13a. Thus, an inert reaction atmosphere and catalytic amount
of base should suppress the aerial oxidation and favor the proton
(6deg) can also be prepared through the reactions of
carbonyl compounds with -substituted phosphonium salts 2def
(entries 5e8). Notably, 1,2,3,4,6-penta-substituted benzenes 7aed are
a,b-unsaturated
a

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Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
Table 3
To examine the generality of the [3þ3] process involving the
Syntheses of multi-substituted benzene derivativesa
proton-transfer-promoted aromatization, more cinnamylidenea-
cetophenone and bisarylideneacetone substrates were prepared
and subjected to the optimized reaction conditions (N2 atmosphere
and DBU as the base). As revealed in Table 4, the reactions pro-
ceeded smoothly under the inert atmosphere, and various electron-
donating groups (e.g., eOMe, eMe) and electron-withdrawing
groups (e.g., eBr, eCl, eCF3) were well tolerated, providing ortho
(11aef) and para (13aed) alkylated benzoate in good to high yields
(Scheme 1 and Table 4).
Table 4
Syntheses of ethidened benzene derivativesa
Entry
1c
Product/yield (%)b
Entry
7d
Product/yield (%)b
2
3
8
Entry
1
Product/yield (%)b
Entry Product/yield (%)b
9d
5
4
10d
2
6c
3
4
7
8
5d
6d
11
12
a
Scale: 0.3 mmol, 8/2a/DBU¼1/1.2/1.4, 9/2a/DBU¼1/1.2/1.6, 48 h.
b
c
Isolated yield.
72 h.
a
Scale: 0.25 mmol, 1/2/DBU¼1/1.4e1.8/3.4, 48 h.
Isolated yield.
b
c
At ꢁ20 ꢀC.
d
As aforementioned, the a,b-unsaturated ketone substrates 8 and
1/2/DBU¼1/2.0/5.2.
9, which have two double bonds conjugating with the ketone
prevailed the proton-transfer-promoted aromatization. In light of
DBU favoring the proton-transfer-promoted aromatization process
(Table 1), we conceived that weaker bases like Cs2CO3 might favor
the oxidative aromatization process to afford alkenylated benzene
derivatives 10 and 12. Thus further optimization of reaction con-
ditions was performed. As shown in Table 5, the reactions pro-
ceeded well in air, and electron-donating group (eMe) and
electron-withdrawing groups (eCl) were well tolerated except for
product 10c, which accompanied with product 11e in similar yields.
A tandem reaction sequence as outlined in Scheme 2 was pro-
posed to explain the product formation. Nucleophilic attack of ylide
transfer path. Fortunately, through the careful choice of base, solvent,
and reaction atmosphere, both the alkenylated benzene derivatives
and phenylethyl substituted benzene derivatives can be obtained
separately in good yields (Scheme 1). To our knowledge, the trans-
formation of dienone substrates like 8a and 9a to alkylated benzenes
like 11a and 13a has not been reported before.
to
a
,b
-unsaturated ketone initiates the [3þ3] reaction sequence,
giving adduct I1, which is later converted to ylide I2 via proton
transfer. Intermediate I2 then undergo an intramolecular Wittig
reaction and the subsequent aerial oxidation, giving the desired
multi-substituted benzene derivatives 3. In fact, I2 (R1, R3¼Ph, R2,
R4¼H) can be intercepted by quenching the reaction in the early
stage with water to give compound I3, which was subsequently
brominated and then converted to its phosphonium salt. Sub-
sequent treatment with DBU under the standard reaction condi-
tions delivered compound 3b in 95% yield, identical to the result
obtained directly with chalcone 1b (entry 2, Table 2). The in-
terception of intermediate I2 and its transformation to 3b with high
yield well confirmed the proposed mechanism.
Scheme 1. Reaction of dienone substrates.

Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
287
Table 5
Syntheses of alkenylated benzene derivativesa
b
Entrya
1
Product/yield (%)
Entryc
4
Product/yield (%)
2
5e
6
Scheme 3. Synthesis of a bradykinin receptor b1 antagonist.
3d
3. Conclusion
A facile and controllable [3þ3] approach for the synthesis of di-,
tri-, tetra-, and, pent-substituted benzene derivatives has been
developed. A broad range of a,b-unsaturated carbonyl compounds
can be efficiently converted to multi-substituted benzenes through
the reaction with crotonate-derived phosphonium ylides. Both the
substituents and their positions on the benzene ring can be easily
controlled by choosing appropriate combination of the starting
a
Scale: 0.3 mmol, 8/2a/Cs2CO3¼1/1.2/2.4, CH3CN, 24 h.
Isolated yield.
Scale: 0.3 mmol, 9/2a/K2CO3¼1/1.2/1.6, DMSO, 48 h.
11e was isolated in 28% yield.
72 h.
b
c
d
e
materials. Widespread presence of a,b-unsaturated carbonyl moi-
ety, readily accessible ylide reagents, and the straightforward
transformation make this [3þ3] approach potentially useful in or-
ganic synthesis and materials science. A rational mechanism is
proposed and a key intermediate is intercepted. Relevant synthetic
applications of the current method are in progress.
4. Experimental section
4.1. General information and materials
All reactions were carried out under dry nitrogen atmosphere.
Acetonitrile was purified according to standard methods unless
otherwise noted. The phosphonium salt 2, enone 1 were prepared
according to literature procedures.16 NMR spectra were recorded on
a Varian Mercury-300 or a Varian Mercury-400 nuclear magnetic
resonance spectrometer. Chemical shifts are reported in parts per
million (ppm) down field from TMS, using residual CDCl3 as an
internal standard. The data is being reported as (s¼singlet,
d¼doublet, t¼triplet, m¼multiplet or unresolved, br¼broad signal,
coupling constant(s) in Hertz, integration).
4.2. Typical procedure for the synthesis of multi-substituted
benzenes
A mixture of unsaturated ketone 1a (60.7 mg, 0.25 mmol) and
phosphonium salt 2a (198.6 mg, 0.45 mmol) in CH3CN (2 mL) was
stirred for 5 min. Then DBU (127 mL) in CH3CN (0.5 mL) was added. The
reaction mixture was stirred at 60 ꢀC for 6 h and then air was
introduced with a balloon for another 42 h. After the reaction was
completed, the reaction mixture was filtered through a short silica gel
column and washed with DCM. The filtrate was concentrated under
reduced pressure and the residue was purified by flash chromatogra-
phy (PE/EtOAc, 60/1) to afford 3a as a colorless oil (69.3 mg, 86% yield).
Scheme 2. A proposed mechanism and the interception of reaction intermediates.
The potential synthetic application of the present reaction was
demonstrated in a short synthesis of 17, a potent bradykinin re-
ceptor b
1 antagonist.15 As described in Scheme 3, 15 was obtained
through the [3þ3] annulation of enone 14 with phosphonium salt
2a under the standard reaction conditions followed by bromination
with NBS/AIBN. Subsequent amination, hydrogenation, and acyla-
tion gave the target molecule 17 in 32.7% yield over five steps.
4.2.1. Methyl 400-chloro-[1,10:30,100-terphenyl]-40-carboxylate (3a).
Colorless oil. Yield: 63.5 mg (86%). 1H NMR (300 MHz, CDCl3):
d
7.95
(d, J¼8.1 Hz, 1H), 7.64e7.60 (m, 3H), 7.53e7.52 (m, 1H), 7.45e7.36 (m,

288
Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
5H), 7.27 (m, 2H), 3.68 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
168.2, 144.3, 142.1, 139.9, 139.5, 133.4, 130.8, 129.7, 129.4, 128.9,128.2,
128.1, 127.2, 126.0, 51.9; IR (KBr)
/cmꢁ1: 3030 (w), 2949 (w), 2341
(w),1726 (s),1603 (m),1477 (m),1433 (m),1289 (s),1257 (s),1100 (m),
1089 (m), 1009 (w), 832 (m), 759 (m); LRMS (EI): m/z (% relative in-
tensity): 322 (Mþ, 84.65), 291 (100); HRMS (EI): calcd for C20H15O2Cl:
322.0761, found: 322.0759.
(dd, J¼8.0, 1.6 Hz, 1H), 7.62 (d, J¼1.6 Hz, 1H), 7.44e7.35 (m, 5H), 3.68
(s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
168.4, 147.5, 146.1, 143.5,
141.5, 140.7, 130.9, 130.8, 129.8, 128.2(4), 128.1(7), 128.1, 127.6, 126.0,
124.2, 52.1; IR (KBr,
/cmꢁ1): 2923 (s), 2852 (m), 1725 (s), 1596 (m),
1517 (s), 1433 (m), 1292 (m), 1254 (m), 1104 (m), 836 (m), 752 (m),
699 (m); LRMS (EI): m/z (% relative intensity): 333 (Mþ,74.61), 302
(100); HRMS (EI): calcd for C20H15NO4: 333.1001, found: 333.0997.
d
d
n
n
4.2.2. Methyl [1,10:30,100-terphenyl]-40-carboxylate (3b). White solid.
4.2.8. Methyl 300-methyl-[1,10:30,100-terphenyl]-40-carboxylate (3h).
Yield: 67.5 mg (92%). 1H NMR (400 MHz, CDCl3):
d
7.93 (d, J¼8.0 Hz,
1H), 7.64e7.60 (m, 4H), 7.46e7.35 (m, 8H), 3.65 (s, 3H); 13C NMR
(100 MHz, CDCl3/TMS): 168.8, 144.1, 143.2, 141.4, 139.8, 130.6,
129.5, 129.3, 128.9, 128.3, 128.1, 128.0, 127.3, 127.2, 125.7, 51.9; IR
(KBr,
/cmꢁ1): 2924 (s), 1716 (s), 1599 (m), 1477 (m), 1443 (m), 1287
Colorless oil. Yield: 68.6 mg (88%).1H NMR (400 MHz, CDCl3):
d 8.06
(d, J¼8.4 Hz,1H), 7.66e7.62 (m, 3H), 7.48 (d, J¼1.6 Hz,1H), 7.45e7.42
d
(m, 2H), 7.38e7.36 (m, 1H), 7.28e7.22 (m, 3H), 7.13 (d, J¼7.6 Hz, 1H),
3.63 (s, 3H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 167.5,
n
144.2,143.6,141.5,139.6,135.3,130.7,129.5,129.4,128.9,128.7,128.4,
(m), 1250 (m), 1099 (m), 839 (w), 755 (m), 697 (m); LRMS (EI): m/z
(% relative intensity): 288 (Mþ, 65.86), 257 (100); HRMS (EI): calcd
for C20H16O2: 288.1150, found: 288.1154.
128.1,127.3,127.2,125.6,125.2, 51.8, 20.1; IR (KBr,
n
/cmꢁ1): 2950 (w),
1714 (s),1599 (m),1285 (s),1254 (s),1142 (m),1094 (s), 845 (m), 755
(s), 696 (m); LRMS (EI): m/z (% relative intensity): 302 (Mþ,55), 271
(100); HRMS (EI): calcd for C21H18O2: 302.1307, found: 302.1304.
4.2.3. Methyl 400-methoxy-[1,10:30,100-terphenyl]-40-carboxylate (3c).
Pale oil. Yield: 72.8 mg (93%). 1H NMR (400 MHz, CDCl3):
d
7.90 (d,
4.2.9. Methyl 200-methyl-[1,10:30,100-terphenyl]-40-carboxylate (3i).
J¼8.0 Hz, 1H), 7.64e7.58 (m, 4H), 7.47e7.38 (m, 3H), 7.30 (d,
Yellow oil. Yield: 64.3 mg (85%). 1H NMR (400 MHz, CDCl3):
J¼8.8 Hz, 2H), 6.97e6.94 (m, 2H), 3.86 (s, 3H), 3.69 (s, 3H); 13C NMR
d
7.91e7.88 (m, 1H), 7.63e7.59 (m, 4H), 7.43 (t, J¼7.2 Hz, 2H), 7.36 (t,
J¼7.2 Hz, 1H), 7.29 (t, J¼7.6 Hz, 1H), 7.18e7.14 (m, 3H), 3.66 (s, 3H),
2.39 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
168.9, 144.0, 143.2,
141.2,139.8,137.6,130.4,129.5,129.3,129.0,128.9,128.0,127.9,127.2,
125.6,125.5, 51.9, 21.4; IR (KBr,
/cmꢁ1): 2947 (w),1715 (s),1601 (m),
(100 MHz, CDCl3/TMS):
d 169.0, 159.0, 144.0, 142.8, 139.9, 133.7,
130.5, 129.6, 129.5, 129.3, 128.9, 128.0, 127.3, 125.4, 113.5, 55.2, 52.0;
d
IR (KBr)
n
/cmꢁ1: 2951 (s), 2924 (s), 2851 (m), 1720 (s), 1605 (m),
1514 (m), 1432 (m), 1379 (w), 1287 (m), 1246 (m), 1096 (m), 1028
(m), 832 (m), 758 (m), 697 (m); LRMS (EI): m/z (% relative in-
tensity): 318 (Mþ,100), 287 (70.21); HRMS (EI): calcd for C21H18O3:
318.1256, found: 318.1251.
n
1432 (m), 1286 (s), 1250 (s), 1100 (s), 1050 (w), 786 (m), 756 (s), 698
(s); LRMS (EI): m/z (% relative intensity): 302 (Mþ,85), 271 (100);
HRMS (EI): calcd for C21H18O2: 302.1307, found: 302.1311.
4.2.4. Methyl 4-methoxy-[1,10:30,100-terphenyl]-40-carboxylate (3d).
4.2.10. Methyl 3-(furan-2-yl)-[1,10-biphenyl]-4-carboxylate
White solid. Yield: 67.0 mg (84%). 1H NMR (400 MHz, CDCl3):
d
7.92
(3j). White solid. Yield: 51.7 mg (73%). 1H NMR (400 MHz,
(d, J¼8.0 Hz, 1H), 7.60e7.55 (m, 4H), 7.42e7.35 (m, 5H), 6.99 (d,
CDCl3):
d
7.82 (d, J¼2.0 Hz, 1H), 7.76 (dd, J¼8.0, 0.8 Hz, 1H),
J¼8.8 Hz, 2H), 3.85 (s, 3H), 3.65 (s, 3H); 13C NMR (100 MHz, CDCl3/
7.64e7.61 (m, 2H), 7.56 (dd, J¼8.0, 1.6 Hz, 1H), 7.512e7.506 (m, 1H),
TMS):
d 168.7, 159.8, 143.7, 143.3, 141.5, 132.1, 130.6, 129.0, 128.5,
7.49e7.44 (m, 2H), 7.41e7.37 (m, 1H), 6.63e6.62 (m, 1H), 6.51e6.49
128.3, 128.0, 127.2, 125.1, 114.3, 55.3, 51.8; IR (KBr)
n
/cmꢁ1: 2923 (s),
(m,1H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d
169.2,152.4,
143.9, 142.8. 139.7, 130.5, 130.0, 128.9, 128.6, 128.1, 127.2, 127.0,
126.2,111.5,108.2, 52.3; IR (KBr)
/cmꢁ1: 2954 (s), 2853 (s),1775(w),
1723 (s), 1602 (s), 1517 (m), 1431 (m), 1287 (s), 1249 (s), 1179 (m),
1099 (m), 827 (m), 760 (m), 692 (m); LRMS (EI): m/z (% relative
intensity): 318 (Mþ, 100), 278 (63.14); HRMS (EI): calcd for
C21H18O3: 318.1256, found: 318.1252.
n
1718 (s), 1594 (w), 1459 (m), 1372 (m), 1289 (s), 759 (m); LRMS (EI):
m/z (% relative intensity): 278 (Mþ, 100); HRMS (EI): calcd for
C18H14O3: 278.0943, found: 278.0948.
4.2.5. Methyl 4-methyl-[1,10:30,100-terphenyl]-40-carboxylate (3e).
White solid. Yield: 64.8 mg (86%). 1H NMR (400 MHz, CDCl3):
d
7.91 (d,
4.2.11. Methyl 5-(furan-2-yl)-[1,10-biphenyl]-2-carboxylate(3k).
J¼8.0 Hz, 1H), 7.61 (dd, J¼8.0, 1.6 Hz, 1H), 7.58 (d, J¼1.6 Hz, 1H),
Yellow oil. Yield: 58.7 mg (84%). 1H NMR (400 MHz, CDCl3):
d 7.89
7.54e7.52 (m, 2H), 7.43e7.34 (m, 5H), 7.25 (d, J¼8.0 Hz, 2H), 3.65 (s,
(d, J¼8.0 Hz, 1H), 7.70e7.66 (m, 2H), 7.50 (d, J¼1.2 Hz, 1H),
3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 168.7, 144.0, 143.2,
7.42e7.33 (m, 5H), 6.76 (d, J¼2.8 Hz, 1H), 6.49 (dd, J¼3.2, 2.0 Hz,
141.5, 138.0, 136.8, 130.6, 129.6, 129.3, 128.9, 128.3, 128.0, 127.2, 127.1,
1H), 3. 64 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 168.4, 152.7,
125.5, 51.9, 21.1; IR (KBr,
n
/cmꢁ1): 2923 (s), 2851 (m),1728 (s),1716 (s),
143.4, 143.0, 141.3, 133.4, 130.7, 128.8, 128.2, 128.0, 127.3, 125.9,
122.1, 111.9, 107.1, 51.9; IR (neat,
(m), 1433 (m), 1287 (s), 1251 (s), 1099 (s), 1010 (m), 761 (m), 738
(m), 699 (s); LRMS (EI): m/z (% relative intensity): 278 (Mþ, 100);
HRMS (EI): calcd for C18H14O3: 278.0943, found: 278.0942.
1456 (m),1434 (m),1288 (m),1251 (m),1102 (m), 810 (w), 762 (m), 700
(m); LRMS (EI): m/z (% relative intensity): 302 (Mþ, 92.62), 271 (100);
HRMS (EI): calcd for C21H18O2: 302.1307, found: 302.1304.
n
/cmꢁ1): 2950 (w), 1715 (s), 1609
4.2.6. Methyl 4-chloro-[1,10:30,100-terphenyl]-40-carboxylate (3f).
Colorless oil. Yield: 74.3 mg (92%). 1H NMR (400 MHz, CDCl3):
d
7.92
(d, J¼8.0 Hz, 1H), 7.59e7.54 (m, 4H), 7.44e7.33 (m, 7H), 3.65 (s, 3H);
13C NMR (100 MHz, CDCl3/TMS):
168.6, 143.4, 142.8, 141.2, 138.2,
134.3, 130.6,129.6,129.3,129.1,128.5,128.3,128.0,127.4,125.5, 51.9;
IR (KBr,
/cmꢁ1): 3028 (w), 2949 (w), 1721 (s), 1603 (m), 1495 (w),
4.2.12. Methyl 5-(thiophen-2-yl)-[1,10-biphenyl]-2-carboxylate (3l).
Yellow oil. Yield: 66.7 mg (90%). 1H NMR (400 MHz, CDCl3):
d
7.88
(d, J¼8.0 Hz, 1H), 7.65e7.60 (m, 2H), 7.42e7.33 (m, 7H), 7.11e7.09
(m, 1H), 3. 46 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
168.4,
143.6, 142.8, 141.2, 137.2, 130.8, 129.0, 128.3, 128.0, 127.4, 126.2,
124.4, 124.2, 51.9; IR (neat,
/cmꢁ1): 3027 (w), 2947 (w), 1724 (s),
d
d
n
1478 (m), 1433 (m), 1381 (m), 1285 (s), 1251 (s), 1189 (w), 1093 (s),
1045 (m), 1008 (m), 822 (s), 785 (m), 763 (s), 733 (m), 699 (s); LRMS
(EI): m/z (% relative intensity): 291 (100), 322 (Mþ,90.90); HRMS
(EI): calcd for C20H15O2Cl: 322.0761, found: 322.0757.
n
1600 (m), 1483 (w), 1432 (m), 1286 (s), 1252 (s), 1098 (s), 825 (m),
762 (m), 697 (s); LRMS (EI): m/z (% relative intensity): 294 (Mþ,
100); HRMS (EI): calcd for C18H14O2S: 294.0715, found: 294.0717.
4.2.7. Methyl 4-nitro-[1,10:30,100-terphenyl]-40-carboxylate (3g).
4.2.13. Methyl 40-methoxy-5-(pyridin-2-yl)-[1,10-biphenyl]-2-
White solid. Yield: 55.1 mg (65%). 1H NMR (400 MHz, CDCl3):
d
8.32
carboxylate (3m). White solid. Yield: 58.7 mg (87%). 1H NMR
(d, J¼9.2 Hz, 2H), 7.97 (d, J¼8.4 Hz, 1H), 7.80 (d, J¼8.4 Hz, 2H), 7.67
(400 MHz, CDCl3):
d 8.72e8.71 (m, 1H), 8.02e8.00 (m, 2H), 7.92 (d,

Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
289
J¼8.8 Hz, 1H), 7.79e7.77 (m, 2H), 7.33e7.26 (m, 3H), 6.95 (dd, J¼6.8,
J¼8.4 Hz, 2H), 7.27 (d, J¼8.4 Hz, 2H), 3.69 (s, 3H); 13C NMR (100 MHz,
2.0 Hz, 2H), 3. 86 (s, 3H), 3. 70 (s, 3H); 13C NMR (100 MHz, CDCl3/
CDCl3/TMS): d 168.2, 143.0, 142.3, 139.7, 138.4, 133.5, 132.1, 130.9,
TMS):
d
169.0, 159.0, 156.2, 149.8, 142.7, 141.9, 136.9, 133.6, 130.8,
129.7, 129.3, 129.2, 128.8, 128.2, 125.8, 122.6, 52.1; IR (KBr, n
/cmꢁ1):
130.4, 129.5, 129.3, 125.1, 122.8, 121.0, 113.5, 55.3, 52.0; IR (neat,
n
/
2949 (w), 2924 (w), 2850 (m),1726 (s),1603 (m),1477 (m),1434 (m),
1286 (s), 1256 (s), 1102 (m), 821 (m), 784 (m); LRMS (EI): m/z (%
relative intensity): 400 (Mþ, 75.09), 402 (100); HRMS (EI): calcd for
C20H14O2ClBr: 399.9866, found: 399.9863.
cmꢁ1): 2950 (w), 1719 (s), 1609 (m), 1585 (m), 1516 (s), 1433 (m),
1287 (s), 1246 (s), 1178 (m), 1102 (m), 834 (m), 773 (s), 742 (m);
LRMS (EI): m/z (% relative intensity): 319 (Mþ, 100); HRMS (EI):
calcd for C20H17NO3: 319.1208, found: 319.1211.
4.2.20. tert-Butyl
boxylate (3t). White solid, Yield: 98.3 mg (89%). 1H NMR (300 MHz,
CDCl3):
7.95 (d, J¼7.8 Hz, 1H), 7.61e7.56 (m, 3H), 7.49e7.46 (m,
4-bromo-400-chloro-[1,10:30,100-terphenyl]-40-car-
4.2.14. Dimethyl [1,10-biphenyl]-2,5-dicarboxylate (3n). Colorless
oil. Yield: 61.6 mg (87%). 1H NMR (400 MHz, CDCl3):
d
8.07e8.05 (m,
2H), 7.85 (d, J¼8.8 Hz, 2H), 7.42e7.32 (m, 5H), 3.94 (s, 3H), 3.66 (s,
3H); 13C NMR (100 MHz, CDCl3/TMS):
168.6, 166.2, 142.4, 140.2,
134.8, 132.4, 131.7, 129.7, 128.2(2), 128.2(1), 128.1, 127.7, 52.4, 52.2;
IR (KBr,
/cmꢁ1): 3016 (w), 2970 (m), 2950 (w), 1737 (s), 1434 (m),
d
3H), 7.38 (d, J¼8.4 Hz, 2H), 7.27 (d, J¼7.9 Hz, 2H), 4.14 (q, J¼7.2 Hz,
d
2H), 1.08 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 167.8,
142.9, 142.2, 139.8, 138.5, 133.4, 132.1, 130.8, 129.8, 129.7, 129.1,
n
128.8, 128.2, 125.8, 122.6, 61.0, 13.8; IR (KBr, n
/cmꢁ1): 2956 (w),
1366 (m), 1289 (w), 1232 (s), 1115 (m), 751 (m), 700 (m); LRMS (EI):
m/z (% relative intensity): 270 (Mþ, 64.28), 239 (100); HRMS (EI):
calcd for C16H14O4: 270.0892, found: 270.0891.
2925 (w), 1716 (s), 1603 (m), 1476 (m), 1378 (m), 1285 (s), 1269 (m),
1102 (m), 1090 (m), 821 (m), 784 (m); LRMS (EI): m/z (% relative
intensity): 416 (Mþ, 32.04), 43 (100); HRMS (EI): calcd for
C21H16O2ClBr: 414.0022, found: 414.0021.
4.2.15. Methyl 5-(diethylcarbamoyl)-[1,10-biphenyl]-2-carboxylate
(3o). White solid. Yield: 69.8 mg (90%). 1H NMR (400 MHz,
4.2.21. Methyl [1,10-biphenyl]-2-carboxylate (5a). Yellow oil. Yield:
CDCl3):
(q, J¼6.0 Hz, 2H), 3.27 (q, J¼6.8 Hz, 2H), 1.26 (br s, 3H), 1.13 (br s,
3H); 13C NMR (100 MHz, CDCl3/TMS):
170.0, 168.5, 142.7, 140.4,
140.0, 131.3, 130.0, 128.4, 128.2, 128.1, 127.5, 124.8, 52.0, 43.2, 39.3,
14.2, 12.8; IR (KBr,
/cmꢁ1): 2963 (w), 1732 (s), 1633 (s), 1434 (m),
d
7.85 (d, J¼8.0 Hz, 1H), 7.41e7.31 (m, 7H), 3.64 (s, 3H), 3.56
41.7 mg (53%). 1H NMR (400 MHz, CDCl3):
d
7.82 (dq, J¼8.0, 0.8 Hz,
1H), 7.52 (t, J¼7.6 Hz, 1H), 7.42e7.30 (m, 7H), 3.63 (s, 3H); 13C NMR
d
(100 MHz, CDCl3/TMS): d 169.1, 142.4, 141.3, 131.2, 130.8, 130.7,
129.7, 128.3, 128.0, 127.2, 127.1, 51.9; IR (KBr, n
/cmꢁ1): 2950 (s), 2925
n
(s), 2853 (m), 1723 (s), 1590 (w), 1476 (m), 1451 (m), 1430 (m), 1125
(s),1089 (s),1049 (s), 964 (w), 745 (m), 699 (m), 664 (m); LRMS (EI):
m/z (% relative intensity): 212 (Mþ, 67.32), 181 (100); HRMS (EI):
calcd for C14H12O2: 212.0837, found: 212.0831.
1283 (m), 1247 (m), 1109 (m), 954 (w), 821 (m), 696 (m); LRMS (EI):
m/z (% relative intensity): 310 (Mþ, 77.32), 239 (100); HRMS (EI):
calcd for C19H21NO3: 311.1521, found: 311.1526.
4.2.16. Methyl 5-methyl-[1,10-biphenyl]-2-carboxylate
4.2.22. 20-Ethyl 40-methyl [1,10:30,100-terphenyl]-20,40-dicarboxylate
(3p). Colorless oil. Yield: 55.5 mg (70%) and trace cyclohexadiene.
(6a). White solid. Yield: 68.5 mg (76%). 1H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CDCl3):
d
7.76 (d, J¼7.6 Hz, 1H), 7.38e7.28 (m, 5H),
7.24e7.17 (m, 2H), 3.61 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3/
TMS): 168.9, 142.8, 141.7, 141.6, 131.6, 130.1, 128.3, 127.9, 127.8, 127.7,
127.0, 51.7, 21.4; IR (KBr,
/cmꢁ1): 3026 (w), 2970 (w), 2949 (w), 1737
d
7.95 (d, J¼8.0 Hz, 1H), 7.45e7.35 (m, 9H), 7.29e7.25 (m, 2H), 3.74
(q, J¼7.2 Hz, 2H), 3.59 (s, 3H), 0.75 (t, J¼7.2 Hz, 3H); 13C NMR
d
(100 MHz, CDCl3/TMS): d 168.1, 167.8, 142.7, 140.2, 139.5, 138.5,
n
135.3, 130.4, 130.3, 128.8, 128.7, 128.4, 128.3, 128.0, 127.5, 60.9, 52.0,
(s),1434 (m),1366 (m),1286 (w),1229 (m),1217 (m), 966 (w), 763(m),
699 (m); LRMS (EI): m/z (% relative intensity): 226 (Mþ, 60.29), 195
(100); HRMS (EI): calcd for C15H14O2: 226.0994, found: 226.0996.
13.4; IR (KBr,
n
/cmꢁ1): 2951 (m), 2924 (m), 2844 (m), 1731 (s), 1588
(m), 1444 (m), 1302 (m), 1227 (s), 1143 (m), 1095 (m), 759 (m), 699
(m); LRMS (EI): m/z (% relative intensity): 360 (Mþ,38.66), 43 (100);
HRMS (EI): calcd for C23H20O4: 360.1362, found: 360.1359.
4.2.17. Methyl 3-pentyl-[1,10-biphenyl]-4-carboxylate (3q). White
solid. Yield: 53 mg (73%). 1H NMR (300 MHz, CDCl3):
d
7.95 (d,
4.2.23. Methyl 20-benzoyl-[1,10:30,100-terphenyl]-40-carboxylate (6b).
J¼5.7 Hz, 1H), 7.62 (d, J¼5.7 Hz, 2H), 7.49e7.33 (m, 5H), 3.91 (s, 3H),
Colorless oil. Yield: 55.5 mg (55%). 1H NMR (400 MHz, CDCl3):
d 8.00
3.02 (t, J¼4.8 Hz, 2H), 1.66e1.62 (m, 2H), 1.40e1.30 (m, 4H),
(d, J¼7.6 Hz, 1H), 7.50 (d, J¼8.4 Hz, 1H), 7.40e7.37 (d, J¼8.4 Hz, 2H),
0.93e0.88 (m, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 168.0, 145.5,
7.29e7.26 (m, 4H), 7.23e7.12 (m, 7H), 7.02 (br s, 1H), 6.89 (br s, 1H),
144.5, 140.2, 131.3, 129.7, 128.8, 128.1, 127.9, 127.2, 124.3, 51.9, 34.7,
3.57 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d
197.5, 168.2, 143.1,
140.3, 140.0, 139.2, 137.8 (4), 137.8 (2), 132.8, 130.9, 130.1, 129.1 (3),
129.1 (2), 129.1, 128.1, 127.9, 127.8, 127.3, 52.1; IR (neat,
/cmꢁ1):
32.0, 31.6, 22.6, 14.1; IR (neat,
n
/cmꢁ1): 2952 (w), 2925 (w), 1720 (s),
1607 (m), 1457 (m), 1433 (m), 1278 (m), 1247 (s), 1190 (m), 1150 (m),
1098 (s), 1081 (s), 756 (s), 696 (s); LRMS (EI): m/z (% relative in-
tensity): 251 (100), 282 (Mþ, 69.2); HRMS (EI): calcd for C19H22O2:
282.1620, found: 282.1622.
n
3059 (w), 2950 (w), 1729 (s), 1671 (s), 1583 (m), 1432 (m), 1299 (m),
1228 (s), 1161 (s), 941 (m), 757 (s), 734 (s), 698 (s); LRMS (EI): m/z (%
relative intensity): 392 (Mþ, 100); HRMS (EI): calcd for C27H20O3:
392.1412, found: 392.1407.
4.2.18. Methyl 4-bromo-400-chloro-[1,10:30,100-terphenyl]-40-carboxyl-
ate (3r). White solid. Yield: 85.3 mg (86%). 1H NMR (300 MHz,
4.2.24. Dimethyl 3-methyl-[1,10-biphenyl]-2,6-dicarboxylate
CDCl3):
d
7.95 (d, J¼8.1 Hz, 1H), 7.61e7.57 (m, 3H), 7.48 (d, J¼8.4 Hz,
(6c). Colorless oil, Yield 35.8 mg (53%). 1H NMR (400 MHz,
3H), 7.38 (d, J¼8.4 Hz, 2H), 7.27 (d, J¼8.4 Hz, 2H), 3.69 (s, 3H); 13C
CDCl3):
J¼8.0 Hz, 0.8 Hz, 1H), 7.22e7.20 (m, 2H), 3.56 (s, 3H), 3.47 (s, 3H),
2.40 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
169.2, 167.8, 140.1,
138.8, 138.5, 135.7, 130.6, 129.1, 128.9, 128.4, 127.6, 127.4, 51.9, 51.8,
19.8; IR (neat,
/cmꢁ1): 2950 (w), 1725 (s), 1593 (w), 1432 (m), 1305
d
7.83 (d, J¼8.0 Hz, 1H), 7.38e7.32 (m, 3H), 7.28 (dd,
NMR (100 MHz, CDCl3/TMS): d 168.2,143.0,142.3,139.7,138.4,133.5,
132.1, 130.9, 129.7, 129.3, 129.2, 128.8, 128.2, 125.8, 122.6, 52.1; IR
d
(KBr,
n
/cmꢁ1): 2949 (w), 2924 (w), 2850 (m),1726 (s),1603 (m),1477
(m), 1434 (m), 1286 (s), 1256 (s), 1102 (m), 821 (m), 784 (m); LRMS
(EI): m/z (% relative intensity): 400 (Mþ, 75.09), 402 (100); HRMS
(EI): calcd for C20H14O2ClBr: 399.9866, found: 399.9863.
n
(m), 1258 (s), 1209 (s), 1144 (m), 997 (m), 795 (m), 700 (s); LRMS
(EI): m/z (% relative intensity): 221 (93.53), 284 (Mþ, 100); HRMS
(EI): calcd for C17H16O4: 284.1049, found: 284.1052.
4.2.19. Ethyl 4-bromo-400-chloro-[1,10:30,100-terphenyl]-40-carboxylate
(3s). White solid. Yield: 92.3 mg (89%). 1H NMR (300 MHz, CDCl3):
4.2.25. Dimethyl [1,10:30,100-terphenyl]-20,50-dicarboxylate (6d).
d
7.95 (d, J¼8.1 Hz,1H), 7.61e7.57 (m, 3H), 7.49e7.46 (m, 3H), 7.38 (d,
White solid. Yield: 60.4 mg (68%). 1H NMR (400 MHz, CDCl3):
d 8.07

290
Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
(d, J¼1.2 Hz 2H), 7.42 (s, 10H), 3.94 (s, 3H), 3.41 (s, 3H); 13C NMR
CDCl3): 7.40e7.30 (m, 10H), 7.26 (s, 1H), 3.50 (s, 3H), 3.27 (s, 3H),
2.43 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
169.2, 168.9, 140.8,
139.8, 138.1, 138.0, 136.3, 133.5, 131.6, 130.6, 128.7, 128.3, 128.2, 127.8
(1), 127.8, 127.7, 51.8, 51.7, 19.7; IR (neat,
/cmꢁ1): 3058 (w), 2949
(w), 1726 (s), 1591 (w), 1496 (w), 1436 (m), 1295 (m), 1248 (m), 1214
(s), 1162 (m), 1113 (m), 1092 (m), 954 (w), 737 (m), 700 (s); LRMS
(EI): m/z (% relative intensity): 297 (100), 360 (Mþ, 99.44); HRMS
(EI): calcd for C23H20O4: 360.1362, found: 360.1364.
(100 MHz, CDCl3/TMS):
d
169.1,166.2,140.7,139.5,136.6,130.9,129.8,
d
128.4, 128.3, 127.9, 52.4, 51.9; IR (KBr, n
/cmꢁ1): 2951 (s), 2925, 1730
(s), 1460 (m), 1438 (m), 1342 (m), 1245 (s), 1124 (m), 1052 (m), 765
(m), 749 (m), 701 (m); LRMS (EI): m/z (% relative intensity): 346 (Mþ,
96.91), 315 (100); calcd for C22H18O4: 346.1205, found: 346.1201.
n
4.2.26. Dimethyl 3-methyl-[1,10-biphenyl]-2,5-dicarboxylate
(6e). White solid. Yield: 37.2 mg (54%). 1H NMR (400 MHz, CDCl3):
d
7.90 (s, 2H), 7.39e7.37 (m, 5H), 3.92 (s, 3H), 3.61 (s, 3H), 2.43 (s, 3H);
4.2.32. 20-Ethyl 40-methyl 50-methoxy-[1,10:30,100-terphenyl]-20,40-di-
13C NMR (100 MHz, CDCl3/TMS):
d
169.5, 166.4, 140.3, 139.8, 137.1,
carboxylate (7d). White solid. Yield: 52.6 mg (53%). 1H NMR
135.8,130.8,129.9,128.4,128.3,128.1,127.7, 52.3, 52.0,19.6; IR (KBr,
n
/
(400 MHz, CDCl3): d 7.41e7.33 (m, 10H), 6.92 (s, 1H), 3.91 (s, 3H),
cmꢁ1): 2951 (s), 2923 (s), 2850 (m),1726 (s),1575 (w),1437 (m),1329
(m),1268 (s),1242 (s),1123 (m),1080 (m), 991 (w), 903 (w), 764 (m),
701 (m); LRMS (EI): m/z (% relative intensity): 284 (Mþ, 86.64), 253
(100); HRMS (EI): calcd for C17H16O4: 284.1049, found: 284.1046.
3.72 (q, J¼7.2 Hz, 2H), 3.53 (s, 3H), 0.71 (t, J¼7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3/TMS):
d 168.1, 167.3, 156.1, 142.9, 140.2, 139.5,
137.4, 128.7, 128.3, 127.9, 127.8 (3), 127.7 (8), 126.9, 123.3, 111.4, 60.7,
56.1, 52.1, 13.3. IR (neat,
n
/cmꢁ1): 3058 (w), 2949 (w), 1726 (s), 1587
(m),1564 (m), 1497 (w),1461 (w), 1345 (m), 1294 (m), 1243 (s), 1221
(s), 1174 (m), 1127 (m), 1075 (s), 979 (s), 922 (w), 859 (w), 755 (m),
735 (m), 700 (s); LRMS (EI): m/z (% relative intensity): 313 (69.54),
390 (Mþ, 100); HRMS (EI): calcd for C24H22O5: 390.1467, found:
390.1460.
4.2.27. Methyl 50-(4-bromophenyl)-4-chloro-[1,10:30,100-terphenyl]-
20-carboxylate (6f). White solid, Yield: 79.3 mg (65%). 1H NMR
(400 MHz, CDCl3):
7.44e7.39 (m, 9H), 3.41 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
169.4, 141.3, 141.1, 140.1, 139.9, 138.7, 138.6, 133.9, 132.0, 131.9,
129.7, 128.8, 128.6, 128.4, 128.3, 127.8, 127.6, 127.1, 122.4, 51.9; IR
(neat,
/cmꢁ1): 2957 (m), 2924 (s), 2854 (m), 1729 (s), 1662 (w),
d 7.60e7.58 (m, 3H), 7.52e7.50 (m, 3H),
d
4.2.33. (E)-Methyl 3-styryl-[1,10-biphenyl]-4-carboxylate
n
(10a). White solid. Yield: 47.9 mg (55%). 1H NMR (400 MHz,
1603 (m), 1491 (s), 1406 (w), 1261 (s), 1213 (w), 1092 (s), 1008 (s),
892 (w), 810 (w), 770 (m), 730 (m), 701 (m); LRMS (EI): m/z (%
relative intensity): 241 (100), 476 (Mþ, 5.43); HRMS (EI): calcd for
C26H18O2ClBr: 476.0179, found: 476.0176.
CDCl3):
d
8.08 (d, J¼16.4 Hz, 1H), 8.00 (d, J¼8.0 Hz, 1H), 7.89 (s, 1H),
7.56e7.50 (m, 5H), 7.36 (t, J¼7.2 Hz, 2H), 7.28 (d, J¼8.0 Hz, 3H), 7.06
(d, J¼16.0 Hz, 1H), 3. 93 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3/TMS):
d 167.7, 144.9, 139.9, 138.1, 137.4, 137.0, 131.5, 131.3,
129.6, 128.6, 127.8, 127.7, 127.1, 126.9, 126.7, 125.6, 125.5, 52.1, 21.1;
4.2.28. Methyl 4-bromo-400-chloro-50-methoxy-[1,10:30,100-terphenyl]-
IR (neat,
n
/cmꢁ1): 2948 (w), 1713 (s), 1599 (m), 1432 (m), 1256 (s),
40-carboxylate (6g). White solid. Yield: 46.0 mg (43%). 1H NMR
1188 (m), 1083 (s), 961 (m), 814 (s), 780 (s), 749 (m), 692 (s); LRMS
(EI): m/z (% relative intensity): 328 (Mþ,100); HRMS (EI): calcd for
C23H20O2: 328.1463, found: 328.1460.
(300 MHz, CDCl3):
7.39e7.34 (m, 4H), 7.11 (d, J¼7.2 Hz, 2H), 3.94 (s, 3H), 3.67 (s, 3H);
13C NMR (100 MHz, CDCl3/TMS):
168.1, 157.0, 142.8, 140.5, 139.2,
138.3, 134.0, 132.0, 129.5, 128.8, 128.6, 122.4, 122.1, 120.6, 108.8,
56.2, 52.3; IR (neat,
/cmꢁ1): 2949 (w), 2848 (w), 1729 (s), 1602 (m),
d
7.58 (d, J¼8.4 Hz, 2H), 7.45 (d, J¼8.4 Hz, 2H),
d
4.2.34. (E)-Methyl 40-methyl-3-styryl-[1,10-biphenyl]-4-carboxylate
n
(10b). White solid. Yield: 47.9 mg (49%). 1H NMR (400 MHz,
1578 (w), 1557 (m), 1494 (s), 1457 (m), 1381 (m), 1264 (s), 1227 (m),
1151 (m), 1103 (s), 1027 (m), 1011 (s), 820 (s), 715 (m); LRMS (EI): m/
z (% relative intensity): 401 (93.08), 430 (Mþ, 75.98); HRMS (EI):
calcd for C21H16O3ClBr: 429.9971, found: 429.9973.
CDCl3):
d
8.08 (d, J¼16.4 Hz, 1H), 8.00 (d, J¼8.0 Hz, 1H), 7.89 (s, 1H),
7.56e7.50 (m, 5H), 7.36 (t, J¼7.2 Hz, 2H), 7.28 (d, J¼8.0 Hz, 3H), 7.06
(d, J¼16.0 Hz, 1H), 3. 93 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3/TMS):
d 167.7, 144.9, 139.9, 138.1, 137.4, 137.0, 131.5, 131.3,
129.6, 128.6, 127.8, 127.7, 127.1, 126.9, 126.7, 125.6, 125.5, 52.1, 21.1;
4.2.29. 20-Ethyl 40-methyl 50-phenyl-[1,10:30,100-terphenyl]-20,40-di-
IR (neat,
n
/cmꢁ1): 2948 (w), 1713 (s), 1599 (m), 1432 (m), 1256 (s),
carboxylate (7a). White solid, Yield: 66.8 mg (60%). 1H NMR
1188 (m), 1083 (s), 961 (m), 814 (s), 780 (s), 749 (m), 692 (s); LRMS
(EI): m/z (% relative intensity): 328 (Mþ,100); HRMS (EI): calcd for
C23H20O2: 328.1463, found: 328.1460.
(400 MHz, CDCl3):
d
7.46e7.34 (m, 16H), 3.78 (q, J¼7.2 Hz, 2H), 3.29
(s, 3H), 0.76 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d
168.8, 168.1, 140.8, 140.6, 139.6 (2), 139.6 (0), 138.3, 137.6, 133.2,
133.0, 130.3, 129.0, 128.4 (4), 128.4 (1), 128.3 (4), 128.3 (1), 127.9 (2),
4.2.35. (E)-Methyl 40-chloro-3-styryl-[1,10-biphenyl]-4-carboxylate
127.9 (0), 127.8 (7), 127.8, 60.9, 51.7, 13.4; IR (neat,
n
/cmꢁ1): 2924
(10c). Yellow oil. Yield: 37.9 mg (36%). 1H NMR (400 MHz, CDCl3):
(w), 1729 (s), 1587 (w), 1494 (m), 1444 (m), 1292 (m), 1243 (s), 1138
(m), 1106 (m), 1029 (w), 796 (m), 700 (s); LRMS (EI): m/z (% relative
intensity): 359 (100), 436 (Mþ, 86.49); HRMS (EI): calcd for
C29H24O4: 436.1675, found: 436.1674.
d
8.06 (d, J¼16.0 Hz, 1H), 8.01 (d, J¼8.0 Hz, 1H), 7.86 (d, J¼2.0 Hz,
1H), 7.59e7.56(m, 4H), 7.48 (dd, J¼8.4, 2.0 Hz, 1H), 7.46e7.43 (m,
2H), 7.37 (t, J¼7.2 Hz, 2H), 7.30e7.26 (m, 1H), 7.06 (d, J¼16.0 Hz, 1H),
3. 94 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 167.5, 143.6, 140.0,
138.4, 137.2, 134.3, 131.8, 131.5, 129.1, 128.7, 128.5, 128.0, 127.4, 127.3,
4.2.30. Methyl 40-benzoyl-50-phenyl-[1,10:30,100-terphenyl]-20-carbox-
126.9, 125.6, 125.5, 52.2; IR (neat,
n
/cmꢁ1): 2924 (w), 1714 (s), 1600
ylate (7b). White solid, Yield: 73.8 mg (55%). 1H NMR (400 MHz,
(w), 1282 (s), 1241 (s), 1085 (s), 962 (m), 823 (s), 782 (s), 750 (m),
691 (m); LRMS (EI): m/z (% relative intensity): 348 (Mþ,100); HRMS
(EI): calcd for C22H17ClO2: 348.0917, found: 348.0919.
CDCl3):
3.30 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
140.5,139.6,139.2,138.5,138.1,137.9,137.1,133.2,132.8,130.6,129.3,
d
7.53e7.48 (m, 5H), 7.46e7.29 (m, 7H), 7.25e6.96 (m, 9H),
d
197.6, 169.0, 141.3,
129.1, 128.5, 128.4, 128.2, 128.0, 127.9, 127.7, 127.6, 51.8; IR (neat,
n
/
4.2.36. (E)-Methyl 5-styryl-[1,10-biphenyl]-2-carboxylate
cmꢁ1): 3058 (w), 2948 (w), 1730 (s), 1671 (s), 1581 (m), 1446 (m),
1390 (m), 1241 (s), 1121 (s), 941 (m), 897 (m), 796 (w), 756 (s), 734
(s), 698 (s); LRMS (EI): m/z (% relative intensity): 105 (100), 468 (Mþ,
92.88); HRMS (EI): calcd for C33H24O3: 468.1725, found: 468.1729.
(12a). Yellow solid. Yield: 67.6 mg (71%). 1H NMR (400 MHz,
CDCl3):
d
7.87 (d, J¼8.0 Hz, 1H), 7.55e7.49 (m, 4H), 7.44e7.29 (m,
8H), 7.22 (d, J¼16.4 Hz, 1H), 7.13 (d, J¼16.4 Hz, 1H), 3. 64 (s, 3H); 13C
NMR (100 MHz, CDCl3/TMS): d 168.4, 143.2, 141.4, 140.2, 136.6, 131.1,
130.5, 129.1,128.8, 128.7, 128.2, 128.1, 127.9, 127.2, 127.2, 126.7,124.9,
51.8; IR (neat,
/cmꢁ1): 2948 (w), 1715 (s), 1599 (w), 1432 (m), 1282
(s), 1189 (w), 1096 (m), 959 (m), 763 (s), 696 (s); LRMS (EI): m/z (%
4.2.31. Dimethyl 50-methyl-[1,10:30,100-terphenyl]-20,40-dicarboxylate
n
(7c). White solid, Yield 58% (average for twice). 1H NMR (400 MHz,

Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
291
relative intensity): 314 (Mþ, 100); HRMS (EI): calcd for C22H18O2:
314.1307, found: 314.1303.
d 167.7, 144.5, 144.2, 142.0, 137.9, 137.1, 131.5, 129.8, 129.5, 128.6,
128.3, 127.6, 127.0, 125.8, 124.4, 51.9, 38.1, 37.1, 21.1; IR (neat, n/
cmꢁ1): 2948 (w), 1716 (s), 1604 (w), 1433 (m), 1248 (s), 1189 (w),
1084 (s), 815 (s), 781 (s), 748 (w), 699 (s); LRMS (EI): m/z (% rel-
ative intensity): 91 (100), 330 (Mþ, 69); HRMS (EI): calcd for
C23H22O2: 330.1620, found: 330.1618.
4.2.37. (E)-Methyl 40-methyl-5-(4-methylstyryl)-[1,10-biphenyl]-2-
carboxylate (12b). White solid. Yield: 63.2 mg (71%). 1H NMR
(400 MHz, CDCl3):
d
7.84 (d, J¼8.0 Hz, 1H), 7.50e7.46 (m, 2H), 7.40
(d, J¼8.0 Hz, 2H), 7.25e7.15 (m, 7H), 7.06 (d, J¼16.8 Hz, 1H), 3. 66 (s,
3H), 2.40 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
4.3.4. Methyl 40-bromo-3-phenethyl-[1,10-biphenyl]-4-carboxylate
d
168.6, 143.3, 140.4, 138.5, 138.2, 136.9, 133.9, 131.0, 130.5, 129.4,
(11d). White solid. Yield: 84.4 mg (71%). 1H NMR (400 MHz,
128.8, 128.7, 128.1, 126.6, 126.3, 124.7, 51.9, 21.3, 21.2; IR (neat,
n
/
CDCl3):
d
7.98 (d, J¼8.0 Hz, 1H), 7.55e7.53 (m, 2H), 7.40 (dd, J¼8.0,
cmꢁ1): 2947 (w), 1717 (s), 1597 (m), 1432 (m), 1280 (s), 1094 (m),
962 (m), 822 (s), 803 (s), 734 (m), 713 (m); LRMS (EI): m/z (% rel-
ative intensity): 342 (Mþ,100); HRMS (EI): calcd for C24H22O2:
342.1620, found: 342.1621.
2.0 Hz, 1H), 7.37e7.35 (m, 2H), 7.30e7.26 (m, 3H), 7.22e7.19 (m,
3H), 3.91 (s, 3H), 3.34e3.30 (m, 2H), 2.96e2.92 (m, 2H); 13C NMR
(100 MHz, CDCl3/TMS):
131.5, 129.8, 128.7, 128.6, 128.29, 128.26, 125.9, 124.4, 122.3, 52.0,
38.0, 37.0; IR (neat,
/cmꢁ1): 2932 (w), 1716 (s), 1604 (w), 1433 (w),
1282 (s), 1249 (m), 1084 (m), 1008 (m), 820 (s), 782 (s), 749 (m), 699
(s); LRMS (EI): m/z (% relative intensity): 91 (100), 394 (Mþ, 30), 396
(Mþ, 30); HRMS (EI): calcd for C22H19O2Br: 394.0568, found:
394.0570.
d 167.5, 144.3, 143.2, 141.7, 138.8, 131.9,
n
4.2.38. (E)-Methyl 40-chloro-5-(4-chlorostyryl)-[1,10-biphenyl]-2-
carboxylate (12c). White solid. Yield: 78.2 mg (68%). 1H NMR
(400 MHz, CDCl3):
d
7.89 (d, J¼8.4 Hz,1H), 7.53 (dd, J¼8.4, 2.0 Hz,1H),
7.45e7.32 (m, 7H), 7.27e7.25 (m, 2H), 7.16 (d, J¼16.4 Hz,1H), 7.08 (d,
J¼16.4 Hz,1H), 3. 68 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):
d 168.0,
142.3, 140.2, 139.8, 135.1, 133.9, 133.4, 130.9, 130.0, 129.6, 129.0 (2),
4.3.5. Methyl 40-chloro-3-phenethyl-[1,10-biphenyl]-4-carboxylate
128.9 (6), 128.8, 128.2, 127.9, 127.7, 125.3, 52.0; IR (neat,
n
/cmꢁ1):
(11e). White solid. Yield: 80% for the yields of two experiments
2949 (w),1717 (s),1597 (w),1489 (m),1260 (s),1012 (m), 831 (s), 809
(m), 735 (s); LRMS (EI): m/z (% relative intensity): 382 (Mþ,100);
HRMS (EI): calcd for C22H16O2Cl2: 382.0527, found: 382.0527.
on average. 1H NMR (400 MHz, CDCl3):
d
7.99 (d, J¼8.4 Hz, 1H),
7.45e7.38 (m, 5H), 7.31e7.27 (m, 3H), 7.23e7.20 (m, 3H), 3.92 (s,
3H), 3.34e3.30 (m, 2H), 2.96e2.92 (m, 2H); 13C NMR (100 MHz,
CDCl3/TMS):
129.0, 128.6, 128.4, 128.3, 128.2, 125.9, 124.5, 52.0, 38.1, 37.0; IR
(neat,
/cmꢁ1): 2951 (w), 1716 (s), 1604 (w), 1433 (w), 1247 (s), 1088
d 167.5, 144.3, 143.2, 141.8, 138.3, 134.1, 131.5, 129.9,
4.3. Procedure for the syntheses of 11 and 13
n
General procedure: A mixture of 8a (70.3 mg, 0.3 mmol) and 1a
(172.2 mg, 0.36 mmol) in DMSO (2.0 mL) was stirred under nitrogen
atmosphere for 5 min at room temperature. Then DBU (0.065 mL,
0.45 mmol), followed by DMSO (1 mL), was added and the resulting
mixture was heated to 80 ꢀC in N2 atmosphere. After the reaction
was complete, the mixture was filtered through a thin layer
(30 mm) of silica gel (100e200 mesh) and washed with DCM. The
filtrate was concentrated under reduced pressure and the residue
was purified by flash chromatography (PE/EtOAc¼60/1) to afford
11a (72.1 mg, 76%).
(s), 823 (m), 782 (m), 753 (w), 699 (m); LRMS (EI): m/z (% relative
intensity): 350 (Mþ, 36); HRMS (EI): calcd for C22H19O2Cl: 350.1074,
found: 350.1078.
4.3.6. Methyl 3-phenethyl-40-(trifluoromethyl)-[1,10-biphenyl]-4-
carboxylate (11f). Yellow oil. Yield: 79.6 mg (69%). 1H NMR
(400 MHz, CDCl3):
d
8.01 (d, J¼8.4 Hz, 1H), 7. 68 (d, J¼8.4 Hz, 2H), 7.
59 (d, J¼8.4 Hz, 2H), 7. 45 (dd, J¼8.4, 2.0 Hz, 1H), 7.31e7.27 (m, 3H),
7.23e7.21 (m, 3H), 3.93 (s, 3H), 3.36e3.32 (m, 2H), 2.98e2.94 (m,
2H); 13C NMR (100 MHz, CDCl3/TMS):
d
167.5, 144.3, 142.9, 141.7,
131.6, 130.3, 128.9, 128.7, 128.3 (4), 128.3 (3), 127.5 (3), 127.5 (1),
125.9, 125.7 (4), 125.7 (1), 124.8, 52.0, 38.0, 37.0; IR (neat,
/cmꢁ1):
4.3.1. Methyl 3-phenethyl-[1,10-biphenyl]-4-carboxylate
n
(11a). Colorless oil. Yield: 72.2 mg (76%). 1H NMR (300 MHz,
2951 (w), 1718 (s), 1606 (w), 1324 (s), 1250 (m), 1164 (m), 1122 (s),
1085 (s), 832 (m), 784 (m), 747 (w), 699 (m); LRMS (EI): m/z (%
relative intensity): 91 (100), 384 (Mþ, 19); HRMS (EI): calcd for
C23H19O2F3: 384.1337, found: 384.1339.
CDCl3):
3.36e3.30 (m, 2H), 2.98e2.92 (m, 2H); 13C NMR (100 MHz, CDCl3/
TMS): 167.6, 144.5, 144.2, 141.9, 139.9, 131.4, 130.0, 128.8, 128.6,
d
7.99 (d, J¼8.4 Hz, 1H), 7.54e7.22 (m, 12H), 3.91 (s, 3H),
d
128.3, 128.0, 127.9, 127.2, 125.8, 124.6, 51.9, 38.1, 37.1; IR (neat, n/
cmꢁ1): 2950 (w), 1706 (s), 1602 (m), 1436 (m), 1285 (m), 1249 (s),
1046 (s), 757 (s), 696 (s); LRMS (EI): m/z (% relative intensity): 316
(Mþ, 53); HRMS (EI): calcd for C22H20O2: 316.1463, found: 316.1465.
4.3.7. Methyl 5-phenethyl-[1,10-biphenyl]-2-carboxylate
(13a). Yellow oil. Yield: 79.6 mg (85%). 1H NMR (400 MHz,
CDCl3):
4H), 7.21e7. 14 (m, 5H), 3.62 (s, 3H), 3.00e3.92 (m, 4H); 13C NMR
(100 MHz, CDCl3/TMS): 168.9,145.4, 142.8, 141.5,141.1,131.0, 130.1,
128.4 (4), 128.3 (9), 128.3, 128.2, 127.9, 127.3, 127.1, 126.1, 51.8, 37.7,
37.5; IR (neat,
/cmꢁ1): 2947 (w), 1716 (s), 1603 (w), 1432 (m), 1281
d
7.77 (d, J¼8.4 Hz, 1H), 7.39e7.35 (m, 3H), 7.30e7.26 (m,
4.3.2. Methyl 40-methoxy-3-phenethyl-[1,10-biphenyl]-4-carboxylate
d
(11b). White solid. Yield: 75.3 mg (73%). 1H NMR (400 MHz,
CDCl3):
d
7.98 (d, J¼8.0 Hz, 1H), 7.48 (dd, J¼6.8, 2.0 Hz, 2H), 7.43 (dd,
n
J¼8.0, 2.0 Hz,1H), 7.33e7.20 (m, 6H), 6.97 (dd, J¼8.8, 2.0 Hz, 2H), 3.91
(s), 1249 (m), 1095 (m), 762 (w), 697 (s); LRMS (EI): m/z (% relative
intensity): 36 (Mþ, 100); HRMS (EI): calcd for C22H20O2: 316.1475,
found: 316.1463.
(s, 3H), 3.84 (s, 3H), 3.34e3.30 (m, 2H), 2.97e2.93 (m, 2H); 13C NMR
(100 MHz, CDCl3/TMS):
131.5,129.5,128.6, 128.2 (9), 128.2 (7),127.2, 125.8, 124.1,114.3, 55.3,
51.9, 38.1, 37.1; IR (neat,
/cmꢁ1): 2948 (w), 1714 (s), 1603 (w), 1433
d167.7,159.7,144.2 (4),144.1 (7),142.0,132.4,
n
4.3.8. Methyl 40-methoxy-5-(4-methoxyphenethyl)-[1,10-biphenyl]-
(w),1278 (m),1246 (s),1085 (m), 827 (m), 783 (m), 749 (w), 699 (m);
LRMS (EI): m/z (% relative intensity): 346 (Mþ,100); HRMS (EI): calcd
for C23H22O3: 346.1569, found: 346.1565.
2-carboxylate (13b). White solid. Yield: 77.8 mg (69%, 3 days). 1H
NMR (400 MHz, CDCl3):
d
7.73 (d, J¼8.0 Hz, 1H), 7.20 (dd, J¼6.8,
1.6 Hz, 2H), 7.15 (d, J¼8.4 Hz, 1H), 7.11 (d, J¼1.2 Hz, 1H), 7.06 (d,
J¼8.4 Hz, 2H), 6.92 (d, J¼8.8 Hz, 2H), 6.82 (d, J¼8.4 Hz, 2H), 3. 83 (s,
3H), 3. 77 (s, 3H), 3. 65 (s, 3H), 2.95e2.83 (m, 4H); 13C NMR
4.3.3. Methyl 40-methyl-3-phenethyl-[1,10-biphenyl]-4-carboxylate
(11c). White solid. Yield: 78.1 mg (78%). 1H NMR (400 MHz,
(100 MHz, CDCl3/TMS):
133.2, 131.1, 130.0, 129.4, 129.3, 128.1, 126.9, 113.7, 113.4, 55.2, 51.8,
37.9, 36.5; IR (neat,
/cmꢁ1): 2928 (w), 1717 (m), 1607 (m), 1511 (m),
1241 (s), 1176 (m), 1029 (s), 831 (m), 715 (m); LRMS (EI): m/z (%
d 169.1, 158.8, 157.9, 145.4, 142.2, 133.8,
CDCl3):
d
7.98 (d, J¼8.0 Hz, 1H), 7.47e7.43 (m, 3H), 7. 36 (d,
J¼1.6 Hz, 1H), 7.31e7.20 (m, 7H), 3.91 (s, 3H), 3.34e3.30 (m, 2H),
n
2.97e2.93 (m, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3/TMS):

292
Z.-C. Shu et al. / Tetrahedron 69 (2013) 284e292
relative intensity): 376 (Mþ, 29.3), 121 (100); HRMS (EI): calcd for
C24H24O4: 376.1675, found: 376.1674.
References and notes
1. (a) Astruc, D. Modern Arene Chemistry; Wiley-VCH: Weinheim, Germany, 2002;
(b) Nicolaou, K. C.; Boddy, C. N. C.; Brase, S.; Winssinger, N. Angew. Chem., Int. Ed.
€
4.3.9. Methyl 40-methyl-5-(4-methylphenethyl)-[1,10-biphenyl]-2-
1999, 38, 2096e2152; (c) Liu, J.-K. Chem. Rev. 2006, 106, 2209e2223; (d) Xiao,
L.-X.; Chen, Z.-J.; Qu, B.; Luo, J.-X.; Kong, S.; Gong, Q.-H. Adv. Mater. 2011, 23,
926e952.
2. (a) March, J. Advanced Organic Chemistry, 4th ed.; Wiley: New York, NY, 1992,
Chapter 11, pp 501e568; (b) Snieckus, V. Chem. Rev. 1990, 90, 879e933; (c)
Trost, B. M.; Fleming, I. Comprehensive Organic Synthesis; Pergamon: Oxford,
1991; Vol. 3e4; (d) Metal-catalyzed Cross-coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: New York, NY, 1998; (e) Ritleng, V.; Sirlin, C.;
Pfeffer, M. Chem. Rev. 2002, 102, 1731e1770.
carboxylate (13c). Yellow oil. Yield: 89.7 mg (87%). 1H NMR
(300 MHz, CDCl3):
(s, 3H), 2.94e2.90 (m, 4H), 2.39 (s, 3H), 2.32 (s, 3H); 13C NMR
(100 MHz, CDCl3/TMS): 168.9, 145.4, 142.7, 138.5, 138.1, 136.7,
135.4, 131.1, 130.0, 129.0, 128.6, 128.3, 128.2, 128.1, 127.0, 51.7, 37.8,
37.0, 21.1, 20.9; IR (neat,
/cmꢁ1): 2922 (w), 1717 (s), 1604 (m), 1432
d7.75 (d, J¼7.8 Hz, 1H), 7.18e7.06 (m, 10H), 3. 65
d
n
(m),1278 (s),1248 (s),1092 (m), 822 (s), 783 (s), 750 (m); LRMS (EI):
m/z (% relative intensity): 105 (100), 344 (Mþ, 25); HRMS (EI): calcd
for C24H24O2: 344.1776, found: 344.1775.
3. For reviews on the syntheses of substituted benzenes, see: (a) Grotjahn, D. B. In
Comprehensive Organometallic Chemistry II; Hegedus, S., Abel, E. W., Stone, F. G.
A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol. 12, pp 741e770; (b)
Bonnemann, H.; Brijoux, W. In Transition Metals for Organic Synthesis; Beller, M.,
Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 1, pp 171e197; (c) Saito, S.;
Yamamoto, Y. Chem. Rev. 2000, 100, 2901e2915; (d) Heller, B.; Hapke, M. Chem.
Soc. Rev. 2007, 36, 1085e1094.
4. For selected examples on the synthesis of benzene derivatives through
[2þ2þ2] cycloaddition, see: (a) Tsuji, H.; Yamagata, K. I.; Fujimoto, T.; Naka-
mura, E. J. Am. Chem. Soc. 2008, 130, 7792e7793; (b) Galan, B. R.; Rovis, T.
Angew. Chem., Int. Ed. 2009, 48, 2830e2834; (c) Qiu, Z.-Z.; Xie, Z.-W. Angew.
Chem., Int. Ed. 2009, 48, 5729e5732; (d) Kuninobu, Y.; Nishi, M.; Kawata, A.;
Takata, H.; Hanatani, Y.; Yudha, S. S.; Iwai, A.; Takai, K. J. Org. Chem. 2010, 75,
334e341.
4.3.10. Methyl
carboxylate (13d). White solid. Yield: 103.7 mg (90%). 1H NMR
(300 MHz, CDCl3):
7.79 (d, J¼8.1 Hz, 1H), 7.35 (d, J¼8.4 Hz, 2H),
7.24e7.16 (m, 5H), 7.04 (d, J¼8.7 Hz, 3H), 3.65 (s, 3H), 2.98e2.84 (m,
4H); 13C NMR (100 MHz, CDCl3/TMS):
168.3, 145.1, 141.7, 139.9,
139.3, 133.2, 131.8, 131.0, 130.4, 129.8, 129.6, 128.4, 128.1, 128.0,
127.6, 51.8, 37.4, 36.7; IR (neat,
/cmꢁ1): 2961 (w), 1720 (s), 1604
40-chloro-5-(4-chlorophenethyl)-[1,10-biphenyl]-2-
d
d
n
5. For selected examples on the synthesis of benzene derivatives through RCM
reaction, see: (a) Donohoe, T. J.; Orr, A. J.; Bingham, M. Angew. Chem., Int. Ed.
2006, 45, 2664e2670; (b) Van Otterlo, W. A. L.; Koning, C. B. Chem. Rev. 2009,
109, 3743e3782; (c) Yoshida, K.; Shida, H.; Takahashi, H.; Yanagisawa, A. Chem.
dEur. J. 2011, 17, 344e349.
(w), 1433 (w), 1259 (s), 1087 (s), 1013 (s), 799 (s), 736 (w), 709 (w);
LRMS (EI): m/z (% relative intensity): 125 (100), 384 (Mþ, 36); HRMS
(EI): calcd for C22H18O2Cl2: 384.0684, found: 384.0683.
6. For selected examples on the synthesis of benzene derivatives through intra-
molecular tandem reaction, see: (a) Zhao, J.; Hughes, C. O.; Toste, F. D. J. Am.
Chem. Soc. 2006, 128, 7436e7437; (b) Blond, G.; Bour, C.; Salem, B.; Suffert, J.
Org. Lett. 2008, 10, 1075e1078.
4.4. Synthesis of bradykinin receptor b1 antagonists (17)
To a solution of 1613 (170.5 mg, 0.43 mmol) in CH2Cl2 (1 mL) at
7. For selected recent other methods on the synthesis of benzenes, see: (a)
Neumann, H.; Von Wangelin, A. J.; Klaus, S.; Strubing, D.; Gordes, D.; Beller, M.
Angew. Chem., Int. Ed. 2003, 42, 4503e4507; (b) Takahashi, T.; Liu, Y.-H.; Iesato,
A.; Chaki, S.; Nakajima, K.; Kanno, K.-I. J. Am. Chem. Soc. 2005, 127,
11928e11929; (c) Serra, S.; Fuganti, C.; Brenna, E. Chem.dEur. J. 2007, 13,
6782e6791; (d) Quiclet-Sire, B.; Revol, G.; Zard, S. Z. Org. Lett. 2009, 11,
2832e2835; (e) Li, C.-K.; Zeng, Y.; Zhang, H.; Feng, J.-J.; Zhang, Y.; Wang, J.-B.
Angew. Chem., Int. Ed. 2010, 49, 6413e6417; (f) Engle, K. M.; Wang, D.-H.; Yu, J.-
Q. Angew. Chem., Int. Ed. 2010, 49, 6169e6173; (g) Li, G.-J.; Liu, Y.-H. J. Org. Chem.
2010, 75, 2903e2909.
8. (a) Sun, X.-L.; Tang, Y. Acc. Chem. Res. 2008, 41, 937e948; (b) Tang, Y.; Ye, S.; Sun,
X.-L. Synlett 2005, 2720e2730; (c) Deng, X.-M.; Cai, P.; Ye, S.; Sun, X.-L.; Liao,
W.-W.; Li, K.; Tang, Y.; Wu, Y.-D.; Dai, L.-X. J. Am. Chem. Soc. 2006, 128,
9730e9740; (d) Ye, L.-W.; Sun, X.-L.; Zhu, C.-Y.; Tang, Y. Org. Lett. 2006, 8,
3853e3856; (e) Ye, L.-W.; Sun, X.-L.; Wang, Q.-G.; Tang, Y. Angew. Chem., Int. Ed.
2007, 46, 5951e5954; (f) Wang, Q.-G.; Deng, X.-M.; Zhu, B.-H.; Ye, L.-W.; Sun,
X.-L.; Li, C.-Y.; Zhu, C.-Y.; Shen, Q.; Tang, Y. J. Am. Chem. Soc. 2008, 130,
5408e5409; (g) Zhu, C.-Y.; Cao, X.-Y.; Zhu, B.-H.; Deng, C.; Sun, X.-L.; Wang, B.-
Q.; Shen, Q.; Tang, Y. Chem.dEur. J. 2009, 15, 11465e11468.
9. For selected reviews on YIMAC reactions, see: (a) Li, A.-H.; Dai, L.-X.; Aggarwal,
V. K. Chem. Rev. 1997, 97, 2341e2372; (b) Aggarwal, V. K.; Winn, C. L. Acc. Chem.
Res. 2004, 37, 611e620; (c) Gaunt, M. J.; Johansson, C. C. Chem. Rev. 2007, 107,
5596e5605; (d) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.;
Aggarwal, V. K. Chem. Rev. 2007, 107, 5841e5883.
10. [3þ3] approaches to benzene derivatives (phenols): (a) Chan, T.-H.; Brown-
bridge, P. J. Am. Chem. Soc. 1980, 102, 3534e3538; (b) Feist, H.; Langer, P. Syn-
thesis 2007, 327e347 (review); (c) Izawa, Y.; Pun, D.; Stahl, S. S. Science 2011,
333, 209e213.
0
ꢀC was added butanoyl chloride (50
L, 0.48 mmol) and N,N-
diisopropylethylamine (90 L, 0.51 mmol). The resulting solution
m
m
was stirred for 2 h at room temperature, and partitioned between
ethyl acetate and water and extracted with ethyl acetate. The or-
ganic layer extract was concentrated under vacuum. Purification
was achieved by flash chromatography (PE/EtOAc¼2/1) to afford 17
(173.5 mg, 86%).
1H NMR (300 MHz, CDCl3):
d 8.04e8.00 (m, 3H), 7.82 (d,
J¼7.5 Hz, 1H), 7.74 (br s, 1H) 7.46 (d, J¼7.8 Hz, 1H), 7.34 (d, J¼7.7 Hz,
2H), 7.23 (d, J¼7.8 Hz, 2H), 6.59 (dd, J¼6.6, 5.1 Hz, 1H), 5.20 (br s,
1H), 4.63 (d, J¼5.1 Hz, 2H), 3.93 (s, 3H), 3.67 (s, 3H), 2.26 (t, J¼7.5 Hz,
2H), 1.67 (q, J¼7.5 Hz, 2H), 0.93 (t, J¼7.2, 3H); 13C NMR (100 MHz,
CDCl3/TMS):
d 172.8, 168.5, 166.1, 152.4, 144.5, 142.1, 139.1, 138.7,
134.4, 132.6, 132.4, 131.7, 129.7, 128.3, 128.0, 127.4, 118.9, 112.8, 52.4,
52.3, 45.1, 38.5, 19.0, 13.6; IR (neat,
n
/cmꢁ1): 3310 (w), 2962 (w),
2874 (w), 1725 (s), 1657 (m), 1586 (w), 1507 (m), 1458 (w), 1418 (m),
1289 (s), 1241 (s), 1115 (m), 1040 (w), 811 (w), 756 (m), 739 (m), 704
(w); LRMS (EI): m/z (% relative intensity): 390 (48.5), 460 (Mþ, 100);
calcd for C26H27N3O5: 461.1951, found: 461.1955.
Acknowledgements
11. (a) Ye, L.-W.; Han, X.; Sun, X.-L.; Tang, Y. Tetrahedron 2008, 64, 8149e8154; (b)
Ye, L.-W.; Wang, S.-B.; Wang, Q.-G.; Sun, X.-L.; Tang, Y.; Zhou, Y.-G. Chem.
Commun. 2009, 3092e3094.
12. DBU can assist the aerial oxidation of cylcohexadiene to benzene, see the
Supplementary data.
13. For details, see the Supplementary data.
14. 2a reacted with sodium hydroxide to generate the corresponding ylide. The
ylide was recrystallized and then reacted with 1q to provide 3q. For details see
the Supplementary data.
We are grateful for the financial support from the National
Natural Sciences Foundation of China (No. 20821002, 20932008,
and 20825205), the Major State Basic Research Development Pro-
gram (Grant No. 2009CB825300) and the Chinese Academy of
Sciences.
15. Kuduk, S.D.; Bock, M.G.; Feng, D.-M.; Wai, M.-C. U.S. Pat. Appl. 2004034064,
2004.
Supplementary data
16. (a) Wattanasin, S.; Murphy, W. S. Synthesis 1980, 647e650; (b) Baeckstrom, P.;
Jacobsson, U.; Norin, T.; Unelius, C. R. Tetrahedron 1988, 44, 2541e2548; (c)
Ishino, Y.; Mihara, M.; Nishihama, S.; Nishiguchi, I. Bull. Chem. Soc. Jpn. 1998, 71,
2669e2672; (d) Graden, H.; Hallberg, J.; Kann, N.; Olsson, T. J. Comb. Chem.
2004, 6, 783e788; (e) Sun, B.-F.; Hong, R.; Kang, Y.-B.; Li, D. J. Am. Chem. Soc.
2009, 131, 10384e10385.
Reaction optimization, procedures, data and copies of 1H and 13
NMR spectra for all new compounds. Supplementary data related to
thisarticle can befound athttp://dx.doi.org/10.1016/j.tet.2012.10.028.
C