Synthesis of functionalized 3,4-diarylbenzophenones and 2,4-diarylbenzophenones by site-selective Suzuki and Sonogashira cross-coupling reactions of bis(triflates) of 3,4- and 2,4-dihydroxybenzophenone

Article abstract of DOI:10.1055/s-0031-1289649

Palladium(0)-catalyzed Suzuki and Sonogashira cross-coupling reactions of the bis(triflates) of 2,4- and 3,4-dihydroxybenzophenone afforded 2,4- and 3,4-diarylbenzophenones, respectively. The reactions proceeded with very good site-selectivity in favor of

Full text of DOI:10.1055/s-0031-1289649

PAPER
219
Synthesis of Functionalized 3,4-Diarylbenzophenones and 2,4-Diarylbenzo-
phenones by Site-Selective Suzuki and Sonogashira Cross-Coupling Reactions
of Bis(triflates) of 3,4- and 2,4-Dihydroxybenzophenone
F
unctionalized 3,
a
4-Diaryl-
a
s
nd 2,4-D
i
h
a
rylbenzophe
e
nones ed Ahmed Khera,a,b,1 Muhammad Nawaz,a,c,1 Holger Feist,a Alexander Villinger,a Peter Langer*a,d
a
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
b
c
d
Department of Chemistry and Biochemistry, University of Agriculture, Faisalabad, Pakistan
Department of Chemistry, Comsats Institute of Information Technology, Campus Abbottabad, Abbottabad, Pakistan
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Received 9 June 2011; revised 9 November 2011
catalyzed cross-coupling reactions of polyhalogenated
heterocycles11 and of poly(triflates)12 of carbacyclic sub-
strates have been reported. We started a program directed
to the application of this strategy to the site-selective syn-
thesis of arylated benzophenones. Recently, we have
reported13 Suzuki–Miyauara reactions of the bis(triflate)
of 3,4-dihydroxybenzophenone. Herein, we report full de-
tails of these studies, a comprehensive study of the scope,
and an extension to the synthesis of alkynylated ben-
zophenones by Sonogashira reactions. In addition, we re-
port, for the first time, site-selective Suzuki–Miyaura and
Sonogashira reactions of the bis(triflate) of parent 2,4-di-
hydroxybenzophenone. All reactions proceed with excel-
lent site-selectivity in favor of position 4.
Abstract: Palladium(0)-catalyzed Suzuki and Sonogashira cross-
coupling reactions of the bis(triflates) of 2,4- and 3,4-dihydroxy-
benzophenone afforded 2,4- and 3,4-diarylbenzophenones, respec-
tively. The reactions proceeded with very good site-selectivity in
favor of position 4.
Key words: benzophenone, cross-coupling, palladium, site-selec-
tivity, Suzuki reaction, Sonogashira reaction
Aryl-substituted benzophenones have been widely used in
medicinal and agricultural chemistry and in material sci-
ences. They show cytotoxic and antimicrobial activity,
and enzyme inhibition.2 Benzoylfluorenones contain the
core structure of arylated benzophenones incorporated in
the fluorenone system; they have been also reported to
show interesting pharmacological properties.3 Naturally
occurring anthraquinones and tetracyclines are often very
complex ring systems containing a hidden 4-arylben-
zophenone unit.4 2-Hydroxy- and amino-substituted ben-
zophenones have been reported to act as antitubulin
agents and are, thus, interesting lead structures in the de-
velopment of anticancer agents.5 Benzophenones have
found applications as sun cremes because of their activi-
ties as photosensitizers and UV-filters. Several benzophe-
none derivatives show fluorescence or phosphorescence,
which allow useful applications in analytical chemistry.6
3,4-Dihydroxybenzophenone
Commercially available 3,4-dihydroxybenzophenone (1)
was transformed into its bis(triflate) 2 in 84% yield
(Scheme 1). 3,4-Diarylbenzophenones 3a–j were pre-
pared by Suzuki reaction of 2 with 2.6 equivalents of var-
ious aryl boronic acids (Scheme 2, Table 1). During the
optimization, it proved to be important to use Pd(PPh3)4 (6
mol%) as the catalyst and to use an excess (2.6 equiv) of
the arylboronic acid. 1,4-Dioxane was employed as the
solvent (reflux, 4 h) and K3PO4 as the base.
O
O
Benzophenones are available by Friedel–Crafts
acylations7 or by reaction of benzaldehydes with aromatic
organometallic reagents and subsequent oxidation of the
alcohol thus formed.8 In the case of functionalized sub-
strates, for example, containing a hydroxy, halide, or ester
group, these methods often give unsatisfactory results,
due to several side-reactions and low chemoselectivity. A
more chemoselective strategy relies on the SmI2-mediated
reaction of benzaldehydes with benzyl halides and subse-
quent oxidation.9 We reported the synthesis of 4-(2-hy-
droxybenzoyl)salicylates by cyclization of 1,3-
bis(silyloxy)buta-1,3-dienes with 3-formylchromones.10
In recent years, a number of site-selective palladium(0)-
OTf
OTf
OH
OH
i
1
2 (84%)
Scheme 1 Synthesis of 2. Reagents and conditions: i) 1 (1.0 equiv),
CH2Cl2, –78 °C, pyridine (4.0 equiv), Tf2O (2.4 equiv), –78 → 0 °C,
4 h.
O
O
OTf
OTf
Ar
Ar
ArB(OH)2
i
2
3a–j
Scheme 2 Synthesis of 3a–j. Reagents and conditions: i) 2 (1.0
equiv), ArB(OH)2 (2.6 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4 (6
mol%), 1,4-dioxane (5 mL per 1 mmol of 2), 110 °C, 4 h.
SYNTHESIS 2012, 44, 219–234
Advanced online publication: 15.12.2011
DOI: 10.1055/s-0031-1289649; Art ID: N60011SS
x
x
.x
x
.2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

220
R. A. Khera et al.
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Table 1 Synthesis of 3a–j
Table 2 Synthesis of 4a–e and 5a–d
3
a
b
c
d
e
f
Ar
Yield (%)a
4
5
a
Ar1
Ar2
Yield (%)a Yield (%)a
4a–e
5a–d
Ph
78
69
75
74
67
54
76
58
78
68
a
b
c
3-MeOC6H4
2,5-(MeO)2C6H3
4-MeC6H5
4-(CH2=CH)C6H4 68
72
68
4-FC6H4
b
–
3,5-Me2C6H3
3,5-(MeO)2C6H3
2-MeOC6H4
4-MeOC6H4
2-EtOC6H4
3,4-Me2C6H3
4-EtC6H4
2-ClC6H4
b
c
4-(CH2=CH)C6H4 64
78
64
62
d
3,4,5-(MeO)3C6H2 4-(CH2=CH)C6H4 76
4-t-BuC6H4 4-(CH2=CH)C6H4 70
e
d
a Yields of isolated products.
g
h
i
b Reaction was not carried out.
O
2
1
OTf
3
H
A
H
j
6'
1'
2'
OMe
OMe
6
4
a Yields of isolated products.
5
B
H
OMe
The palladium-catalyzed Suzuki reaction of 2 with boron-
ic acids (1.3 equiv) resulted in site-selective attack at
carbon atom C-4 to give 4-aryl-3-(trifluoromethylsulfon-
yloxy)benzophenones 4a–e (Scheme 3, Table 2). In the
reactions, Pd(PPh3)4 (3 mol%) was used as the catalyst.
The pure mono-coupled product had to be purified from
bis-coupled products by chromatography. 3,4-Diarylben-
zophenone 5a–d, containing two different aryl groups,
were prepared by reaction of 4a–e with (4-vinylphen-
yl)boronic acid (1.3 equiv).
Figure 1 Relevant NOESY correlations for compound 4d
The first attack of site-selective palladium(0)-catalyzed
cross coupling reactions generally occurs at the sterically
less encumbered and electronically more deficient posi-
tion. The site-selective formation of 4a–e can be ex-
plained by the fact that carbon atom C-4 (located para to
the keto group) is more electron-deficient than C-3 (locat-
ed meta to the keto group). In contrast, the steric environ-
ment of positions 3 and 4 is similar and should have no
influence on the selectivity (Figure 2).
O
O
OTf
Ar1
OTf
OTf
Ar1B(OH)2
i
carbon C-3 less
electron-deficient
2
4a–e
O
ii
Ar2B(OH)2
OTf
O
Ar2
Ar1
OTf
carbon C-4 more
electron-deficient
5a–d
Scheme 3 Synthesis of 4a–e and 5a–d. Reagents and conditions: i)
2 (1.0 equiv), boronic acid (1.3 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4
(3 mol%), 1,4-dioxane, 110 °C, 4 h; ii) 4a–e (1.0 equiv), (4-vinylphe-
nyl)boronic acid (1.3 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4 (3 mol%),
1,4-dioxane, 110 °C, 4 h.
Figure 2 Possible explanation for the site-selective formation of
products 4a–e
We were interested in the question whether a high degree
of site-selectivity can be also obtained for Sonogashira
cross-coupling reactions. The Sonogashira reaction of 2
with various alkynes (2.6 equiv) afforded the 3,4-dialky-
nylbenzophenones 6a–f in good yields (Scheme 4,
Table 3). The best yields were obtained when
Pd(PPh3)2Cl2 (6 mol%) was used as the catalyst with 2.6
equivalents of the alkyne and when the reaction was car-
ried out in DMF (reflux, 4 h) using Et3N as the base.
The structure of compound 4d was unambiguously con-
firmed by 2D-NMR techniques (Figure 1). In the NOESY
spectrum, an interaction was observed between the aro-
matic proton 5-H of ring A, to that of the aromatic protons
of ring B attached to the carbons atoms C-2¢ and C-6¢.
This confirmed that the first attack of boronic acid takes
place at carbon C-4 of the bis(triflate).
Synthesis 2012, 44, 219–234
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Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
221
O
R
R
O
R
OTf
OTf
i
2
6a–f
Scheme 4 Synthesis of 6a–f. Reagents and conditions: i) 2 (1.0
equiv), alkyne (2.0 equiv), anhyd CuI (10 mol%), Pd(PPh3)2Cl2 (6
mol%), Et3N (1.25 equiv), DMF, 110 °C, 4 h.
Table 3 Synthesis of 6a–f
6
a
b
c
d
e
f
R
Yield (%)a
Figure 3 ORTEP plot of 8
4-t-BuC6H4
Ph
78
54
64
66
60
58
2,4-Dihydroxybenzophenone
We next decided to extend the scope of the study to the
bis(triflate) derived from commercially available 2,4-di-
hydroxybenzophenone (9). The reaction of 9 with trifluo-
romethanesulfonic anhydride resulted in the formation of
2,4-bis(trifluoromethylsulfonyloxy)benzophenone (10) in
88% yield (Scheme 6).
3-MeOC6H4
4-MeC6H4
4-FC6H4
3-MeC6H4
a Yields of isolated products.
O
OH
O
OTf
The Sonogashira reaction of 3,4-bis(trifluoromethylsulfo-
nyloxy)benzophenone (2) with p-tolylacetylene (1.3
equiv), in the presence of Pd(PPh3)2Cl2 (3 mol%), pro-
ceeded with very good site-selectivity (attack at carbon
atom C-4) to give product 7 (Scheme 5). Product 7 was
treated with 4-methylphenylboronic acid (1.0 equiv), in
the presence of K3PO4 as a base and Pd(PPh3)4 (3 mol%)
as the catalyst in 1,4-dioxane at 90 °C, to give product 8
in good yield (64%). The structure of 8 was independently
confirmed by X-ray crystal structure analysis (Figure 3).14
i
OH
OTf
10 88 %
9
Scheme 6 Synthesis of 10. Reagents and conditions: i) 9 (1.0
equiv), CH2Cl2, –78 °C, pyridine (4.0 equiv), Tf2O (2.4 equiv),
–78 °C, 4 h.
The Suzuki–Miyaura reaction of 10 with different aryl bo-
ronic acids (2.6 equiv) afforded the 2,4-diarylbenzophe-
nones 11a–d in good yields (Scheme 7, Table 4). The
reactions were carried out under the conditions reported
for the synthesis of 3a–j.
O
O
OTf
OTf
O
OTf
O
Ar
OTf
i
2
ArB(OH)2
i
7
+
OTf
Ar
ii
10
11a–d
B(OH)2
O
Scheme 7 Synthesis of 11a–d. Reagents and conditions: i) 10 (1.0
equiv), boronic acid (2.6 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4 (6
mol%), 1,4-dioxane (5 mL per 1 mmol of 10), 110 °C, 4 h.
Table 4 Synthesis of 11a–d
8
11
a
Ar
Yield (%)a
Scheme 5 Synthesis of 7 and 8. Reagents and conditions: i) 2 (1.0
equiv), alkyne (1.0 equiv), anhyd CuI (10 mol%), Pd(PPh3)2Cl2
(6 mol%), Et3N (1.25 equiv), DMF, 90 °C, 8 h; ii) 7 (1.0 equiv),
4-methylphenylboronic acid (1.3 equiv), K3PO4 (1.5 equiv),
Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 °C, 4 h.
Ph
82
84
75
71
b
4-MeC6H4
3-ClC6H4
4-MeOC6H4
c
d
a Yields of isolated products.
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222
R. A. Khera et al.
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O
Ar2
O
OTf
O
OTf
Ar1B(OH)2
i
Ar2B(OH)2
ii
Ar1
OTf
Ar1
10
12a–i
12j
Scheme 8 Synthesis of 12a–i. Reagents and conditions: i) 10 (1.0 equiv), boronic acid (2.6 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol%),
1,4-dioxane, 90 °C, 4 h; ii) boronic acid (1.3 equiv), 12e (1.0 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol%), 1,4-dioxane, 90 °C, 4 h.
The Suzuki–Miyaura reaction of 10 with 1.3 equivalents The Sonogashira reaction of 10 with different alkynes re-
of different arylboronic acids, in the presence of sulted in the formation of the 2,4-dialkynylbenzophe-
Pd(PPh3)4 (3 mol%), resulted in site-selective attack at nones 13a–d (Scheme 9, Table 6). The reactions were
carbon atom C-4 to give the 4-aryl-2-(trifluoromethylsul- accomplished using the catalyst Pd(PPh3)2Cl2 (6 mol%),
fonyloxy)benzophenones 12a–i (Scheme 8, Table 5). The 2.2 equivalents of the terminal alkynes, anhydrous CuI
reaction of 12e with 4-methoxyphenylboronic acid (1.3 (20 mol%), and NBu4I (15 mol%) in DMF. All reactions
equiv) gave the aryl substituted benzophenone 12j, which proceeded in good yields.
have two different aryl substituents at the positions 2 and
4 (Scheme 8, Table 5).
Table 6 Synthesis of 13a–d
13
a
R
Yield (%)a
Table 5 Synthesis of 12a–j
12 Ar1
Ph
78
74
77
74
Yield (%)a Ar2
12
Yield (%)a
12j
b
3-MeC6H4
4-MeC6H4
n-C8H17
a
b
c
d
e
f
4-MeC6H4
73
75
68
67
c
4-EtC6H4
d
a Yields of isolated products.
3,4-(Me)2C6H3
3,5-Me2C6H3
4-t-BuC6H4
3-ClC6H4
Site-selective Sonogashira reactions of 10 were next stud-
ied. The reaction of 10 with aliphatic and aromatic
alkynes afforded the 4-alkynyl-2-(trifluoromethylsulfo-
nyloxy)benzophenones 14a–c in good yields (Scheme 10,
Table 7). The best yields were obtained with Pd(PPh3)2Cl2
(3 mol%) as the catalyst using 1.1 equivalents of the ter-
minal alkyne in the presence of CuI (10 mol%) and NBu4I
(15 mol%) in DMF. The Suzuki reaction of product 14c
with 4-tert-butylphenylboronic acid (1.2 equiv), in the
presence of K3PO4 (1.5 equiv) and Pd(PPh3)4 (3 mol%),
76
65
64
63
58
4-MeOC6H4 71
g
h
i
3-MeOC6H4
4-MeOC6H4
3,4,5-(MeO)3C6H2
a Yields of isolated products.
R
Table 7 Synthesis of 14a–c and 15
O
OTf
14
R
Yield (%)a
14
Ar
Yield (%)a
15
O
R
a
b
c
n-Pr
78
81
68
OTf
i
n-C8H17
4-MeOC6H4
R
10
13a–d
4-t-BuC6H4
73
Scheme 9 Synthesis of 13a–d. Reagents and conditions: i) 10 (1.0
equiv), alkyne (2.2 equiv), anhyd CuI (10%), Pd(PPh3)2Cl2 (6 mol%),
Et3N (1.25 equiv), NBu4I (15 mol%), DMF, 90 °C, 4 h.
a Yields of isolated products.
O
OTf
O
OTf
O
Ar
R
ArB(OH)2
ii
OTf
i
R
R
10
14a–c
15
Scheme 10 Synthesis of 14a–c and 15. Reagents and conditions: i) 10 (1.0 equiv), alkyne (1.1 equiv), anhyd CuI (10%), Pd(PPh3)2Cl2 (3%),
Et3N (1.25 equiv), DMF, 90 °C, 8 h; ii) 14c (1.0 equiv), 4-tert-butylphenylboronic acid (1.3 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol%),
1,4-dioxane, 90 °C, 4 h.
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Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
223
IR (KBr): 3061 (w), 1598, 1589, 1580 (m), 1496, 1431, 1414, 1319,
1291 (m), 1265 (s), 1165, 1077, 1028, 989, 976, 932 (m), 887, 787,
757 (s), 680, 595, 572 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.44–7.60 (m, 5 H, ArH), 7.68–
7.72 (m, 2 H, ArH), 7.86 (s, 1 H, ArH),
gave product 15 in good yield (73%). The structure of 14c
was independently confirmed by X-ray crystal structure
analysis (Figure 4).14
13C NMR (62.89 MHz, CDCl3): d = 115.9 (q, JF,C = 320.0 Hz, CF3),
121.1 (q, JF,C = 321.3 Hz, CF3), 123.6, 125.2, 128.7, 129.9, 130.9,
133.6 (CHAr), 135.7, 138.7, 140.2, 142.9 (CAr), 192.6 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.3, 72.0 (2 CF).
GC-MS (EI, 70 eV): m/z (%) = 478 (M+, 74), 401 (05), 345 (08), 253
(26), 225 (32), 204 (04), 167 (22), 156 (06), 128 (27), 105 (100), 77
(43), 69 (30), 51 (14).
HRMS (EI): m/z calcd for C15H8F6O7S2 [M+]: 477.96041; found:
477.960958.
2,4-Bis(trifluoromethylsulfonyloxy)benzophenone (10)
Starting from 9 (214 mg, 1.0 mmol), pyridine (0.32 mL, 4.0 mmol),
and Tf2O (0.40 mL, 2.4 mmol), 10 was isolated by chromatography
(flash silica gel, heptanes–EtOAc, 10:1) as a highly viscous oil (420
mg, 88%).
IR (KBr): 3303, 3092 (w), 1657 (s), 1600, 1597, 1493, 1433, 1427
(m), 1319 (w), 1295, 1274, 1242, 1216 (m), 1189, 1133 (s), 1087,
966, 936, 923, 892, 859, 854, 795, 752, 693, 664, 603, 584, 570
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 6.54–6.55 (m, 1 H, ArH), 6.59–
6.69 (m, 3 H, ArH), 7.79–6.87 (m, 2 H, ArH), 6.93–6.96 (m, 2 H,
ArH).
13C NMR (62.8 MHz, CDCl3): d = 114.0 (q, JF,C = 320 Hz, CF3),
122.9 (q, JF,C = 320 Hz, CF3), 116.5, 121.2, 128.8, 130.1, 132.5
(CHAr), 132.7 (CAr), 134.3 (CHAr), 135.7, 147.0, 150.5 (CAr), 190.9
(C=O).
Figure 4 ORTEP plot of 14c (50% probability level)
19F NMR (282 MHz, CDCl3): d = –73.7, –73.0 (CF).
GC-MS (EI, 70 eV): m/z (%) = 478 (M+, 50), 401 (22), 184 (19), 156
(10), 128 (8), 105 (100), 77 (34), 69 (27), 51 (10).
HRMS (EI, 70 eV): m/z calcd for C15H8F6O7S2 [M+]: 477.96101;
found: 477.961098.
In conclusion, we have reported the synthesis of various
substituted benzophenones by Suzuki and Sonogashira re-
actions of the bis(triflates) of 3,4- and 2,4-dihydroxyben-
zophenone. The reactions proceed with excellent site-
selectivity in favor of position 4.
Suzuki Cross-Coupling Reactions; General Procedure
1,4-Dioxane solution of the arylboronic acid, K3PO4,Pd(PPh3)4, and
the aromatic triflate was stirred in a pressure tube at the denoted
temperature for 4 h under argon atmosphere. After cooling to 20 °C,
sat. aq NH4Cl (50 mL) was added, the organic and aqueous layers
were separated, and the latter was extracted with CH2Cl2 (3 × 15
mL). The combined organic layers were dried (Na2SO4), filtered,
and the filtrate was concentrated in vacuo. The residue was purified
by column chromatography.
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere. For 1H and 13C NMR spectra,
the deuterated solvents indicated were used. Mass spectrometric
data were obtained by electron ionization (EI, 70 eV), chemical ion-
ization (CI, isobutane), or electrospray ionization (ESI). For prepar-
ative scale chromatography, silica gel 60 (0.063–0.200 mm, 70–
230 mesh) was used.
Phenyl([1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone (3a)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), phenylboronic acid (129 mg, 1.06 mmol), and
1,4-dioxane (5 mL/mmol of triflate), 3a was isolated by chromatog-
raphy (flash silica gel, heptanes–EtOAc, 10:1) as a colorless solid;
reaction temperature 110 °C; yield: 108 mg (78%); mp 138–
140 °C.
Triflates 2 and 10; General Procedure
To a stirred solution of 1 and/or 9 (1.0 equiv) in CH2Cl2 (10 mL/
mmol) was added pyridine (4.0 equiv) at –78 °C under an argon at-
mosphere. After 10 min, Tf2O (2.4 equiv) was added at –78 °C. The
mixture was allowed to warm up to 0 °C and stirred for 4 h. The
mixture was filtered and the filtrate was concentrated in vacuo. The
products of the reaction mixture were isolated by rapid column
chromatography (flash silica gel, heptanes–EtOAc).
IR (KBr): 3286, 3010, 2912, 2854, 2728 (w), 1728 (s), 1574, 1502
(m), 1492, 1452, 1436, 1386, 1328, 1294 (m), 1250 (s), 1198, 1116,
1064, 1036, 959, 902 (m), 882, 840, 793, 738 (s), 695, 648, 594, 563
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.00–7.12 (m, 10 H, ArH), 7.38–
7.47 (m, 4 H, ArH), 7.72 (d, J = 6.5 Hz, 1 H, ArH), 7.74–7.80 (m, 3
H, ArH).
3,4-Bis(trifluoromethylsulfonyloxy)benzophenone (2)
Starting from 1 (168 mg, 0.78 mmol), pyridine (0.25 mL, 3.12
mmol), and Tf2O (0.30 mL, 1.8 mmol), 2 was isolated by chroma-
tography (flash silica gel, heptanes–EtOAc, 10:1) as a colorless oil
(318 mg, 84%).
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R. A. Khera et al.
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13C NMR (75.47 MHz, CDCl3): d = 126.9, 127.2, 128.0, 128.1,
128.4, 129.1, 129.7, 129.8, 130.0, 130.6, 132.2, 132.5 (CHAr),
136.5, 137.7, 138.3, 140.6, 140.7, 144.7 (CAr), 196.3 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 334 (M+, 100), 257 (52), 228 (31),
202 (07), 128 (06), 105 (24), 77 (20).
HRMS (EI): m/z calcd for C25H18O [M+]: 334.13522; found:
334.135837.
IR (KBr): 3288, 3012, 2914, 2856, 2730 (w), 1731 (s), 1572, 1505
(m), 1495, 1455, 1436, 1386, 1328, 1296 (m), 1250 (s), 1199, 1118,
1067, 1036, 959, 902 (m), 882, 842, 793, 738 (s), 695, 648, 596, 567
cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 3.53, 3.55, 3.77, 3.78 (s, 12 H,
4 OCH3), 6.35–6.41 (m, 3 H, ArH), 6.93 (t, J = 8.9 Hz, 1 H, ArH),
7.48–7.57 (m, 5 H, ArH), 7.81–7.92 (m, 5 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 55.1, 55.3 (4 OCH3), 98.2,
103.9, 104.0 (CHAr), 123.03, 123.07 (CAr), 128.1, 128.4, 130.0,
131.0, 131.5, 132.0, 133.1 (CHAr), 135.6, 138.0, 142.9, 157.1, 160.0
(CAr), 196.3 (C=O).
Phenyl(4,4¢¢-difluoro[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone (3b)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 4-fluorophenylboronic acid (148 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3b was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a yel-
low oil; reaction temperature 110 °C; yield: 107 mg (69%).
GC-MS (EI, 70 eV): m/z (%) = 454 (M+, 100), 377 (03), 227 (05),
105 (37).
HRMS (EI): m/z calcd for C29H26O5 [M+]: 454.17748; found:
454.177627.
IR (KBr): 3052, 3020, 2996, 2830 (w), 1716 (s), 1656, 1596 (m),
1490, 1456, 1432, 1398, 1317, 1273 (m), 1178, 1118, 1072, 1054,
945, 936 (m), 843, 827, 796, 746 (s), 695, 642, 581, 532 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 6.82–6.90 (m, 3 H, ArH), 6.99–
7.10 (m, 4 H, ArH), 7.40–7.55 (m, 5 H, ArH), 7.73–7.80 (m, 4 H,
ArH).
13C NMR (75.47 MHz, CDCl3): d = 115.0, 115.3, 128.4, 129.3,
130.0, 130.5, 131.1, 131.4, 132.1, 132.5 (CHAr), 136.3, 136.8,
137.5, 138.2, 139.7, 143.5, 160.5, 163.7 (CAr), 196.1 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 370 (M+, 100), 293 (58), 264 (17),
244 (19), 105 (22), 77 (16);
HRMS (EI): m/z calcd for C25H16F2O [M+]: 370.11637; found:
370.116463.
Phenyl(2,2¢¢-dimethoxy-[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone
(3e)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 2-methoxyphenylboronic acid (161 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3e was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less solid; reaction temperature 110 °C; yield: 110 mg (67%);
mp 152–154 °C.
IR (KBr): 3055, 3024, 2998, 2832 (w), 1712 (s), 1654, 1597 (m),
1493, 1459, 1434, 1396, 1317, 1273 (m), 1178, 1118, 1074, 1051,
946, 932 (m), 843, 827, 796, 748 (s), 695, 642, 581, 531 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 3.39, 3.41 (s, 6 H, 2 OCH3), 6.61–
6.77 (m, 2 H, ArH), 6.94–7.09 (m, 5 H, ArH), 7.35–7.46 (m, 4 H,
ArH), 7.75–7.82 (m, 5 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 54.9 (2 OCH3), 110.3, 110.4,
119.9, 120.0, 128.2, 128.5, 128.7, 128.8 (CHAr), 130.0 (CAr) 130.1,
130.7, 131.2, 131.3, 132.1, 132.7 (CHAr), 135.9, 137.9, 138.4,
143.0, 156.0, 156.8 (CAr), 196.3 (C=O).
Phenyl(3,5,3¢¢,5¢¢-tetramethyl[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)meth-
anone (3c)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 3,5-dimethylphenylboronic acid (159 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3c was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less crystalline solid; reaction temperature 110 °C; yield: 123 mg
(75%); mp 140–142 °C.
GC-MS (EI, 70 eV): m/z (%) = 394 (M+, 100), 363 (21), 317 (80),
289 (20), 274 (46), 259 (11), 202 (18), 158 (15), 105 (83), 77 (68).
IR (KBr): 3289, 3013, 2916, 2857, 2732 (w), 1732 (s), 1574, 1505
(m), 1495, 1455, 1436, 1386, 1328, 1296 (m), 1250 (s), 1199, 1118,
1067, 1036, 959, 902 (m), 882, 842, 793, 738 (s), 695, 648, 596, 567
cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 2.09 (s, 6 H, 2 CH3), 2.11 (s, 6 H,
2 CH3), 6.68 (d, J = 4.45 Hz, 3 H, ArH), 6.75 (d, J = 6.55 Hz, 2 H,
ArH), 7.38–7.48 (m, 5 H, ArH), 7.68, 7.72 (dd, J = 1.85, 9.8 Hz, 1
H, ArH), 7.75 (m, 3 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 21.2 (2 CH3), 21.3 (2 CH3),
125.1, 127.5, 127.7, 128.3, 128.6, 128.8, 130.0, 130.4, 132.1, 132.3
(CHAr), 136.3, 137.1, 137.8, 138.1, 140.4, 140.5, 140.9, 144.9 (CAr),
196.4 (C=O).
HRMS (EI): m/z calcd for C27H22O3 [M+]: 394.15635; found:
394.156782.
Phenyl(4,4¢-dimethoxy[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone
(3f)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 4-methoxyphenylboronic acid (161 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3f was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a yel-
low oil; reaction temperature 110 °C; yield: 90 mg (54%).
IR (KBr): 3052, 3022, 2996, 2830 (w), 1716 (s), 1652, 1596 (m),
1492, 1456, 1432, 1394, 1316, 1272 (m), 1176, 1116, 1072, 1050,
945, 932 (m), 843, 827, 796, 748 (s), 692, 642, 579, 529 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.68, 3.69 (s, 6 H, 2 OCH3), 6.66–
6.71 (m, 4 H, ArH), 6.96–7.04 (m, 4 H, ArH), 7.37–7.46 (m, 3 H,
ArH), 7.68, 7.71 (d, J = 1.80, 9.75 Hz, 1 H, ArH), 7.74–7.79 (m, 4
H, ArH).
GC-MS (EI, 70 eV): m/z (%) = 390 (M+, 100), 313 (29), 270 (13),
239 (07), 148 (04), 105 (22), 77 (11).
HRMS (EI): m/z calcd for C29H26O [M+]: 390.19782; found:
390.197629.
Phenyl(2,4,2¢¢,4¢¢-tetramethoxy[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)meth-
anone (3d)
13C NMR (62.90 MHz, CDCl3): d = 55.1 (2 OCH3), 113.5 (CAr),
113.6, 128.3, 128.8, 130.0, 130.5, 130.8, 131.0, 132.3, 132.4, 132.9
(CHAr), 133.0, 136.2, 137.8, 140.1, 144.2, 158.8 (CAr), 196.3
(C=O).
GC-MS (EI, 70 eV): m/z (%) = 394 (M+, 100), 317 (11), 289 (04),
258 (03), 202 (07), 105 (24).
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 2,4-dimethoxyphenylboronic acid (192 mg,
1.06 mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3d was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a colorless solid; reaction temperature 110 °C; yield: 140 mg
(74%); mp 136–138 °C.
HRMS (EI): m/z calcd for C27H22O3 [M+]: 394.15635; found:
394.156091.
Synthesis 2012, 44, 219–234
© Thieme Stuttgart · New York

PAPER
Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
225
Phenyl(2,2¢-diethoxy[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone (3g)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 2-ethoxyphenylboronic acid (175 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3g was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less solid; reaction temperature 110 °C; yield: 135 mg (76%);
mp 168–170 °C.
(CAr), 130.0, 130.7, 132.3, 132.4 (CHAr), 133.0, 136.6, 137.4, 138.6,
137.1 138.7, 142.7 (CAr), 196.3 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 390 (M+, 100), 375 (06), 313 (16),
241 (12), 105 (58), 77 (17).
HRMS (EI): m/z calcd for C29H26O [M+]: 390.19782; found:
390.197382.
IR (KBr): 3048, 3024, 2994, 2832 (w), 1718 (s), 1654, 1598 (m),
1494, 1452, 1430, 1396, 1318, 1274 (m), 1178, 1116, 1074, 1052,
947, 932 (m), 843, 823, 798, 748 (s), 690, 644, 577, 527 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.09–1.15 (m, 6 H, 2 CH3), 3.64
(q, J = 6.8 Hz, 4 H, 2 CH2), 6.59–6.70 (m, 4 H, ArH), 6.90–6.96 (m,
2 H, ArH), 7.00–7.10 (m, 2 H, ArH), 7.32–7.44 (m, 4 H, ArH), 7.72
(dd, J = 1.86, 7.89 Hz, 1 H, ArH), 7.77–7.81 (m, 3 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 14.5, 14.7 (2 CH3), 63.1, 63.3
(2 CH2), 111.3, 111.4, 119.6, 119.7, 128.2, 128.3, 128.6, 130.0
(CHAr), 130.1 (CAr), 131.0, 131.5, 131.7, 132.1, 132.9 (CHAr),
135.6, 138.0, 138.5, 143.1, 155.5, 155.6 (CAr), 196.5 (C=O).
Phenyl(2,2¢-dichloro[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone (3j)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd (PPh3)4 (6 mol%), 2-chlorophenylboronic acid (165 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3j was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less oil; reaction temperature 110 °C; yield: 115 mg (68%).
IR (KBr): 3054, 2958, 2842 (w), 1662, 1594 (s), 1558, 1486 (m),
1442, 1428, 1396, 1312, 1276, 1242 (m), 1211 (s), 1160, 1132,
1096, 1024, 983 (m), 873, 816, 792, 761 (s), 692, 672, 571 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 6.96–7.06 (m, 5 H, ArH), 7.20–
7.26 (m, 2 H, ArH), 7.39–7.50 (m, 5 H, ArH), 7.80–7.86 (m, 4 H,
ArH).
GC-MS (EI, 70 eV): m/z (%) = 422 (M+, 100), 407 (07), 365 (06),
347 (04), 289 (08), 261 (11), 202 (08), 144 (05), 105 (89), 77 (33).
HRMS (EI): m/z calcd for C29H26O3 [M+]: 422.18765; found:
422.187400.
13C NMR (62.90 MHz, CDCl3): d = 126.2, 127.2, 128.3, 128.9,
129.1, 129.7, 130.0, 130.1, 130.9, 131.2, 132.5, 132.8 (CHAr),
133.0, 136.6, 137.4, 138.6, 138.7, 142.7 (CAr), 196.0 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.4 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 402 (M+, 100, 35Cl), 367 (09), 325
(81), 291 (07), 262 (61), 226 (80), 200 (07), 150 (05), 113 (06), 105
(64), 77 (36), 51 (06).
HRMS (EI): m/z calcd for C25H16Cl2O [M+, 35Cl]: 402.05782;
found: 402.057942.
Phenyl(3,4,3¢¢,4¢¢-tetramethyl[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)meth-
anone (3h)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 3,4-dimethylphenylboronic acid (159 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3h was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less oil; reaction temperature 110 °C; yield: 96 mg (58%).
4-Benzoyl-3¢-methoxybiphenyl-2-yl Trifluoromethanesulfonate
(4a)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd (PPh3)4 (3 mol%), 3-methoxyphenylboronic acid (80 mg, 0.53
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 4a was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less viscous oil; reaction temperature 110 °C; yield: 124 mg (68%).
IR (KBr): 3044, 3020, 2990, 2838 (w), 1716 (s), 1656, 1594 (m),
1492, 1450, 1432, 1396, 1318, 1270 (m), 1172, 1118, 1072, 1050,
945, 930 (m), 841, 821, 796, 746 (s), 692, 644, 575, 525 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.03, 2.05, 2.06, 2.08 (s, 12 H, 4
CH3), 6.71–6.83 (m, 4 H, ArH), 6.90 (d, J = 6.8 Hz, 2 H, ArH),
7.30–7.41 (m, 5 H, ArH), 7.64, 7.66 (dd, J = 1.8, 7.9 Hz, 1 H, ArH),
7.72, 7.74 (dd, J = 1.9, 4.5 Hz, 2 H, ArH).
IR (KBr): 3063, 3003, 2940 (w), 1660, 1598 (s), 1580, 1552, 1479
(m), 1447, 1421, 1396, 1317, 1278, 1244 (m), 1204 (s), 1179, 1167,
1047, 1020, 990 (m), 883, 841, 788, 762 (s), 695, 629, 597, 568
cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 3.76 (s, 3 H, OCH3), 6.89–7.01
(m, 4 H, ArH), 7.28 (d, J = 7.8 Hz, 1 H, ArH), 7.40–7.54 (m, 4 H,
ArH), 7.73–7.81 (m, 3 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 55.3 (OCH3), 114.7, 114.8
(CHAr), 121.7 (q, JF,C = 320 Hz, CF3), 122.2, 123.8, 128.6, 129.8,
129.9, 130.0, 131.9, 133.1, 133.6 (CHAr), 135.9, 136.5, 138.2,
139.2, 146.4, 159.7 (CAr), 194.0 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.8 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 436 (M+, 80), 303 (07), 225 (03), 202
(05), 183 (04), 155 (06), 127 (05), 105 (100), 77 (32).
HRMS (EI): m/z calcd for C21H15F3O5S [M+]: 436.05868; found:
13C NMR (62.90 MHz, CDCl3): d = 19.4, 19.5, 19.7, 19.8 (4 CH3),
126.7, 127.3, 128.3, 128.8, 129.2, 130.0, 130.6, 130.8, 130.9, 132.3
(CHAr), 135.0, 135.4, 136.1, 137.8, 138.2, 140.7, 144.7 (CAr), 196.4
(C=O).
GC-MS (EI, 70 eV): m/z (%) = 390 (M+, 100), 375 (04), 313 (15),
285 (04), 270 (18), 239 (08), 148 (05), 105 (42), 77 (13).
HRMS (EI): m/z calcd for C29H26O [M+]: 390.19782; found:
390.197714.
Phenyl(4,4¢-diethyl[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)methanone (3i)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd(PPh3)4 (6 mol%), 4-ethylphenylboronic acid (159 mg, 1.06
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 3i was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less solid; reaction temperature 110 °C; yield: 128 mg (78%);
mp 138–140 °C.
436.058307.
IR (KBr): 3046, 3026, 2992, 2834 (w), 1716 (s), 1652, 1596 (m),
1492, 1454, 1432, 1394, 1316, 1276 (m), 1176, 1114, 1072, 1054,
945, 934 (m), 841, 825, 796, 746 (s), 692, 642, 574, 524 cm–1 (m).
4-Benzoyl-2¢,5¢-dimethoxybiphenyl-2-yl Trifluoromethane-
sulfonate (4b)
1H NMR (300 MHz, CDCl3): d = 1.06–1.13 (m, 6 H, 2 CH3), 2.45–
2.54 (m, 4 H, 2 CH2), 6.95–7.02 (m, 8 H, ArH), 7.32–7.45 (m, 4 H,
ArH), 7.69, 7.71 (dd, J = 1.8, 7.9 Hz, 1 H, ArH), 7.72–7.77 (m, 3 H,
ArH).
13C NMR (62.90 MHz, CDCl3): d = 15.3 (2 CH3), 28.4, 28.5 (2
CH2), 127.5, 127.6, 128.3, 128.9, 129.6, 129.7 (CHAr), 127.9, 128.3
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd (PPh3)4 (3 mol%), 2,5-dimethoxyphenylboronic acid (96 mg,
0.53 mmol), and 1,4-dioxane (5 mL/mmol of triflate), 4b was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a colorless solid; reaction temperature 110 °C; yield: 140 mg
(72%); mp 138–140 °C.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 219–234

226
R. A. Khera et al.
PAPER
IR (KBr): 3061, 3005, 2929 (w), 1661, 1590 (s), 1554, 1472 (m),
1446, 1418, 1399, 1317, 1280, 1244 (m), 1204 (s), 1169, 1137,
1087, 1033, 985 (m), 880, 844, 794, 766 (s), 699, 671, 587 cm–1 (m).
HRMS (EI): m/z calcd for C23H19F3O7S [M+]: 496.07981; found:
496.079887.
4-Benzoyl-4¢-tert-butylbiphenyl-2-yl Trifluoromethane-
sulfonate (4e)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd (PPh3)4 (3 mol%), 4-tert-butylphenylboronic acid (94 mg, 0.53
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 4e was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less viscous oil; reaction temperature 110 °C; yield: 136 mg (70%).
1H NMR (250 MHz, CDCl3): d = 3.69 (s, 6 H, 2 OCH3), 6.61 (d,
J = 8.4 Hz, 1 H, ArH), 7.18 (s, 1 H, ArH), 7.28–7.38 (m, 2 H, ArH),
7.42–7.56 (m, 3 H, ArH), 7.70–7.84 (m, 4 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 55.8 (2 OCH3), 103.8, 104.0,
121.1 (q, JF,C = 320 Hz, CF3), 122.7, 128.3, 128.4, 129.0, 130.0,
130.1, 131.0, 132.8, 133.8 (CHAr), 136.1, 136.8, 137.1, 137.9,
148.0, 157.7 (CAr), 194.3 (C=O).
IR (KBr): 3060, 2904, 2868 (w), 1713, 1610, 1579, 1518, 1462,
1446 (w), 1392, 1317, 1278, 1268, 1178, 1117, 1027, 1016, 1001,
973, 954, 854, 765 (m), 734, 698, 605 (w), 565 cm–1 (m).
19F NMR (282 MHz, CDCl3): d = –74.6 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 466 (M+, 100), 333 (28), 302 (24),
1H NMR (300 MHz, CDCl3): d = 1.19, 1.21 (s, 6 H, 2 CH3), 1.28 (s,
3 H, CH3), 6.97–7.00 (dd, J = 1.80, 8.90 Hz, 1 H, ArH), 7.12–7.15
(dd, J = 2.1, 8.4 Hz, 1 H, ArH), 7.34–7.45 (m, 3 H, ArH), 7.48–7.54
(m, 3 H, ArH), 7.72–7.80 (m, 4 H, ArH).
225 (32), 197 (04), 105 (84), 77 (28).
HRMS (EI): m/z calcd for C22H17F3O6S [M+]: 466.06925; found:
466.069859.
13C NMR (75.47 MHz, CDCl3): d = 31.2 (2 CH3), 31.3 (CH3), 34.7
(C), 120 (q, JF,C = 320 Hz, CF3), 123.9, 124.8, 125.6, 128.3, 129.0,
129.4, 130.0, 131.9, 133.0 (CHAr), 136.6, 137.9, 138.0, 141.0,
146.6, 152.3 (CAr), 194.8 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.8 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 462 (M+, 39), 447 (100), 299 (35),
4-Benzoyl-4¢-methylbiphenyl-2-yl Trifluoromethanesulfonate
(4c)
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd (PPh3)4 (3 mol%), 4-methoxyphenylboronic acid (80 mg, 0.53
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 4c was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a red
viscous oil; reaction temperature 110 °C; yield: 112 mg (64%).
273 (07), 209 (05), 165 (06), 105 (30), 77 (15), 57 (09).
HRMS (EI): m/z calcd for C24H21F3O4S [M+]: 462.11072; found:
462.110624.
IR (KBr): 3060, 3027, 2922 (w), 1660, 1597 (s), 1549, 1484 (m),
1446, 1421, 1317, 1277, 1244 (m), 1204 (s), 1167, 1135, 1098,
1037, 985 (m), 876, 814, 788, 762 (s), 697, 669, 573 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 2.33 (s, 3 H, OCH3), 7.19 (d,
J = 7.8 Hz, 3 H, ArH), 7.34 (d, J = 8.2 Hz, 1 H, ArH), 7.40–7.55 (m,
5 H, ArH), 7.72–7.77 (m, 3 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 21.3 (CH3), 121.1 (q, JF,C = 321
Hz, CF3), 123.8, 128.5, 129.1, 129.4, 129.9, 130.0, 131.9, 133.0
(CHAr), 137.6, 138.7, 139.1, 139.5, 146.5, 149.2 (CAr), 194.1
(C=O).
19F NMR (282 MHz, CDCl3): d = –73.8 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 420 (M+, 59), 209 (04), 181 (04), 139
(06), 105 (100), 77 (29).
HRMS (EI): m/z calcd for C21H15F3O4S [M+]: 420.06377; found:
(3-Methoxy-4¢¢-vinyl[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)phenylmeth-
anone (5a)
Starting from 4a (70 mg, 0.16 mmol), K3PO4 (101 mg, 0.48 mmol),
Pd (PPh3)4 (3 mol%), 4-vinylphenylboronic acid (29 mg, 0.20
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 5a was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less viscous oil; reaction temperature 110 °C; yield: 42 mg (68%).
IR (KBr): 3055, 3003, 2953, 2833 (w), 1655 (s), 1628 (w), 1595 (s),
1513 (w), 1494, 1464, 1427, 1389, 1294 (m), 1248 (s), 1177, 1114,
1074, 1018, 989, 947 (m), 869, 842, 783, 765 (s), 696, 638, 564, 540
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.53 (s, 3 H, OCH3), 5.10 (dd,
J = 1.4, 9.8 Hz, 1 H, CH2), 5.58 (dd, J = 1.2, 8.1 Hz, 1 H, CH2), 6.52
(dd, J = 1.3, 8.2 Hz, 1 H, CH), 6.52–6.72 (m, 3 H, ArH), 7.00–7.20
(m, 5 H, ArH), 7.37–7.50 (m, 4 H, ArH), 7.72–7.79 (m, 4 H, ArH).
420.063160.
4-Benzoyl-3¢,4¢,5¢-trimethoxybiphenyl-2-yl Trifluoromethane-
sulfonate (4d)
13C NMR (62.89 MHz, CDCl3): d = 55.1 (OCH3), 113.2 (CHAr),
113.9 (CH2vinyl), 113.2, 115.1, 122.1, 125.9, 128.3, 129.1, 129.2,
129.9, 130.0, 132.1, 132.4, 136.3 (CHAr, CHvinyl), 136.7, 137.6,
140.0, 140.1, 140.3, 141.8, 144.4, 159.2 (CAr), 196.2 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 390 (M+, 100), 349 (03), 313 (15),
285 (04), 239 (09), 105 (33), 77 (16).
Starting from 2 (200 mg, 0.41 mmol), K3PO4 (260 mg, 1.23 mmol),
Pd (PPh3)4 (3 mol%), 3,4,5-trimethoxyphenylboronic acid (112 mg,
0.53 mmol), and 1,4-dioxane (5 mL/mmol of triflate), 4d was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a yellow solid; reaction temperature 110 °C; yield: 159 mg
(76%); mp 152–154 °C.
IR (KBr): 3065, 2999, 2936 (w), 1660, 1609 (s), 1584, 1514, 1488
(m), 1463, 1418, 1393, 1317, 1291, 1278 (m), 1241 (s), 1170, 1104,
1063, 1001, 978 (m), 889, 831, 790, 745 (s), 675, 630, 598, 569
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.82 (s, 6 H, 2 OCH3), 3.83 (s, 3
H, OCH3), 6.62 (s, 2 H, ArH), 7.39–7.47 (m, 3 H, ArH), 7.56 (s, 1
H, ArH), 7.68–7.78 (m, 3 H, ArH), 7.88 (d, J = 6.4 Hz, 1 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 56.2 (2 OCH3), 61.0 (OCH3),
106.8 (CHAr), 120 (q, JF,C = 320 Hz, CF3), 122.0, 128.5, 130.0,
130.4, 133.1, 133.3 (CHAr), 135.8, 136.7, 137.7, 138.6, 149.0, 153.3
(CAr), 194.8 (C=O).
HRMS (EI): m/z calcd for C28H22O2 [M+]: 390.16143; found:
390.161704.
(4-Methyl-4¢¢-vinyl[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)phenylmethanone
(5b)
Starting from 4c (70 mg, 0.16 mmol), K3PO4 (101 mg, 0.48 mmol),
Pd (PPh3)4 (3 mol%), 4-vinylphenylboronic acid (29 mg, 0.20
mmol) and 1,4-dioxane (5 mL/mmol of triflate), 5b was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less solid; reaction temperature 110 °C; yield: 48 mg (78%);
mp 148–150 °C.
19F NMR (282 MHz, CDCl3): d = –73.8 (CF3).
GC-MS (EI, 70 eV): m/z (%) = 496 (M+, 92), 363 (26), 332 (100),
IR (KBr): 3052, 3002, 2952, 2830 (w), 1654 (s), 1630 (w), 1596 (s),
1512 (w), 1496, 1462, 1428, 1390, 1296 (m), 1246 (s), 1178, 1116,
1072, 1016, 987, 945 (m), 869, 842, 781, 765 (s), 696, 634, 564, 542
cm–1 (m).
317 (17), 255 (12), 227 (07), 185 (05), 105 (57), 77 (19).
Synthesis 2012, 44, 219–234
© Thieme Stuttgart · New York

PAPER
Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
227
1H NMR (300 MHz, CDCl3): d = 2.24 (s, 3 H, CH3), 5.15 (d,
J = 10.8 Hz, 1 H, CH2), 5.66 (d, J = 9.6 Hz, 1 H, CH2), 6.63 (dd,
J = 1.3, 8.2 Hz, 1 H, CH), 6.96–7.00 (m, 2 H, ArH), 7.16–7.21 (m,
3 H, ArH), 7.41–7.51 (m, 6 H, ArH), 7.72–7.80 (m, 5 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 21.1 (CH3), 113.8 (CH2vinyl),
125.9, 128.3, 128.8, 129.1, 129.5, 130.0, 130.6, 132.2, 132.4, 136.4
(CHAr, CHvinyl), 136.9, 137.5, 137.8, 140.1, 140.3, 144.6, 144.4,
159.2 (CAr), 196.2 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 374 (M+, 100), 359 (04), 297 (19),
253 (10), 148 (04), 105 (24), 77 (12).
HRMS (EI): m/z calcd for C28H22O [M+]: 374.16652; found:
374.166329.
HRMS (EI): m/z calcd for C31H28O [M+]: 416.21347; found:
416.213534.
Sonogashira Cross-Coupling Reactions; General Procedure
In a pressure tube, a suspension of Pd(PPh3)2Cl2, aromatic triflate,
alkyne, (Bu)4NI, CuI, Et3N, and for the synthesis of compounds 13
and 14, also Bu4NI in DMF, was purged with argon and stirred at
first at 20 °C for 10 min. Stirring was continued at the given tem-
perature for the given time. The reaction mixture was cooled to
20 °C, poured into H2O (25 mL) and CH2Cl2 (25 mL), and the or-
ganic and the aqueous layers were separated. The latter was extract-
ed with CH2Cl2 (3 × 25 mL). The combined organic layers were
washed with H2O (3 × 20 mL), dried (Na2SO4), concentrated in vac-
uo, and the residue was purified by chromatography (flash silica
gel, heptanes–EtOAc).
Phenyl(3,4,5-trimethoxy-4¢¢-vinyl[1,1¢;2¢,1¢¢]terphenyl-4¢-
yl)methanone (5c)
Starting from 4d (70 mg, 0.14 mmol), K3PO4 (89 mg, 0.42 mmol),
Pd (PPh3)4 (3 mol%), 4-vinylphenylboronic acid (26 mg, 0.18
mmol), and 1,4-dioxane (5 mL/mmol of triflate), 5c was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less viscous oil; reaction temperature 110 °C; yield: 40 mg (64%).
{3,4-Bis[(4-tert-butylphenyl)ethynyl]phenyl}phenylmethanone
(6a)
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), 4-tert-butylphe-
nylacetylene (158 mg, 1.0 mmol) and DMF (5 mL per 1 mmol of 2),
6a was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 110 °C; reac-
tion time 4 h; yield: 192 mg (78%).
IR (KBr): 3054, 3002, 2952, 2830 (w), 1654 (s), 1630 (w), 1596 (s),
1512 (w), 1496, 1462, 1428, 1390, 1296 (m), 1246 (s), 1178, 1116,
1072, 1016, 987, 945 (m), 869, 842, 781, 765 (s), 696, 634, 564, 542
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.54 (s, 6 H, 2 OCH3), 3.75 (s, 3
H, OCH3), 5.19 (dd, J = 1.3, 10.8 Hz, 1 H, CH2), 5.69 (dd, J = 2.1,
9.6 Hz, 1 H, CH2), 6.63 (dd, J = 1.3, 8.2 Hz, 1 H, CH), 7.09 (d,
J = 8.2 Hz, 1 H, ArH), 7.24–7.36 (m, 4 H, ArH), 7.40–7.48 (m, 3 H,
ArH), 7.50–7.65 (m, 3 H, ArH), 7.71 (dd, J = 1.8, 7.9 Hz, 1 H,
ArH), 7.80–7.86 (m, 2 H, ArH).
IR (KBr): 3083, 3060, 2959, 2866, 2211 (w), 1714 (s), 1659 (s),
1591, 1506, 1462, 1406, 1363, 1322 (m), 1268 (s), 1201, 1163,
1104, 1084, 982, 968, 882, 872, 792, 742, 651, 615, 528 cm–1 (w).
1H NMR (250 MHz, CDCl3): d = 1.26, 1.27 (s, 18 H, 6 CH3), 7.16
(s, 1 H, ArH), 7.28–7.33 (m, 3 H, ArH), 7.41–7.48 (m, 3 H, ArH),
7.51–7.59 (m, 3 H, ArH), 7.64–7.75 (m, 5 H, ArH), 7.88 (d, J = 1.65
Hz, 1 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 30.9, 31.1 (6 CH3), 87.0, 87.4,
94.6, 96.8 (C), 119.8, 119.9 (CAr), 125.4, 125.5 (CHAr), 126.0 (CAr),
128.4, 128.9 (CHAr), 129.7 (CAr), 129.9, 131.4, 131.6, 131.7, 132.6,
133.3 (CHAr), 136.4, 137.2, 152.0, 152.2 (CAr), 195.3 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 494 (M+, 100), 479 (50), 262 (04),
232 (19), 204 (05), 105 (18), 77 (04).
13C NMR (62.90 MHz, CDCl3): d = 55.9 (2 OCH3), 60.9 (OCH3),
114.2 (CH2vinyl), 125.9, 128.0, 128.3, 129.6, 130.0, 131.6, 135.0,
135.8, 136.4 (CHAr, CHvinyl), 136.9, 137.5, 137.8, 140.1, 140.3,
144.6, 144.4, 152.7 (CAr), 196.2 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 450 (M+, 100), 435 (20), 332 (05),
207 (07), 105 (33), 77 (20).
HRMS (EI): m/z calcd for C37H34O [M+]: 494.26042; found:
494.260148.
HRMS (EI): m/z calcd for C30H26O4 [M+]: 450.18256; found:
450.182820.
[3,4-Bis(phenylethynyl)phenyl]phenylmethanone (6b)
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), phenylacetylene
(102 mg, 1.0 mmol), and DMF (5 mL per 1 mmol of 2), 6b was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a light yellow oil; reaction temperature 110 °C; reaction time 4 h;
yield: 103 mg (54%).
(4-tert-Butyl-4¢¢-vinyl[1,1¢;2¢,1¢¢]terphenyl-4¢-yl)phenylmeth-
anone (5d)
Starting from 4e (70 mg, 0.15 mmol), K3PO4 (95 mg, 0.45 mmol),
Pd (PPh3)4 (3 mol%), 4-vinylphenylboronic acid (28 mg, 0.19
mmol) and 1,4-dioxane (5 mL/mmol of triflate), 5d was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less solid; reaction temperature 110 °C; yield: 39 mg (62%);
mp 138–140 °C.
IR (KBr): 3081, 3062, 2958, 2864, 2210 (w), 1716 (s), 1658 (s),
1592, 1508, 1464, 1408, 1362, 1320 (m), 1266 (s), 1203, 1161,
1106, 1082, 981, 967, 881, 873, 792, 741, 653, 613, 523 cm–1 (w).
1H NMR (250 MHz, CDCl3): d = 7.23–7.27 (m, 4 H, ArH), 7.37 (s,
1 H, ArH), 7.40–7.54 (m, 6 H, ArH), 7.57 (s, 1 H, ArH), 7.62 (d,
J = 1.72 Hz, 1 H, ArH), 7.66 (d, J = 1.72 Hz, 1 H, ArH), 7.69–7.73
(m, 3 H, ArH), 7.88 (d, J = 1.62 Hz, 1 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 87.5, 87.9, 94.5, 96.6 (C),
120.4, 122.8 (CAr), 125.3, 128.2, 128.4, 128.5, 128.7, 128.9, 129.1,
129.9, 131.7, 131.8, 132.7, 133.3 (CHAr), 133.5, 136.7, 137.1 (CAr),
195.2 (C=O).
IR (KBr): 3052, 3006, 2956, 2832 (w), 1656 (s), 1632 (w), 1598 (s),
1516 (w), 1496, 1464, 1432, 1392, 1298 (m), 1246 (s), 1178, 1118,
1072, 1014, 985, 943 (m), 869, 842, 785, 765 (s), 694, 634, 562, 541
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.21 (s, 3 H, CH3), 1.22 (s, 6 H, 2
CH3), 5.13 (dd, J = 1.2, 10.6 Hz, 1 H, CH2), 5.61 (dd, J = 2.4, 9.5
Hz, 1 H, CH2), 6.55 (dd, J = 1.3, 8.2 Hz, 1 H, CH), 7.00–7.10 (m, 4
H, ArH), 7.15–7.23 (m, 4 H, ArH), 7.40–7.54 (m, 4 H, ArH), 7.72–
7.81 (m, 4 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 31.3 (2 CH3), 34.5 (CH3), 113.8
(CH2vinyl), 125.0, 125.8, 128.3, 129.1, 129.3, 129.6, 130.0, 130.7,
132.2, 132.3, 136.4 (CHAr, CHvinyl), 136.9, 137.1, 137.3, 137.7,
140.1, 140.2, 144.5, 150.2 (CAr), 196.2 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 382 (M+, 100), 352 (18), 305 (06),
276 (28), 250 (04), 176 (08), 77 (11).
HRMS (EI): m/z calcd for C29H18O [M+]: 382.13522; found:
382.135497.
GC-MS (EI, 70 eV): m/z (%) = 416 (M+, 87), 401 (100), 252 (06),
105 (53), 77 (23).
© Thieme Stuttgart · New York
Synthesis 2012, 44, 219–234

228
R. A. Khera et al.
PAPER
{3,4-Bis[(3-methoxyphenyl)ethynyl]phenyl}phenylmethanone
(6c)
ArH), 7.53–7.61 (m, 2 H, ArH), 7.66 (d, J = 1.47 Hz, 1 H, ArH),
7.70–7.75 (m, 1 H, ArH), 7.90 (d, J = 1.12 Hz, 1 H, ArH)).
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), 3-methoxyphe-
nylacetylene (132 mg, 1.0 mmol), and DMF (5 mL per 1 mmol of
2), 6c was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a viscous oil; reaction temperature 110 °C; reac-
tion time 4 h; yield: 142 mg (64%).
13C NMR (62.90 MHz, CDCl3): d = 86.1, 86.9, 92.5, 96.9 (C),
120.4, 122.8 (CAr), 125.1, 127.2, 127.9, 128.2, 128.7, 129.1, 129.9,
131.7, 132.7, 133.3 (CHAr), 134.0, 135.0, 136.7, 137.0, 137.1 (CAr),
195.2 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 418 (M+, 100), 389 (05), 341 (34),
312 (40), 293 (07), 216 (05), 187 (05), 147 (06), 105 (30), 77 (12).
IR (KBr): 3061 (w), 2998, 2832 (m), 2203 (w), 1656 (m), 1591 (s),
1540, 1488, 1446, 1402, 1317 (m), 1279, 1219 (s), 1179, 1127,
1091, 985, 972, 869, 848 (m), 777, 710, 681 (s), 603, 562 cm–1 (w).
HRMS (EI): m/z calcd for C29H16F2O [M+]: 418.11637; found:
418.116424.
1H NMR (300 MHz, CDCl3): d = 3.68, 3.69 (s, 6 H, 2 OCH3), 6.81–
6.87 (m, 2 H, ArH), 7.00–7.06 (m, 2 H, ArH), 7.08–7.20 (m, 4 H,
ArH), 7.41–7.46 (m, 2 H, ArH), 7.52–7.60 (m, 2 H, ArH), 7.66–7.69
(dd, J = 1.74, 8.07 Hz, 1 H, ArH), 7.72–7.75 (m, 2 H, ArH), 7.90 (d,
J = 1.71 Hz, 1 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 55.2 (2 OCH3), 87.3, 87.6,
94.4, 96.5 (4C), 115.6, 115.8, 116.2, 116.3 (CHAr), 123.7, 123.8
(CAr), 124.2, 124.3 (CHAr), 126.0 (CAr), 128.4, 129.2, 129.4, 129.5
(CHAr), 129.6 (CAr), 129.9, 131.6, 132.7, 133.2 (CHAr), 136.7,
137.1, 159.4 (CAr), 195.2 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 442 (M+, 100), 427 (05), 399 (12),
365 (18), 337 (07), 250 (12), 105 (37), 77 (15), 57 (05), 44 (41).
HRMS (EI): m/z calcd for C31H22O3 [M+]: 442.15689; found:
442.156582.
[3,4-Bis(m-tolylethynyl)phenyl]phenylmethanone (6f)
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), 3-methylphen-
ylacetylene (116 mg, 1.0 mmol), and DMF (5 mL per 1 mmol of 2),
6f was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a yellow oil, reaction temperature 110 °C; reaction
time 4 h; yield: 120 mg (58%).
IR (KBr): 3056, 3021, 2914, 2857, 2206 (w), 1653, 1585, 1513,
1441, 1402, 1315 (m), 1265, 1245 (m), 1177, 1104, 1040 (w), 981,
913, 871, 834, 787, 664 (m), 612, 586, 560 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 2.17, 2.18 (s, 6 H, 2 CH3), 7.02–
7.10 (m, 4 H, ArH), 7.35–7.45 (m, 6 H, ArH), 7.52–7.59 (m, 2 H,
ArH), 7.62 (dd, J = 1.77 8.10 Hz, 1 H, ArH), 7.68–7.72 (m, 2 H,
ArH), 7.85 (d, J = 1.71 Hz, 1 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 21.2, 21.5 (2 CH3), 87.1, 87.9,
94.8, 96.7 (C), 123.6, 125.3, 126.0, 126.8 (CAr), 128.3, 128.4, 128.8,
128.9, 129.1, 129.7, 129.9, 131.5, 132.4, 132.5, 132.7, 133.1, 133.5
(CHAr), 136.2, 137.6, 138.5, 139.6 (CAr), 195.1 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 410 (M+, 100), 333 (23), 305 (08),
289 (34), 207 (07), 105 (15), 77 (15).
[3,4-Bis(p-tolylethynyl)phenyl]phenylmethanone (6d)
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), 4-methylphen-
ylacetylene (116 mg, 1.0 mmol), and DMF (5 mL per 1 mmol of 2),
6d was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a red viscous oil; reaction temperature 110 °C; re-
action time 4 h; yield: 135 mg (66%).
HRMS (EI): m/z calcd for C31H22O [M+]: 410.16652; found:
410.166081.
IR (KBr): 3058, 3025, 2916, 2858, 2204 (w), 1651, 1587, 1514,
1444, 1404, 1317 (m), 1267, 1246 (m), 1177, 1104, 1040 (w), 981,
913, 871, 834, 787, 664 (m), 612, 586, 560 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 2.28, 2.29 (s, 6 H, 2 CH3), 7.00–
7.10 (m, 4 H, ArH), 7.36–7.44 (m, 6 H, ArH), 7.50–7.57 (m, 2 H,
ArH), 7.63 (dd, J = 1.77 8.10 Hz, 1 H, ArH), 7.70–7.74 (m, 2 H,
ArH), 7.87 (d, J = 1.71 Hz, 1 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 21.2, 21.5 (2 CH3), 87.0, 87.4,
94.7, 96.9 (C), 123.8, 125.2, 126.0, 126.6 (CAr), 128.4, 128.9, 129.2,
129.3, 129.5, 129.9, 131.6, 131.7, 132.6, 133.2 (CHAr), 136.4,
137.2, 138.9, 139.2 (CAr), 195.3 (C=O).
3-Trifluorosulfonyloxy-4-methylphenylaceylenebenzophenone
(7)
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), 4-methylphen-
ylacetylene (58 mg, 0.50 mmol), and DMF (5 mL per 1 mmol of 2),
7 was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a light brown viscous oil; reaction temperature
90 °C; reaction time 8 h; yield: 156 mg (70%).
IR (KBr): 3305, 3062, 2922, 2867, 1909 (w), 1659, 1599 (m), 1515,
1446 (w), 1423 (s), 1319 (m), 1290, 1244 (m), 1171, 1076, 976 (m),
883, 844, 815 (s), 754, 733, 639, 532 cm–1 (m).
GC-MS (EI, 70 eV): m/z (%) = 410 (M+, 100), 409 (33), 408 (15),
395 (29), 393 (12), 289 (16), 181 (10), 77 (10).
HRMS (EI): m/z calcd for C31H22O [M+]: 410.16652; found:
410.166081.
1H NMR (300 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 7.12 (d,
J = 7.92 Hz, 2 H, ArH), 7.42–7.47 (m, 4 H, ArH), 7.55 (d, J = 7.13
Hz, 1 H, ArH), 7.63–7.67 (m, 2 H, ArH), 7.70–7.74 (m, 3 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 21.6 (CH3), 81.7, 99.9 (C),
118.6 (CAr), 122.6 (q, JC,F = 320.0 Hz, CF3), 123.1, 128.6, 129.3,
129.4, 129.9, 131.9, 133.1, 133.3 (CHAr), 136.4, 138.0, 140.0, 149.3
(CAr), 193.7 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 444 (M+, 100), 311 (46), 255 (22),
176 (08), 115 (05), 105 (39), 77 (28), 51 (05).
{3,4-Bis[(4-fluorophenyl)ethynyl]phenyl}phenylmethanone
(6e)
Starting from 2 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), Et3N (0.086 mL, 0.62 mmol), 4-flourophen-
ylacetylene (120 mg, 1.0 mmol), and DMF (5 mL per 1 mmol of 2),
6e was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a brown oil; reaction temperature 110 °C; reaction
time 4 h; yield: 126 mg (60%).
HRMS (EI): m/z calcd for C23H15F3O4S [M+]: 444.06377; found:
444.063860.
IR (KBr): 3066, 2918, 2859, 2207, 1681 (w), 1648 (s), 1589, 1547,
1486, 1434, 1405, 1278, 1210, 1138, 1114, 1089, 1073, 937, 918,
867, 777, 695 (m), 605, 596, 546 cm–1 (w).
1H NMR (250 MHz, CDCl3): d = 6.99–7.04 (m, 2 H, ArH), 7.14–
7.23 (m, 4 H, ArH), 7.25–7.30 (m, 3 H, ArH), 7.42–7.47 (m, 2 H,
[4¢-Methyl-6-(p-tolylethynyl)biphenyl-3-yl]phenylmethanone
(8)
Starting from 7 (100 mg, 0.22 mmol), K3PO4 (69 mg, 0.33 mmol),
Pd (PPh3)4 (3 mol%), 4-methylphenylboronic acid (38 mg, 0.28
mmol), and 1,4-dioxane (5 mL/mmol of 7), 8 was isolated by chro-
Synthesis 2012, 44, 219–234
© Thieme Stuttgart · New York

PAPER
Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
229
matography (flash silica gel, heptanes–EtOAc, 10:1) as a colorless
oil; reaction temperature 90 °C; yield: 55 mg (64%).
[2,4-Bis(3-chlorophenyl)phenyl]phenylmethanone (11c)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (292 mg, 1.38
mmol), Pd(PPh3)4 (6 mol%), 3-chlorophenylboronic acid (187 mg,
1.2 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 11c was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a white solid; reaction temperature 110 °C; yield: 138 mg (75%).
IR (KBr): 3078, 3057, 3028, 2916, 2858, 2209 (w), 1651, 1591 (s),
1512, 1442, 1412, 1394 (w), 1267, 1245 (m), 1182, 1143, 1075,
1040, 1016, 999 (w), 951 (m), 909, 857, 838 (w), 748, 697 (m), 610,
586 cm–1.
IR (KBr): 3080, 3034 (w), 1665 (s), 1595, 1545, 1494, 1443, 1430,
1316, 1285, 1244, 1180, 1135, 1071, 1002, 915, 837 (m), 753 (s),
700 (m), 787 (s), 671, 667, 624, 530 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.06–7.08 (m, 2 H, ArH), 7.23–
7.40 (m, 6 H, ArH), 7.45–7.53 (m, 2 H, ArH), 7.54–7.61 (m, 6 H,
ArH).
13C NMR (75 MHz, CDCl3): d = 125.4, 126.1, 127.2, 127.4, 127.6,
128.1, 128.2, 128.4, 128.7, 128.9, 129.5, 129.7, 130.2, 133.0
(CHAr), 133.0, 134.2, 134.9, 137.2, 137.7, 138.1, 140.5, 141.6,
142.0 (CAr), 197.9 (C=O).
MS (EI, 70 eV): m/z (%) = 404 ([M, 37Cl2, 63]+), 402 ([M, 35Cl2,
100]+), 401 (49), 369 (12), 368 (10), 367 (36), 329 (10), 328 (11),
327 (55), 326 (20), 325 (85), 290 (12), 264 (14), 263 (10), 262 (44),
227 (13), 226 (54), 225 (10), 224 (14), 184 (20), 105 (39), 77 (33).
1H NMR (300 MHz, CDCl3): d = 2.26, 2.33 (s, 6 H, 2 CH3), 7.05 (d,
J = 7.89 Hz, 2 H, ArH), 7.16–7.20 (m, 4 H, ArH), 7.40–7.52 (m, 5
H, ArH), 7.60–7.64 (m, 2 H, ArH), 7.73 (d, J = 1.53 Hz, 1 H, ArH),
7.76–7.80 (m, 2 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 21.2, 21.5 (2 CH3), 88.4, 95.4
(2 C), 125.9 (CAr), 128.2, 128.3, 128.7, 129.1, 129.2, 129.9, 130.9,
131.4, 132.4, 132.7 (CHAr), 132.7, 136.7, 136.8, 137.5, 137.6,
138.8, 143.5 (CAr), 195.9 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 386 (M+, 100), 371 (05), 309 (27),
281 (12), 266 (36), 239 (05), 132 (05), 105 (39), 77 (22).
HRMS (EI): m/z calcd for C29H22O [M+]: 386.16652; found:
386.166115.
[2,4-Bis(phenyl)phenyl]phenylmethanone (11a)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (292 mg, 1.38
mmol), Pd(PPh3)4 (6 mol%), phenylboronic acid (146 mg, 1.2
mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 11a was isolated
by chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a
colorless oil; reaction temperature 110 °C; yield: 125 mg (82%).
HRMS (EI): m/z calcd for C25H16Cl2O [(M+, 35Cl, 37Cl)]+:
402.05727; found: 402.056201.
[2,4-Bis(4-methoxyphenyl)phenyl]phenylmethanone (11d)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (292 mg, 1.38
mmol), Pd(PPh3)4 (6 mol%), 4-methoxyphenylboronic acid (182
mg, 1.2 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 11d was
isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 110 °C; yield:
128 mg (71%).
IR (KBr): 3050, 3026, 2923, 2853 (w), 1657 (s), 1595 (m), 1552,
1496 (w), 1441, 1393, 1315 (m), 1279 (s), 1234, 1158, 1132, 1073,
1025, 960, 936, 922, 902, 843, 800, 773 (m), 760, 742, 690 (s), 638,
584 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 7.06–7.09 (m, 2 H, ArH), 7.11–
7.15 (m, 2 H, ArH), 7.17–7.23 (m, 3 H, ArH), 7.27–7.33 (m, 3 H,
ArH), 7.35–7.40 (m, 2 H, ArH), 7.49–7.51 (m, 1 H, ArH), 7.56–7.61
(m, 5 H, ArH).
13C NMR (75.4 MHz, CDCl3): d = 125.7, 127.3, 127.4, 128.0,
128.1, 128.3, 128.9, 129.0, 129.1, 129.6, 129.9, 132.8 (CHAr),
137.5, 137.7, 140.1, 140.2, 141.9, 143.3 (CAr), 198.5 (C=O).
MS (EI, 70 eV): m/z (%) = 334 (M+, 100), 333 (73), 258 (18), 257
(85), 229 (14), 228 (35), 227 (15), 226 (21), 105 (12), 77 (18).
IR (KBr): 3061, 2937 (w), 2842 (m), 1657, 1601 (s), 1526, 1490,
1443, 1425 (m), 1396 (s), 1296, 1246, 1211, 1139, 1062, 971, 910
(m), 832, 694 (s), 611, 539 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.65 (s, 3 H, OCH3), 3.80 (s, 3 H,
OCH3), 6.66–6.69 (m, 1 H, ArH), 6.92–6.97 (m, 2 H, ArH), 7.13–
7.18 (m, 2 H, ArH), 7.41–7.53 (m, 9 H, ArH), 7.75–7.78 (m, 2 H,
ArH).
13C NMR (62.8 MHz, CDCl3): d = 55.3, 55.4 (OCH3), 114.3, 114.6,
12.7, 128.0, 128.3, 129.4, 128.5, 130.1, 130.9, 133.6 (CHAr), 136.7,
137.5, 141.4, 142.7, 145.9, 147.4, 158.9, 159.6 (CAr), 197.8 (C=O).
HRMS (EI): m/z calcd for C25H18O [M]+: 334.13522; found:
334.135618.
MS (EI, 70 eV): m/z (%) = 394 (M+, 100), 333 (73), 258 (18), 257
(85), 229 (14), 228 (35), 227 (15), 226 (21), 105 (12), 77 (18).
HRMS (EI): m/z calcd for C25H18O [M]+: 394.04522; found:
394.044518.
[2,4-Bis(p-tolyl)phenyl]phenylmethanone (11b)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (292 mg, 1.38
mmol), Pd(PPh3)4 (6 mol%), 4-tolylboronic acid (163 mg, 1.2
mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 11b was isolated
by chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a
colorless oil; reaction temperature 110 °C; yield: 139 mg (84%).
4-Benzoyl-4¢-methylbiphenyl-3-yl Trifluoromethanesulfonate
(12a)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 4-tolylboronic acid (81 mg, 0.6
mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12a was isolated
by chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a
colorless oil; reaction temperature 90 °C; yield: 141 mg 73%).
IR (KBr): 3079, 3032, 1661, 1596, 1490, 1445, 1426, 1314, 1283,
1242, 1178, 1138, 1069, 999, 914, 835, 751 (s), 698 (m), 785 (s) 621
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.16 (s, 3 H, CH3), 2.33 (s, 3 H,
CH3), 6.93–6.96 (m, 2 H, ArH), 7.04–7.13 (m, 2 H, ArH), 7.19–7.25
(m, 4 H, ArH), 7.27–7.37 (m, 2 H, ArH), 7.45–7.51 (m, 3 H, ArH),
7.53–7.65 (m, 3 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.1 (CH3), 21.2 (CH3), 127.1,
128.1, 128.6, 128.7, 128.8, 129.0, 129.5, 129.6, 129.9, 130.0
(CHAr), 136.3, 137.5, 137.7, 140.1, 140.2, 141.9, 143.3 (CAr), 198.5
(C=O).
IR (KBr): 3026, 2950, 2857 (w), 1657, 1615, 1598 (m), 1548, 1448
(w), 1422 (s), 1286, 1242 (m), 1206, 1136 (s), 1085 (m), 1018 (w),
945, 899 (m), 814 (s), 746, 703, 622, 604, 540 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.33 (s, 3 H, CH3), 7.20–7.23 (m,
2 H, ArH), 7.39–7.43 (m, 4 H, ArH), 7.49–7.56 (m, 4 H, ArH),
7.74–7.77 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.2 (CH3), 120.5 (q, J = 321 Hz,
CF3), 120.7, 126.1, 127.0, 128.5, 130.0, 130.1 (CHAr), 130.3 (CAr),
131.9, 133.6 (CHAr), 135.2, 136.7, 139.2, 146.3, 147.4 (CAr), 192.5
(C=O).
MS (EI, 70 eV): m/z (%) = 362 (M+, 100), 333 (73), 258 (18), 257
(85), 229 (14), 228 (35), 227 (15), 226 (21), 105 (12), 77 (18).
HRMS (EI): m/z calcd for C27H22O [M]+: 362.13522; found:
362.134518.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 219–234

230
R. A. Khera et al.
PAPER
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 420 (M+, 100), 343 (36), 287 (23), 210
(10), 105 (32), 77 (17).
HRMS (EI): m/z calcd for C21H15F3O4S [M]+: 420.06377; found:
IR (KBr): 3028, 2952, 2859 (w), 1667, 1612, 1597 (m), 1553 (w),
1423 (s), 1389, 1315, 1285, 1246 (m), 1204, 1135 (s), 1069 (m),
1000 (w), 955, 899 (m), 836 (s), 755, 696, 602, 544 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 6 H, CH3), 6.98 (s, 1 H,
ArH), 7.11 (s, 2 H, ArH), 7.34–7.39 (m, 2 H, ArH), 7.48–7.56 (m,
4 H, ArH), 7.72–7.75 (m, 2 H, ArH).
420.063866.
4-Benzoyl-4¢-ethylbiphenyl-3-yl Trifluoromethanesulfonate
(12b)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 4-ethylphenylboronic acid (90 mg, 0.6
mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12b was isolated
by chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a
colorless oil; reaction temperature 90 °C; yield: 150 mg (75%).
13C NMR (75 MHz, CDCl3): d = 21.3 (2 CH3), 120.6 (q, J = 319
Hz, CF3), 121.0, 125.1, 126.4, 128.5, 130.1 (CHAr), 130.4 (CAr),
130.7, 131.8, 133.7 (CHAr), 136.7, 138.1, 138.9, 146.7, 147.3 (CAr),
192.5 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 434 (M+, 100), 357 (37), 301 (23), 258
(10), 152 (10), 105 (33), 77 (17).
HRMS (EI): m/z calcd for C22H17O4F3S [M]+: 434.07942; found:
434.079065.
IR (KBr): 3025, 2961, 2918, 2854 (w), 1655, 1615 (m), 1523, 1448
(w), 1422 (s), 1322, 1285, 1240 (m), 1205, 1137 (s), 1086 (m),
1018, 979 (w), 930, 898 (m), 828 (s), 798, 703, 603, 534 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.20 (t, J = 7.6 Hz, 3 H, CH3),
2.64 (q, J = 7.6 Hz, 2 H, CH2), 7.16–7.27 (m, 2 H, ArH), 7.38–7.47
(m, 4 H, ArH), 7.50–7.60 (m, 4 H, ArH), 7.75–7.78 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 15.4 (CH3), 28.6 (CH2), 118.5 (q,
J = 319.1 Hz, CF3), 120.7, 126.1, 127.1, 128.5, 128.8, 130.1
(CHAr), 131.6 (CAr), 131.8, 133.6 (CHAr), 135.4, 136.7, 145.5,
146.3, 147.3 (CAr), 192.5 (C=O).
4-Benzoyl-4¢-tert-butylbiphenyl-3-yl Trifluoromethane-
sulfonate (12e)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 4-tert-butylphenylboronic acid (106
mg, 0.60 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12e was
isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 90 °C; yield:
161 mg (76%).
19F NMR (282 MHz, CDCl3): d = –73.3.
IR (KBr): 3060, 2959, 2866 (w), 1660, 1614, 1596 (m), 1554 (w),
1462, 1415, 1318, 1241 (m), 1207, 1137 (s), 1089, 948, 895 (m),
810 (s), 696, 603, 569 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.28 (s, 9 H, CH3), 7.37–7.42 (m,
3 H, ArH), 7.45–7.51 (m, 6 H, ArH), 7.52–7.60 (m, 3 H, ArH).
MS (EI, 70 eV): m/z (%) = 434 (M+, 100), 419 (10), 357 (31), 301
(16), 105 (33), 77 (16).
HRMS (EI): m/z calcd for C22H17F3O4S [M]+: 434.07942; found:
434.078943.
4-Benzoyl-3¢,4¢-dimethylbiphenyl-3-yl Trifluoromethane-
sulfonate (12c)
13C NMR (75 MHz, CDCl3): d = 31.2 (3CH3), 34.7 (C), 120.7,
120.6 (q, J = 319 Hz, CF3), 121.7, 126.2, 126.3, 126.9, 128.5, 130.1
(CHAr), 130.3 (CAr), 131.9, 133.6 (CHAr), 136.7, 146.2, 147.4, 152.4
(CAr), 192.5 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 462 (M+, 33), 447 (100), 313 (15).
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 3,4-dimethylphenylboronic acid (90
mg, 0.60 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12c was
isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 90 °C; yield:
135 mg (68%).
HRMS (EI): m/z calcd for C24H21O4F3S [M]+: 462.11072; found:
462.110339.
IR (KBr): 3022, 2946, 2858, 2659 (w), 1655, 1614, 1598, 1513,
1447 (m), 1421 (s), 1319, 1280, 1242 (m), 1208, 1138 (s), 1084,
953, 862, 822, 742, 701, 651, 607, 572 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.23 (s, 3 H, CH3), 2.26 (s, 3 H,
CH3), 7.14–7.27 (m, 3 H, ArH), 7.36–7.41 (m, 2 H, ArH), 7.48–7.58
(m, 4 H, ArH), 7.73–7.76 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 19.5 (CH3), 19.9 (CH3), 118.5 (q,
J = 320.5 Hz, CF3), 120.7, 124.5, 126.1, 128.3, 128.5, 130.1, 130.5,
131.8, 133.6 (CHAr), 135.6, 136.7, 137.6, 139.0, 146.5, 147.3, 153.8
(CAr), 192.5 (C=O).
4-Benzoyl-3¢-chlorobiphenyl-3-yl Trifluoromethanesulfonate
(12f)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 3-chlorophenylboronic acid (93 mg,
0.60 mmol) and 1,4-dioxane (5 mL per 1 mmol of 10), 12f was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a colorless oil; reaction temperature 90 °C; yield: 131 mg (65%).
IR (KBr): 3085, 3034 (w), 1665 (s), 1593, 1545, 1493, 1447, 1429,
1317, 1286, 1245, 1182, 1141, 1071, 997, 915, 833 (m), 746 (s), 696
(m), 783 (s), 671, 666, 621, 527 cm–1 (m).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 434 (M+, 100), 357 (29), 301 (22), 258
(10), 105 (29), 77 (15).
1H NMR (300 MHz, CDCl3): d = 6.83–6.93 (m, 5 H, ArH), 6.98–
7.07 (m, 5 H, ArH), 7.24–7.27 (m, 2 H, ArH).
HRMS (EI): m/z calcd for C22H17O4F3S [M]+: 434.07942; found:
434.079871.
13C NMR (75 MHz, CDCl3): d = 118.5 (q, J = 319.1 Hz, CF3),
121.0, 125.4, 126.5, 127.3, 128.6, 129.0, 130.1, 130.5, 131.9, 133.8
(CHAr), 135.2, 136.5, 139.9, 144.7, 147.2, 160.2 (CAr), 192.3
(C=O).
19F NMR (282 MHz, CDCl3): d = –73.9.
MS (EI, 70 eV): m/z (%) = 442 ([M, 37Cl, 40]+), 440 (M+, 100), 365
(20), 363 (52), 309 (10), 307 (27), 244 (21), 230 (13), 215 (19), 139
(27), 105 (76), 77 (31).
4-Benzoyl-3¢,5¢-dimethylbiphenyl-3-yl Trifluoromethane-
sulfonate (12d)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 3,5-dimethylphenylboronic acid (81
mg, 0.6 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12d was
isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 90 °C; yield:
133 mg (67%).
HRMS (EI): m/z calcd for C20H12ClF3O4S [M+, 35Cl]: 440.00914;
found: 440.00857.
Synthesis 2012, 44, 219–234
© Thieme Stuttgart · New York

PAPER
Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
231
4-Benzoyl-3¢-methoxybiphenyl-3-yl Trifluoromethanesulfonate
(12g)
130.1, 131.8, 133.7 (CHAr), 133.9, 136.6, 139.0, 146.4, 147.2, 153.8
(CAr), 192.3 (C=O).
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 3-methoxyphenylboronic acid (91 mg,
0.60 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12g was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a colorless oil; reaction temperature 90 °C; yield: 128 mg (64%).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 496 (M+, 100), 481 (28), 105 (17), 77
(10).
HRMS (EI): m/z calcd for C23H19F3O7S [M]+: 496.07981; found:
496.079565.
IR (KBr): 3078, 3030 (w), 1663 (s), 1596, 1540, 1492, 1443, 1428,
1316, 1285, 1244, 1180, 1140, 1071, 998, 913, 833 (m), 753 (s), 697
(m), 783 (s), 667, 529 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.79 (s, 3 H, OCH3), 6.88–7.11
(m, 3 H, ArH), 7.30–7.42 (m, 3 H, ArH), 7.49–7.60 (m, 4 H, ArH),
7.74–7.77 (m, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.4 (OCH3), 113.2, 114.1, 119.6
(CHAr), 120.7 (q, J = 319.7 Hz, CF3), 121.0, 126.5, 128.5, 130.1,
130.3 (CHAr), 130.8 (CAr), 131.8, 133.7 (CHAr), 136.6, 139.5, 146.2,
147.2, 160.2 (CAr), 192.4 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 436 (M+, 100), 359 (24), 303 (14), 260
(14), 226 (11), 105 (28), 77 (16).
HRMS (EI): m/z calcd For C21H15O5S [M]+: 436.05868; found:
Phenyl[4-(4-tert-butylphenyl)-2-(4-methoxyphenyl)phe-
nyl]methanone (12j)
Starting from 12e (161 mg, 0.35 mmol), K3PO4 (111 mg, 0.52
mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid (68 mg,
0.45 mmol), and 1,4-dioxane (5 mL per 1 mmol of 13b), 12j was
isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 90 °C; yield:
104 mg (71%).
IR (KBr): 3081, 3033 (w), 1663 (s), 1596, 1541, 1492, 1447, 1428,
1316, 1285, 1243, 1179, 1140, 1072, 1006, 913, 832, 698 (m), 785
(s), 670, 621, 529 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 1.30 (s, 9 H, 3 CH3), 3.65 (s, 3 H,
OCH3), 6.65–6.69 (m, 2 H, ArH), 7.13–7.24 (m, 5 H, ArH), 7.41–
7.49 (m, 4 H, ArH), 7.53–7.65 (m, 7 H, ArH).
13C NMR (62.8 MHz, CDCl3): d = 31.3 (3 CH3), 34.6 (C), 55.1
(OCH3), 113.7, 125.1, 125.8, 126.9, 128.0, 128.6, 129.4, 129.9,
130.1, 132.7 (CH), 137.2, 137.3, 137.5, 139.1, 141.3, 143.0, 151.0,
158.9 (C), 198.3 (C=O).
436.058189.
4-Benzoyl-4¢-methoxybiphenyl-3-yl Trifluoromethanesulfonate
(12h)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 4-methoxyphenylboronic acid (91 mg,
0.60 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12h was iso-
lated by chromatography (flash silica gel, heptanes–EtOAc, 10:1)
as a colorless oil; reaction temperature 90 °C; yield: 126 mg (63%).
MS (EI, 70 eV): m/z (%) = 421 (30), 420 (100), 419 (19), 406 (24),
405 (79), 443 (10), 105 (17).
HRMS (EI): m/z calcd for C30H28O2 [M]+: 421.07981; found:
421.079910.
IR (KBr): 3082, 2962, 2867 (w), 1662, 1613, 1599 (m), 1556 (w),
1463, 1414, 1317, 1243 (m), 1209, 1136 (s), 1092, 947, 893 (m),
809 (s), 697, 605, 570 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.78 (s, 3 H, OCH3), 6.92–6.96
(m, 2 H, ArH), 7.37–7.43 (m, 4 H, ArH), 7.46–7.52 (m, 4 H, ArH),
7.54–7.55 (m, 2 H, ArH).
13C NMR (62.8 MHz, CDCl3): d = 55.4 (OCH3), 114.6 (CHAr),
118.4 (q, J = 319 Hz, CF3), 120.3, 125.7, 128.4, 128.5 (CHAr),
129.8 (CAr), 130.1, 131.9, 133.6 (CHAr), 136.7, 145.9, 147.4, 160.5
(CAr), 192.5 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 436 (M+, 100), 359 (14), 303 (15), 226
(15), 105 (35), 77 (16).
HRMS (EI): m/z calcd for C21H15O5F3S [M]+: 436.05868; found:
[2,4-Bis(phenylethynyl)phenyl]phenylmethanone (13a)
Starting from 10 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (20 mol%), (Bu)4NI (15 mol%), and Et3N (252 mg, 2.5
mmol), 1-ethynylbenzene (112 mg, 1.1 mmol) was added in DMF
(5 mL per 1 mmol of 10) to the reaction mixture. After completion
of the reaction and workup, 13a was isolated by chromatography
(flash silica gel, heptanes–EtOAc, 10:1) as a colorless oil; reaction
temperature 90 °C; reaction time 4 h; yield: 149 mg (78%).
IR (KBr): 3079, 3032 (w), 1661, 1596, 1541, 1490, 1445, 1426,
1314, 1283, 1242, 1178, 1138, 1069, 999, 914, 835 (m), 751 (s), 698
(m), 785 (s), 669, 666, 621, 528 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 6.94–6.97 (m, 2 H, ArH), 7.08–
7.15 (m, 3 H, ArH), 7.26–7.29 (m, 3 H, ArH), 7.34–7.48 (m, 7 H,
ArH), 7.69–7.80 (m, 3 H, ArH).
13C NMR (75 MHz, CDCl3): d = 86.8, 87.9, 91.9, 95.7 (C), 122.4,
125.9 (CAr), 126.1, 128.4, 128.6, 128.8 (CHAr), 129.3 (CAr), 129.0,
130.2, 131.0 (CHAr), 131.3 (CAr), 131.5, 131.8, 131.9, 133.2, 135.5
(CHAr), 137.2, 140.6 (CAr), 196.4 (C=O).
MS (EI, 70 eV): m/z (%) = 382 (M+, 100), 381 (57), 365 (19), 353
(13), 352 (20), 351 (11), 350 (14), 276 (28), 274 (19), 77 (10).
HRMS (EI): m/z calcd for C29H18O [M]+: 382.02323; found:
382.023235.
436.058078.
4-Benzoyl-3¢,4¢,5¢-trimethoxybiphenyl-3-yl Trifluoromethane-
sulfonate (12i)
Starting from 10 (220 mg, 0.46 mmol), K3PO4 (146 mg, 0.69
mmol), Pd(PPh3)4 (3 mol%), 3,4,5-trimethoxyphenylboronic acid
(127 mg, 0.60 mmol), and 1,4-dioxane (5 mL per 1 mmol of 10), 12i
was isolated by chromatography (flash silica gel, heptanes–
EtOAc, 10:1) as a colorless oil; reaction temperature 90 °C; yield:
132 mg (58%).
IR (KBr): 3062 (w), 2923 (m), 2851 (w), 1665, 1611, 1585, 1515,
1487, 1412, 1316, 1272 (m), 1204, 1138, 1095, 965, 913, 854, 824,
756, 700, 646, 597 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.82 (s, 3 H, OCH3), 3.85 (s, 6 H,
OCH3), 6.70 (s, 2 H, ArH), 7.36–7.46 (m, 3 H, ArH), 7.50–7.55 (m,
3 H, ArH), 7.73–7.75 (m, 2 H, ArH).
[2,4-Bis(3-tolylethynyl)phenyl]phenylmethanone (13b)
Starting from 10 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (20 mol%), (Bu)4NI (15 mol%), and Et3N (252 mg, 2.5
mmol), 1-ethynyl-3-methylbenzene (128 mg, 1.1 mmol) was added
in DMF (5 mL per 1 mmol of 10) to the reaction mixture. After
completion of the reaction and workup, 13b was isolated by chro-
matography (flash silica gel, heptanes–EtOAc, 10:1) as a colorless
13C NMR (75 MHz, CDCl3): d = 56.3 (2 OCH3), 60.9 (OCH3),
104.6 120.9 (CHAr), 122.5 (q, J = 319.5Hz, CF3), 126.4, 128.5,
© Thieme Stuttgart · New York
Synthesis 2012, 44, 219–234

232
R. A. Khera et al.
PAPER
oil; reaction temperature 90 °C; reaction time 4 h; yield: 151 mg
(74%).
13C NMR (125 MHz, CDCl3): d = 14.0 (2 CH3), 19.6, 19.8, 22.6,
28.6, 28.7, 28.9, 29.1, 29.2, 31.8 (CH2), 78.8, 79.3, 95.3, 97.7 (C),
126. 5 (CAr), 128.3, 128.4, 129.9 (CHAr), 130.4 (CAr), 131.7, 132.4
133.3 (CHAr), 135.9, 137.3 (CAr), 195.4 (C=O).
IR (KBr): 3055, 2918, 2858, 1660, 1594, 1579, 1539, 1485, 1447,
1314, 1283, 1243, 1192, 1154, 1093, 1039, 999, 962, 922, 834 (m),
780 (s), 748, 700, 686 (s), 669, 624, 584 cm–1 (m).
MS (EI, 70 eV): m/z (%) = 454 (M+, 6), 285 (10), 105 (100), 77 (15).
1H NMR (300 MHz, CDCl3): d = 2.14 (s, 3 H, CH3), 2.26 (s, 3 H,
CH3), 6.71–6.78 (m, 2 H, ArH), 6.93–7.18 (m, 4 H, ArH), 7.26–7.50
(m, 7 H, ArH), 7.66–7.80 (m, 3 H, ArH).
HRMS (EI): m/z calcd for C33H42O [M]+: 454.32302; found:
454.313394.
2-Benzoyl-5-(hept-1-ynyl)phenyl Trifluoromethanesulfonate
(14a)
13C NMR (62.8 MHz, CDCl3): d = 21.1, 21.2 (2 CH3), 86.5, 87.6,
92.1, 96.0 (C), 122.2, 122.4, 126.0 (CAr), 128.0 (CHAr), 128.1 (CAr),
128.4, 128.8, 129.0, 129.5, 129.7, 130.1, 130.2, 130.9, 132.1, 132.3,
133.2, 135.4 (CHAr), 137.2, 137.8, 138.1, 140.5 (CAr), 196.4 (C=O).
MS (EI, 70 eV): m/z (%) = 410 (M+, 100), 409 (33), 408 (15), 395
(29), 393 (12), 289 (16), 181 (10), 77 (10).
Starting from 10 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (3 mol%), an-
hyd CuI (10 mol%), (Bu)4NI (27 mg, 15mol%), and Et3N (126 mg,
1.25 mmol), hept-1-yne (53 mg, 0.55 mmol) was added in DMF (5
mL per 1 mmol of 10) to the reaction mixture. After completion of
the reaction and workup, 14a was isolated by chromatography
(flash silica gel, heptanes–EtOAc, 10:1) as a colorless oil; reaction
temperature 90 °C; reaction time 8 h; yield: 165 mg (78%).
HRMS (EI): m/z calcd for C31H22O [M]+: 410.16652; found:
410.16873.
IR (KBr): 3065 (w), 2931 (m), 2860 (w), 1668 (s), 1608, 1598 (m),
1493 (w), 1448 (s), 1317, 1283, 1236 (m), 1205, 1136 (s), 1086 (m),
1000 (w), 941, 970, 839, 803, 762, 697, 602 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.85 (t, J = 7.2 Hz, 3 H, CH3),
1.25–1.36 (m, 4 H, 2 CH2), 1.51–1.58 (m, 2 H, CH2), 2.36 (t, J = 7.2
Hz, 2 H, CH2), 7.31 (s, 1 H, ArH), 7.38–7.41(m, 4 H, ArH), 7.50–
7.53 (m, 1 H, ArH), 7.68–7.72 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 19.4, 22.1, 28.0, 31.1
(CH2), 78.4, 95.9 (C), 118.4 (q, J = 320 Hz, CF3), 125.2, 128.5
(CHAr), 129.3 (CAr), 130.1, 130.9 (CHAr), 131.0 (CAr), 131.1, 133.7
(CHAr), 136.4, 146.6 (CAr), 192.2 (C=O).
[2,4-Bis(p-tolylethynyl)phenyl]phenylmethanone (13c)
Starting from 10 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (20 mol%), (Bu)4NI (15 mol%), and Et3N (252 mg, 2.5
mmol), 1-ethynyl-4-methylbenzene (128 mg, 1.1 mmol) was added
in DMF (5 mL per 1 mmol of 10) to the reaction mixture. After
completion of the reaction and workup, 13c was isolated by chro-
matography (flash silica gel, heptanes–EtOAc, 10:1) as a colorless
oil; reaction temperature 90 °C; reaction time 4 h; yield: 159 mg
(77%).
IR (KBr): 3055, 3025, 2916, 2860 (w), 1659, 1591, 1555, 1477,
1445, 1406, 1316, 1286, 1241, 1178, 1116, 1088, 1037, 999, 917,
836 (m), 812 (s), 699 (m), 686 (s), 651, 621, 596 cm–1 (m).
19F NMR (282 MHz, CDCl3): d = –73.4.
1H NMR (300 MHz, CDCl3): d = 2.22 (s, 3 H, CH3), 2.31 (s, 3 H,
CH3), 6.84–6.95 (m, 4 H, ArH), 7.10–7.18 (m, 3 H, ArH), 7.37–7.51
(m, 6 H, ArH), 7.68–7.82 (m, 3 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.4, 21.5 (2 CH3), 86.2, 86.8,
87.3, 92.1 (C), 119.3, 119.5, 122.5, 126.0 (CAr), 128.4, 128.8, 129.0,
129.2, 130.1, 130.7, 131.3, 131.6, 133.1, 135.3 (CHAr), 137.3,
138.7, 139.0, 140.3 (CAr), 196.5 (C=O).
MS (EI, 70 eV): m/z (%) = 424 (M+, 6), 295 (10), 105 (100), 77 (15),
29 (10).
HRMS (EI): m/z calcd For C21H19F3O4S [M]+: 424.09507; found:
424.09464.
2-Benzoyl-5-(dec-1-ynyl)phenyl Trifluoromethanesulfonate
(14b)
Starting from 10 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (3 mol%), an-
hyd CuI (10 mol%), (Bu)4NI (27 mg, 15 mol%), and Et3N (126 mg,
1.25 mmol), dec-1-yne (76 mg, 0.55 mmol) was added in DMF (5
mL per 1 mmol of 10) to the reaction mixture. After completion of
the reaction and workup, 14b was isolated by chromatography
(flash silica gel, heptanes–EtOAc, 10:1) as a colorless oil; reaction
temperature 90 °C; reaction time 8 h; yield: 188 mg (81%).
MS (EI, 70 eV): m/z (%) = 410 (M+, 100), 409 (17), 408 (15), 396
(12), 395 (28), 366 (14), 204 (14), 197 (10), 196 (23), 191 (10), 190
(18), 182 (59), 181 (16), 176 (33), 170 (17), 123 144 (13), 143 (14),
131 (12), 77 (13).
HRMS (EI): m/z calcd for C31H22O [M]+: 410.16652; found:
410.16813.
IR (KBr): 2924 (m), 2854 (w), 1669 (s), 1608, 1542, 1465 (m), 1426
(s), 1316, 1283, 1235 (m), 1206, 1138 (s), 1087, 1013, 970, 939,
884, 798, 698, 661, 603 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.80 (t, J = 7.3 Hz, 3 H, CH3),
1.17–1.26 (m, 8 H, 4 CH2), 1.33–1.38 (m, 2 H, CH2), 1.50–1.55 (m,
2 H, CH2), 2.36 (t, J = 6.9 Hz, 2 H, CH2), 7.32 (s, 1 H, ArH), 7.37–
7.42 (m, 4 H, ArH), 7.51–7.55 (m, 1 H, ArH), 7.69–7.72 (m, 2 H,
ArH).
[2,4-Di(dec-1-ynyl)phenyl]phenylmethanone (13d)
Starting from 10 (144 mg, 0.30 mmol), Pd(PPh3)2Cl2 (6 mol%), an-
hyd CuI (10 mol%), (Bu)4NI (15 mol%), and Et3N (151 mg, 1.49
mmol), dec-1-yne (45 mg, 0.33 mmol) was added in DMF (5 mL
per 1 mmol of 10) to the reaction mixture. After completion of the
reaction and workup, 13d was isolated by chromatography (flash
silica gel, heptanes–EtOAc, 10:1) as a colorless oil; reaction tem-
perature 90 °C; reaction time 4 h; yield: 100 mg (74%).
IR (KBr): 3059 (w), 2952 (m), 2922 (s), 2852 (m), 2224 (w), 1659,
1593, 1543, 1481, 1446, 1404, 1317, 1292, 1264, 1239, 1177, 1159,
1123, 1027, 939, 841, 793, 744 (m), 713 (s), 694, 666 (m), 615 (w),
594 cm–1 (m).
13C NMR (75 MHz, CDCl3): d = 14.0 (CH3), 19.5, 22.6, 28.3, 28.9,
29.0, 29.1, 31.8 (CH2), 78.4, 95.9 (C), 114.2 (q, J = 320 Hz, CF3),
125.2, 128.5 (CHAr), 129.3 (CAr), 130.1, 130.9 (CHAr), 131.0 (CAr),
131.1, 133.7 (CHAr), 136.5, 146.6 (CAr), 192.2 (C=O).
1H NMR (500 MHz, CDCl3): d = 0.78–0.82 (m, 6 H, 2 CH3), 1.16–
1.28 (m, 20 H, 10 CH2), 1.36–1.44 (m, 4 H, 2 CH2), 1.51–1.60 (m,
4 H, 2 CH2), 7.37–7.41 (m, 3 H, ArH), 7.48–7.54 (m, 3 H, ArH),
7.67–7.71 (m, 2 H, ArH).
19F NMR (282 MHz, CDCl3): d = –73.4.
MS (EI, 70 eV): m/z (%) = 466 (M+, 9), 410 (14), 396 (10), 395 (10),
105 (100), 77 (16).
HRMS (EI): m/z calcd for C24H25F3O4S [M]+: 466.14202; found:
466.14314.
Synthesis 2012, 44, 219–234
© Thieme Stuttgart · New York

PAPER
Functionalized 3,4-Diaryl- and 2,4-Diarylbenzophenones
233
2-Benzoyl-5-[(4-methoxyphenyl)ethynyl]phenyl Trifluoro-
methanesulfonate (14c)
Agnihotri, A.; Srivastava, A. K. Indian J. Chem. Sect. B:
Org. Chem. Incl. Med. Chem. 1984, 23, 154. (d) Inhibition
of the interleukin (IL-1) biosynthesis: Batt, D. G.; Goodman,
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1993, 36, 1434. (e) Inhibition of the human type-2 steroid
5a-reductase: Holt, D. A.; Yamashita, D. S.; Konialian-
Beck, A. L.; Luengo, J. I.; Abell, A. D. J. Med. Chem. 1995,
38, 13. (f) Inhibition of COX-1: Dannhardt, G.; Fiebich, B.
L.; Schweppenhaeuser, J. Eur. J. Med. Chem. Chim. Ther.
2002, 37, 147. (g) Inhibition of human liver microsomes:
Lenhart, A.; Reinert, D. J.; Aebi, J. D.; Dehmlow, H.;
Morand, O. H.; Schulz, G. E. J. Med. Chem. 2003, 46, 2083.
(3) Guarnieri, A.; Burnelli, S.; Varoli, L.; Busacchi, I.; Barbaro,
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(4) Aburaki, S.; Okuyama, S.; Hoshi, H.; Kamachi, H.; Nishio,
M. J. Antibiot. 1993, 46, 1447.
Starting from 10 (238 mg, 0.50 mmol), Pd(PPh3)2Cl2 (3 mol%), an-
hyd CuI (10 mol%), (Bu)4NI (27 mg, 15 mol%), and Et3N (126 mg,
1.25 mmol), 4-methoxyphenylacetylene (72 mg, 0.55 mmol) was
added in DMF (5 mL per 1 mmol of 10) to the reaction mixture. Af-
ter completion of the reaction and workup, 14c was isolated by
chromatography (flash silica gel, heptanes–EtOAc, 10:1) as a color-
less oil; reaction temperature 90 °C; reaction time 8 h; yield: 156
mg (68%).
IR (KBr): 3085 (w), 2958 (m), 2837 (w), 1665 (s), 1596, 1539, 1513
(m), 1428 (s), 1394, 1282, 1246 (m), 1207, 1139 (s), 1076, 1025,
968, 912, 849 (m), 829 (s), 801, 745, 695, 653 (m), 600 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 3.71 (s, 3 H, OCH3), 6.78–6.81
(m, 2 H, ArH), 7.34–7.50 (m, 8 H, ArH), 7.68–7.71 (m, 2 H, ArH).
13C NMR (CDCl3, 75 MHz): d = 55.3 (OCH3), 85.7, 94.3 (C), 114.2
(CHAr), 117.5 (q, J = 320 Hz, CF3), 124.8, 128.6 (CHAr), 128.8
(CAr), 130.1, 130.7 (CHAr), 131.0 131.2 (CAr), 131.3, 133.4, 133.8
(CHAr), 136.4, 146.7, 160.4 (CAr), 192.2 (C=O).
19F NMR (282 MHz, CDCl3): d = –73.3.
MS (EI, 70 eV): m/z (%) = 460 (M+, 100), 327 (21), 312 (12), 105
(5) (a) Pettit, G. R.; Toki, B.; Herald, D. L.; Verdier-Pinard, P.;
Boyd, M. R.; Hamel, E.; Pettit, R. K. J. Med. Chem. 1998,
41, 1688. (b) Liou, J.-P.; Chang, J.-Y.; Chang, C.-W.;
Chang, C.-Y.; Mahindroo, N.; Kuo, F.-M.; Hsieh, H.-P.
J. Med. Chem. 2004, 47, 2897. (c) Liou, J.-P.; Chang,
C.-W.; Song, J. S.; Yang, Y. S.; Yeh, C. F.; Tseng, H. Y.; Lo,
Y. K.; Chang, C.-L.; Chang, C.-M.; Hsieh, H.-P. J. Med.
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(16), 77 (11).
(6) (a) Cai, X.; Sakamoto, M.; Fujitsuka, M.; Majima, T. Chem.
Eur. J. 2005, 11, 6471; and references cited therein.
(b) Langhals, H.; Fuchs, K. Chem. Unserer Zeit 2004, 38,
98; and references cited therein. (c) Lamola, A. A.;
Hammond, G. H. J. Chem. Phys. 1965, 43, 2129.
(d) Kearns, D. R.; Case, W. A. J. Am. Chem. Soc. 1966, 88,
5087. (e) Schimada, R.; Goodman, L. J. Chem. Phys. 1965,
43, 2027. (f) Lower, S. K.; El-Sayed, M. A. Chem. Rev.
1966, 66, 199.
(7) Buchta, E.; Egger, H. Chem. Ber. 1957, 90, 2760.
(8) Liou, J.-P.; Chang, J.-Y.; Chang, C.-W.; Chang, C.-Y.;
Mahindroo, N.; Kuo, F.-M.; Hsieh, H.-P. J. Med. Chem.
2004, 47, 2897.
HRMS (EI): m/z calcd for C23H15F3O5S [M]+: 460.32357; found:
460.323471.
{4¢-tert-Butyl-5-[(4-methoxyphenyl)ethynyl]biphenyl-2-yl}phe-
nylmethanone (15)
Starting from 14c (92 mg, 0.20 mmol), K3PO4 (63 mg, 0.30 mmol),
Pd(PPh3)4 (3 mol%), 4-tert-butylphenylboronic acid (46 mg, 0.26
mmol), and 1,4-dioxane (5 mL per 1 mmol of 14c), 15 was isolated
as a white solid; reaction temperature 90 °C; yield: 65 mg (73%);
mp 131 °C.
IR (KBr): 3057, 3031 (w), 2957 (m), 2903, 2866, 2837 (w), 2220,
2201, 1713 (m), 1663 (s), 1593, 1543 (m), 1509 (s), 1462 (m), 1446
(w), 1412, 1362, 1280, 126 (m), 1245 (s), 1217, 1173, 1105, 1027,
927, 887 (m), 829 (s), 802, 762 (m), 701 (s), 655, 621, 536 cm–1 (m).
(9) Shiue, J.-S.; Lin, M.-H.; Fang, J.-M. J. Org. Chem. 1997, 62,
4643.
1H NMR (300 MHz, CDCl3): d = 1.14 (s, 9 H, 3 CH3), 3.77 (s, 3 H,
OCH3), 6.81–6.84 (m, 2 H, ArH), 7.11–7.31 (m, 6 H, ArH), 7.40–
7.56 (m, 8 H, ArH).
13C NMR (75 MHz, CDCl3): d = 31.1 (3 CH3), 34.3 (C), 55.3
(OCH3), 87.5, 91.2 (C), 114.0 (CHAr), 114.9 (CAr), 125.1 (CHAr),
125.8 (CAr), 127.9, 128.6, 129.0, 129.7, 132.6, 132.9, 133.2 (CHAr),
136.4, 137.4, 138.0, 141.5, 150.4, 159.9 (CAr), 198.3 (C=O).
(10) Appel, B.; Rotzoll, S.; Kranich, R.; Reinke, H.; Langer, P.
Eur. J. Org. Chem. 2006, 3638.
(11) For reviews of site-selective palladium(0)-catalyzed cross-
coupling reactions, see: (a) Schröter, S.; Stock, C.; Bach, T.
Tetrahedron 2005, 61, 2245. (b) Schnürch, M.; Flasik, R.;
Khan, A. F.; Spina, M.; Mihovilovic, M. D.; Stanetty, P. Eur.
J. Org. Chem. 2006, 3283. (c) Wang, R.; Manabe, K.
Synthesis 2009, 1405.
MS (EI, 70 eV): m/z (%) = 444 (M+, 100), 430 (17), 429 (42), 387
(12) For Suzuki–Miyaura reactions of bis(triflates) of benzene
derivatives and other arenes, see for example: (a) Takeuchi,
M.; Tuihiji, T.; Nishimura, J. J. Org. Chem. 1993, 58, 7388.
(b) Sugiura, H.; Nigorikawa, Y.; Saiki, Y.; Nakamura, K.;
Yamaguchi, M. J. Am. Chem. Soc. 2004, 126, 14858.
(c) Akimoto, K.; Suzuki, H.; Kondo, Y.; Endo, K.; Akiba,
U.; Aoyama, Y.; Hamada, F. Tetrahedron 2007, 63, 6887.
(d) Akimoto, K.; Kondo, Y.; Endo, K.; Yamada, M.;
Aoyama, Y.; Hamada, F. Tetrahedron Lett. 2008, 49, 7361.
(e) Hosokawa, S.; Fumiyama, H.; Fukuda, H.; Fukuda, T.;
Seki, M.; Tatsuta, K. Tetrahedron Lett. 2007, 48, 7305.
(f) Nawaz, M.; Adeel, M.; Ibad, M. F.; Langer, P. Synlett
2009, 2154. (g) Mahal, A.; Villinger, A.; Langer, P. Synlett
2010, 1085. (h) Abid, O.-U.-R.; Ibad, M. F.; Nawaz, M.; Ali,
A.; Sher, M.; Rama, N. H.; Villinger, A.; Langer, P.
Tetrahedron Lett. 2010, 51, 1541. (i) Akrawi, O. A.;
Hussain, M.; Langer, P. Tetrahedron Lett. 2011, 52, 1093.
(13) Nawaz, M.; Khera, R. A.; Malik, I.; Ibad, F. A.; Villinger, A.
M.; Langer, P. Synlett 2010, 979.
(10), 105 (24), 77 (13).
HRMS (EI): m/z calcd for C32H28O2 [M]+: 444.20838; found:
444.208616.
Acknowledgment
Financial support by the State of Mecklenburg-Vorpommern and by
the DAAD (scholarship for M. N.) is gratefully acknowledged.
References
(1) Authors R.A.K. and M.N. contributed equally to this
manuscript.
(2) (a) De Souza, A. O.; Santos, R. R.; Melo, P. S.; Alderete, J.
B.; De Conti, R.; Haun, M.; Sato, D. N.; Duran, N.
Pharmazie 2001, 56, 871. (b) De Souza, A. O.; Alderete, J.
B.; Schmidt, F.; Sato, D. N.; Duran, N. Arzneim. Forsch.
1999, 49, 1025. (c) Kumar, S.; Seth, M.; Bhaduri, A. P.;
© Thieme Stuttgart · New York
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PAPER
(14) CCDC-853438 (8) and CCDC-853439 (14c) contain all
crystallographic details of this publication and are available
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html
or can be ordered from the following address: Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; Fax: +44 (1223)336033; or email:
deposit@ccdc.cam.ac.uk.
Synthesis 2012, 44, 219–234
© Thieme Stuttgart · New York