Synthesis of 1,2-diarylnaphthalenes by chemoselective Suzuki-Miyaura reactions of 2-bromo-1-(trifluoromethanesulfonyloxy)naphthalene

Article abstract of DOI:10.1055/s-0030-1260955

Suzuki-Miyaura reactions of 2-bromo-1-(trifluoromethanesulfonyloxy) naphthalene, readily available from 1-tetralone in two steps, afforded a variety of 1,2-diarylnaphthalenes. The reactions proceed with excellent chemoselectivity in favor of the bromide position, while the triflate remained unattacked. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0030-1260955

LETTER
1827
Synthesis of 1,2-Diarylnaphthalenes by Chemoselective Suzuki–Miyaura
Reactions of 2-Bromo-1-(trifluoromethanesulfonyloxy)naphthalene
S
ynthesis of 1,2
a
-Diarylnap
h
hthalene
s
id Hassan,a Munawar Hussain,a Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
b
Received 14 March 2011
OH
Me
OH
Abstract: Suzuki–Miyaura reactions of 2-bromo-1-(trifluo-
romethanesulfonyloxy)naphthalene, readily available from 1-tetral-
one in two steps, afforded a variety of 1,2-diarylnaphthalenes. The
reactions proceed with excellent chemoselectivity in favor of the
bromide position, while the triflate remained unattacked.
NH
OH
Me
Me
OH
OH OMe
HO
2
Key words: catalysis, palladium, Suzuki–Miyaura reaction, naph-
thalene, chemoselectivity
OH
OMe OH
HO
Me
Me
Various naturally occurring naphthalenes possess a biaryl
linkage. The biaryl axis governs the biological activity of
these natural products and is responsible to introduce at-
ropisomerism into some of these compounds due to re-
stricted rotation along the biaryl axis. For example,
naphthylisoquinolines, such as the michellamines [e.g.,
michellamine A (1), Figure 1] isolated from Ancistrocla-
dus korupensis, have attracted the scientific community
primarily because of their antimalaria and anti-HIV activ-
ity.1–3 Resveratrol (2) is a naturally occurring potent anti-
cancer drug, which, however, suffers from chemical and
metabolic instability.4,5 To overcome these limitations a
series of arylated naphthalenes were synthesized in which
the stilbene double bond was substituted by a naphthalene
ring. Among these compounds, which are stable and
structurally more rigid, derivative 3 was found to be most
active against human breast cancer cell line B. Konzik et
al. have shown that the phenyl substituents of naphtha-
lenes have a strong influence on their fungistatic activity.6
OH
NH
HO
OH Me
3
1
Figure 1 Pharmacologically important naphthalene derivatives
on the chemoselectivity of substrates containing different
leaving groups (e.g., triflate and bromide). Recent reports
show that several parameters influence the chemoselec-
tivity of Suzuki–Miyaura reactions of arenes containing a
bromide and a triflate group.10 While various palladium-
catalyzed cross-coupling reactions of naphthalene deriva-
tives have been reported,3 regio- and chemoselective
transformations of naphthalenes containing two or more
reactive sites, such as bromide or triflate groups, have
only scarcely been studied so far. Recently, we have re-
ported regioselective palladium-catalyzed Suzuki cross-
coupling reactions of the bis(triflate) of phenyl 1,4-dihy-
In the literature, several synthetic approaches to 1,2- droxy-2-naphthoate.11 Herein, we wish to report what are,
diphenylnaphthalenes have been described. However, to the best of our knowledge, the first Suzuki–Miyaura re-
classic approaches have limitations with regard to low actions of 2-bromo-1-(trifluoromethanesulfonyloxy)naph-
yields, need of several synthetic steps, availability of the thalene. These reactions proceed with excellent chemose-
starting materials, and low regioselectivity.7 For example, lectivity and provide a convenient approach to various
Bergmann et al. prepared 1,2-diphenylnaphthalene from arylated naphthalene derivatives which are not readily
a-phenyltetralone and phenyl magnesium bromide in available by other methods.
three steps in 46% overall yield.7b
The bromination of naphth-1-ol is known to result in the
In recent years, regioselective palladium-catalyzed reac- formation of mixtures of 2- and 4-brominated naphtha-
tions of polyhalogenated arenes or heteroarenes and of lenes. In 2005, Bekaert et al. reported12 the selective syn-
bis(triflates) have been widely studied.8,9 In general, the thesis of 2-bromonaphth-1-ol (5) by reaction of 1-
first attack occurs at the sterically less hindered and elec- tetralone (4) with N-methylpyrrolidin-2-one hydrotribro-
tronically most deficient position. Another strategy for the mide {MPHT, [NMP]2HBr3}. We have developed an al-
selective functionalization of arenes or heteroarenes relies ternative approach to 5 which relies on the bromination13
of 4 using NBS (2.2 equiv) and (PhCOO)2 (5 mol%,
Scheme 1).14 The advantage of this method is that the
product is formed in very good yield (84%) and that inex-
pensive reagents are used. It is noteworthy that, although
SYNLETT 2011, No. 13, pp 1827–1830
Advanced online publication: 14.07.2011
DOI: 10.1055/s-0030-1260955; Art ID: B06011ST
x
x
.x
x
.2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

1828
Z. Hassan et al.
LETTER
free-radical conditions were applied, bromination at posi-
tion 4 was not observed. 2-Bromonaphth-1-ol (5) was
transformed to its triflate 6 in very good yield.15
Table 1 Synthesis of 1,2-Diarylnaphthalenes 8a–e
7,8
a
Ar
Yield of 8 (%)a
2-MeOC6H4
4-t-BuC6H4
4-MeC6H4
4-ClC6H4
4-FC6H4
62
71
79
94
86
O
OH
b
Br
c
i
4
5 (84%)
d
e
ii
OTf
a Yields of isolated compounds.
Br
Table 2).16,17 The reactions proceeded with very good
chemoselectivity in favor of the bromide position, while
the triflate remained unattacked. During the optimization,
it proved to be important to use exactly 1.0 equivalent of
the arylboronic acid and Pd(PPh3)4 (5 mol%) as the cata-
lyst. The temperature played an important role as well. A
good selectivity was achieved only when the reaction was
carried out at 90 °C (instead of 110 °C) because the reac-
tion of the triflate was slow at this temperature. The reac-
tions were successful for both electron-rich and electron-
poor arylboronic acids, but again electron-poor boronic
acids provided better yields. The structures of the prod-
ucts could be easily established based on the fact that the
triflate group is still present in the molecule (13C NMR,
19F NMR).
6 (92%)
Scheme 1 Synthesis of 5 and 6. Reagents and conditions: i, 4 (1.0
equiv), NBS (2.2 equiv), (PhCOO)2 (5 mol%), benzene, reflux, 5 h;
ii, 5 (1.0 equiv), Tf2O (1.2 equiv), pyridine (2.0 equiv), CH2Cl2,
20 °C, 12 h.
The structure of product 5 was elucidated by 2D NMR
spectroscopy (NOESY, COSY, HMBC, HMQC). A
NOESY correlation between hydrogen atoms H-4
(d = 7.44 ppm, d, J = 8.8 Hz) and H-5 (d = 7.72 ppm, m)
was observed (Figure 2).
H
OH
H
H
Br
H
OTf
OTf
Ar1B(OH)2
7a,c–f
Br
Ar1
H
H
i
6
9a–e
Figure 2 Important HMBC (single head arrows), NOESY (dashed
arrows), and COSY (double head arrows) correlations of 5
Scheme 3 Synthesis of 9a–e. Reagents and conditions: i, 6 (1.0
equiv), Ar1B(OH)2 (1.0 equiv), Pd(PPh3)4 (5 mol%), K3PO4 (1.5
equiv), dioxane, 90 °C, 4 h.
The Suzuki–Miyaura reaction of 6 with arylboronic acids
7a–e (2.2 equiv) afforded the 1,2-diarylnaphthalenes 8a–
e in 62–94% yield (Scheme 2, Table 1).16 Both electron-
poor and electron-rich arylboronic acids could be success-
fully employed. Arylboronic acids bearing electron-with-
drawing groups provided better yields than those
containing electron-donating groups. The best yields were
obtained using Pd(PPh3)4 (5 mol%) as the catalyst and
K3PO4 (3.0 equiv) as the base. The reactions were carried
out in 1,4-dioxane at 110 °C.
Table 2 Synthesis of 9a–e
7
a
c
f
9
a
b
c
Ar1
Yield of 9 (%)a
2-MeOC6H4
4-MeC6H4
Ph
60
73
77
88
85
d
d
4-ClC6H4
4-FC6H4
e
e
The Suzuki–Miyaura reaction of 6 with arylboronic acids
7a,c–f (1.0 equiv) afforded the 2-arylnaphth-1-yl trifluo-
romethanesulfonates 9a–e in 60–88% yields (Scheme 3,
a Yields of isolated compounds.
OTf
Ar
The Suzuki–Miyaura reaction of 9a–e with arylboronic
acids 7a,b,g–i (1.1 equiv) afforded the 1,2-diarylnaphtha-
lenes 10a–e containing two different aryl groups
(Scheme 4, Table 3).16,18 The reactions were carried out at
110 °C. The application of a one-pot synthesis of products
10 by sequential addition of two different arylboronic ac-
ids to 6 resulted in a decrease of the yield (with respect to
ArB(OH)2
Br
Ar
7a–e
i
6
8a–e
Scheme 2 Synthesis of 8a–e. Reagents and conditions: i, 6 (1.0
equiv), ArB(OH)2 (2.2 equiv), Pd(PPh3)4 (5 mol%), K3PO4 (3.0
equiv), dioxane, 110 °C, 4 h.
Synlett 2011, No. 13, 1827–1830 © Thieme Stuttgart · New York

LETTER
Synthesis of 1,2-Diarylnaphthalenes
1829
D. W.; Dawson, M. I. Chem. Commun. 1996, 923.
the stepwise protocol). Therefore, this approach was not
further investigated.
(e) Bringmann, G.; Harmsen, S.; Holenz, J.; Geuder, T.;
Gotz, R.; Keller, P. A.; Walter, R.; Hallock, Y. F.;
Cardellina, J. H. II.; Boyd, M. R. Tetrahedron 1994, 50,
9643. (f) Kelly, T. R.; Garcia, A.; Lang, F.; Walsh, J. J.;
Bhaskar, K. V.; Boyd, M. R.; Gotz, R.; Keller, P. A.; Walter,
R.; Bringmann, G. Tetrahedron Lett. 1994, 35, 7621.
(g) Hoye, T. R.; Chen, M.; Mi, L.; Priest, O. P. Tetrahedron
Lett. 1994, 47, 8747.
Ar2
OTf
Ar2B(OH)2
7a,b,g–i
Ar1
Ar1
i
9a–e
10a–e
(4) Aggarwal, B. B.; Bhardwaj, A.; Aggarwal, R. S.; Seeram, N.
P.; Shishodia, S.; Takada, Y. Anticancer Res. 2004, 24,
2783.
(5) Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas,
C. F.; Beecher, C. W.; Fong, H. H.; Farnsworth, N. R.;
Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M.
Science 1997, 275, 218.
(6) (a) Signorelli, P.; Ghidoni, R. J. Nutr. Biochem. 2005, 16,
449. (b) Minutolo, F.; Sala, G.; Bagnacani, A.; Bertini, S.;
Carboni, I.; Placanica, G.; Prota, G.; Rapposelli, S.; Sacchi,
N.; Macchia, M.; Ghadoni, R. J. Med. Chem. 2005, 48,
6783. (c) Viswanathan, G. S.; Wang, M.; Li, C. J. Angew.
Chem. Int. Ed. 2002, 41, 2138. (d) Kozik1, B.; Burgie, Z. J.;
Sepiot, J. J.; Wilamowski, J.; Kuczynski, M.; Góra1, M.
Environ. Biotechnol. 2006, 20.
(7) (a) Crawford, G. J. Am. Chem. Soc. 1939, 61, 608.
(b) Bergmann, F.; Echinazi, E.; Schapiro, D. J. Am. Chem.
Soc. 1942, 64, 557.
(8) For reviews of cross-coupling reactions of polyhalogenated
heterocycles, 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.
(9) For palladium-catalyzed reactions from our group, see for
example: (a) Dang, T. T.; Dang, T. T.; Ahmad, R.; Reinke,
H.; Langer, P. Tetrahedron Lett. 2008, 49, 1698. (b) Dang,
T. T.; Villinger, A.; Langer, P. Adv. Synth. Catal. 2008, 350,
2109. (c) Hussain, M.; Nguyen, T. H.; Langer, P.
Tetrahedron Lett. 2009, 50, 3929. (d) Dang, T. T.; Dang, T.
T.; Rasool, N.; Villinger, A.; Langer, P. Adv. Synth. Catal.
2009, 351, 1595.
(10) (a) Kamikawa, T.; Hayashi, T. Tetrahedron Lett. 1997, 38,
7087. (b) Littke, A. F.; Dai, C. Y.; Fu, G. C. J. Am. Chem.
Soc. 2000, 122, 4020. (c) Roy, A. H.; Hartwig, J. F.
Organometallics 2004, 23, 194. (d) Espinet, P.; Echavarren,
A. M. Angew. Chem. Int. Ed. 2004, 43, 4704. (e) Espino,
G.; Kurbangalieva, A.; Brown, J. M. Chem. Comm. 2007,
1742; and references cited therein.
Scheme 4 Synthesis of 10a–e. Reagents and conditions: i, 9a–e (1.0
equiv), Ar2B(OH)2 (1.1 equiv), Pd(PPh3)4 (5 mol%), K3PO4 (1.5
equiv), dioxane, 110 °C, 4 h.
Table 3 Synthesis of 10a–e
10
7
9
Ar1
Ar2
Yield of 10
(%)a
a
b
c
b
g
a
h
i
a
b
c
2-MeOC6H4
4-MeC6H4
Ph
4-t-BuC6H4
80
65
69
72
77
2,5-(MeO)2C6H3
2-MeOC6H4
3,5-Me2C6H3
3-MeC6H4
d
e
d
e
4-ClC6H4
4-FC6H4
a Yields of isolated compounds.
Aryl bromides usually undergo Suzuki–Miyaura reactions
more rapidly than aryl triflates.10 This reactivity order is
different for other palladium-catalyzed cross-coupling re-
actions. One of the explanations for that is based on the
high borane–halide affinity. However, other parameters
influence the selectivity as well.10e
In conclusion, we have reported chemoselective Suzuki–
Miyaura reactions of 2-bromo-1-(trifluoromethanesulfo-
nyloxy)naphthalene which is readily available from 1-te-
tralone in two steps. The strategy outlined herein provides
a convenient approach to 1,2-diarylnaphthalenes which
are not readily available by other methods.
Acknowledgment
(11) Abid, O.-u.-R.; Ibad, M. F.; Nawaz, M.; Sher, M.; Rama, N.
H.; Villinger, A.; Langer, P. Tetrahedron Lett. 2010, 51,
1541.
(12) Bekaert, A.; Provot, O.; Rasolojaona, O.; Alami, M.; Brion,
J.-D. Tetrahedron Lett. 2005, 46, 4187.
Financial support by the State of Pakistan and by the State of Meck-
lenburg-Vorpommern (scholarships for M.H.) is gratefully acknow-
ledged.
(13) (a) Bolton, R. In Bromine Compounds: Chemistry and
Applications; Price, D.; Iddon, B.; Wakefield, B. J., Eds.;
Elsevier: Amsterdam, 1988, 151. (b) de Kimpe, N.; Verhé,
R. In The Chemistry of a-Haloketones, a-Haloaldehydes and
a-Haloimines; Patai, S.; Rappoport, Z., Eds.; Wiley: New
York, 1988.
References and Notes
(1) De Koning, C. B.; Michael, J. P.; van Otterlo, W. A. L.
Tetrahedron Lett. 1999, 40, 3037.
(2) Manfredi, K. P.; Blunt, J. W.; Cardellina, J. H. II.;
Macmahon, J. B.; Pannell, L. K.; Cragg, G. M.; Boyd, M. R.
J. Med. Chem. 1991, 34, 3402.
(14) Synthesis of 2-Bromonaphth-1-ol (5)
(3) (a) Bringmann, G.; Gotz, R.; Keller, P. A.; Walter, R.; Boyd,
M. R.; Lang, F.; Garcia, A.; Walsh, J. J.; Tellitu, I.; Bhaskar,
K. V.; Kelly, T. R. J. Org. Chem. 1998, 63, 1090.
(b) Bringmann, G.; Gotz, R.; Harmsen, S.; Holenz, J.;
Walter, R. Liebigs Ann. Chem. 1996, 2045. (c) Hobbs, P.
D.; Upender, V.; Dawson, M. I. Synlett 1997, 965.
(d) Hobbs, P. D.; Upender, V.; Liu, J.; Pollart, D. J.; Thomas,
A benzene suspension (30 mL) of 1-tetralone (4, 1.8 mL,
13.7 mmol), NBS (5.4 g, 30.2 mmol), and (PhCOO)2 (0.17
g, 5mol%) was refluxed under Argon atmosphere for 4 h and
then cooled to 20 °C. To the reaction mixture was added
Et3N (1 mL), and the solvent was removed in vacuo. The
reaction mixture was diluted with H2O and extracted with
CH2Cl2 (3 × 25 mL). The combined organic layers were
dried (Na2SO4), filtered, and the filtrate was concentrated in
Synlett 2011, No. 13, 1827–1830 © Thieme Stuttgart · New York

1830
Z. Hassan et al.
LETTER
vacuo. The residue was purified by flash chromatography
(silica gel, heptane–EtOAc) to give 5 as a colorless solid
(2.57 g, 84%). Rf = 0.54 (heptane–EtOAC = 4:1). 1H NMR
(250 MHz, CDCl3): d = 5.89 (s, 1 H, OH), 7.24 (d, 1 H,
J = 8.8 Hz), 7.38–7.41 (d, 1 H, J = 8.8 Hz), 7.43–7.46 (m, 2
H), 7.66–7.75 (m, 1 H), 8.12–8.19 (m, 1 H). 13C NMR (75.5
MHz, CDCl3): d = 104.0 (C), 121.3, 122.2, 124.1 (CH),
124.4 (C), 124.8, 127.5, 128.3 (CH), 133.7, 148.1 (C). IR
(KBr): n = 3400 (s), 3051, 1958, 1931, 1883, 1877, 1624
(w), 1586, 1574 (m), 1504 (w), 1453, 1396, 1384, 1347,
1240, 1212, 1202, 1140, 1126, 1054, 1021, 876, 856 (m),
829, 792, 768, 736 (s), 716, 641, 600, 561 (m) cm–1. GC-MS
(EI, 70 eV): m/z (%) = 222 (98) [M]+, 115 (92). HRMS (EI,
70 eV): m/z calcd for C10H7BrO [M]+: 221.96803; found:
221.96799.
dried (Na2SO4), filtered, and the filtrate was concentrated in
vacuo. The residue was purified by column chromatography.
(17) Synthesis of 2-(4-Fluorophenyl)naphth-1-yl
Trifluoromethanesulfonate (9e)
Starting with 6 (200 mg, 0.73 mmol), 4-fluorophenylboronic
acid 7e (102 mg, 0.73 mmol), Pd(PPh3)4 (42 mg, 5 mol%),
K3PO4 (232 mg, 1.5 mmol), and 1,4-dioxane (5 mL), 9e was
isolated as a highly viscous oil (229 mg, 85%). Rf = 0.51
(heptane–EtOAc, 4:1). 1H NMR (300 MHz, CDCl3):
d = 7.05–7.15 (m, 2 H), 7.38–7.45 (m, 3 H), 7.49–7.62 (m, 2
H), 7.80–7.59 (m, 2 H), 8.09 (d, 1 H, J = 8.4 Hz, ArH). 19
NMR (282.4 MHz, CDCl3): d = –113.2, –74.0. 13C NMR
(62.9 MHz, CDCl3): d = 115.6 (d, JF,C = 21.4 Hz, 2 CH),
117.1 (q, JF,C = 316.2 Hz, CF3), 119.7 (C), 121.7, 127.3,
128.0 (CH), 128.2 (d, JF,C = 2.6 Hz, 2 CH), 128.6, 131.4,
131.6 (CH), 132.3, 132.4, 134.1, 141.9 (C), 161.9 (d,
F
(15) Synthesis of 2-Bromonaphth-1-yl
Trifluoromethanesulfonate (6)
JF,C = 248.5 Hz, CF). IR (KBr): n = 2961, 1606 (w), 1513,
1498 (m), 1405 (s), 1341 (w), 1201 (s), 1159 (m), 1132 (s),
1088, 1018, 1007 (m), 894 (s), 867 (m), 816, 804 (s), 764
(m), 749 (s), 703, 683, 622, 598, 556, (m) cm–1. GC-MS (EI,
70 eV): m/z (%) = 370 (19) [M+], 237 (100), 209 (51), 183
(12). HRMS (EI, 70 eV): m/z calcd for C17H10F4O3S [M]+:
370.02813; found: 370.02763.
To a solution of 5 (2.4 g, 10.8 mmol) in CH2Cl2 (25 mL) was
added pyridine (1.8 mL, 21.6 mmol) at 20 °C under an argon
atmosphere. After stirring for 10 min at 0 °C, Tf2O (2.7 mL,
16.4 mmol) was added. The mixture was allowed to warm to
20 °C and stirred for further 6 h. The reaction mixture was
filtered, and the filtrate was concentrated in vacuo. The
residue was directly purified by chromatography without
aqueous workup (flash silica gel, heptane–EtOAc) to give 6
as a light yellow oil (3.53 g, 92%). Rf = 0.71 (heptane–
EtOAc, 4:1). 1H NMR (300 MHz, CDCl3): d = 7.56–7.69
(m, 4 H), 7.83 (d, 1 H, J = 7.8 Hz), 8.13 (d, 1 H, J = 8.1 Hz).
19F NMR (282.4 MHz, CDCl3): d = –73.0. 13C NMR (75.5
MHz, CDCl3): d = 114.1 (C), 118.5 (q, JF,C = 321.0 Hz,
CF3), 121.2, 127.5 (CH), 127.9 (C), 128.1, 128.5, 129.4,
129.9 (CH), 133.7, 142.6 (C). IR (KBr): n = 1589, 1501,
1457 (m), 1408 (s), 1370, 1365 (m), 1203, 1181 (s), 1124 (s),
1032, (m)1018, 890, 801, 761 (s), 743, 703, 665, 616, 587,
(m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 354 (100) [M]+,
223 (52). HRMS (EI, 70 eV): m/z calcd for C11H6BrF3O3S:
353.91731 [M]+; found: 353.91711.
(18) Synthesis of 2-(4-Fluorophenyl)-1-(m-tolyl)naphthalene
(10e)
Starting with 9e (100 mg, 0.27 mmol), 3-tolylboronic acid
(40 mg, 0.29 mmol), Pd(PPh3)4 (16 mg, 5 mol%), K3PO4 (86
mg, 0.41 mmol), and 1,4-dioxane (5 mL), 10e was isolated
as a highly viscous oil (65 mg, 77%). Rf = 0.44 (heptane–
EtOAc, 4:1). 1H NMR (300 MHz, CDCl3): d = 2.2 (s, 3 H,
CH3), 6.75–6.91 (m, 4 H), 7.00–7.05 (m, 3 H), 7.10 (t, 1 H,
J = 7.4 Hz), 7.28–7.40 (m, 2 H), 7.43 (d, 1 H, J = 8.6 Hz),
7.58 (br d, 1 H, J = 8.5 Hz), 7.81 (d, 2 H, J = 8.2 Hz). 19
F
NMR (282.4 MHz, CDCl3): d = –116.6. 13C NMR (75.5
MHz, CDCl3): d = 114.5 (d, JF,C = 21.3 Hz, 2 CH), 125.8,
126.3, 126.9, 127.6, 127.8, 127.9, 128.1, 128.5, 131.5,
131.6, 132.1 (CH), 132.7, 132.8, 137.2, 137.4, 137.9, 138.1
(d, JF,C = 3.3 Hz, C), 138.7 (C), 161.5 (d, JF,C = 245.6 Hz,
CF). IR (KBr): n = 3050, 2920 (m), 2852 (w), 1601 (m),
1499 (s), 1457 (m), 1234 (w), 1218 (s), 1155, 1092, 1023
(m), 962 (w), 863, 841 (m), 817, 803, 778, 743, 713, 693 (s),
653, 544 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 312 (100)
[M+], 222 (55), 204 (7). HRMS (EI, 70 eV): m/z calcd for
C23H17F [M]+: 312.13143; found: 312.13133.
(16) General Procedure for Suzuki–Miyaura Reactions
A 1,4-dioxane (5 mL per 1 mmol) solution of 6 or 9a–e (1.0
equiv), K3PO4 (1.5 equiv per cross-coupling step), Pd(PPh3)4
(5 mol%), and arylboronic acid 3 (1.0–1.1 equiv per cross-
coupling step) was stirred at 90–110 °C for 4 h. After
cooling to 20 °C, H2O was added. The organic and the
aqueous layers were separated, and the latter was extracted
with CH2Cl2 (15 × 3 mL). The combined organic layer was
Synlett 2011, No. 13, 1827–1830 © Thieme Stuttgart · New York