Synthesis of bis(diaryl)sulfones by site-selective suzuki-miyaura reactions of 2,4-bis(trifluoromethylsulfonyloxy)diphenylsulfone

Article abstract of DOI:10.1055/s-0029-1219343

The Suzuki-Miyaura reaction of the bis(triflate) of 2,4-bis(hydroxy) diphenylsulfone with two equivalents of boronic acids gave 2,4-bis(aryl) diphenylsulfones. The reaction with one equivalent of arylboronic acids resulted in site-selective attack onto ca

Full text of DOI:10.1055/s-0029-1219343

LETTER
731
Synthesis of Bis(diaryl)sulfones by Site-Selective Suzuki–Miyaura Reactions of
2,4¢-Bis(trifluoromethylsulfonyloxy)diphenylsulfone
S
ynthesis of Bis(d
s
iaryl)sulfo
a
nes d Ali,a Rasheed Ahmad Khera,a Muhammad Farooq Ibad,a Munawar Hussain,a Peter Langer*a,b
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
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Received 17 November 2009
were carried out using Pd(PPh3)4 (6 mol%) as the catalyst.
The employment of other catalysts, such as PdOAc)2/
XPhos, resulted in a decreased yield. A slight excess (2.6
equiv) of the boronic acid was used. Potassium phosphate
(K3PO4) was used as the base. 1,4-Dioxane (110 °C, 4 h)
was used as the solvent.12,13
Abstract: The Suzuki–Miyaura reaction of the bis(triflate) of 2,4¢-
bis(hydroxy)diphenylsulfone with two equivalents of boronic acids
gave 2,4¢-bis(aryl)diphenylsulfones. The reaction with one equiva-
lent of arylboronic acids resulted in site-selective attack onto carbon
atom C-4¢.
Key words: catalysis, palladium, Suzuki–Miyaura reaction, site
selectivity, sulfones
R2
R3
R3
R4
R1
R2
R1
R4
Diarylsulfones are of considerable pharmacological rele-
vance.1 Diaryl sulfones have been prepared by oxidation
of diaryl sulfides,2 by Friedel–Crafts-type acylation of
anisole with phenylsulfonic acid chloride,3 and by reac-
tion of phenol with benzenesulfonic acid.4 These methods
suffer from low yields, harsh reaction conditions, and low
regioselectivities. Transition-metal-mediated syntheses of
diaryl sulfones include the CuI/proline-mediated reaction
of aryl iodides with sodium benzenesulfinate,5 Suzuki re-
actions of 4-methoxybenzeneboronic acid with phenylsul-
fonic acid chloride,6 and Cu(OAc)2-catalyzed reaction of
4-methoxybenzeneboronic acid with sodium benzene-
sulfinate.7 Diaryl sulfones have also been prepared by cy-
clization reactions of sulfone-containing building blocks.8
Herein, we report the synthesis of bis(diaryl)sulfones by
site-selective9,10 Suzuki–Miyaura reactions of the bis(tri-
flate) of 2,4¢-bis(dihydroxy)diphenylsulfone.
B(OH)2
O
S
3a–j
ii
R1
+
O
R2
R3
OTf
O
S
4a–j
O
R4
OTf
2
Scheme 2 Synthesis of 4a–j. Reagents and conditions: i, 2 (1.0
equiv), 3a–j (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.
Table 1 Synthesis of 4a–j
3, 4
a
b
c
R1
H
R2
H
R3
H
R4
H
Yield of 4 (%)a
75
70
60
62
65
70
55
65
60
72
Commercially available 2,4¢-bis(hydroxy)diphenylsul-
fone (1) was transformed into its bis(triflate) 2 in 81%
yield (Scheme 1).11
H
H
Me
H
H
H
CF3
H
H
d
e
OMe
H
H
H
OTf
O
S
OH
O
S
H
CF3
t-Bu
F
H
i
O
O
f
H
H
H
OTf
OH
2 (81%)
1
g
h
i
H
H
H
Scheme 1 Synthesis of 2. Reagents and conditions: i, CH2Cl2, 1 (1.0
equiv), –78 °C, pyridine (4.0 equiv), Tf2O (2.4 equiv), –78 °C to 0 °C,
4 h.
H
H
vinyl
H
H
H
Me
OMe
Me
OMe
j
H
H
The Suzuki reaction of 2 with arylboronic acids 3a–j (2.6
equiv) afforded the novel 2,4¢-bis(aryl)diphenylsulfones
4a–j in good yields (Scheme 2, Table 1). The reactions
a Yields of isolated products.
The Suzuki–Miyaura reaction of 2 with boronic acids
3b,f,k–m (1.1 equiv), in the presence of Pd(PPh3)4 (3
mol%), proceeded with very good site selectivity (attack
at carbon atom C-4¢) to give the 2-trifluoromethylsulfonyl-
SYNLETT 2010, No. 5, pp 0731–0734
Advanced online publication: 19.01.2010
DOI: 10.1055/s-0029-1219343; Art ID: G36209ST
© Georg Thieme Verlag Stuttgart · New York
1
9.
1
.2
0
1
0

732
A. Ali et al.
LETTER
oxy-4¢-(aryl)diphenylsulfones
5a–e
(Scheme 3,
Table 3 Synthesis of 6a–c
Table 2).12,14 All products were isolated in pure form by
chromatographic purification. In most cases, a small
amount of the biscoupled product could be detected in the
3
k
a
l
6
a
b
c
R
Yield of 6 (%)a
Et
60
57
50
1
crude product before chromatography (by H NMR and
H
GC-MS). The reaction of 5e with arylboronic acids 3a,k,l
(1.1 equiv) gave the unsymmetrical 2,4¢-bis(aryl)diphe-
nylsulfones 6a–c containing two different aryl groups
(Scheme 4, Table 3).12,15 The structures of the products
were proved by 2D NMR experiments (NOESY, HMBC).
OMe
a Yields of isolated products.
can be explained by the fact that carbon atom C-4¢ is less
sterically hindered.
R2
R3
R4
R1
In conclusion, we have reported the synthesis of 2,4¢-
bis(aryl)diphenylsulfones based on what are, to the best of
our knowledge, the first palladium(0)-catalyzed cross-
coupling reactions of bis(triflates) of 2,4¢-bis(hy-
droxy)diphenylsulfone. The reactions proceed with very
good site selectivity.
OTf
O
S
B(OH)2
R1
3b,f,k–m
i
O
R2
R3
+
OTf
O
S
5a–e
R4
Acknowledgment
O
OTf
Financial support by the DAAD (scholarships for A.A. and R.A.K.)
is gratefully acknowledged.
2
Scheme 3 Synthesis of 5a–e. Reagents and conditions: i, 2 (1.0
equiv), 3b,f,k–m (1.1 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol%),
1,4-dioxane (5 mL per 1 mmol of 2), 110 °C, 4 h.
References and Notes
(1) Antibacterial activity: (a) Shrimali, S. S.; Joshi, B. C.;
Kishore, D. J. Indian Chem. Soc. 1988, 65, 438.
Table 2 Synthesis of 5a–e
(b) Upadhyay, P. S.; Vansdadia, R. N.; Baxi, A. J. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1990, 29, 793.
Inhibition of phospholipidase A2: (c) Teshirogi, I.;
Matsutani, S.; Shirahase, K.; Fujii, Y.; Yoshida, T. J. Med.
Chem. 1996, 39, 5183. Inhibition of catechol O-
methyltransferase: (d) Paulini, R.; Lerner, C.; Diederich, F.;
Jakob-Roetne, R.; Zuercher, G.; Borroni, E. Helv. Chim.
Acta 2006, 89, 1856. Inhibition of dihydropteroate synthase
of Escherichia coli: (e) de Benedetti, P. G.; Iarossi, D.;
Menziani, C.; Caiolfa, V.; Frassineti, C.; Cennamo, C.
J. Med. Chem. 1987, 30, 459. (f) de Benedetti, P. G.;
Iarossi, D.; Folli, U.; Frassineti, C.; Menziani, M. C.;
Cennamo, C. J. Med. Chem. 1989, 32, 2396.
3
k
l
5
a
b
c
R1
H
R2
H
R3
R4
H
H
H
H
H
Yield of 5 (%)a
Et
75
76
70
55
62
H
H
OMe
t-Bu
H
f
H
H
m
b
d
e
OMe
H
OMe
H
Me
a Yields of isolated products.
Hypolipidemic activity: (g) Sircar, I.; Hoefle, M.; Maxwell,
R. E. J. Med. Chem. 1983, 26, 1020. Cytotoxicity against
HeLa cells and the antipicornavirus: (h) Markley, L. D.;
Tong, Y. C.; Dulworth, J. K.; Steward, D. L.; Goralski, C. T.
J. Med. Chem. 1986, 29, 427. Neuropeptide Y1 receptor
binding activity: (i) Wright, J.; Bolton, G.; Creswell, M.;
Downing, D.; Georgic, L. Bioorg. Med. Chem. Lett. 1996, 6,
1809. Anti-HIV activity: (j) Neamati, N.; Mazumder, A.;
Zhao, H.; Sunder, S.; Burke, T. R. Jr.; Schultz, R. J.;
Pommier, Y. Antimicrob. Agents Chemother. 1997, 41, 385.
(k) Chan, J. H.; Hong, J. S.; Hunter, R. N.; Orr, G. F.;
Cowan, J. R.; Sherman, D. B.; Sparks, S. M.; Reitter, B. E.;
Andrews, C. W.; Hazen Richard, J.; Clair, M. S. J. Med.
Chem. 2001, 44, 1866. (l) Tagat, J. R.; McCombie, S. W.;
Steensma, R. W.; Lin, S.-I.; Nazareno, D. V.; Baroudy, B.;
Vantuno, N.; Xu, S.; Liu, J. Bioorg. Med. Chem. Lett. 2001,
11, 2143. Anticholesteremic activity: (m) Stanton, J. L.;
Cahill, E.; Dotson, R.; Tan, J.; Tomaselli, H. C.; Wasvary, J.
M.; Stephan, Z. F.; Steele, R. E. Bioorg. Med. Chem. Lett.
2000, 10, 1661. Binding to human muscarinic M1 and M2
receptors: (n) Kozlowski, J. A.; Zhou, G.; Tagat, J. R.; Lin,
S.-I.; McCombie, S. W.; Ruperto, V. B.; Duffy, R. A.;
R
R
B(OH)2
3a,k,l
i
O
S
+
OTf
O
S
O
O
6a–c
5e
Scheme 4 Synthesis of 6a–c. Reagents and conditions: ii, 5e (1.0
equiv), 3a,k,l (1.1 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol%),
1,4-dioxane, 110 °C, 4 h.
The oxidative addition of palladium usually occurs first at
the most electron-deficient carbon atom.9 Carbon atoms
C-2 and C-4¢ of bis(triflate) 2 are expected to be equally
electron deficient. The site-selective formation of 5a–e
Synlett 2010, No. 5, 731–734 © Thieme Stuttgart · New York

LETTER
McQuade, R. A.; Crosby, G.; Taylor, L. A.; Billard, W.
Synthesis of Bis(diaryl)sulfones
733
L.; Delamano, J.; Gomes, A.; Lopez, C.; Tojo, G. J. Org.
Chem. 1996, 61, 1188. (k) Shkoor, M.; Riahi, A.; Fatunsin,
O.; Reinke, H.; Fischer, C.; Langer, P. Synthesis 2009, 2223.
(9) For a review of site-selective palladium(0)-catalyzed cross-
coupling reactions, see: Schröter, S.; Stock, C.; Bach, T.
Tetrahedron 2005, 61, 2245.
(10) For site-selective reactions of bis(triflates) of 2,4¢-dihydro-
xybenzophenones, see: (a) Nawaz, M.; Adeel, M.; Farooq,
M.; Langer, P. Synlett 2009, 2154. For reactions of the
bis(triflate) of methyl 2,5-dihydroxybenzoate, see:
(b) Nawaz, M.; Farooq, M.; Obaid-Ur-Rahman, A.; Khera,
R. A.; Villinger, A.; Langer, P. Synlett 2010, 150.
(11) Synthesis of 2,4¢-Bis(trifluoromethylsulfonyloxy)-
diphenylsulfone (2)
Bioorg. Med. Chem. Lett. 2002, 12, 791. (o) Wang, Y.;
Chackalamannil, S.; Hu, Z.; Clader, J. W.; Greenlee, W.;
Billard, W.; Binch, H.; Crosby, G.; Ruperto, V.; Duffy, R.
A.; McQuade, R.; Lachowicz, J. E. Bioorg. Med. Chem. Lett.
2000, 10, 2247. (p) Boyle, C. D.; Chackalamannil, S.; Chen,
L.-Y.; Dugar, S.; Pushpavanam, P.; Billard, W.; Binch, H.;
Crosby, G.; Cohen-Williams, M.; Coffin, V. L.; Duffy, R. A.
Bioorg. Med. Chem. Lett. 2000, 10, 2727. (q) Wang, Y.;
Chackalamannil, S.; Chang, W.; Greenlee, W.; Ruperto, V.;
Duffy, R. A.; McQuade, R.; Lachowicz, J. E. Bioorg. Med.
Chem. Lett. 2001, 11, 891. (r) Tagat, J. R.; McCombie, S.
W.; Steensma, R. W.; Lin, S.-I.; Nazareno, D. V.; Baroudy,
B.; Vantuno, N.; Xu, S.; Liu, J. Bioorg. Med. Chem. Lett.
2001, 11, 2143. (s) Boyle, C. D.; Chackalamannil, S.;
Clader, J. W.; Greenlee, W. J.; Josien, H. B.; Kaminski, J. J.;
Kozlowski, J. A.; McCombie, S. W.; Nazareno, D. V.;
Tagat, J. R.; Wang, Y. Bioorg. Med. Chem. Lett. 2001, 11,
2311. (t) Boyle, C. D.; Vice, S. F.; Campion, J.;
Chackalamannil, S.; Lankin, C. M.; McCombie, S. W.;
Billard, W.; Binch, H.; Crosby, G.; Williams, M.-C.; Coffin,
V. L. Bioorg. Med. Chem. Lett. 2002, 12, 3479. Histamine
H3-receptor antagonistic activity: (u)Sasse, A.; Ligneau, X.;
Sadek, B.; Elz, S.; Pertz, H. H.; Ganellin, C. R.; Arrang, J.-
M.; Schwartz, J.-C.; Schunack, W.; Stark, H. Arch. Pharm.
(Weinheim, Ger.) 2001, 334, 45. Antiprotozoal activity:
(v) Langler, R. F.; Paddock, R. L.; Thompson, D. B.;
Crandall, I.; Ciach, M.; Kain, K. C. Aust. J. Chem. 2003, 56,
1127. Binding to the human cannabinoid CB1 receptor:
(w) Lavey, B. J.; Kozlowski, J. A.; Hipkin, R. W.;
Gonsiorek, W.; Lundell, D. J.; Piwinski, J. J.; Narula, S.;
Lunn, C. A. Bioorg. Med. Chem. Lett. 2005, 15, 783.
Inhibition of the main protease of the recombinant SARS
coronavirus: (x) Lu, I.-L.; Mahindroo, N.; Liang, P.-H.;
Peng, Y.-H.; Kuo, C.-J.; Tsai, K.-C.; Hsieh, H.-P.; Chao,
Y.-S.; Wu, S.-Y. J. Med. Chem. 2006, 9, 5154.
To a solution of 1 (1.0 equiv) in CH2Cl2 (10 mL per 1 mmol
of 1) was added pyridine (4.0 equiv) at –78 °C under an
argon atmosphere. After stirring for 10 min, Tf2O (2.4 equiv)
was added at –78 °C. The mixture was allowed to warm to
0 °C and stirred for 4 h. The reaction 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). Starting
with 1 (250 mg, 1.0 mmol), pyridine (0.32 mL, 4.0 mmol),
and Tf2O (0.40 mL, 2.4 mmol), compound 2 was isolated as
a white solid (416 mg, 81%), mp 112 °C.
1H NMR (300 MHz, CDCl3): d = 7.32–7.39 (m, 3 H, ArH),
7.50–7.56 (m, 1 H, ArH), 7.63–7.69 (m, 1 H, ArH), 7.99–
8.04 (m, 2 H, ArH), 8.21–8.24 (m, 1 H, ArH). 19F NMR (282
MHz, CDCl3): d = –73.2, –73.3 CF. 13C NMR (75 MHz,
CDCl3): d = 114. 5 (q, JCF = 324.2 Hz, CF3), 121.8 (q,
JCF = 324.2 Hz, CF3), 122.4, 122.5, 128.9, 131.1, 131.4
(CH), 133.3 (C), 136.4 (CH), 140.5, 146.5, 152.9 (C). IR
(KBr): n = 3104 (w), 1594 (w), 1484 (w), 1434 (s), 1404 (w),
1325 (m), 1272 (w), 1203 (s), 1161 (s), 1127 (s), 1089 (m),
1054 (m), 992 (w), 966 (w), 870 (s), 749 (s), 781 (m), 726
(m), 688 (m), 629 (m), 599 (s), 562 (s), 552 (s) cm–1. GC-MS
(EI, 70 eV): m/z (%) = 514 (44) [M]+, 317 (1), 273 (27), 225
(05), 209 (33), 177 (100), 155 (06), 115 (17). HRMS (EI, 70
eV): m/z calcd for C14H8F6O8S3: 514.39262; found: 514.
39351.
(2) Joseph, J. K.; Jain, S. L.; Sain, B. Synth. Commun. 2006, 36,
2743.
(3) (a) Chen, D.-W.; Kubiak, R. J.; Ashley, J. A.; Janda, K. D.
J. Chem. Soc., Perkin Trans. 1 2001, 21, 2796. (b)Marquie,
J.; Laporterie, A.; Dubac, J.; Roques, N.; Desmurs, J.-R.
J. Org. Chem. 2001, 66, 421. (c) Repichet, S.; Le Roux, C.;
Dubac, J. Tetrahedron Lett. 1999, 40, 9233. (d) Hajipour,
A. R.; Zarei, A.; Khazdooz, L.; Pourmousavi, S. A.;
Mirjalili, B. B. F.; Ruoho, A. E. Phosphorus, Sulfur Silicon
Relat. Elem. 2005, 180, 2029.
(12) General Procedure for the Synthesis of 4a–j, 5a–e, and
6a–c
A 1,4-dioxane solution of the arylboronic acid, K3PO4,
Pd(PPh3)4, and 2 or 5 was stirred at 110 °C for 4 h under
argon atmosphere. After cooling to 20 °C, a sat. aq solution
of NH4Cl was added. The organic and the aqueous layer
were separated, and the latter was extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered,
and the filtrate was concentrated in vacuo. The residue was
purified by column chromatography.
(4) Woroshzow, V.; Kutschkarow, V. Zh. Obshch. Khim. 1949,
19, 1943; Chem. Abstr. 1950, 1922.
(5) Zhu, W.; Ma, D. J. Org. Chem. 2005, 70, 2696.
(6) Bandgar, B. P.; Bettigeri, S. V.; Phopase, J. Org. Lett. 2004,
6, 2105.
(13) 2,4¢-Bis(4-tolyl)diphenylsulfone (4b)
(7) Huang, F.; Batey, R. A. Tetrahedron 2007, 63, 7667.
(8) (a) Erian, A. W.; Issac, Y.; Sherif, S. M.; Mahmoud, F. F.
J. Chem. Soc., Perkin Trans. 1 2000, 3686. (b) Ogura, K.;
Takeda, M.; Xie, J. R.; Akazome, M.; Matsumoto, S.
Tetrahedron Lett. 2001, 42, 1923. (c) Matsumoto, S.;
Kumazawa, K.; Ogura, K. Bull. Chem. Soc. Jpn. 2003, 76,
2179. (d) Bianchi, L.; Dell’Erba, C.; Maccagno, M.;
Mugnoli, A.; Novi, M.; Petrillo, G.; Sancassan, F.; Tavani,
C. J. Org. Chem. 2003, 68, 5254. (e) Mutsuhiro, Y.;
Watanabe, M.; Furukawa, S. Chem. Pharm. Bull. 1990, 38,
902. (f) Padwa, A.; Gareau, Y.; Harrison, B.; Rodriguez, A.
J. Org. Chem. 1992, 57, 3540. (g) Hayakawa, K.;
Starting with 2 (205 mg, 0.4 mmol), K3PO4 (254 mg, 1.2
mmol), Pd(PPh3)4 (6 mol%), 4-methylphenylboronic acid
(136 mg, 1.0 mmol), and 1,4-dioxane (5 mL per 1 mmol of
2), compound 4b was isolated as a white solid (112 mg,
70%), mp 131 °C. 1H NMR (300 MHz, CDCl3): d = 2.29 (s,
3 H, CH3), 2.30 (s, 3 H, CH3), 6.77–6.80 (m, 2 H, ArH),
6.89–6.92 (m, 2 H, ArH), 7.11–7.20 (m, 6 H, ArH), 7.26–
7.33 (m, 2 H, ArH), 7.44–7.52 (m, 3 H, ArH), 8.31–8.35 (m,
1 H, ArH). 13C NMR (75 MHz, CDCl3): d = 21.2, 21.3
(CH3), 126.6, 127.1, 127.6, 127.8, 128.2, 128.5, 129.8,
130.0, 132.8, 132.9 (CH), 135.4, 136.5, 137.4, 138.5, 139.3,
140.1, 142.3, 145.3 (C). IR (KBr): n = 3058 (w), 2921 (w),
2854 (w), 1731 (w), 1613 (m), 1484 (m), 4163 (m), 1404
(m), 1392 (m), 1313 (s), 1247 (w), 1151 (s), 1091 (m), 959
(w), 820 (m), 757 (s), 670 (m), 585 (s), 532 (s) cm–1. GC-MS
(EI, 70 eV): m/z (%) = 398 (100) [M]+, 366 (2), 318 (22),
Nishiyama, H.; Kanematsu, K. J. Org. Chem. 1985, 50, 512.
(h) Nakayama, J.; Hirashima, A. J. Am. Chem. Soc. 1990,
112, 7648. (i) Hu, C.-M.; Hong, F.; Jiang, B.; Xu, Y.
J. Fluorine Chem. 1994, 66, 215. (j) Antelo, B.; Castedo,
Synlett 2010, No. 5, 731–734 © Thieme Stuttgart · New York

734
A. Ali et al.
LETTER
215 (6), 198 (4), 183 (22), 165 (46), 155 (7), 152 (38), 115
(6). HRMS (EI, 70 eV): m/z calcd for C26H22O2S [M]+:
398.13350; found: 398.133551.
HRMS (EI, 70 eV): m/z calcd for C21H17O5S2F3 [M + H]+:
471.05423; found: 471.05405.
(15) 2-(4-Ethylphenyl)-4¢-(4-methylphenyl)diphenyl-sulfone
(14) 2-(Trifluoromethylsulfonyloxy)-4¢-(4-ethylphenyl)-
(6a)
diphenylsulfone (5a)
Starting with 5e (182 mg, 0.40 mmol), K3PO4 (127 mg, 0.60
mmol), Pd(PPh3)4 (3 mol%), 4-ethylphenylboronic acid (66
mg, 0.44 mmol), and 1,4-dioxane (5 mL per 1 mmol of 5e),
compound 6a was isolated as a solid (98 mg, 60%). 1H NMR
(300 MHz, CDCl3): d = 1.18 (t, J = 7.7 Hz, 3 H, CH2CH3),
2.31 (s, 3 H, CH3), 2.61 (q, J = 7.6Hz, 2 H, CH2CH3), 6.80–
6.82 (m, 2 H, ArH), 6.89–6.93 (m, 2 H, ArH), 7.07–7.20 (m,
5 H, ArH), 7.23–7.36 (m, 4 H, ArH), 7.44–7.48 (m, 2 H,
ArH), 8.32–8.36 (m, 1 H, ArH). 13C NMR (75 MHz, CDCl3):
d = 15.4, 21.1 (CH3), 28.5 (CH2), 127.1 (C), 127.2, 127.3,
127.5, 127.6, 128.6, 128.9, 129.8, 130.9, 135.5, 136.1 (CH),
138.3, 138.8, 139.7, 145.1, 146.5, 146.7, 146.9 (C). IR
(KBr): n = 3104 (w)3058 (w), 2967 (w), 2920 (w), 2873 (w),
1592 (m), 1555 (w), 1484 (w), 1450 (w), 1423 (s), 1406 (w),
1333 (s), 1297 (m), 1228 (m), 1209 (s), 1157 (s), 1128 (s),
1089 (m), 1054 (m), 1003 (m), 958 (w), 884 (s), 781 (m), 717
(m), 685 (m), 622 (m), 595 (s), 560 (s) cm–1. GC-MS (EI, 70
eV): m/z (%) = 412 (100) [M]+, 348 (12), 333 (22), 318 (26),
197 (26), 165 (50), 152 (32). HRMS (EI, 70 eV): m/z calcd
for C27H24O2S: 412.14973; found: 412.14882.
Starting with with 2 (205 mg, 0.4 mmol), K3PO4 (127 mg,
0.6 mmol), Pd(PPh3)4 (3 mol%), 4-ethylphenylboronic acid
(66 mg, 0.44 mmol), and 1,4-dioxane (5 mL per 1 mmol of
2), compound 5a was isolated as a white solid (141 mg,
75%), mp 78 °C. 1H NMR (300 MHz, CDCl3): d = 1.19 (t,
J = 7.6 Hz, 3 H, CH3), 2.64 (q, J = 7.6 Hz, 2 H, CH2CH3),
7.18–7.24 (m, 2 H, ArH), 7.32–7.35 (m, 1 H, ArH), 7.42–
7.53 (m, 3 H, ArH), 7.58–7.66 (m, 3 H, ArH), 7.93–7.97 (m,
2 H, ArH), 8.23–8.27 (m, 1 H, ArH). 19F NMR (282 MHz,
CDCl3): d = –73.4. 13C NMR (75 MHz, CDCl3): d = 15.4
(CH3), 28.5 (CH2), 118.8 (q, JCF = 320.1 Hz, CF3), 122.2,
127.3, 127.5, 128.5, 128.6, 128.9, 130.9 (CH), 134.4 (C),
135.5 (CH), 136.3, 138.3, 145.1, 146.5, 146.9 (C). IR (KBr):
n = 3108, 3053, 2965, 2852 (w), 1591 (m), 1555, 1520, 1448
(w), 1468 (m), 1433 (s), 1391, 1267 (w), 1247 (m), 1200,
1157, 1128, 1056 (s), 1002 (m), 965 (w), 870, 818, 786 (s),
739, 716, 684 (m), 619, 584, 545 (s) cm–1. GC-MS (EI, 70
eV): m/z (%) = 470 (100) [M]+, 337 (10), 309 (02), 244 (42),
229 (16), 197 (24), 181 (07), 165 (28), 152 (15), 115 (05).
Synlett 2010, No. 5, 731–734 © Thieme Stuttgart · New York

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