Palladium-catalyzed perarylation of 3-thiophene- and 3-furancarboxylic acids accompanied by C-H bond cleavage and decarboxylation

Article abstract of DOI:10.1021/ol800466b

3-Thiophene- and 3-furancarboxylic acids efficiently undergo perarylation accompanied by cleavage of the three C-H bonds and decarboxylation upon treatment with excess aryl bromides in the presence of a palladium catalyst to give the corresponding tetraarylated products in good yields.

Full text of DOI:10.1021/ol800466b

Supporting Information
For
Palladium-Catalyzed Perarylation of 3-Thiophene- and 3-Furancarboxilic Acids
Accompanied by C-H Bond Cleavage and Decarboxylation
Masaya Nakano, Hayato Tsurugi, Tetsuya Satoh, and Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita,
Osaka 565-0871, Japan
e-mail: miura@chem.eng.osaka-u.ac.jp
List of Contents for Experimental Section
General: S-2
Tetraphenylation of 3-Thiophenecarboxylic acid (2) with Bromobenzene (1a)
(Table 1, entry 8): S-2
Triphenylation of N-Phenyl-3-thiophenecarboxamide (5) with Bromobenzene
(1a) (Scheme 2): S-2
Diphenylation of Ethyl 3-Thiophenecarboxylate (7) with Bromobenzene (1a)
(Scheme 3): S-3
Diarylation of 2,5-Diphenyl-3-thiophenecarboxylic Acid
4-Bromoanisole (1d): S-3
(11) with
Characterization Data of Products: S-4 - S-7
References: S-8
1H and13C NMR of Products: S-9 - S-27
S-1

Experimental Section
1
13
General: H and C NMR spectra were recorded at 400 MHz and 100 MHz,
respectively, for CDCl3 solutions. MS data were obtained by EI. GC analysis was
carried out using a silicon OV-17 column (i. d. 2.6 mm x 1.5 m) or a CBP-1 capillary
column (i. d. 0.5 mm x 25 m). GC-MS analysis was carried out using a CBP-1 capillary
column (i. d. 0.25 mm x 25 m).
N-Phenyl-3-thiophenecarboxamide (5) was prepared by the reaction of
3-thiophenecarbonyl chloride with aniline in the presence of pyridine in ether. Ethyl
3-thiophenecarboxylate (7) was prepared by esterification of 3-thiophenecarboxylic acid
(2) in the presence of a catalytic amount of sulfuric acid in refluxing ethanol. Other
starting materials were commercially available.
The following experimental procedure may be regarded as typical in
methodology and scale.
Tetraphenylation of 3-Thiophenecarboxylic acid (2) with Bromobenzene
(1a) (Table 1, entry 8): In a 20 cm3 two-necked flask were added the bromide 1a (2.5
mmol, 393 mg), the acid 2 (0.5 mmol, 64 mg), Pd(OAc)2 (0.05 mmol, 11.2 mg), PCy3
(0.2 mmol, 56 mg), Cs2CO3 (2.5 mmol, 815 mg), MS4A (150 mg), 1-methylnaphthalene
(94 mg) as internal standard, and mesitylene (5 mL). The resulting mixture was stirred
o
under N2 (balloon) at 170 C (bath temperature) for 8 h. After cooling, analysis of the
mixture by GC and GC-MS confirmed formation of 2,3,4,5-tetraphenylthiophene (4a)
(163 mg, 83%) together with 2,3,5-triphenylthiophene (3) (25 mg, 16%). The
tetraphenylthiophene 4a (161 mg, 82 %) was also isolated by filtration of the mixture
with a filter paper with ether, evaporation of the solvents, and chromatography on silca
gel using hexane-ethyl acetate (99:1, v/v).
Triphenylation
of
N-Phenyl-3-thiophenecarboxamide
(5)
with
Bromobenzene (1a) (Scheme 2): In a 20 cm3 two-necked flask were added the bromide
S-2

1a (3 mmol, 471 mg), the amide 5 (0.5 mmol, 102 mg), Pd(OAc)2 (0.05 mmol, 11.2 mg),
PPh3 (0.1 mmol, 26 mg), Cs2CO3 (3 mmol, 978 mg), 1-methylnaphthalene (55 mg) as
internal standard, and o-xylene (2.5 mL). The resulting mixture was stirred under N2
(balloon) at 170 oC (bath temperature) for 10 h. After cooling,
N,2,4,5-tetraphenyl-3-thiophenecarboxamide 6 (182 mg, 84 %) was isolated by
filtration of the mixture with a filter paper with ether, evaporation of the solvents, and
chromatography on silca gel using hexane-ethyl acetate (94:6, v/v).
Diphenylation of Ethyl 3-Thiophenecarboxylate (7) with Bromobenzene
(1a) (Scheme 3): In a 100 cm3 two-necked flask were added the bromide 1a (12 mmol,
1.88 g), the ester 7 (4 mmol, 625 mg), Pd(OAc)2 (0.4 mmol, 90 mg),
P(biphenyl-2-yl)tBu2 (0.8 mmol, 239 mg), Cs2CO3 (12 mmol, 3.90 g), MS4A (1.2 g),
and DMF (40 mL). The resulting mixture was stirred under N2 (balloon) at 150 oC (bath
temperature) for 11 h. After cooling, the mixture was poured into water and extracted
with diethyl ether. The solvent was dried over sodium sulfate and evaporated. The
residue was chromatographed on silica gel using hexane-ethyl acetate (99.5:0.5, v/v) to
afford ethyl 2,5-diphenyl-3-thiophenecarboxylate (8) (1.13 g, 91%). Hydrolysis of 8 (2
mmol) with KOH (10 mmol) in refluxing ethanol (15 mL) for 10 h and acidification
with dilute HCl gave 2,5-diphenyl-3-thiophenecarboxylic acid (11) quantitatively.
Diarylation of 2,5-Diphenyl-3-thiophenecarboxylic acid
(11) with
4-Bromoanisole (1d) (Table 3): In a 20 cm3 two-necked flask were added the bromide
1d (1.5 mmol, 281 mg), the acid 11 (0.5 mmol, 140 mg), Pd(OAc)2 (0.05 mmol, 11.2
mg), PCy3 (0.2 mmol, 56 mg), Cs2CO3 (1.5 mmol, 487 mg), MS4A (150 mg), dibenzyl
(56 mg) as internal standard, and mesitylene (5 mL). The resulting mixture was stirred
under N2 (balloon) at 170 oC (bath temperature) for 9 h. After cooling,
3,4-bis(4-methoxyphenyl)-2,5-diphenylthiophene (12) (106 mg, 47%) was isolated by
filtration of the mixture with a filter paper with ether, evaporation of the solvents, and
chromatography on silca gel using hexane-ethyl acetate (99:1, v/v).
S-3

Characterization Data of Products.
o
1
2,3,4,5-Tetraphenylthiophene (4a):1 mp 184-185 C; H NMR (400 MHz,
13
CDCl3) d 6.95-6.98 (m, 4H), 7.08-7.14 (m, 6H), 7.19-7.25 (m, 10H); C NMR (100
MHz, CDCl3) d 126.58, 127.20, 127.82, 128.29, 129.20, 130.86, 134.25, 136.46, 138.55,
139.48; HRMS m/z (M+) Calcd for C28H20S 388.1286. Found 388.1283.
o
1
2,3,4,5-Tetrakis(4-methylphenyl)thiophene (4b):2 mp 227-228 C; H NMR
(400 MHz, CDCl3) d 2.26 (s, 6H), 2.29 (s, 6H), 6.84 (d, J = 8.1 Hz, 4H), 6.91 (d, J = 8.1
13
Hz, 4H), 7.01 (d, J = 8.1 Hz, 4H), 7.12 (d, J = 8.1 Hz, 4H); C NMR (100 MHz,
CDCl3) d 21.15, 21.22, 128.52, 128.96, 129.00, 130.67, 131.62, 133.66, 135.86, 136.74,
137.96, 139.09; HRMS m/z (M+) Calcd for C32H28S 444.1912. Found 444.1913.
o
2,3,4,5-Tetrakis(4-tert-butylphenyl)thiophene (4c): mp 193-194 C; H NMR
1
(400 MHz, CDCl3) d 1.24 (s, 18H), 1.28 (s, 18H), 6.87 (d, J = 8.4 Hz, 4H), 7.09 (d, J =
13
8.4 Hz, 4H), 7.17-7.23 (m, 8H); C NMR (100 MHz, CDCl3) d 31.26, 31.30, 34.36,
34.49, 124.40, 125.11, 128.49, 130.41, 131.61, 133.87, 137.55, 139.63, 149.10, 149.80;
HRMS m/z (M+) Calcd for C44H52S 612.3790. Found 612.3792.
1
2,3,4,5-Tetrakis(4-methoxyphenyl)thiophene (4d):3 mp 217-218 oC; H NMR
(400 MHz, CDCl3) d 3.74 (s, 6H), 3.77 (s, 6H), 6.67 (d, J = 8.8 Hz, 4H), 6.76 (d, J = 9.2
13
Hz, 4H), 6.87 (d, J = 8.8 Hz, 4H), 7.15 (d, J = 9.2 Hz, 4H); C NMR (100 MHz,
CDCl3) d 55.03, 55.18, 113.30, 113.72, 127.08, 129.12, 130.30, 131.95, 137.18, 138.35,
158.06, 158.64; HRMS m/z (M+) Calcd for C32H28O4S 508.1708. Found 508.1712.
o
2,3,4,5-Tetrakis(4-trifluoromethylphenyl)thiophene (4e): mp 166-167 C; H
1
NMR (400 MHz, CDCl3) d 7.06 (d, J = 8.1 Hz, 4H), 7.30 (d, J = 8.1 Hz, 4H), 7.44 (d, J
13
= 8.1 Hz, 4H), 7.53 (d, J = 8.1 Hz, 4H); C NMR (100 MHz, CDCl3) d 123.88 (q, J =
272.3 Hz), 123.91 (q, J = 272.4 Hz), 125.68 (q, J = 4 Hz), 125.37 (q, J = 4 Hz), 129.17,
129.66 (q, J = 32.1 Hz), 129.98 (q, J = 32.8 Hz), 130.92, 133.66, 138.76, 138.89,
139.18; HRMS m/z (M+) Calcd for C32H16F12S 660.0781. Found 660.0780.
S-4

o
1
2,3,4,5-Tetrakis(4-ethoxycarbonylphenyl)thiophene (4f):4 mp 81-82 C; H
NMR (400 MHz, CDCl3) d 1.371 (t, J = 7.0 Hz, 6H), 1.374 (t, J = 7.0 Hz, 6H), 4.34 (q,
J = 7.0 Hz, 4H), 4.36 (q, J = 7.0 Hz, 4H), 7.01 (d, J = 8.1 Hz, 4H), 7.26 (d, J = 8.4 Hz,
4H), 7.82 (d, J = 8.1 Hz, 4H), 7.91 (d, J = 8.4 Hz, 4H); 13C NMR (100 MHz, CDCl3) d
14.28, 14.30, 61.05, 61.06, 128.97, 129.28, 129.47, 129.61, 129.78, 130.63, 137.73,
139.34, 139.36, 140.25, 166.08, 166.26; HRMS m/z (M+) Calcd for C40H36O8S 676.2131.
Found 676.2170.
1
2,3,4,5-Tetrakis(biphenyl-4-yl)thiophene (4g): mp 180-181oC; H NMR (400
MHz, CDCl3) d 7.12 (d, J = 8.4 Hz, 4H), 7.27-7.34 (m, 4H), 7.35-7.44 (m,16H), 7.49 (d,
13
J = 8.4 Hz, 4H), 7.58 (d, J = 8.1 Hz, 8H); C NMR (100 MHz, CDCl3) d 126.54,
126.84, 126.90, 127.01, 127.21, 127.36, 128.70, 128.77, 129.52, 131.32, 133.22, 135.47,
138.48, 139.11, 139.23, 139.88, 140.40, 140.51; HRMS m/z (M+) Calcd for C52H36S
692.2538. Found 692.2545.
o
1
N,2,4,5-Tetraphenyl-3-thiophenecarboxamide (6): mp 214-215 C; H NMR
(400 MHz, CDCl3) d 7.00-7.11 (m, 3H), 7.18-7.23 (m, 7H), 7.27-7.43 (m, 8H), 7.66 (d,
J = 7.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 120.18, 124.56, 127.69, 127.71, 128.46,
128.49, 128.56, 128.58, 128.81, 128.91, 129.18, 129.90, 132.74, 133.30, 135.03, 135.48,
137.36, 137.65, 139.73, 142.25, 163.78; HRMS m/z (M+) Calcd for C29H21NOS
431.1344. Found 431.1349.
o
1
Ethyl 2,5-Diphenyl-3-thiophenecarboxylate (8):5 mp 45-46 C; H NMR
(400 MHz, CDCl3) d 1.20 (t, J = 7.1 Hz, 3H), 4.22 (q, J = 7.1 Hz, 2H ), 7.32 (t, J = 7.3
Hz, 1H), 7.38-7.43 (m, 5H), 7.52-7.55 (m, 2H), 7.62 (d, J = 7.33 Hz, 2H), 7.71 (s, 1H);
13C NMR (100 MHz, CDCl3) d 14.02, 60.57, 125.42, 125.72, 127.92, 128.01, 128.58,
128.96, 129.01, 129.78, 133.34, 133.38, 142.46, 149.71, 163.27; HRMS m/z (M+) Calcd
for C19H16O2S 308.0871. Found 308.0878.
Ethyl 2,5-Bis(4-methoxyphenyl)-3-thiophenecarboxylate (9): mp 92-93 oC;
1H NMR (400 MHz, CDCl3) d 1.24 (t, J = 7.1 Hz, 3H), 3.84 (s, 3H), 3.85 (s, 3H), 4.23
S-5

(q, J = 7.1 Hz, 2H), 6.93 (d, J = 9.2 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.8
13
Hz, 2H), 7.53 (d, J = 9.2 Hz, 2H); C NMR (100 MHz, CDCl3) d 14.14, 55.32, 55.36,
60.45, 113.37, 114.38, 124.35, 125.72, 126.29, 126.97, 128.21, 131.07, 141.73, 149.09,
159.51, 159.92, 163.41; HRMS m/z (M+) Calcd for C21H20O4S 368.1082. Found
368.1086.
o
1
2,5-Diphenyl-3-thiophenecarboxylic Acid (10):6 mp 196-197 C; H NMR
(400 MHz, DMSO-d6) d 7.36 (t, J = 7.3 1H), 7.41-7.47 (m, 5H), 7.53-7.56 (m, 2H), 7.7
13
(d, J = 7.3 Hz, 2H), 7.79 (s, 1H); C NMR (100 MHz, DMSO-d6) d 125.29, 125.84,
128.06, 128.16, 128.53, 129.17, 129.32, 129.98, 132.53, 132.77, 141.56, 147.76,
163.92; HRMS m/z (M+) Calcd for C17H12O2S 280.0558. Found 280.0551.
2,5-Bis(4-methoxyphenyl)-3-thiophenecarboxylic Acid (11): mp 223-224
oC; 1H NMR (400 MHz, DMSO-d6) d 3.79 (s, 3H), 3.80 (s, 3H), 6.96-7.01 (m, 4H), 7.47
13
(d, J = 8.8 Hz, 2H), 7.61 (d, J = 9.2 Hz, 2H), 7.62 (s, 1H); C NMR (100 MHz,
DMSO-d6) d 55.17, 55.19, 113.52, 114.56, 124.61, 125.10, 125.32, 126.62, 129.15,
130.65, 140.81, 147.05, 159.22, 159.5, 164.08; HRMS m/z (M+) Calcd for C19H16O4S
340.0769. Found 340.0778.
o
1
3,4-Bis(4-methoxyphenyl)-2,5-diphenylthiophene (12): mp 210-211 C; H
NMR (400 MHz, CDCl3) d 3.74 (s, 6H), 6.67 (d, J = 9.0 Hz, 4H), 8.79 (d, J = 9.0 Hz,
4H), 7.17-7.26 (m, 10H); 13C NMR (100 MHz, CDCl3) d 55.04, 113.33, 127.05, 128.27,
128.86, 129.17, 131.93, 134.50, 138.05, 139.14, 158.18; HRMS m/z (M+) Calcd for
C30H24O2S 448.1497. Found 448.1494.
2,5-Diphenyl-3,4-bis(4-trifluoromethyl-phenyl)thiophene (13): mp 141-142
1
oC; H NMR (400 MHz, CDCl3) d 7.05 (d, J = 8.1 Hz, 4H), 7.18-7.21 (m, 4H),
7.24-7.27 (m, 6H), 7.39 (d, J = 8.1 Hz, 4H); 13C NMR (100 MHz, CDCl3) d 124.09 (q, J
= 272 Hz), 125.02 (q, J = 4 Hz), 127.81, 128.58, 129.00 (q, J = 32 Hz), 129.31, 131.10,
133.37, 137.37, 139.77, 140.16; HRMS m/z (M+) Calcd for C30H18F6S 524.1033. Found
524.1029.
S-6

1
2,5-Bis(4-methoxyphenyl)-3,4-diphenylthiophene (14):7 mp 196-197 oC; H
NMR (400 MHz, CDCl3) d 3.76 (s, 6H), 6.75 (d, J = 8.8 Hz, 4H), 6.94-6.98 (m, 4H),
13
7.08-7.13 (m, 6H), 7.15 (d, J = 8.8 Hz, 4H); C NMR (100 MHz, CDCl3) d 55.17,
113.73, 126.42, 126.81, 127.78, 130.32, 130.88, 136.71, 137.68, 138.70, 158.75; HRMS
m/z (M+) Calcd for C30H24O2S 448.1497. Found 448.1490.
2,5-Bis(4-methoxyphenyl)-3,4-bis(4-trifluoromethylphenyl)thiophene
1
(15): mp 172-173 oC; H NMR (400 MHz, CDCl3) d 3.78 (s, 6H), 6.78 (d, J = 8.8 Hz,
13
4H), 7.04 (d, J = 7.9 Hz, 4H), 7.10 (d, J = 8.8 Hz, 4H), 7.39 (d, J = 7.9 Hz, 4H); C
NMR (100 MHz, CDCl3) d 55.22, 114.0, 124.13 (q, J = 272 Hz), 124.98 (q, J = 4 Hz),
125.83, 128.81 (q, J = 32 Hz), 130.48, 131.13, 136.62, 139.37, 140.05, 159.20; HRMS
m/z (M+) Calcd for C32H22F6O2S 584.1245. Found 584.1247.
o
1
2,3,4,5-Tetraphenylfuran (17a):8 mp 172-173 C; H NMR (400 MHz,
13
CDCl3) d 7.14-7.28 (m, 16H), 7.50-7.51 (m, 2H), 7.52-7.53 (m, 2H); C NMR (100
MHz, CDCl3) d 125.13, 125.86, 127.14, 127.29, 128.34, 128.36, 130.41, 130.91, 133.19,
147.72; HRMS m/z (M+) Calcd for C28H20O 372.1514. Found 372.1517.
o
1
2,3,4,5-Tetrakis(4-methoxyphenyl)furan (17d):9 mp 208-209 C; H NMR
(400 MHz, CDCl3) d 3.79 (s, 6H), 3.79 (s, 6H), 6.79 (d, J = 8.8 Hz, 4H), 6.80 (d, J = 9.2
13
Hz, 4H), 7.06 (d, J = 8.8 Hz, 4H), 7.44 (d, J = 9.2 Hz, 4H); C NMR (100 MHz,
CDCl3) d 55.10, 55.22, 113.82, 113.83, 123.24, 124.15, 125.80, 127.14, 131.53, 147.10,
158.53, 158.72; HRMS m/z (M+) Calcd for C32H28O5 492.1937. Found 492.1934.
o
1
2,3,4,5-Tetrakis(4-trifluoromethyl-phenyl)furan (17e): mp 196-197 C; H
NMR (400 MHz, CDCl3) d 7.27 (d, J = 8.1 Hz, 4H), 7.57-7.59 (m, 12H); 13C NMR (100
MHz, CDCl3:DMSO-d6 = 4:1) d 123.57 (q, J = 272 Hz), 123.58 (q, J = 272 Hz), 124.89,
125.22 (q, J = 4 Hz), 125.38 (q, J = 4 Hz), 125.80, 128.95 (q, J = 32 Hz), 129.33 (q, J =
32 Hz), 130.26, 132.66, 135.30, 147.35; HRMS m/z (M+) Calcd for C32H16F12O
644.1010. Found 644.1004.
S-7

References in Supporting Information
(1) Braye, E. H.; Hübel, W.; Caplier, I. J. Am. Chem. Soc. 1961, 83, 4406.
(2) Xing, Y.; Xu, X.; Wang, F.; Lu, P. Opt. Mat. 2006, 29, 407.
(3) Arumugam, K.; Bollinger, J. E.; Fink, M.; Donahue, J. P. Inorg. Chem. 2007,
46, 3283.
(4) Hopff, H.; von der Crone, J. Chimia 1959, 13, 107.
(5) Potts, K. T.; Datta, S. K.; Marshall, J. L. J. Org. Chem. 1979, 44. 622.
(6) Gotthart, H.; Weisshuhn, M. C.; Christl, B. Chem. Ber. 1976, 109, 753.
(7) Dang, Y.; Chen, Y. J. Org. Chem. 2007, 72, 6901.
(8) Tseng, J.-C.; Chen, J.-H.; Luh, T.-Y. Synlett 2006, 1209.
(9) Mortensen, D. S.; Rodriguez, A. L.; Carlson, K. E.; Sun, J.;
Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2001, 44,
3838.
S-8

1H and 13C NMR of Compound 4a
S-9

1H and 13C NMR of Compound 4b
S-10

1H and 13C NMR of Compound 4c
S-11

1H and 13C NMR of Compound 4d
S-12

1H and 13C NMR of Compound 4e
S-13

1H and 13C NMR of Compound 4f
S-14

1H and 13C NMR of Compound 4g
S-15

1H and 13C NMR of Compound 6
S-16

1H and 13C NMR of Compound 8
S-17

1H and 13C NMR of Compound 9
S-18

1H and 13C NMR of Compound 10
S-19

1H and 13C NMR of Compound 11
S-20

1H and 13C NMR of Compound 12
S-21

1H and 13C NMR of Compound 13
S-22

1H and 13C NMR of Compound 14
S-23

1H and 13C NMR of Compound 15
S-24

1H and 13C NMR of Compound 17a
S-25

1H and 13C NMR of Compound 17d
S-26

1H and 13C NMR of Compound 17e
S-27