6926 J . Org. Chem., Vol. 62, No. 20, 1997
Rieke et al.
dissolved in THF, the supernatant was then transferred to a
mixture of aryl iodide (4 mmol) and Ni(dppe)Cl2 (0.4 mol %)
with stirring in THF (5 mL) at room temperature. 3-Thienyl-
benzene (3a ) was obtained in 80% isolated yield based upon
3-iodothiophene. Other arylthiophenes were prepared in a
similar way using either Ni(dppe)Cl2 or Pd(PPh3)4 as catalyst
in 40-80% isolated yields.
1-Hep tyl-1-(3-th ien yl)m eth a n ol (5d ): 1H NMR δ 7.30-
7.28 (m, 1H), 7.17-7.16 (m, 1H), 7.08-7.06 (m, 1H), 4.74 (t, J
) 6.68 Hz, 1H), 2.00 (s, 1H), 1.79-1.25 (m, 12H), 0.88 (t, J )
7.16, 3H); 13C NMR δ 146.42, 125.94, 125.62, 120.56, 70.61,
38.35, 31.75, 29.40, 29.17, 25.65, 22.58, 14.02.
P r ep a r a tion of 2-(Hexylth io)th iop h en e (8): 1H NMR δ
7.33-7.31 (m, 1H), 7.11-7.10 (m, 1H), 6.98-6.95 (m, 1H), 2.83
(t, J ) 7.17 Hz, 2H), 1.62-1.61 (m, 2H), 1.42-1.31 (m, 6H),
0.91 (t, J ) 6.58 Hz, 3H); 13C NMR δ 134.97, 133.14, 128.80,
38.93, 31.30, 29.31, 28.05, 22.48, 13.98; HRMS calcd for
C10H16S2 200.0693, found 200.0690.
3-Th ien ylben zen e (3a ): 1H NMR δ 7.69-7.66 (m, 2H),
7.51-7.42 (m, 5H), 7.39-7.36 (m, 1H); 13C NMR δ 142.36,
135.86, 128.78, 127.10, 126.44, 126.32, 126.16, 120.25; HRMS
calcd for C10H8S 160.0347, found 160.0343. Anal. Calcd for
C10H8S: C, 74.96; H, 5.03; S, 20.01. Found: C, 74.99; H, 4.92;
S, 19.88.
Eth yl p-(3-th ien yl)ben zoa te (3b): 1H NMR δ 8.10-8.07
(m, 2H), 7.68-7.65 (m, 2H), 7.57-7.56 (m, 1H), 7.44-7.42 (m,
2H), 4.42 (q, J ) 7.25 Hz, 2H), 1.42 (t, J ) 6.85 Hz, 3H) 13C
NMR δ 166.34, 141.22, 139.89, 130.12, 128.98, 126.59, 126.14,
126.11, 121.77; HRMS calcd for C13H12O2S 232.0558, found
232.0554. Anal. Calcd for C13H12O2S: C, 67.22; H, 5.21; O,
13.77; S, 13.80. Found: C, 67.16; H, 5.07; O, 13.74; S, 13.45.
p-(3-Th ien yl)n itr oben zen e (3c): 1H NMR δ 8.27-8.24 (m,
2H), 7.75-7.72 (m, 2H), 7.64-7.63 (m, 1H), 7.48-7.43 (m, 2H);
13C NMR δ 146.63, 141.88, 139.92, 127.27, 126.79, 126.00,
124.26, 123.17; HRMS calcd for C10H7NO2S 205.0197, found
205.0190; Anal. Calcd for C10H7NO2S: C, 58.52; H, 3.44; N,
6.82; O, 15.59; S, 15.62. Found: C, 58.39; H, 3.25; N, 6.65; O,
15.64; S, 15.24.
p-(3-Th ien yl)a cetop h en on e (3d ): 1H NMR δ 8.01-7.98
(m, 2H), 7.70-7.67 (m, 2H), 7.59-7.57 (m, 1H), 7.44-7.43 (m,
2H), 2.62 (s, 3H); 13C NMR δ 197.48, 141.06, 140.17, 135.64,
129.03, 126.73, 126.34, 126.14, 122.00, 26.54; HRMS calcd for
C12H10OS 202.0450, found 202.0450. Anal. Calcd for
C12H10OS: C, 71.26; H, 4.98. Found: C, 71.01; H, 4.98.
p-(3-Th ien yl)a n isole (3e): 1H NMR δ 7.55-7.52 (m, 2H),
7.36-7.35 (m, 3H), 6.96-6.93 (m, 2H), 3.85 (s, 3H); 13C NMR
δ 158.90, 142.01, 128.76, 126.24, 126.03, 118.92, 114.19, 55.34;
HRMS calcd for C11H10OS 190.0452, found 190.0457. Anal.
Calcd for C11H10OS: C, 69.22; H, 5.21; O, 8.41; S, 13.80.
Found: C, 69.25; H, 5.15; O, 8.60; S, 16.75.
Typ ica l P r oced u r e for th e P r ep a r a tion of 3-Th ien yl-
m a n ga n ese Br om id es a n d Th eir Cou p lin g Rea ction s
w ith Acid Ch lor id es (Sch em e 4). To a slurry of Rieke
manganese (10.0 mmol) in THF (10 mL) under argon was
added 3,4-dibromothiophene (5.0 mmol) at room temperature,
and the mixture was stirred at room temperature for 5 h. 1,2-
Dibromoethane21 (6.0 mmol) was added neat to the reaction
mixture at 0 °C, and the mixture was allowed to warm to room
temperature over 20 min. To the resulting organomanganese
reagent was added acid chloride (3.0 mmol) neat at room
temperature via syringe. The resulting mixture was sitrred
at room temperature for 30 min. The mixture was quenched
with 3 M HCl (10 mL) and extracted with ether (2 x 10 mL),
and the combined organic layers were sequentially washed
with saturated NaHCO3, Na2S2O3 and NaCl solutions, dried
over MgSO4, and concentrated. Flash chromatography (ethyl
acetate/hexanes) afforded the corresponding ketones in 34-
91% isolated yield.
3-(2-Br om oben zoyl)th iop h en e (11a ): 1H NMR δ 7.80 (dd,
J ) 2.86, 2.86 Hz, 1H), 7.65 (dd, J ) 7.87, 7.63 Hz, 1H), 7.57
(dd, J ) 5.01, 5.25, 1H), 7.41-7.31 (m, 4H); 13C NMR δ 189.18,
142.40, 141.11, 136.00, 135.91, 133.28, 131.14, 128.59, 127.59,
127.06, 126.70, 119.22; HRMS calcd for C11H7BrOS 266.0490,
found 265.9401.
3-(3-Br om oben zoyl)th iop h en e (11b): 1H NMR δ 7.96-
7.92 (m, 2H), 7.76-7.68 (m, 2H), 7.57 (dd, J ) 5.01, 5.01 Hz,
1H), 7.46-7.33 (m, 2H); 13C NMR δ 188.22, 140.67, 140.39,
135.16, 134.22, 132.11, 129.93, 128.39, 127.79, 126.51, 122.59;
HRMS calcd for C11H7BrOS 266.0490 found,
p-(3-Th ien yl)tolu en e (3f): 1H NMR δ 7.52-7.50 (m, 2H),
7.43-7.39 (m, 3H), 7.26-7.21 (m, 2H), 2.40 (s, 3H); 13C NMR
δ 142.36, 136.82, 133.12, 129.46, 126.32, 126.31, 125.99, 21.07;
HRMS calcd for C11H10S 175.0502, found 174.0503.
P r epar ation of 3-Th ien ylm agn esiu m Iodide an d 3-Su b-
stitu ted Th iop h en es 5a -d . 3-Iodothiophene (5 mmol) was
added to the washed Mg* (7.5 mmol) in THF (15 mL) with
stirring at room temperature. The slurry was stirred for 5-7
h at room temperature. After completion of oxidative addition,
the excess active magnesium was allowed to settle out of the
organomagnesium solution. The supernatant was cannulated
to different electrophiles (4 mmol) in THF (10 mL) at different
temperatures. After the mixture was stirred, the reaction was
quenched with saturated aqueous NH4Cl solution (20 mL) and
extracted with diethyl ether (20 mL × 2). The combined
organic layers were washed with brine (20 mL × 2), dried over
anhydrous MgSO4, and concentrated using a rotary evapora-
tor. Flash column chromatography (ethyl acetate/hexanes)
afforded 3-substituted thiophenes 5a -d in 33-87% isolated
yields.
3-Ben zoylth iop h en e (5a ): 1H NMR 7.93-7.92 (m, 1H),
7.86-7.83 (m, 2H), 7.61-7.55 (m, 2H), 7.50-7.45 (m, 2H),
7.39-7.36 (m, 1H); 13C NMR δ 189.88, 141.18, 138.52, 133.83,
132.20, 129.26, 128.49, 128.27, 126.12; HRMS calcd for C11H8OS
188.0296, found 188.0291.
3-(Hexylth io)th iop h en e (5b): 1H NMR δ 7.33-7.30 (m,
1H), 7.11-7.10 (m, 1H), 7.02-7.00 (m, 1H), 2.83 (t, J ) 7.17
Hz, 2H), 1.61 (q, J ) 7.17 Hz, 2H), 1.45-1.26 (m, 6H), 0.88 (t,
J ) 6.59 Hz, 3H); 13C NMR δ 132.34, 129.64, 125.98, 122.85.
Anal. Calcd for C10H16S2: C, 59.95; H, 7.99; S, 32.00. Found:
C, 59.86; H, 8.30; S, 32.37.
3-(4-Br om oben zoyl)th iop h en e (11c): 1H NMR δ 7.92-
7.91 (m, 1H), 7.74-7.71 (m, 2H), 7.66-7.62 (m, 2H), 7.59 (ddd,
J ) 5.01, 5.00, 5.25 Hz, 1H), 7.41-7.39 (m, 1H); 13C NMR δ
188.84, 140.89, 137.31, 133.96, 133.87, 131.69, 130.89, 128.47,
127.32, 126.48; HRMS calcd for C11H7BrOS 266.0490, found
265.9401.
3-Br om o-4-ben zoylth iop h en e (11d ): 1H NMR δ 7.88-
7.84 (m, 2H), 7.68-7.58 (m, 2H), 7.51-7.46 (m, 2H), 7.38 (d,
J ) 3.34 Hz, 1H); 13C NMR 189.79, 139.21, 137.44, 133.25,
132.26, 130.05, 128.46, 125.08, 110.56; HRMS calcd for
C11H7BrOS 266.0490, found 265.9401.
3-Br om o-4-(3-br om oben zoyl)th iop h en e (11e): 1H NMR
δ 7.97-7.96 (m, 1H), 7.77-7.68 (m, 3H), 7.40-7.33 (m, 2H);
13C NMR δ 188.16, 139.21, 138.56, 136.03, 132.85, 132.81,
132.75, 132.65, 130.03, 128.52, 125.43, 122.70, 110.46; HRMS
calcd for C11H16Br2OS 343.8506, found 343.8508; EIMS m/z
(relative intensity) 347.84 (31), 346.85 (7), 345.84 (62), 343.85
(30), 190.89 (98), 188.90 (100), 184.94 (26), 182.94 (25).
3-Br om o-4-(4-br om oben zoyl)th iop h en e (11f): 1H NMR
δ 7.72-7.59 (m, 5H), 7.39 (d, J ) 3.57 Hz, 1H); 13C NMR δ
188.67, 138.79, 136.09, 132.33, 132.29, 131.75, 131.40, 128.46,
125.30, 110.35; EIMS m/z (relative intensity) 348.80 (33),
345.80 (M+, 14), 344.80 (43), 190.85 (99), 188.85 (100), 184.80
(41).
Typ ica l P r oced u r e for P d -Ca ta lyzed Cou p lin g Rea c-
tion of 3-Th ien ylm a n ga n ese Br om id es w ith Ar yl Iod id e
(11g-i). 3-Thienylmanganese bromides were prepared as
before. After being stirred, the mixture was allowed to cool
down and 1,2-dibromoethane (3.01 mmol) was syringed neat
at 0 °C. Then the mixture was gradually warmed to room
temperature over 20 min. The resulting 3-thienylmanganese
bromide was added via cannula to a mixture of ethyl 4-iodo-
1-P h en yl-1-(3-th ien yl)m eth a n ol (5c): 1H NMR δ 7.42-
7.26 (m, 6H), 7.19-7.18 (m, 1H), 7.01-6.99 (m, 1H), 5.88 (s,
1H), 2.34 (s, 1H); 13C NMR δ 145.26, 143.31, 128.46, 127.71,
126.44, 126.35, 126.14, 121.61, 72.75; HRMS calcd for C11H10OS
190.0452, found 190.0444.
(21) 1,2-Dibromoethane was used to consume the remaining active
manganese in the reaction mixture because Mn* was active to
additional electrophile to give a homocoupling product.