PAPER
Chiral Thiophene-Type S,S- and N,S-Ligands from (+)-Nopinon
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1H NMR: d (significant signals) = 4.66 (q, 2 H, J = 7.0 Hz, CH2O),
4.53 (s, 1 H, OH), 4.05–3.95 (m, 1 H, CHOH), 3.74 (dd, J = 13.8,
2.4 Hz, 1 H, CHS), 3.28 (dd, J = 13.8, 7.5 Hz, 1 H, CHS), 1.45 (t,
J = 7.0 Hz, 3 H, CH3CH2O), 1.35 (s, 3 H), 0.95 (s, 3 H).
and the residue was dissolved in hexanes (22 mL) and filtered. The
filtrate was dried in vacuum to afford 1.5 g of stannylated product 6
as a yellow liquid. This compound was used for the next reaction
without further purification.
Anal. Calcd for C14H22O3S2: C, 55.60; H, 7.33. Found: C, 55.44; H,
7.38.
1H NMR: d = 6.88 (s, 1 H), 2.94–2.87 (m, 2 H), 2.81 (dd, J = 16.4,
2.8 Hz, 1 H), 2.69 (dt, J = 9.2, 6.0 Hz, 1 H), 1.62–1.53 (m, 6 H), 1.41
(d, J = 9.6 Hz, 2 H), 1.38–1.29 (m, 6 H), 1.32 (s, 3 H), 1.09–1.05
(m, 6 H), 0.90 (t, J = 5.1 Hz, 9 H), 0.64 (s, 3 H).
(5R,7R)-5,7-Methano-6,6-dimethyl-4,5,6,7-tetrahydroben-
zo[b]thiophene (3)
A flask containing 1-methylpiperazine (26 mL) was degassed by
bubbling N2 for a 15 min. Then, the flask was cooled to 0 °C and a
solution of 2 (4.26 g, 15.3 mmol) in CH2Cl2 (8 mL) was added dur-
ing 15 min. After stirring for 3 h at 0 °C, aq 37% HCl (39 mL) was
added dropwise and the resulting solution was allowed to reach r.t.
(overnight). The mixture was taken up with H2O (50 mL) and the
organic phase was separated. The aqueous phase was extracted with
Et2O (3 × 30 mL). The combined organic layers were washed sev-
eral times with H2O and dried (Na2SO4). The solvent was evaporat-
ed and the residue was purified by flash chromatography (PE–
EtOAc, 95:5) to give pure 3 as a pale-yellow oil; yield: 1.69 g
(62%); [a]D25 –60.6 (c = 2.11, CHCl3).
(5R,7R)-5,7-Methano-6,6-dimethyl-4,5,6,7-tetrahydroben-
zo[b]thiophen-2-yl)pyridine (7)
A mixture of 2-bromopyridine (118.5 mg, 0.5 mmol), crude tribu-
tylstannylthiophene 6 (0.51 g, 0.55 mmol), Pd(PPh3)4 (28.8 mg,
0.025 mmol) in anhyd and degassed (by bubbling argon for 15 min)
DMF (5 mL) was heated at 90 °C under argon for 10 h. After re-
moval of the DMF under vacuum, the residue was purified by flash
chromatography (PE–EtOAc, 95:5) to give pure 7 as a pale-yellow
oil; yield: 85.4 mg (67%); [a]D25 –42.8 (c = 0.027, CHCl3).
IR (neat): 2929, 1587, 1475, 1431, 1382, 1291, 1172, 1090, 996,
836, 774, 737 cm–1.
1H NMR: d = 8.50–8.47 (m, 1 H), 7.64–7.52 (m, 2 H), 7.35 (s, 1 H),
7.07–7.01 (m, 1 H), 2.90–2.78 (m, 3 H), 2.78–2.65 (m, 1 H), 2.34–
2.26 (m, 1 H), 1.43 (d, J = 9.0 Hz, 1 H), 1.40 (s, 3 H), 0.72 (s, 3 H).
13C NMR: d = 153.14, 149.26, 147.67, 139.19, 136.31, 133.17,
124.53, 120.80, 117.96, 43.00, 41.50, 40.87, 33.51, 30.05, 26.18,
21.00.
IR (neat): 2923, 2360, 1650, 1438, 1382, 1365, 1263, 1153, 1183,
1049, 873, 694 cm–1.
1H NMR: d = 6.91 (d, J = 4.8 Hz, 1 H), 6.83 (d, J = 4.8 Hz, 1 H),
2.93–2.74 (m, 3 H), 2.74–2.65 (m, 1 H), 2.35–2.25 (m, 1 H), 1.42–
1.36 (overlapping d, 1 H), 1.39 (s, 3 H), 0.66 (s, 3 H).
13C NMR: d = 143.89, 131.83, 126.47, 119.59, 42.67, 41.53, 41.07,
33.71, 29.99, 26.30, 21.03.
Anal. Calcd for C16H17NS: C, 75.25; H, 6.71; N, 5.48. Found: C,
75.44; H, 6.76; N, 5.43.
Anal. Calcd for C11H14S: C, 74.10; H, 7.91. Found: C, 74.22; H,
7.93.
2,6-Bis[(5R,7R)-5,7-methano-6,6-dimethyl-4,5,6,7-tetrahydro-
benzo[b]thiophen-2-yl]pyridine (8)
(5R,7R,5¢R,7¢R)-5,7,5¢,7¢-Dimethano-6,6,6¢,6¢-tetramethyl-
4,4¢,5,5¢,6,6¢,7,7¢-octahydro-2,2¢-bibenzo[b]thiophene (5)
A solution of tetrahydrobenzo[b]thiophene 3 (0.352 g, 2.0 mmol)
and N,N,N¢,N¢-tetramethylethylenediamine (0.233 g, 4.0 mmol) in
anhyd THF (7 mL) was cooled to –20 °C under argon. Then, n-BuLi
(2.0 mmol, 0.8 mL of 2.5 M in hexane) was added dropwise to this
solution. After addition, stirring was continued for another 30 min
at 0 °C. This solution was then added dropwise (over a period of 30
min) to refluxing THF (7 mL) containing Fe(acac)3 (0.71 g, 2.0
mmol) under argon. After a 6 h at refluxing temperature, the THF
was evaporated. The resulting red solid was dissolved in CH2Cl2 (10
mL) and quickly passed through a short bed of silica gel using
CH2Cl2 as the eluent. The CH2Cl2 solution was evaporated and the
residue was purified by flash chromatography (PE–EtOAc, 95:5) to
give pure 5 as a white solid; yield: 0.23 g (65%); mp 173–174 °C;
[a]D25 –50.6 (c = 0.018, CHCl3).
A mixture of 2,6-dibromopyridine (79.0 mg, 0.5 mmol), crude
tributylstannylthiophene 6 (0.51 g, 0.55 mmol), Pd(PPh3)4 (28.8
mg, 0.025 mmol) in anhyd and degassed (by bubbling argon for 15
min) DMF (5 mL) was heated at 90 °C under argon for 10 h. After
removal of the DMF under vacuum, the residue was purified by
flash chromatography (PE–EtOAc, 95:5) to give pure 8 as a white
solid; yield: 0.18 g (83%); mp 214–215 °C; [a]D25 –5.5 (c = 0.017,
CHCl3).
IR (KBr): 2927, 1561, 1465, 1379, 1271, 1174, 1076, 862, 801, 735
cm–1.
1H NMR: d = 7.55 (t, J = 8.0 Hz, 1 H), 7.39 (s, 2 H), 7.30 (d, J = 8.0
Hz, 2 H), 2.90–2.78 (m, 6 H), 2.78–2.69 (m, 2 H), 2.35–2.28 (m, 2
H), 1.44 (d, J = 9.0 Hz, 2 H), 1.41 (s, 6 H), 0.73 (s, 6 H).
13C NMR: d = 152.48, 147.77, 139.60, 136.86, 133.07, 124.50,
115.03, 43.11, 41.61, 40.99, 33.60, 30.16, 26.32, 21.14.
IR (KBr): 2931, 1538, 1441, 1380, 1365, 1262, 1148, 1133, 1079,
Anal. Calcd for C27H29NS2: C, 75.13; H, 6.77; N, 3.24. Found: C,
74.83; H, 6.73; N, 3.26.
813, 523 cm–1.
1H NMR: d = 6.83 (s, 1 H), 2.90–2.64 (m, 4 H), 2.31–2.45 (m, 1 H),
1.43 (d, J = 9.0 Hz, 1 H), 1.38 (s, 3 H), 0.71 (s, 3 H).
13C NMR: d = 142.42, 133.09, 132.54, 122.20, 42.73, 41.67, 40.99,
33.74, 30.15, 26.28, 21.10.
2,5-Bis[(6R,7R)-5,7-methano-6,6-dimethyl-4,5,6,7-tetrahydro-
benzo[b]thiophen-2-yl]thiophene (9)
A mixture of 2,5-dibromothiophene (121.0 mg, 0.5 mmol), crude
tributylstannylthiophene 6 (0.51 g, 0.55 mmol), Pd2dba3 (22.9 mg,
0.025 mmol), and Ph3P (13.0 mg, 0.05 mmol) in anhyd and de-
gassed (by bubbling argon for 15 min) DMF (5 mL) was heated at
90 °C under argon for 24 h. After removal of the DMF under
vacuum, the residue was purified by flash chromatography using PE
give pure 9 as a white solid; yield: 0.135 g (62%); mp 164–165 °C;
[a]D25 –84.0 (c = 0.005, CHCl3).
Anal. Calcd for C22H26S2: C, 74.52; H, 7.39. Found: C, 74.77; H,
7.42.
(5R,7R)-5,7-Methano-6,6-dimethyl-2-tributylstannyl-4,5,6,7-
tetrahydrobenzo[b]thiophene (6)
n-BuLi (2.50 mmol, 1.0 mL of 2.5 M in hexane) was added drop-
wise to a cooled solution (–78 °C) of tetrahydrobenzo[b]thiophene
3 (0.4 g, 2.25 mmol) in anhyd THF (3 mL) under argon. The solu-
tion was stirred for 0.5 h and then warmed to –40 °C. Bu3SnCl (1.0
g, 2.63 mmol) was added at –40 °C, the solution was then warmed
to r.t. and the stirring continued for 8 h. The solvent was evaporated
IR (KBr): 2919, 1524, 1443, 1379, 1364, 1260, 1159, 1133, 1078,
821, 791 cm–1.
1H NMR: d = 6.92 (s, 2 H), 6.91 (s, 2 H), 2.91–2.67 (m, 8 H) 2.32–
2.27 (m, 2 H), 1.44 (d, J = 9.0 Hz, 2 H), 1.40 (s, 6 H), 0.73 (s, 6 H).
Synthesis 2011, No. 15, 2441–2444 © Thieme Stuttgart · New York