Synthesis of Thieno[2,3-c]furans and Furo[3,4-b]indoles
16 as a pale yellow oil: IR (neat) 2932, 1680, 1445, 1225, 1040,
J . Org. Chem., Vol. 61, No. 18, 1996 6171
2H), 7.58 (d, 1H, J ) 8.4 Hz), 7.76 (d, 1H, J ) 8.4 Hz), and
7.93 (d, 1H, J ) 8.4 Hz); 13C-NMR (CDCl3) δ 22.9, 23.2, 25.7,
30.4, 122.7, 124.6, 125.6, 125.7, 128.2, 128.3, 131.5, 132.0,
132.5, and 134.3; MS m/ e 182 (M+, base), 165, 154, and 141.
N -Me t h oxy-N -m e t h yl-3-m e t h ylt h iop h e n e -2-ca r b ox-
a m id e (27). To a mixture containing 14.2 g (0.1 mol) of acid
26 and 200 mL of dry benzene was added 23.8 g (0.2 mol) of
thionyl chloride. The mixture was stirred for 24 h at 50 °C.
After the reaction was complete, the solvent and excess reagent
were removed under reduced pressure and the crude acid
chloride was dried under vacuum. The crude compound was
dissolved in 400 mL of dry CH2Cl2, and 10.72 g (0.11 mol) of
N,O-dimethylhydroxylamine hydrochloride was added. The
mixture was stirred under argon at 0 °C while 18.2 g (0.23
mol) of pyridine was added dropwise via syringe. Stirring was
continued for 2 h at rt, and then the mixture was washed with
brine and extracted with ether. The organic layer was dried
over Na2SO4 and concentrated under reduced pressure to give
15.9 g (86%) of 27 as a colorless oil which was used without
further purification in the next step: IR (neat) 1631, 1413,
1355, 1200, and 977 cm-1; 1H-NMR (CDCl3) δ 2.55 (s, 3H), 3.33
(s, 3H), 3.71 (s, 3H), 6.90 (d, 1H, J ) 5.0 Hz), and 7.37 (d, 1H,
J ) 5.0 Hz); 13C-NMR (CDCl3) δ 16.8, 33.1, 61.5, 124.8, 128.9,
130.7, 146.2, and 164.0; MS m/ e 185 (M+), 125 (base), 97, 69,
53, and 45; HRMS (EI) calcd for C8H11NO2S 185.0511, found
185.0512.
N-Meth oxy-N-m eth yl-3-((eth ylth io)m eth yl)th iop h en e-
2-ca r boxa m id e (28). A mixture containing 9.25 g (50 mmol)
of amide 27, 9.79 g (55 mmol) of N-bromosuccinimide, 200 mg
of benzoyl peroxide, and 200 mL of carbon tetrachloride was
heated at reflux under argon for 1 h. The mixture was cooled
to rt and was filtered from the precipitated succinimide.
Evaporation of the solvent under reduced pressure left the
crude bromomethyl intermediate as a clear oil: 1H-NMR
(CDCl3) δ 3.37 (s, 3H), 3.72 (s, 3H), 4.98 (s, 2H), 7.18 (d, 1H,
J ) 5.0 Hz), and 7.45 (d, 1H, J ) 5.0 Hz). This material was
used in the next step without further purification.
1
1018, and 762 cm-1; H-NMR (CDCl3) δ 1.26 (t, 3H, J ) 7.5
Hz), 1.71 (quint, 2H, J ) 7.2 Hz), 2.03 (q, 2H, J ) 7.2 Hz),
2.57-2.77 (m, 2H), 2.87 (m, 2H), 3.84 (d, 1H, J ) 12.3 Hz),
4.52 (d, 1H, J ) 12.3 Hz), 4.91 (m, 2H), 5.71 (m, 1H), 7.29-
7.41 (m, 3H), and 7.72 (d, 1H, J ) 6.9 Hz); 13C-NMR (CDCl3)
δ 6.4, 22.8, 32.6, 39.7, 45.1, 56.4, 114.9, 127.9, 129.1, 130.8,
131.5, 132.8, 136.8, 137.5, and 203.2.
1-(2-((Eth ylsu lfin yl)m eth yl)ph en yl)h ept-6-en -1-on e (17).
A 2.20 g (8.4 mmol) sample of sulfide 15 was oxidized in a
manner similar to that described above using sulfide 14 and
sodium periodate/methanol to give 17 (88%) as a pale yellow
oil: IR (neat) 2931, 1680, 1443, 1221, 1041, 1017, and 904
cm-1 1H-NMR (CDCl3) δ 1.36 (t, 3H, J ) 7.5 Hz), 1.44 (m,
;
2H), 2.07 (m, 2H), 2.76 (m, 2H), 2.97 (t, 2H, J ) 7.5 Hz), 3.88
(d, 1H, J ) 12.0 Hz), 4.64 (d, 1H, J ) 12.0 Hz), 4.98 (m, 2H),
5.76 (m, 1H), 7.37-7.51 (m, 3H), and 7.82 (d, 1H, J ) 7.4 Hz);
13C-NMR (CDCl3) δ 6.4, 23.4, 28.0, 33.2, 40.4, 45.1, 56.6, 114.3,
127.9, 129.2, 131.0, 131.6, 132.8, 136.8, 138.0, and 203.3;
HRMS (EI) calcd for C16H22O2S 278.1341, found 278.1331.
Gen er a l P r oced u r e for t h e Ta n d em P u m m er er -
Diels-Ald er Rea ction Sequ en ce. A mixture of dry toluene
(10 mL), acetic anhydride (0.5 mL), and the appropriate
dienophile (1 mmol) containing a catalytic amount of p-
toluenesulfonic acid (ca. 1 mg) was heated at reflux under
argon. To this mixture was added dropwise a solution of the
appropriate sulfoxide (0.5 mmol) in dry toluene (5 mL) via
syringe over a 20 min period. For the intramolecular cyclo-
additions, the addition was carried out over a 1 h interval
using 25 mL of solvent. After the addition was complete, the
solution was heated at reflux for an additional 20 min until
no more sulfoxide was detected by TLC. The mixture was
evaporated to dryness and the crude residue was purified by
flash silica gel chromatography or by recrystallization.
5-(E t h ylt h io)-2,3-d ih yd r o-1H -cyclop en t a [a ]n a p h t h a -
len e (22) was obtained from 132 mg (0.5 mmol) sulfoxide 16
in 84% yield as a colorless oil: IR (neat) 2926, 1582, 1440,
1
1367, and 751 cm-1; H-NMR (CDCl3) δ 1.27 (t, 3H, J ) 7.5
To a solution containing 3.10 g (50 mmol) of ethanethiol in
200 mL of dry benzene was added dropwise 7.60 g (50 mmol)
of DBU. After stirring at 25 °C for 20 min, a solution of the
above bromomethyl derivative in 70 mL of dry benzene was
added dropwise within 30 min. After stirring for 2 h at rt,
the precipitated hydrobromide salt was filtered, and the
remaining solution was concentrated under reduced pressure
to leave behind an oil which was purified by flash silica gel
chromatography to give 8.70 g (71%) of 28 as a colorless oil:
Hz), 2.20 (quint, 2H, J ) 7.2 Hz), 2.93 (q, 2H, J ) 7.5 Hz),
3.06 (t, 2H, J ) 7.2 Hz), 3.20 (t, 2H, J ) 7.2 Hz), 7.44 (m, 2H),
7.56 (s, 1H), 7.76 (m, 1H), and 8.44 (m, 1H); 13C-NMR (CDCl3)
δ 14.5, 24.3, 29.0, 31.1, 33.7, 124.9, 125.0, 126.0, 126.8, 130.9,
131.4, 132.2, 139.1, and 140.7; MS m/ e 228 (M+, base), 199,
165, and 152; HRMS (EI) calcd for C15H16S 228.0973, found
228.0983.
9-(Eth ylth io)-1,2,3,4-tetr a h yd r op h en a n th r en e (23) was
obtained from 139 mg (0.5 mmol) of sulfoxide 17 in 81% yield
as a colorless oil: IR (neat) 2925, 1584, 1445, 1370, and 751
IR (neat) 1626, 1519, 1452, 1418, and 1360 cm-1
;
1H-NMR
(CDCl3) δ 1.23 (t, 3H, J ) 7.5 Hz), 2.52 (q, 2H, J ) 7.5 Hz),
3.34 (s, 3H), 3.70 (s, 3H), 4.18 (s, 2H), 7.14 (d, 1H, J ) 5.0
Hz), and 7.41 (d, 1H, J ) 5.0 Hz); 13C-NMR (CDCl3) δ 14.3,
25.59, 29.4, 32.9, 61.3, 125.6, 129.0, 129.5, 146.7, and 163.1;
MS m/ e 245 (M+), 214, 185, 157 (base), 153, 125, 96, 70, and
45; HRMS (EI) calcd for C10H15NO2S2 245.0544, found 245.0539.
2-Ben zoyl-3-((et h ylt h io)m et h yl)t h iop h en e (29). To a
solution containing 2.45 g (10 mmol) of amide 28 in 30 mL of
dry THF was added dropwise via syringe a solution of
phenylmagnesium Grignard (25 mmol, 25 mL of 1M THF
solution) at 0 °C under argon. After stirring for 2 h at 0 °C,
the mixture was poured into 5% HCl/ice and was extracted
with ether. The combined organic layer was washed with
water, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by flash silica gel chro-
matography to give 2.20 g (84%) of sulfide 29 as a colorless
oil: IR (neat) 1632, 1402, 1269, and 692 cm-1; 1H-NMR (CDCl3)
δ 1.19 (t, 3H, J ) 7.5 Hz), 2.47 (q, 2H, J ) 7.5 Hz), 4.07 (s,
2H), 7.25 (d, 1H, J ) 5.0 Hz), 7.42-7.55 (m, 4H), and 7.83
(dd, 2H, J ) 7.8 and 1.2 Hz); 13C-NMR (CDCl3) δ 14.4, 25.8,
29.3, 128.0, 129.0, 130.8, 131.1, 132.2, 135.1, 139.5, 146.7, and
189.0; MS m/ e 262 (M+), 233, 216, 202, 201 (base), 200, 199,
183, 171, 105, and 77; HRMS (EI) calcd for C14H14OS2
262.0486, found 262.0484.
1
cm-1; H-NMR (CDCl3) δ 1.39 (t, 3H, J ) 7.5 Hz), 1.90-2.00
(m, 4H), 2.95 (t, 2H, J ) 6 Hz), 3.02 (q, 2H, J ) 7.5 Hz), 3.13
(t, 2H, J ) 6 Hz), 7.43 (s, 1H), 7.59 (m, 2H), 8.02 (m, 1H), and
8.54 (m, 1H); 13C-NMR (CDCl3) δ 14.5, 22.8, 23.1, 25.5, 28.7,
30.3, 123.2, 125.0, 126.0, 125.9, 130.3, 131.1, 131.4, 131.8,
133.1, and 134.1; MS m/ e 242 (M+, base), 213, 181, and 165;
HRMS (EI) calcd for C16H18S 242.1129, found 242.1130.
2,3-Dih ydr o-1H-cyclop en ta [a ]n a p h th a len e (24). A mix-
ture of 228 mg (1 mmol) of 22, 25 mL of ethanol, 5 mL of water,
and 1 mL of Raney-Ni (50% slurry in water) was heated at
reflux for 48 h. After the sulfide had been consumed, the
mixture was filtered, and the catalyst was washed with warm
ethanol. The clear solution was concentrated under reduced
pressure and the residue was purified by flash silica gel
chromatography to give the known35 cyclopenta[a]naphthalene
24 (92%) as a colorless oil: 1H-NMR (CDCl3) δ 2.13 (quint,
2H, J ) 7.4 Hz), 3.02 (t, 2H, J ) 7.4 Hz), 3.15 (t, 2H, J ) 7.4
Hz), 7.30-7.43 (m, 3H), 7.60 (d, 1H, J ) 8.3 Hz), 7.71 (d, 1H,
J ) 8.1 Hz), and 7.77 (d, 1H, J ) 7.9 Hz); 13C-NMR (CDCl3) δ
24.5, 31.0, 33.7, 123.2, 124.2, 125.7, 126.6, 128.3, 130.4, 132.5,
139.3, and 140.8; MS m/ e 168 (M+, base), 167, 165, 152, and
115.
1,2,3,4-Tetr a h yd r op h en a n th r en e (25) was prepared in
an analogous fashion by treating 242 mg (1 mmol) of 23 with
Raney-Ni to give the known tetrahydrophenanthrene 25 (92%)
as a white solid: mp 32-34 °C (lit.36 mp 34-35 °C); 1H-NMR
(CDCl3) δ 1.85 (m, 2H), 1.94 (m, 2H), 2.88 (t, 2H, J ) 6 Hz),
3.08 (t, 2H, J ) 6 Hz), 7.17 (d, 1H, J ) 8.4 Hz), 7.37-7.48 (m,
2-Ben zoyl-3-((eth ylsu lfin yl)m eth yl)th iop h en e (30). A
262 mg (1 mmol) sample of sulfide 29 was oxidized in a manner
similar to that described with 14 using sodium periodate as
the oxidant to give 30 (88%) as a white solid: mp 86-87 °C;
IR (KBr) 1633, 1401, 1273, 1047, 1019, and 693 cm-1; 1H-NMR