The Journal of Organic Chemistry
Article
+
4
1.0, 33.5, 33.4, 32.6, 21.64, 21.59, 21.5. HRMS (ESI): m/z [M + H]+
calcd for C H O NS 490.1894, found 490.1880.
2
37.3, 36.5, 28.3. HRMS (ESI): m/z [M + H] calcd for C H O N
15 18 3
260.1281, found 260.1278.
Data for compound 19 are as follows. R = 0.4 (petroleum ether/
25
32
7
-Isopropyl 1-Methyl (2S,3aS)-5-Methoxy-9-(phenylthio)-
,3,3a,4,9,9a-hexahydro-1H-benzo[f ]indole-1,2-dicarboxylate
17). To a solution of sulfoxide 14 (0.70 g, 1.48 mmol) in anhydrous
CH Cl (10 mL) under an atmosphere of argon at 0 °C was slowly
f
−
1
2
(
ethyl acetate, 70/30). IR (CHCl , cm ): ν 3017, 1678, 1548, 1535,
3 max
1
1
219, 772. [α] = +164.84 (c 1.5, CHCl ). H NMR (400 MHz,
3
2
2
CDCl ): δ 7.14 (t, J = 7.88 Hz, 1H), 6.77 (d, J = 7.75 Hz, 1H) 6.69 (d, J
3
added thionyl chloride (0.16 mL, 2.22 mmol, 1.5 equiv) diluted in
anhydrous CH Cl . After the resulting solution was stirred at the same
=
8.13 Hz, 1H), 4.18 (br s, 1H), 3.82 (s, 3H), 3.77 (s, 3H) 3.72 (dd, J =
7.50, 10.38 Hz, 1H), 3.65 (br s, 2H) 3.33 (td, J = 4.63, 10.94 Hz, 1H),
.15 (dd, J = 4.63, 16.63 Hz, 1H), 2.76−2.70 (m, 1H), 2.30 (dd, J =
2
2
temperature for 1 h, the organic solvent and excess thionyl choride were
evaporated on a rotary evaporator. The obtained residue was taken up
in anhydrous CH Cl (10 mL) and cooled to 0 °C before dropwise
3
12.51, 16.13 Hz, 1H), 2.15−2.04 (m, 1H), 2.00 (br s, 1H), 1.79 (td, J =
1
3
1
2
2
9.07, 12.35 Hz, 1H). C{ H} NMR (100 MHz, CDCl ): δ 157.3 (2C),
3
addition of SnCl (0.26 mL, 2.22 mmol, 1.5 equiv). After the mixture
136.6, 126.7, 124.7, 122.1, 107.3, 67.7, 62.0, 61.3, 55.2, 52.7, 40.9, 37.3,
32.8, 28.5. HRMS (ESI): m/z [M + H] calcd for C H O N
4
+
was stirred for 15 min at 0 °C, an aqueous saturated NaHCO solution
3
16 22
4
was added and the reaction mixture was extracted with CH Cl (3 × 50
292.1543, found 292.1540.
2
2
mL). The combined organic layers were washed with brine (30 mL),
(−)-((2S,3aS,9aR)-5-Methoxy-1-propyl-2,3,3a,4,9,9a-hexahy-
dro-1H-benzo[f ]indol-2-yl)methanol (5). A mixture of compound
18 (0.10 g, 0.38 mmol) and potassium hydroxide (1.3 g, 23.14 mmol,
60 equiv) in methanol (10 mL) was stirred and refluxed for 1 h. After
complete consumption of the starting material as checked by TLC, 3 N
aqueous HCl (30 mL) was added to the reaction mixture at 0 °C. Most
of the methanol was then evaporated on a rotary evaporator. The pH of
the reaction mixture was adjusted to 8−9 with a saturated aqueous
sodium hydrogen carbonate solution. The aqueous phase was then
dried over anhydrous Na SO , filtered, and evaporated on a rotary
2
4
evaporator under reduced pressure. The obtained residue was purified
using flash silica gel column chromatography with 10% ethyl acetate in
petroleum ether as eluent to afford pure 17 (451.00 mg, 67%) as a
colorless oil. R = 0.5 (petroleum ether/ethyl acetate, 80/20). IR
f
−
1
1
(
CHCl , cm ): ν 1697, 1641, 1434, 1380, 1215, 772. H NMR (400
3 max
MHz, CDCl ), mixture of diastereomers and their rotamers was
3
observed: δ 7.62−7.50 (m, 1.4H), 7.37−7.25 (m, 3H), 7.23−7.15 (m,
1
4
3
0
H), 7.11−6.95 (m, 1H), 6.87−6.63 (m, 1.7 H), 5.46−4.93 (m, 2H),
.60−4.24 (m, 1H), 3.97−3.74 (m, 4H), 3.70−3.45 (m, 2.2H), 3.26−
.10 (m, 1.3H), 2.82−2.51 (m, 2H), 2.35 (m, 1H), 1.98−1.87 (m,
extracted with CH
dried over anhydrous Na
evaporator under reduced pressure. The obtained residue and K
Cl
2
2
(5 × 50 mL). The combined organic layers were
SO , filtered, and evaporated on a rotary
CO
2
4
2
3
1
3
1
.3H), 1.75−1.63 (m, 0.7H), 1.31−1.21 (m, 6H). C{ H} NMR (100
(69.00 mg, 0.50 mmol, 1.3 equiv) were taken up in anhydrous
acetonitrile (3 mL) and cooled to 0 °C before dropwise addition of n-
propyl iodide (0.04 mL, 0.42 mmol, 1.2 equiv). The reaction mixture
was stirred at room temperature for 12 h, and after complete
consumption of starting material as monitored by TLC, the mixture
MHz, CDCl ), mixture of diastereomers and their rotamers was
3
observed: δ 172.6, 172.4, 172.1, 157.0, 156.9, 154.8, 154.6, 154.4, 138.3,
1
1
1
6
5
2
38.0, 135.5, 134.8, 134.3, 134.1, 132.1, 131.4, 131.3, 131.0, 128.9,
28.7, 128.6, 127.9, 127.7, 127.6, 127.4, 127.2, 127.0, 126.8, 124.2,
23.5, 123.1, 122.8, 120.1, 110.2, 108.3, 108.2, 68.5, 68.4, 68.4, 64.4,
3.8, 63.5, 61.8, 61.3, 60.5, 59.7, 55.3, 55.22, 55.18, 53.7, 52.3, 52.1,
1.80, 51.78, 39.6, 36.6, 35.9, 35.4, 34.8, 34.7, 33.9, 28.6, 28.5, 21.7,
was extracted with CH
Cl
2
(5 × 25 mL). The combined organic layers
2
were dried over anhydrous Na
SO , filtered, and evaporated on a rotary
2
4
evaporator under reduced pressure to obtain the crude product, which
was purified by using flash silica gel column chromatography with ethyl
acetate as the eluent to afford pure 5 (48. 00 mg, 45%, over 2 steps) as a
+
1.6. HRMS (ESI): m/z [M + H] calcd for C H O NS 456.1839,
2
5
30
5
found 456.1832.
(
−)-(4aR,10aS,11aS)-9-Methoxy-4a,5,10,10a,11,11a-hexahy-
dro-1H,3H-benzo[f ]oxazolo[3,4-a]indol-3-one (18) and
−)-Methyl (2S,3aS,9aS)-2-(Hydroxymethyl)-5-methoxy-
,3,3a,4,9,9a-hexahydro-1H-benzo[f ]indole-1-carboxylate
19). To a magnetically stirred solution of 17 (1.00 g, 2.20 mmol) in
colorless liquid. R = 0.5 (MeOH/ethyl acetate, 05/95). IR (CHCl ,
f
3
−
1
1
cm ): ν 3019, 2400, 1216, 666. [α] = −33.27 (c 1, CHCl ). H
NMR (500 MHz, CDCl ): δ 7.12 (t, J = 8.0 Hz, 1H), 6.76 (d, J = 7.6 Hz,
max
3
(
3
2
1
1
5
H), 6.69 (d, J = 8.0 Hz, 1H), 3.82 (s, 3H), 3.68 (dd, J = 4.0, 11.1 Hz,
H), 3.58 (dd, J = 5.3, 11.4 Hz, 1H), 3.54−3.46 (m, 2H), 3.23 (dd, J =
.3, 16.8 Hz, 1H), 3.11 (dd, J = 3.8, 14.5 Hz, 1H), 3.04−2.99 (m, 1H),
(
anhydrous THF (10 mL) under an atmosphere of argon at 0 °C was
added LiBH (57.00 mg, 2.63 mmol, 1.2 equiv), and the reaction
mixture was stirred for 24 h at room temperature. After complete
consumption of the starting material as checked by TLC, excess LiBH4
was destroyed with 2 N HCl solution (10 mL). The organic solvent was
evaporated on a rotary evaporator under reduced pressure. The
aqueous layer was extracted with CH Cl (3 × 50 mL). The combined
organic layers were washed with brine (30 mL), dried over anhydrous
Na SO , filtered, and evaporated on a rotary evaporator to obtain a
residue. To a magnetically stirred solution of the above obtained residue
in THF (10 mL) was added freshly prepared Raney Ni (excess amount)
at room temperature. The mixture was stirred at the same temperature
for 1 h. After complete consumption of the starting material as checked
by TLC, the reaction mixture was filtered through a pad of Celite with
ethyl acetate washing (3 × 50 mL). The organic filtrate was evaporated
on a rotary evaporator under reduced pressure, and the residue
obtained was purified by using flash silica gel column chromatography
with 30% ethyl acetate in petroleum ether as the eluent to afford
compound 18 (402.00 mg, 63%) as a colorless solid and compound 19
4
2.94−2.85 (m, 2H), 2.59−2.54 (m, 1H), 2.35−2.26 (m, 2H), 2.01−
1
.93 (m, 1H), 1.72−1.64 (m, 2H), 1.53−1.41 (m, 1H), 0.96 (t, J = 7.2
13 1
Hz, 3H). C{ H} NMR (125 MHz, CDCl ): δ 157.3, 136.1, 126.6,
3
1
2
24.8, 122.0, 107.4, 65.3, 64.0, 62.7, 55.2, 51.1, 39.4, 33.7, 33.3, 29.5,
2.0, 11.8. HRMS (ESI): m/z [M + H] calcd for C H O N
+
1
7
26
2
2
2
276.1958, found 276.1957.
(
−)-(3R,4aS,10aR)-6-Methoxy-1-propyl-1,2,3,4,4a,5,10,10a-
3
2
4
octahydrobenzo[g]quinolin-3-ol (20). To a magnetically stirred
solution of compound 5 (0.10 g, 0.36 mmol) in anhydrous THF (5 mL)
placed in a sealed tube under an atmosphere of argon at −78 °C was
added trifluoroacetic anhydride (TFAA) (0.07 mL, 0.47 mmol, 1.3
equiv). After 1 h at −78 °C, triethylamine (0.30 mL, 1.82 mmol, 5
equiv) was added dropwise. The reaction mixture was stirred for 1 h at−
78 °C and then heated at 120 °C in the sealed tube. After 24 h, aqueous
2 M NaOH solution (3 mL) was added to the reaction mixture at 0 °C
and stirred for 1 h at room temperature. The organic solvent was
evaporated on a rotary evaporator, and the water layer was extracted
with CH Cl (5 × 25 mL). The combined organic layers were dried
2
2
(134.00 mg, 21%) as a colorless liquid in 3:1 ratio.
over anhydrous Na SO , filtered, and evaporated on a rotary evaporator
under reduced pressure to obtain the crude product 20, which was
purified using flash silica gel column chromatography with ethyl acetate
as an elutent to provide 20 (87.00 mg, 87%) as a colorless oil. R = 0.5
(petroleum ether/ethyl acetate, 10/90). IR (CHCl , cm ): ν 2942,
1688, 1219, 771. [α] = −49.59 (c 1, CHCl ). H NMR (400 MHz,
CDCl ): δ 7.11 (t, J = 7.9 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.67 (d, J =
7.9 Hz, 1H), 3.99−3.93 (m, 1H), 3.82 (s, 3H), 3.24 (d, J = 8.5 Hz, 1H),
3.16 (dd, J = 4.6, 16.2 Hz, 1H), 3.00 (dd, J = 4.9, 17.7 Hz, 1H), 2.86−
2.60 (m, 4H), 2.30−2.16 (m, 4H), 1.82−1.74 (m, 1H), 1.62−1.52 (m,
2 4
Data for compound 18 are as follows. R = 0.5 (petroleum ether/
f
−
1
ethyl acetate, 70/30). IR (CHCl , cm ): ν 1745, 1451, 1217, 766.
3
max
1
[
α] = −404.13 (c 0.5, CHCl ). Mp: 95−98 °C. H NMR (400 MHz,
3
f
−
1
CDCl ): δ 7.14 (t, J = 7.9 Hz, 1H), 6.77 (d, J = 7.3 Hz, 1H), 6.70 (d, J =
3
3 max
1
7
3
1
.9 Hz, 1H), 4.60−4.58 (m, 1H), 4.32−4.23 (m, 2H), 3.82 (s, 3H),
.47−3.39 (m, 2H), 3.19 (dd, J = 4.9, 16.5 Hz, 1H), 2.87−2.80 (m,
H), 2.50−2.43 (m, 1H), 2.29−2.24 (m, 1H), 2.22−2.14 (m, 1H), 1.51
3
3
1
3
1
(q, J = 11.0 Hz, 1H). C{ H} NMR (100 MHz, CDCl ): δ 162.1,
3
157.2, 136.2, 126.9, 124.6, 122.3, 107.4, 69.1, 62.1, 60.4, 55.2, 45.2,
9
350
J. Org. Chem. 2021, 86, 9344−9352