E
N. Denizot et al.
Special Topic
Synthesis
N-Methyl-benzofuroindoline 20a
Flash chromatography on silica gel (cyclohexane/EtOAc, 1:1) afforded
the N-substituted indole 18 in 54% yield (42.0 mg, 0.135 mmol) as a
yellow oil.
To a solution of N-methyl-tetrahydrocarbazole 19a (53.0 mg, 0.286
mmol) in CH2Cl2 (2.8 mL) at 0 °C were added p-methoxyphenol (7a)
(88.0 mg, 0.715 mmol) and NIS (103.0 mg, 0.458 mmol), followed af-
ter 5 min by AgBF4 (89.0 mg, 0.458 mmol). The resulting mixture was
slowly warmed to r.t. and stirred for 3 h. The reaction was quenched
by addition of a saturated aqueous NH4Cl solution (1 mL), and then
filtered through a pad of Celite. The filtrate was concentrated under
reduced pressure. Preparative TLC purification (cyclohexane/EtOAc,
95:5) afforded N-methyl-benzofuroindoline 20a (48.0 mg, 0.156
mmol) in 55% yield as a colorless oil.
Rf = 0.40 (EtOAc).
IR (NaCl): 3442, 3056, 2951, 1751, 1662, 1609, 1465, 1424, 1351,
1207, 1059, 817, 746, 731 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 2.38 (tt, J = 17.4, 2.5 Hz, 1 H), 2.66
(ddd, J = 17.4, 4.1, 6.7 Hz, 1 H), 2.80–2.92 (m, 3 H), 3.77 (s, 3 H), 4.73
(d, J = 18.0 Hz, 1 H), 4.81 (d, J = 18.0 Hz, 1 H), 4.87 (dd, J = 13.5, 3.9 Hz,
1 H), 4.99–5.02 (m, 1 H), 6.12 (dd, J = 9.8, 2.9 Hz, 1 H), 6.66 (ddd, J =
9.4, 6.8, 2.1 Hz, 1 H), 7.15–7.27 (m, 3 H), 7.56 (d, J = 7.8 Hz, 1 H).
13C NMR (90 MHz, CDCl3): δ = 21.5, 32.1, 38.8, 45.8, 51.5, 52.9, 109.1,
111.6, 119.0, 120.6, 122.8, 125.9, 126.8, 133.4, 138.2, 138.3, 164.9,
169.0.
Rf = 0.70 (cyclohexane/EtOAc, 95:5).
IR (NaCl): 2935, 2856, 1603, 1487, 1205, 1030, 800, 746 cm–1
.
1H NMR (250 MHz, CDCl3): δ = 1.26–1.39 (m, 2 H), 1.40–1.47 (m, 1 H),
1.54–1.64 (m, 1 H), 1.69–1.90 (m, 2 H), 2.26–2.37 (m, 2 H), 2.97 (s, 3
H), 3.76 (s, 3 H), 6.53 (d, J = 8.0 Hz, 1 H), 6.60–6.62 (m, 2 H), 6.72 (t, J =
7.6 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 7.06 (d, J = 6.5 Hz, 1 H), 7.10 (dt,
J = 7.7, 1.3 Hz, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = 20.0, 20.3, 28.3, 28.6, 32.5, 56.3, 56.5,
107.2, 109.8, 109.9, 112.3, 112.5, 119.0, 122.4, 128.2, 133.6, 134.0,
149.4, 153.0, 154.6.
HRMS (ESI+): m/z [M + H]+ calcd for C18H19N2O3: 311.1390; found:
311.1379.
Benzofuroindoline 26
To a solution of ABCE tetracyclic indole 25 (115.0 mg, 0.238 mmol) in
CH2Cl2 (2.4 mL) at 0 °C were added p-methoxyphenol (7a) (59.0 mg,
0.476 mmol) and NIS (59.0 mg, 0.262 mmol), followed after 3 min by
AgBF4 (92.3 mg, 0.476 mmol). The resulting mixture was slowly
warmed to r.t. and stirred for 4 h. The reaction was quenched by addi-
tion of a saturated aqueous NH4Cl solution (0.5 mL), then filtered
through a pad of Celite. The filtrate was concentrated under reduced
pressure. Preparative TLC purification (cyclohexane/EtOAc, 50:50) af-
forded benzofuroindoline 26 (80.0 mg, 0.132 mmol) in 55% yield as a
colorless oil.
HRMS (ESI+): m/z [M + H]+ calcd for C20H22NO2: 308.1645; found:
308.1641.
N-Acetyl-benzofuroindoline 20b
To a solution of N-acetyl-tetrahydrocarbazole 19b (61.0 mg, 0.286
mmol) in CH2Cl2 (3 mL) at 0 °C were added p-methoxyphenol (7a)
(88.0 mg, 0.715 mmol) and NIS (71.0 mg, 0.315 mmol), followed after
5 min by AgBF4 (111 mg, 0.572 mmol). The resulting mixture was
slowly warmed to r.t. and stirred for 3 h. The reaction was quenched
by addition of a saturated aqueous NH4Cl solution (1 mL), and then
filtered through a pad of Celite. The filtrate was concentrated under
reduced pressure. Preparative TLC purification (cyclohexane/EtOAc,
90:10) afforded N-acetyl-benzofuroindoline 20b (35.0 mg, 0.104
mmol) in 36% yield as a colorless oil.
Rf = 0.54 (cyclohexane/EtOAc, 50:50).
IR (NaCl): 2953, 1739, 1599, 1488, 1266, 1164, 1024, 740 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 1.83 (dd, J = 12.8, 3.3 Hz, 1 H), 2.11 (dd,
J = 14.3, 3.3 Hz, 1 H), 2.33–2.37 (m, 1 H), 2.36 (s, 3 H), 2.43 (d, J = 16.4
Hz, 1 H), 2.58 (td, J = 12.4, 3.3 Hz, 1 H), 2.68 (dd, J = 14.1, 3.3 Hz, 1 H),
3.31 (d, J = 12.2 Hz, 1 H), 3.50–3.54 (m, 1 H), 3.59 (t, J = 2.5 Hz, 1 H),
3.68 (s, 3 H), 3.71 (s, 3 H), 3.78 (s, 3 H), 6.43 (d, J = 6.9 Hz, 1 H), 6.48–
6.55 (m, 2 H), 6.71 (d, J = 2.8 Hz, 1 H), 6.74–6.78 (m, 1 H), 7.01 (d, J =
7.5 Hz, 2 H), 7.19 (d, J = 8.2 Hz, 2 H), 7.60 (d, J = 8.2 Hz, 2 H).
Rf = 0.35 (cyclohexane/EtOAc, 90:10).
IR (NaCl): 2939, 1665, 1598, 1487, 1377, 1209, 1168, 1029, 755 cm–1
.
1H NMR (250 MHz, CDCl3): δ = 1.30–1.38 (m, 1 H), 1.44–1.51 (m, 1 H),
1.54–1.31 (m, 2 H), 1.87–1.64 (m, 1 H), 2.00–2.05 (m, 1 H), 2.30–2.38
(m, 1 H), 2.52 (s, 3 H), 2.66 (dt, J = 14.3, 4.8 Hz, 1 H), 3.71 (s, 3 H),
6.65–6.68 (m, 2 H), 6.79 (dd, J = 7.4, 1.1 Hz, 1 H), 7.11 (td, J = 7.4, 1.1
Hz, 1 H), 7.21 (td, J = 7.8, 1.5 Hz, 1 H), 7.35 (dd, J = 7.2, 1.5 Hz, 1 H),
8.17 (d, J = 8.1 Hz, 1 H).
13C NMR (62.5 MHz, CDCl3): δ = 18.1, 18.4, 24.7, 30.6, 31.6, 56.2, 57.7,
108.1, 109.6, 110.6, 113.6, 117.4, 122.0, 124.4, 128.5, 132.8, 134.2,
142.5, 150.9, 156.6, 170.5.
13C NMR (90 MHz, CDCl3): δ = 21.6, 23.0, 26.7, 32.4, 41.8, 51.6, 52.8,
53.5, 54.7, 56.1, 66.6, 106.1, 109.5, 109.9, 111.3, 112.6, 120.7, 122.8,
127.3 (2 C), 127.8, 129.9 (2 C), 131.8, 132.5, 136.1, 143.9, 145.8, 152.1,
154.9, 170.0, 170.4.
HRMS (ESI+): m/z [M + H]+ calcd for C32H33N2O8S: 605.1952; found:
605.1956.
Benzodioxinoindoline 28
To a solution of tetrahydrocarbazole 19c (51.0 mg, 0.298 mmol) in
CH2Cl2 (2 mL) under argon was added NIS (74.0 mg, 0.328 mmol). The
solution was stirred for 30 min, then cooled to 0 °C and 3-methoxyca-
thecol (27) (104.0 mg, 0.742 mmol), AgBF4 (116.0 mg, 0.596 mmol)
and NaOH (60 mg, 1.49 mmol) were added. The resulting mixture was
stirred for 3 h prior to being quenched with a saturated aqueous
NH4Cl solution (0.5 mL) and filtered through a pad of Celite. Prepara-
tive TLC (cyclohexane/EtOAc, 9:1) afforded benzodioxinoindoline
(13.0 mg, 0.042 mmol) in 14% yield as a white solid.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H21NO3Na: 358.1414; found:
358.1411.
Methyl-2-(N-indolyl) Acetate 18
To a solution of ABCD tetracyclic indole 11 (60.0 mg, 0.252 mmol) in
degassed DMF (1.6 mL) under argon was added KHMDS (75.0 mg,
0.376 mmol) at r.t. The reaction was stirred 15 min, then methyl 2-
bromoacetate (0.03 mL, 0.353 mmol) was added dropwise and the re-
sulting mixture was stirred for 7 h at r.t. prior to being quenched with
a saturated aqueous NH4Cl solution. The solution was diluted with
H2O, extracted with EtOAc and the combined organic layers washed
with H2O and brine, dried and concentrated under reduced pressure.
Rf = 0.30 (cyclohexane/EtOAc, 9:1).
IR (NaCl): 3341, 2936, 1604, 1498, 1474, 1098, 1019, 746 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F