1670
D. Kajiyama et al.
PAPER
was used for column chromatography. All reactions were carried
out under an argon atmosphere. When necessary, solvents were
dried prior to use. Anhydrous solvents were purchased from Kanto
Chemical Co. Inc. and stored over 4Å MS under an Ar atmosphere.
1 H), 5.68 (s, 1 H), 3.73 (ddd, J = 14.0, 8.8, 4.0 Hz, 1 H), 3.31 (td,
J = 9.2, 6.8 Hz, 1 H), 3.08 (s, 3 H), 3.03 (s, 3 H), 2.39–2.31 (m,
2 H), 2.11 (s, 3 H).
13C NMR: δ = 170.6, 152.2, 130.4, 125.5, 123.8, 117.8, 107.8, 92.2,
82.0, 52.7, 46.7, 38.7, 33.8, 22.4.
HRMS (ESI): m/z [M + H]+ calcd for C14H19N2O2: 247.1450; found:
247.1447.
Oxidation to 1-Acetyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]in-
dol-3a-yl acetate (2a); Typical Procedure
To a stirred solution of 1 (R1 = H, R2 = Ac; 44 mg, 0.22 mmo1) in
TFE (22 mL) and NaOAc (54 mg, 0.66 mmol), was added PIDA (56
mg, 0.17 mmo1) at 0 °C. The resulting mixture was stirred at the
same temperature for 2 h. Concentration in vacuo gave a residue
that was subjected to silica gel column chromatography (CHC13–
MeOH, 15:1) to give 2a.
To a solution of the acetamide (13 mg, 0.052 mmo1) in MeOH (1.0
mL) and H2O (0.2 mL) was added KOH (397 mg, 7.08 mmol). After
stirring at reflux for 20 h, the mixture was diluted with H2O (1 mL)
and extracted with EtOAc (3 × 1 mL). The combined organic ex-
tracts were dried (Na2SO4), and concentrated in vacuo. The residue
was subjected to silica gel column chromatography (CHC13–
MeOH, 10:1) to give 4.
Yield: 32.8 mg (58%); yellow oil.
IR (film): 3315, 2953, 2879, 1740 cm–1.
1H NMR: δ = 7.54 (dd, J = 8.0, 0.8 Hz, 1 H), 7.17 (td, J = 7.6,
0.8 Hz, 1 H), 6.77 (td, J = 7.6, 1.2 Hz, 1 H), 6.63 (d, J = 8.0 Hz,
1 H), 5.62 (s, 1 H), 5.31 (br s, 1 H), 3.72 (ddd, J = 10.0, 8.8, 1.6 Hz,
1 H), 3.30 (td, J = 11.0, 6.8 Hz, 1 H), 3.05 (ddd, J = 12.9, 6.4,
1.6 Hz, 1 H), 2.61 (ddd, J = 13.6, 8.8, 2.4 Hz, 1 H), 2.02 (s, 3 H),
2.01 (s, 3 H).
13C NMR: δ = 170.2, 169.9, 150.7, 131.0, 126.6, 125.3, 119.0,
110.1, 919, 79.7, 47.0, 35.0, 22.1, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C14H17N2O3: 261.1239; found:
261.1233.
Yield: 10.1 mg (95%); colorless oil.
IR (film): 2934, 2825, 1609 cm–1.
1H NMR: δ = 7.26–7.16 (m, 2 H), 6.71 (td, J = 7.6, 0.8 Hz, 1 H),
6.43 (d, J = 7.6 Hz, 1 H), 4.82 (s, 1 H), 3.20–3.14 (m, 1 H), 3.09 (s,
3 H), 2.89 (s, 3 H), 2.77 (td, J = 13.8 H, 1 H), 2.49 (br s, 1 H), 2.25–
2.21 (m, 2 H).
13C NMR: δ = 152.3, 129.8, 126.8, 124.4, 117.0, 105.9, 94.7, 86.4,
52.9, 45.5, 42.0, 31.7.
HRMS (ESI): m/z [M + H]+ calcd for C12H17N2O: 205.1341; found:
205.1318.
1-{3a-(2-Trifluoroethoxy)-3,3a-dihydropyrrolo[2,3-b]indol-
1(2H)-yl}acetate (2b)
CPC-1 (5)
To a solution of 4 (6 mg, 0.026 mmo1) in MeOH (0.35 mL) was
added CH2O (37% aqueous solution, 20 μL, 0.26 mmol) at 0 °C.
The resulting mixture was stirred at r.t. for 5 h. NaBH3CN (12.7 mg,
0.195 mmo1) was added at 0 °C and the mixture was stirred at r.t.
for 4 h, then diluted by addition of H2O (2 mL) and extracted with
EtOAc (3 × 2 mL). The combined organic extracts were dried
(Na2SO4) and concentrated in vacuo. The residue was subjected to
silica gel preparative thin layer chromatography (CHC13–MeOH,
10:1) to give 5.
Yield: 10.8 mg (30%); yellow oil.
IR (film): 2933, 2869, 1653, 1173 cm–1.
1H NMR: δ = 7.35 (td, J = 8.0, 1.2 Hz, 1 H), 7.30–7.27 (m, 2 H),
7.17 (td, J = 8.0, 1.2 Hz, 1 H), 4.95–4.71 (m, 2 H), 3.71 (m, 2 H),
2.13–1.93 (m, 2 H), 2.01 (s, 3 H).
13C NMR: δ = 176.5, 156.3, 150.0, 136.4, 130.6, 125.4, 122.8,
119.5, 80.8, 65.3, 64.9, 38.4, 25.6, 21.7.
HRMS (ESI): m/z [M + H]+ calcd for C14H14F3N2O2: 299.1007;
found: 299.1015.
Yield: 4.2 mg (74%); colorless oil.
IR (film): 2927, 2790, 1608 cm–1.
3-(2-Acetamidoethyl)-1H-indol-2-yl Acetate (3a)
Yield: 6.8 mg (16%); pale yellow oil.
IR (film): 3285, 1772, 1654, 1496, 1364 cm–1.
1H NMR: δ = 8.48 (s, 1 H), 7.53 (d, J = 8.0 Hz, 1 H), 7.30 (d,
J = 8.0 Hz, 1 H), 7.20 (td, J = 8.0, 0.8 Hz, 1 H), 7.14 (td, J = 8.0,
0.8 Hz, 1 H), 5.68 (s, 1 H), 3.56 (q, J = 6.0 Hz, 2 H), 2.86 (t,
J = 6.0 Hz, 2 H), 2.37 (s, 3 H), 1.88 (s, 3 H).
13C NMR: δ = 174.6, 170.1, 131.5, 128.3, 126.3, 122.0, 120.2,
118.5, 111.0, 97.6, 39.0, 23.2, 22.6, 20.8.
1H NMR: δ = 7.19 (td, J = 7.6, 0.9 Hz, 1 H), 7.15 (dd, J = 7.5,
0.9 Hz, 1 H), 6.74 (td, J = 7.5, 0.9 Hz, 1 H), 6.50 (d, J = 8.2 Hz,
1 H), 4.36 (s, 1 H), 3.03 (s, 3 H), 2.96 (s, 3 H), 2.80 (ddd, J = 11.9,
4.5, 2.5 Hz, 1 H), 2.62 (td, J = 8.8, 4.8 Hz, 1 H), 2.57 (s, 3 H), 2.35
(ddd, J = 13.8, 6.2, 2.8 Hz, 1 H), 2.13 (ddd, J = 12.4, 6.2, 2.0 Hz,
1 H).
13C NMR: δ = 153.1, 129.7, 128.0, 124.0, 117.9, 107.8, 94.0, 91.6,
52.5, 52.4, 39.3, 38.6, 36.2.
HRMS (ESI): m/z [M + H]+ calcd for C13H19N2O: 219.1497; found:
219.1493.
HRMS (ESI): m/z [M + H]+ calcd for C14H17N2O3: 261.1239; found:
261.1230.
8-(3-Methylbut-2-en-1-yl)-1,2,3,3a,8,8a-hexahydro-pyrro-
lo[2,3-b]indo-3a-ol (6)
3a-Methoxy-8-methyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-
b]lindole (4)
To a solution of 2a (14 mg, 0.05 mmol) in acetone (0.5 mL) were
added prenyl bromide (18 μL, 0.156 mmol) and K2CO3 (22 mg, 0.16
mmol). The resulting mixture was stirred at r.t. overnight, diluted by
the addition of H2O (3 mL), and extracted with EtOAc (3 × 3 mL).
The combined organic extracts were dried (Na2SO4) and concentrat-
ed in vacuo. The residue was dissolved in MeOH (0.5 mL) and H2O
(0.1 mL) containing KOH (624 mg, 11 mmol). The mixture was
stirred at reflux for 20 h, cooled, and partitioned between H2O
(3 mL) and EtOAc (3 mL). The organic layer was dried (Na2SO4)
and concentrated in vacuo, giving a residue that was subjected to sil-
ica gel column chromatography (CHC13–MeOH, 10:1) to give 6.
To a solution of 2a (16 mg, 0.062 mmo1) in THF (0.5 mL) at 0 °C,
was added, in portions, NaH (60% in mineral oil, 12 mg, 0.25
mmol). After 10 min, MeI (15 μL, 0.25 mmo1) was added slowly,
and the mixture was stirred at 60 °C overnight. Addition of H2O
(3 mL) followed by extraction with EtOAc (3 × 3 mL) gave organic
extracts that were dried (Na2SO4), and concentrated in vacuo. The
residue was subjected to silica gel column chromatography
(EtOAc) to give acetamide.
Yield: 6.2 mg (41%); pale yellow oil.
IR (film): 2933, 2825, 1651, 1610 cm–1.
1H NMR: δ = 7.24 (td, J = 7.6, 1.6 Hz, 1 H), 7.16 (dd, J = 7.4,
0.8 Hz, 1 H), 6.76 (td, J = 7.4, 0.8 Hz, 1 H), 6.48 (d, J = 8.0 Hz,
Yield: 8.6 mg (68%); colorless oil.
IR (film): 3242, 2967, 2927, 2855, 1608 cm–1.
Synthesis 2012, 44, 1667–1671
© Georg Thieme Verlag Stuttgart · New York