Organic & Biomolecular Chemistry
Paper
under reduced pressure. Purification by silica gel column 3.49–3.46 (m, 1H), 3.38–3.33 (m, 1H), 3.22–3.18 (dd, J = 14.1,
chromatography afforded N-protected ( )-10 (60 mg, 92%) as a 4.1 Hz, 1H), 2.72–2.68 (m, 1H), 2.60–2.56 (tt, J = 7.9, 3.8 Hz,
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pale yellow liquid; H NMR (400 MHz, CDCl3) δ 7.36–7.28 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 177.8, 139.0, 134.0,
3H). 7.18–7.14 (m, 4H), 6.93 (s, 1H), 6.83–6.82 (m, 1H), 5.30 (s, 132.0, 129.0, 127.8, 127.7, 127.6, 124.0, 122.6, 113.8, 110.5,
2H), 4.06 (d, J = 10.4 Hz, 1H), 3.86 (s, 3H), 3.74 (ddd, J = 10.9, 108.8, 59.6, 57.1, 49.7, 48.2, 46.0, 28.6; IR (thin film,
10.9, 3.9 Hz, 1H), 3.44 (dd, J = 13.8, 4.2 Hz, 1H), 3.00 (s, 3H), νmax/cm−1): 3385, 3214, 2920, 2849, 1693, 1503, 1027, 745;
2.94 (dd, J = 12.8, 12.8 Hz, 1H), 1.54 (s, 3H); 13C NMR HRMS (ESI) m/z: [M + H]+ calcd for C21H21N2O2 333.1598,
(100 MHz, CDCl3) δ 175.3 (C), 173.1 (C), 137.6 (C), 134.4 (C), found 333.1595.
128.8 (CH), 128.0 (C), 127.8 (CH), 127.4 (C), 126.9 (CH), 123.3
(CH), 122.8 (CH), 114.0 (CH), 109.4 (C), 108.4 (CH), 60.2 (CH),
(4-Benzyl-8-oxo-6,6a,7,8,9,9a-hexahydro-4H-indolo[6,5,4-cd]indol-
9-yl)methyl methanesulfonate [( )-12]
53.5 (C), 52.8 (CH), 50.3 (CH2), 49.9 (CH3), 27.8 (CH3), 27.0
(CH2), 12.4 (CH3); IR (thin film, νmax/cm−1): 2920, 2850, 1738, To a solution of β-hydroxyl lactam ( )-11 (0.4 g, 1.0 equiv.,
1696, 1317, 1250, 747; HRMS (ESI) m/z: [M + H]+ calcd for 1.2 mmol) in dry CH2Cl2 (20 mL) were added dry Et3N (0.9 mL,
C24H25N2O3 389.1860, found 389.1857.
5.0 equiv., 6.0 mmol) and an excess of MsCl (0.9 mL, 10.0
equiv., 12.0 mmol). The reaction mixture was stirred for
4 hours and a saturated NH4Cl solution was added into the
reaction mixture. The organic layer was separated and the
Allyl 4-benzyl-7,9-dimethyl-8-oxo-6,6a,7,8,9,9a-hexahydro-
4H-indolo[6,5,4-cd]indole-9-carboxylate [( )-4]
To a solution of N-protected ( )-10 (0.12 g, 1.0 equiv., aqueous layer was extracted with CH2Cl2. The combined
0.3 mmol) in toluene (5 mL) were added zinc powder (4 mg, organic layers were washed with water and brine, dried over
0.2 equiv., 0.06 mmol) and an excess of allyl alcohol (0.1 mL, anhydrous Na2SO4, and concentrated under reduced pressure.
5.0 equiv., 1.5 mmol). The reaction mixture was heated to The crude product was purified by flash chromatography on
reflux for 5 hours and then cooled to room temperature. The silica gel (CH2Cl2/MeOH = 30 : 1, Rf = 0.14) to give methane-
organic solvent was removed under reduced pressure, and the sulfonate ( )-12 as a colorless solid (0.48 g, 98% yield):
crude product was purified by silica gel column chromato- m.p. 240–243 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.39 (br, 1H),
graphy to give a single product allyl carboxylate ( )-4 (0.122 g, 7.33–7.21 (m, 7H), 7.04 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 7.1 Hz,
95%) as a pale yellow solid: mp = 49–52 °C; 1H NMR 1H), 5.36 (s, 2H), 4.80–4.64 (m, 2H), 3.60–3.54 (m, 1H),
(400 MHz, CDCl3) δ 7.36–7.29 (m, 3H), 7.19–7.13 (m, 4H), 6.92 3.36–3.33 (m, 1H), 3.24–3.18 (m, 1H), 3.20 (s, 3H), 3.05–3.00
(d, J = 1.1 Hz, 1H), 6.82–6.80 (m, 1H), 5.95–5.93 (m, 1H), (m, 1H), 2.73 (t, J = 12.6 Hz, 1H); 13C NMR (100 MHz, DMSO-
5.41–5.36 (m, 1H), 5.30 (s, 2H), 5.24 (dd, J = 10.4, 1.2 Hz, 1H), d6) δ 175.4, 139.0, 134.0, 130.7, 129.0, 127.8, 127.7, 127.6,
4.79–4.76 (m, 2H), 4.07 (d, J = 10.0, 1H), 3.74–3.72 (m, 1H), 124.2, 122.7, 113.4, 110.2, 109.2, 68.6, 57.0, 49.8, 45.9, 45.3,
3.43 (dd, J = 13.8, 4.4 Hz, 1H), 3.0 (s, 3H), 2.97 (dd, J = 13.2, 28.3; IR (thin film, νmax/cm−1): 3393, 2920, 2849, 1691, 1166,
13.2 Hz, 1H), 1.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 175.3 1092, 1027, 751; HRMS (ESI) m/z: [M + H]+ calcd for
(C), 172.3 (C), 137.6 (C), 134.4 (C), 131.9 (CH), 128.8 (CH), C22H23N2O4S 411.1373, found 411.1368.
128.0 (C), 127.8 (CH), 127.4 (C), 127.0 (CH), 123.3 (CH), 122.8
(CH), 118.4 (CH2), 114.0 (CH), 109.4 (C), 108.4 (CH), 66.2
(CH2), 60.2 (CH3), 53.6 (C), 50.3 (CH2), 49.9 (CH), 27.8 (CH),
4-Benzyl-9-methyl-4,6,6a,7-tetrahydro-8H-indolo[6,5,4-cd]indol-
8-one [( )-13]
27.0 (CH2), 12.4 (CH3); IR (thin film, νmax/cm−1): 3358, 3186, To a solution of methanesulfonate ( )-12 (0.1 g, 1.0 equiv.,
2920, 2850, 1736, 1697, 1454, 1244, 747; HRMS (ESI) m/z: 0.25 mmol) in dry CH2Cl2 (10 mL) was added DBU (0.5 mL,
[M + H]+ calcd for C26H27N2O3 415.2016, found 415.2017.
14.0 equiv., 3.5 mmol) at room temperature. The reaction
mixture was stirred for about 1 hour, and then a saturated
NH4Cl solution was added. The organic layer was separated
and the aqueous layer was extracted with CH2Cl2. The com-
4-Benzyl-9-(hydroxymethyl)-4,6,6a,7,9,9a-hexahydro-8H-
indolo[6,5,4-cd]indol-8-one [( )-11]
To a suspension of LiAlH4 (91.2 mg, 3.0 equiv., 2.4 mmol) in bined organic layers were washed with water and brine, dried
THF (10 mL) was added dropwise the solution of tetracyclic over anhydrous Na2SO4, and concentrated under reduced
lactam ( )-9 (0.3 g, 1.0 equiv., 0.8 mmol) in anhydrous THF pressure. The crude product was purified by flash chromato-
(20 mL). The mixture was refluxed for 4 hours, and cooled to graphy on silica gel (CH2Cl2/MeOH = 30 : 1, Rf = 0.10) to give
0 °C. Water, sodium hydroxide solution (10%), and water α,β-unsaturated tetracyclic lactam ( )-13 as a pale claybank
(v/v/v = 1 : 2 : 3) were slowly added dropwise with vigorous stir- liquid (70 mg, 92% yield); 1H NMR (400 MHz, DMSO-d6) δ 8.42
ring. The reaction mixture was filtered with Celite, washed (s, 1H), 7.44 (d, J = 7.7 Hz, 1H), 7.34–7.19 (m, 8H), 5.39 (s, 2H),
with ethyl acetate, dried over anhydrous Na2SO4, and concen- 4.36–4.31 (m, 1H), 3.45–3.35 (m, 1H), 2.52–2.50 (m, 1H), 2.04
trated under reduced pressure. The crude product was purified (d, J = 1.6 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 174.2,
by flash chromatography on silica gel (CH2Cl2/MeOH = 20 : 1, 148.2, 138.8, 134.5, 129.0, 127.9, 127.9, 127.7, 126.7, 125.2,
Rf = 0.10) to give β-hydroxyl lactam ( )-11 as a colorless foamed 124.1, 123.0, 115.6, 111.2, 109.2, 56.0, 49.8, 28.8, 9.8; IR (thin
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solid (0.25 g, 90% yield): m.p. 257–260 °C; H NMR (400 MHz, film, νmax/cm−1): 3389, 3204, 3061, 2921, 2850, 1676, 1606,
DMSO-d6) δ 8.10 (s, 1H), 7.33–7.19 (m, 7H), 7.04–6.96 (m, 2H), 746; HRMS (ESI) m/z: [M + H]+ calcd for C21H19N2O 315.1492,
5.34 (s, 2H), 4.80 (t, J = 5.1 Hz, 1H), 4.02–3.92 (m, 2H), found 315.1489.
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