TOTAL SYNTHESIS OF (ꢀ)-NUCIFERINES
3461
CH2Cl2 (3 ꢃ 50.0 mL). After the removal of solvent, the residue was subjected to
flash chromatography (SiO2, CH2Cl2-ethyl acetate–MeOH 10:2:1) to provide the
1
desired 13 (0.50 g, 67%) as an oil. H NMR [(CD3)2CO] d :1.45 (d, J ¼ 6.0 Hz,
6H), 2.42 (s, 3H), 2.44–2.81 (m, 4H), 2.99–3.15 (m, 2H), 3.56 (s, 3H), 3.63 (t,
J ¼ 6.0 Hz, 1H), 3.82 (s, 3H), 4.52 (hept, J ¼ 6.0 Hz, 1H), 6.32 (s, 1H), 6.57 (s,
1H), 6.74 (d, J ¼ 8.4 Hz, 2H), 7.01 (d, J ¼ 8.4 Hz, 2H); 13C NMR [(CD3)2CO] :d
21.4, 25.3, 39.9, 42.1, 47.0, 54.9, 55.0, 64.7, 69.1, 111.5, 111.7, 115.1, 126.4, 129.6,
130.7, 132.0, 147.0, 147.6, 156.1; HRMS (EI) calcd. for C22H29NO3 (Mþ)
355.2147; found 355.2142.
1,2-Dimethoxy-4,5,6a,7-tetrahydrodibenzo[de,g]
quinoline-6-carboxylic Acid Methyl Ester (15a)[2c]
Compound 15a was prepared, using the previous procedure, from 12a (0.30 g,
1.3 mmol) and 10c (0.50 g, 2.5 mmol) in mixed solvents of CH2Cl2 and CHCl3 (20.0=
20.0 mL), followed by dropwise addition of BF3-OEt2 (0.3 mL, 2.5 mmol) at ꢂ 78 ꢁC
for 1 h by TLC monitoring. The reaction was quenched with saturated aqueous sol-
ution of NaHCO3 (10.0 mL), which was extracted with CH2Cl2 (3 ꢃ 50.0 mL). After
the removal of solvent, the crude 14a was directly used no further purification. A
mixture of 14a (0.53 g, 1.3 mmol), AIBN (0.01 g, 63.2 mmol), and Bu3SnH (0.37 g,
1.3 mmol) in dried toluene (35.0 mL) was heated to reflux under N2. The reaction
was monitored by TLC and quenched with addition of cyclohexane (10.0 mL),
which was extracted with CH2Cl2 (3 ꢃ 35.0 mL). After the removal of solvent, the
residue was subjected to flash chromatography (SiO2, hexane–ethyl acetate 5:1) to
obtain the desired 15a (0.22 g, 52%) as an oil.1H NMR d 2.51 (d, J ¼ 15.0 Hz, 1H),
2.66–2.89 (m, 4H), 3.52 (s, 3H), 3.62 (s, 3H), 3.74 (s, 3H), 4.31 (d, J ¼ 10.5 Hz,
1H), 4.61 (d, J ¼ 12.9 Hz, 1H), 6.53 (s, 1H), 7.10–7.20 (m, 3H), 8.31 (d, J ¼ 7.8 Hz,
1H); 13C NMR d 30.2, 35.2, 38.9, 51.6, 52.6, 55.9, 59.9, 111.5, 126.0, 127.0, 127.5,
127.6, 128.3, 128.4, 129.6, 131.7, 136.7, 145.6, 152.0, 155.9.
1,2-Dimethoxy-4,5,6a,7-tetrahydrodibenzo[de,g]
quinoline-6-carboxylic Acid tert-Butyl Ester (15b)[2c]
A mixture of 12b (0.28 g, 1.0 mmol) and 10c (0.39 g, 2.0 mmol) in mixed sol-
vents of CH2Cl2 and CHCl3 (20.0=20.0 mL) was stirred and followed by dropwise
addition of BF3-OEt2 (0.3 mL, 2.5 mmol) at ꢂ 78 ꢁC for 1 h by TLC monitoring.
The reaction was quenched with saturated aqueous solution of NaHCO3
(10.0 mL), which was extracted with CH2Cl2 (3 ꢃ 50.0 mL). After the removal of sol-
vent, the crude 14b was directly used no further purification. A mixture of 14b
(0.46 g, 1.0 mmol), AIBN (0.01 g, 63.2 lmol), and Bu3SnH (0.29 g, 1.0 mmol) in dried
toluene (30.0 mL) was heated to reflux under N2. The reaction was monitored by
TLC and quenched with addition of cyclohexane (10.0 mL), which was extracted
with CH2Cl2 (3 ꢃ 30.0 mL). After the removal of solvent, the residue was subjected
to flash chromatography (SiO2, hexane–ethyl acetate 4:1) to obtain the desired 15b
1
(0.21 g, 56%) as a white solid: mp 184–185 ꢁC, H NMR d 1.41 (s, 9H), :2.56 (d,
J ¼ 14.4 Hz, 1H), 2.70–2.90 (m, 4H), 3.64 (s, 3H), 3.81 (s, 3H), 4.34 (d, J ¼ 9.9 Hz,
1H), 4.58 (d, J ¼ 12.9 Hz, 1H), 6.59 (s, 1H), 7.12–7.25 (m, 3H), 8.35 (d, J ¼ 7.8 Hz,