8360 J . Org. Chem., Vol. 64, No. 22, 1999
Boger and Garbaccio
CH3OH was treated with Pd/C (1.0 mg, 10 wt %) and
stirred under H2 for 10 min at 25 °C. The reaction
mixture was filtered through Celite, and the Celite was
washed thoroughly with CH3OH. The combined organic
layers were then washed with H2O and saturated aque-
ous NaCl, dried (Na2SO4), and concentrated under re-
duced pressure to yield pure 30 as a clear oil: 1H NMR
(C6D6, 400 MHz) δ 10.63 (s, 1H), 5.23 (s, 1H), 3.98 (m,
3H), 3.71 (s, 3H), 3.68 (m, 1H), 3.49 (dd, J ) 9.5, 10.7
Hz, 1H), 2.16 (s, 3H), 1.52 (s, 9H); 13C NMR (CDCl3, 100
MHz) δ 154.8, 142.9, 137.9, 136.6, 124.5, 120.3, 114.8,
83.0, 61.1, 53.4, 45.6, 40.7, 28.1, 10.0; IR (film) νmax 3422,
2980, 1667, 1471 cm-1; FABHRMS (NBA/NaI) m/z
366.1078 (C16H22NO5Cl + Na+ requires 366.1084); (+)-
(3R)-30: [R]25 +6.5 (c 0.40, CH2Cl2); (-)-(3S)-30: [R]25
was treated with salcomine (catalytic), and O2 was
bubbled through the solution for 1 h at 25 °C. The
reaction mixture was filtered through Celite, and the
Celite was washed thoroughly with EtOAc. The solution
was then concentrated under reduced pressure and
subjected directly to flash chromatography (SiO2, 1.5 ×
5 cm, 20% EtOAc/hexane) to provide 43 (7.2 mg, 78%) as
a bright yellow oil: 1H NMR (CDCl3, 400 MHz) δ 7.99
(m, 2H), 7.67 (m, 2H), 4.15 (dd, J ) 10.5, 11.9 Hz, 1H),
4.06 (dd, J ) 5.7, 11.9 Hz, 1H), 3.87 (m, 2H), 3.81 (m,
1H), 1.51 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 182.2,
177.2, 151.5, 150.1, 133.6, 133.4, 133.3, 132.2, 130.0,
126.7, 125.7, 83.0, 53.3, 45.3, 41.1, 27.9; IR (film) νmax
2978, 2929, 1721, 1644, 1597, 1403 cm-1; FABHRMS
(NBA/NaI) m/z 370.0820 (C18H18NO4Cl + Na+ requires
370.0822).
D
D
-6.1 (c 0.38, CH2Cl2).
3-(Ch lor om eth yl)-4,7-dih ydr oxy-5-m eth oxy-6-m eth -
yl-1-[(5,6,7-tr im eth oxyin d ol-2-yl)ca r bon yl]-2,3-d ih y-
d r oin d ole (31). A sample of 30 (6.9 mg, 20.0 µmol) was
dissolved in 3.6 N HCl/EtOAc (1.5 mL), and the solution
was stirred for 30 min at 25 °C. The solvents were
removed under reduced pressure, and the residual salt
was thoroughly dried under high vacuum. The salt was
dissolved in anhydrous DMF (1.0 mL) and treated with
2629 (5.6 mg, 22.0 µmol) and EDCI (11.4 mg, 60.0 µmol).
The resulting solution was stirred at 25 °C for 3 h under
Ar. The reaction mixture was then diluted with H2O, and
extracted with EtOAc. The combined organic layer was
dried (Na2SO4) and concentrated under reduced pressure.
Flash chromatography (SiO2, 1.5 × 10 cm, 0-50% EtOAc/
hexane gradient) yielded 31 (4.2 mg, 44%) as a yellow
oil: 1H NMR (C6D6, 400 MHz) δ 10.87 (s, 1H), 9.32 (br s,
1H), 6.63 (d, J ) 2.4 Hz, 1H), 6.62 (s, 1H), 5.06 (s, 1H),
4.23 (m, 1H), 3.86 (m, 2H), 3.79 (s, 3H), 3.69 (s, 3H), 3.53
(m, 1H), 3.51 (s, 3H), 3.21 (s, 3H), 3.18 (m, 1H), 2.41 (s,
3H); 13C NMR (C6D6, 125 MHz) δ 160.5, 151.2, 145.1,
139.7, 139.5, 138.3, 129.0, 126.6, 126.4, 123.9, 121.6,
115.6, 108.2, 98.2, 61.1, 60.7, 60.5, 56.1, 56.0, 45.3, 42.2,
10.7; IR (film) νmax 3425, 2939, 1574, 1432 cm-1; FAB-
HRMS (NBA/NaI) m/z 476.1338 (C23H25N2O7Cl requires
3-(Ch lor om eth yl)-1-[(5,6,7-tr im eth oxyin d ol-2-yl)-
ca r bon yl]-2,3-d ih yd r o-1H-ben zo[f]in d ole-4,9-d ion e
(44). A solution of 42 (2.5 mg, 5.34 µmol) in 1.0 mL of
anhydrous CH3CN was treated with salcomine (catalytic),
and O2 was bubbled through the solution for 1 h at 25
°C. The reaction mixture was filtered through Celite, and
the Celite was washed thoroughly with EtOAc. The
solution was then concentrated under reduced pressure
and subjected HPLC purification. Semipreparative reverse-
phase HPLC (Waters Bondapak C-18 column, 300 Å, 25
× 100 mm, gradient 10-90% CH3CN/H2O over 30 min,
10 mL/min) afforded 44 (tR ) 25 min, 1.8 mg, 70%) as a
bright yellow oil: 1H NMR (C6D6, 400 MHz) δ 9.12 (s,
1H), 8.01 (d, J ) 7.3 Hz, 1H), 7.78 (d, J ) 7.3 Hz, 1H),
6.97 (m, 1H), 6.88 (m, 1H), 6.71 (d, J ) 2.1 Hz, 1H), 6.55
(s, 1H), 3.93 (dd, J ) 5.4, 11.0 Hz, 1H), 3.78 (m, 1H),
3.76 (s, 3H), 3.63 (s, 3H), 3.57 (dd, J ) 6.2, 11.0 Hz, 1H),
3.44 (s, 3H), 3.38 (dd, J ) 3.2, 11.4 Hz, 1H), 3.15 (m, 1H);
IR (film) νmax 3320, 2926, 1682, 1644, 1596, 1463 cm-1
;
FABHRMS (NBA/NaI) m/z 481.1153 (C25H21N2O6Cl + H+
requires 481.1166).
3-(Ch lor om eth yl)-4-h yd r oxy-1-[(n a p h th -2-yl)ca r -
bon yl]-2,3-d ih yr d o-1H-ben zo[f] in d ole (45). A sample
of 41 (11.8 mg, 31.2 µmol) was dissolved in 3.6 N HCl/
EtOAc (2.0 mL), and the solution was stirred for 30 min
at 25 °C. The solvents were removed under reduced
pressure, and the residual salt was thoroughly dried
under high vacuum. The salt was dissolved in anhydrous
DMF (1.0 mL) and treated with naphthalene-2-carboxylic
acid (6.4 mg, 37.0 µmol) and EDCI (17.8 mg, 93.0 µmol).
The resulting solution was stirred at 25 °C for 3 h under
Ar. The reaction mixture was then diluted with H2O and
extracted with EtOAc. The combined organic layer was
dried (Na2SO4) and concentrated under reduced pressure.
Flash chromatography (SiO2, 1.5 × 10 cm, 0-30% EtOAc/
hexane gradient) yielded 45 (5.7 mg, 47%) as a colorless
film: 1H NMR (acetone-d6, 400 MHz) δ 8.88 (s, 1H), 8.20
(m, 2H), 8.03 (m, 4H), 7.74 (dd, J ) 1.6, 8.4 Hz, 1H), 7.70
(br s, 1H), 7.63 (m, 2H), 7.43 (m, 1H), 7.37 (m, 1H), 4.39
(dd, J ) 9.2, 11.4 Hz, 1H), 4.19 (m, 1H), 4.08-4.01 (m,
2H), 3.85 (dd, J ) 8.9, 10.6 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ 169.9, 150.3, 143.3, 137.0, 136.3, 135.4, 132.2,
130.6, 130.0, 129.7, 129.2, 129.1, 128.7, 128.3, 127.8,
126.8, 125.7, 125.0, 122.6, 116.2, 56.0, 46.9, 41.6; IR (film)
476.1350); (-)-(3R)-31: [R]25 -30 (c 0.21, CH2Cl2); (+)-
D
(3S)-31: [R]25 +31 (c 0.13, CH2Cl2).
D
3-(Ch lor om et h yl)-5-m et h oxy-6-m et h yl-1-[(5,6,7-
t r im et h oxyin d ol-2-yl)ca r b on yl]-2,3-d ih yd r oin d ol-
4,7-d ion e (7). A solution of 31 (3.0 mg, 6.2 µmol) in 1.5
mL of anhydrous EtOAc was treated with Pd/C (4.5 mg,
150 wt %) and stirred under air for 6 h at 25 °C. The
reaction mixture was filtered through Celite, and the
Celite was washed thoroughly with EtOAc. The solution
was concentrated under reduced pressure to yield pure
7 (2.9 mg, 97%) as an orange oil: 1H NMR (C6D6, 400
MHz) δ 9.10 (s, 1H), 6.69 (d, J ) 2.3 Hz, 1H), 6.61 (s,
1H), 3.91 (dd, J ) 5.4, 11.2 Hz, 1H), 3.76 (m, 1H), 3.76
(s, 3H), 3.66 (s, 3H), 3.63 (s, 3H), 3.49 (dd, J ) 6.2, 11.2
Hz, 1H), 3.47 (s, 3H), 3.27 (dd, J ) 3.2, 11.2 Hz, 1H),
3.01 (m, 1H), 1.80 (s, 3H); 13C NMR (C6D6, 100 MHz) δ
180.4, 179.4, 162.3, 155.5, 151.3, 150.1, 141.7, 139.6,
130.0, 127.9, 127.2, 126.3, 123.5, 108.7, 98.1, 61.1, 60.65,
60.64, 56.3, 55.9, 45.1, 42.0, 9.0; IR (film) νmax 3298, 2938,
1651, 1586 cm-1; FABHRMS (NBA/NaI) m/z 607.0227
(C23H23N2O7Cl + Cs+ requires 607.0248); (-)-(3R)-7:
[R]25D -81 (c 0.15, CH2Cl2); (+)-(3S)-7: [R]25D +80 (c 0.10,
CH2Cl2).
ν
max 2923, 1688, 1598, 1468 cm-1; FABHRMS (NBA/NaI)
m/z 388.1097 (C24H18NO2Cl + H+ requires 388.1104).
3-(Ch lor om et h yl)-1-[(n a p h t h -2-yl)ca r b on yl]-2,3-
d ih yd r o-1H-ben zo[f]in d ole-4,9-d ion e (46). A solution
of 45 (2.0 mg, 5.17 µmol) in 1.0 mL of anhydrous CH3CN
was treated with salcomine (catalytic), and O2 was
1-(ter t-Bu tyloxyca r bon yl)-3-(ch lor om eth yl)-2,3-d i-
h yd r o-1H-ben zo[f]in d ole-4,9-d ion e (43). A solution of
41 (8.0 mg, 26.6 µmol) in 1.5 mL of anhydrous CH3CN