Comins et al.
(neat) 2360, 1717, 1322, 1204, 1148, 1130, 738, 698, 668 cm-1
0.74 mmol) of 41 in 2 mL of THF at -78 °C was added 888 µL
(0.09 mmol, 1.0 M) of NaHMDS in THF. The solution was
stirred for 30 min and then 182 µL (1.48 mmol) of pivaloyl
chloride was added. After the solution was stirred for 2 h at
-78 °C, the reaction was quenched with saturated aqueous
NaHCO3 (1 mL). The aqueous layer was extracted with Et2O
(3 × 1 mL). The combined organic extracts were washed with
brine (1 mL) and dried over K2CO3. The solvent was removed
under reduced pressure and the residue was purified by radial
PLC (silica gel, 5% EtOAc/hexanes) to afford 235 mg (70%) of
43 as a clear oil: IR (neat) 2959, 2866, 2360, 2340, 1721, 1650,
;
1H NMR (CDCl3, 300 MHz) δ1.25-1.71 (m, 4H), 2.00-2.06 (m,
2H), 2.33 (d, 1H, J ) 17.4 Hz), 2.75-2.86 (m, 2H), 3.47 (m,
1H), 3.65 (m, 1H), 4.32 (br s, H), 4.44 (d, 1H, J ) 11.2 Hz),
4.35-4.59 (m, 4H), 5.48 (br s, 1H), 5.97 (s, 1H), 6.98 (d, 1H, J
) 8.0 Hz), 7.15 (t, 2H, J ) 7.6 Hz), 7.26-7.41 (m, 8H), 7.67 (t,
2H, J ) 7.6 Hz), 7.90 (d, 1H, J ) 8.4 Hz); 13C NMR (CDCl3, 75
MHz) δ 22.3, 26.3, 28.0, 29.9, 34.7, 39.5, 50.6, 51.3, 59.1, 62.3,
66.8, 69.7, 73.6, 116.8, 121.6, 125.0, 125.5, 128.2, 128.6, 129.3,
133.6, 134.2, 135.6, 136.1, 137.4, 138.5, 150.9, 155.0; HRMS
calcd for C32H33NO8S2 ([M + H]+) 624.1726, found 624.1761.
1
1645, 1311, 1196 cm-1; H NMR (CDCl3, 400 MHz) δ 1.20 (s,
(2R*,5S*,6aS*,12aR*,12bR*)-2-(3-Benzyloxypropyl)-5-
ethoxycarbonylmethyl-1-(phenoxycarbonyl)-7,7,12,12-
tetraoxo-3,5,6,6a,7,12,12a,12b-octahydro-2H-7λ6,12 l6-di-
thiabenzo[R]anthracene (47). To a solution of 10.5 mg
(0.017 mmol) of 46 (10.5 mg, 0.017 mmol) in 2 mL of triethyl
orthoacetate was added 1 drop of a 1:10 propionic acid:triethyl
orthoacetate solution. The resulting mixture was refluxed for
3 h and then concentrated under reduced pressure. Purifica-
tion by radial PLC (silica gel, 5% EtOAc/5% CH2Cl2/ 90%
hexanes) gave 7.8 mg of 47 (67%) as a white solid, mp 180.5-
181.5 °C; IR (neat) 2979, 2938, 2863, 1716, 1686, 1495, 1455,
9H), 1.61-2.26 (m, 7H), 3.45-3.51 (m, 2H), 4.42-4.50 (m, 3H),
4.94 (m, 2H), 5.73 (d, 1H, J ) 4.0 Hz), 6.26 (m, 1H), 7.11-
7.41 (m, 10H); 13C NMR (CDCl3, 100 MHz) δ 27.3, 28.9, 29.3
(due to rotamers), 30.6, 39.1, 50.1, 50.7 (due to rotamers), 62.1,
70.1, 73.3, 77.4, 110.7, 111.0 (due to rotamers), 116.1, 116.6
(due to rotamers), 121.7, 126.0, 127.7, 127.8, 128.2, 128.5,
129.7, 134.7, 138.5, 151.0, 151.7, 152.2 (due to rotamers), 178.1;
HRMS calcd for C29H35NO5 ([M]+) 477.2515, found 477.2523.
Diels-Alder Reaction of 43 with Benzodithiin Tet-
raoxide. To a solution of 33 mg (0.07 mmol) of 43 in 2 mL of
toluene was added 16 mg (0.07 mmol) of benzodithiin tetra-
oxide.17 The solution was degassed with argon and then heated
to reflux for 12 h. After being cooled to room temperature, the
solution was concentrated under reduced pressure and the
residue was purified by radial PLC (silica gel, 5-10% EtOAc/
hexanes) to give 29 mg (60%) of (2R*,4S*,6aR*,12aS*,12bS*)-
2-(3-benzyloxypropyl)-4-(2,2-dimethylpropionyloxy)-1-(phe-
noxycarbonyl)-7,7,12,12-tetraoxa-3,4,6,6a,7,7,12,12a,12b-oc-
tahydro-2H-7λ6,12λ6-dithia-1-azabenzo[R]anthracene (44) as a
white solid: mp 164.5-165.0 °C; IR (neat) 2966, 2926, 2857,
1726, 1457, 1326, 1279, 1203, 1149, 752 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.10-1.40 (m, 9H), 1.70-1.90 (q, 2H, J ) 5.3 Hz),
1.95-2.20 (m, 2H), 2.23-2.40 (m, 3H), 2.80-3.01 (m, 2H),
3.45-3.65 (m, 2H), 3.85 (t, 1H, J ) 9.6), 4.16 (q, 1H, J ) 7.3),
4.55 (s, 2H), 5.17-5.30 (br s, 1H), 5.62 (d, 1H, J ) 9.2 Hz),
6.13 (s, 1H), 7.10-7.60 (m, 10H), 7.78-8.00 (m, 2H), 8.04, (d,
2H, J ) 8.0 Hz); 13 CNMR (CDCl3) 400 MHz) δ 22.0, 26.1, 27.7,
34.2, 37.0, 50.2, 51.0, 58.4, 62.0, 69.4, 70.6, 73.3, 82.9, 118.0,
121.4, 124.9, 125.4, 127.9, 128.0, 128.3, 128.5, 129.1, 130.9,
133.4, 134.0, 136.9, 138.4, 150.7, 152.1, 154.6; HRMS calcd
for C37H41NO9S2 ([M + H]+) 708.2301, found 708.2315.
1
1355, 1320, 1194, 1148, 748, 701 cm-1; H NMR (CDCl3, 300
MHz) δ 1.24 (t, 3H, J ) 7.2 Hz), 1.58-1.80 (m, 4H), 2.15-
2.26 (m, 1H), 2.48-2.61 (m, 3H), 2.42 (br d, 1H, J ) 12.9 Hz),
3.37 (q, 1H, J ) 5.1 Hz), 3.50 (s, 2H), 3.85 (dt, 1H, J ) 10.8
and 2.7 Hz), 4.04-4.18 (m, 2H), 4.48 (s, 2H), 4.59-4.63 (m,
2H), 5.98 (d, 1H, J ) 5.4 Hz), 6.21 (s, 1H), 7.13-7.36 (m, 11H),
7.74-7.82 (m, 2H), 7.96 (t, 2H, J ) 4.5 Hz); 13C NMR (CDCl3,
100 MHz) δ 14.5, 26.7, 27.3, 27.6, 31.0, 37.0, 39.4, 52.3, 53.1,
59.1, 59.7, 61.1, 70.1, 73.2, 122.1, 124.6, 124.9, 125.2, 126.0,
127.8, 127.9, 128.6, 129.7, 133.6, 134.2, 134.7, 138.6, 140.9,
151.3, 156.2, 171.2; HRMS for C36H39NO9S2 ([M + H]+)
694.4125, found 694.2147.
(1R*)-[3-(9,10-Dioxo-9,10-dihydroanthracen-2-yl)-3-oxo-
1-phenylpropyl]carbamic Acid Phenyl Ester (50). To a
solution of 70 mg (0.219 mmol) of 5 in 10 mL of toluene was
added 41 mg (0.259 mmol) of 1,4-naphthoquinone. The mixture
was heated at reflux for 12 h, cooled to room temperature, and
concentrated under reduced pressure. The residue was rapidly
purified by radial PLC (silica gel, EtOAc/hexanes) to give 87
mg (84%) of (2R*,6aS*,12aS*,12bR*)-4,7,12-trioxo-1-((phe-
noxy)carbonyl)-2-phenyl-3,4,6,6a,7,12,12a,12b-octahydro-2H-
naphtho[2,3-h]quinoline (48) as a colorless foam: IR (thin film)
The minor isomer (9 mg, 19%) was identified as (2S*,6aR*,-
12aS*,12bS*)-2-(3-benzyloxypropyl)-4,7,7,12,12-pentaoxo-3,4,6,-
6a,7,12,12a,12b-octahydro-2H-7λ6,12λ6-dithia-1-azabenzo[a]-
anthracene-1-carboxylic acid phenyl ester (45) and was isolated
as a white solid: mp 148.0-149.0 °C; IR (neat) 2985, 2924,
3027, 2910, 1699, 1623, 1592, 1483, 1350, 1255, 1203 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 2.31 (m, 1H), 2.78 (m, 1H), 3.00
(dt, 1H, J ) 16.0 and 3.7 Hz), 3.58 (m, 1H), 3.82 (m, 1H), 5.00
(m, 1H), 6.10 (m, 1H), 6.66 (m, 1H), 6.76 (m, 2H), 7.21 (m,
9H), 7.77 (m, 2H), 7.96 (m, 1H), 8.05 (m, 1H); 13C NMR (CDCl3,
75 MHz) δ 27.1, 43.7, 47.3, 49.7, 55.9, 57.8, 121.7, 125.8, 126.2,
126.6, 127.6, 128.0, 129.3, 129.4, 132.5, 133.8, 134.7, 134.9,
135.0, 141.1, 150.8, 155.3, 194.8, 196.3, 196.6; HRMS calcd
for C30H23NO5 ([M + H]+) 478.1654, found 478.1652.
1
2871, 2359, 2341, 1721, 1324, 1205, 1150, 751, 699 cm-1; H
NMR (CDCl3, 300 MHz) δ 1.45-1.56 (s, 9H), 1.58-1.68 (m,
1H), 2.01-2.08 (m, 2H), 2.33 (d, 1H, J ) 17.2 Hz), 2.77-2.93
(m, 2H), 3.43 (t, 1H, J ) 9.6 Hz), 3.62-3.66 (m, 1H), 4.43 (d,
1H, J ) 11.2 Hz), 4.55-4.62 (m, 6H), 5.19 (br s, 1H), 5.54 (br
s, 1H), 5.94 (s, 1H), 7.00 (d, 2H, J ) 7.2 Hz), 7.14 (t, 1H, J )
6.8 Hz), 7.25-7.40 (m, 8H), 7.62 (t, 2H, J ) 7.6 Hz), 7.92 (d,
1H, J ) 8.0 Hz); 13C NMR (CDCl3, 75 MHz) δ 22.2, 26.0, 27.9,
29.9, 34.6, 39.4, 50.5, 51.3, 59.1, 62.2, 66.8, 69.7, 73.6, 77.4,
116.8, 121.6, 124.9, 125.1, 125.5, 128.1, 128.6, 129.2, 133.5,
134.2, 135.6, 136.1, 137.3, 138.5, 150.9, 155.0, 176.9; HRMS
calcd for C37H41NO9S2 ([M + H]+) 708.2301, found 708.2355.
To a solution of 85 mg (0.178 mmol) of 48 in 10 mL of
CH2Cl2 was added 1.0 g of silica gel. The mixture was stirred
at room temperature for 18 h, filtered, and concentrated under
reduced pressure. The crude residue was purified by radial
PLC (silica gel, EtOAc/hexanes) to give 75 mg (88%) of 50 as
a light yellow foam: IR (thin film) 3338, 1694, 1672, 1590,
1523, 1485, 1361, 1291, 1199 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 3.70 (dd, 1H, J ) 16.8 and 5.8 Hz), 3.97 (m, 1H), 5.45 (m,
1H), 6.02 (br s, 1H), 7.29 (m, 11H), 7.85 (m, 2H), 8.35 (m, 3H),
8.80 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ 29.9, 44.6, 52.2,
121.8, 125.6, 126.7, 127.2, 127.7, 128.2, 129.1, 129.5, 133.1,
133.6, 134.0, 134.8, 140.7, 151.1, 154.2, 182.6, 189.0, 196.8;
HRMS calcd for C30H21NO5 ([M + H]+) 476.1498, found
476.1516.
(2S*,4R*,6aS*,12aR*,12bR*)-2-(3-Benzyloxypropyl)-4-
hydroxy-1-(phenoxy carbonyl)-7,7,12,12-tetraoxa-3,4,6,-
6a,7,7,12,12a,12b-octahydro-2H-7λ6,12λ6-dithia-1-azabenzo-
[r]anthracene (46). To a -78 °C solution of 20 mg (0.028
mmol) of 44 in 2 mL of CH2Cl2 was added 70.6 µL (0.070 mmol)
of 1.0 M DIBALH in toluene. After 2 h at -78 °C, the reaction
was quenched with MeOH (1 mL) and diluted with brine (1
mL). The solution was extracted with CH2Cl2 (3 × 1 mL). The
combined organic extracts were dried over MgSO4, filtered, and
concentrated under reduced pressure. Purification of the
residue by radial PLC (silica gel, 40% EtOAc/hexanes) gave
13 mg (78%) of 46 as a white solid, mp 132.0-132.5 °C; IR
(1R*)-[3-(5,8-Dioxo-5,8-dihydronaphthalen-2-yl)-3-oxo-
1-phenylpropyl]carbamic Acid Phenyl Ester (51). To a
solution of 30 mg (0.094 mmol) of 5 in 7 mL of toluene was
added 12 mg (0.111 mmol) of 1,4-benzoquinone. The mixture
was heated at reflux for 12 h, cooled to room temperature, and
5232 J. Org. Chem., Vol. 70, No. 13, 2005