The Journal of Organic Chemistry
Article
127.6, 132.6, 143.7, 146.7, 147.1, 148.8, 148.9, 150.0, 150.1, 161.7.
Anal. Calcd for C36H43NO10: C, 66.55; H, 6.67; N, 2.16. Found: C,
66.45; H, 6.89; N, 2.12.
1H), 6.78 (d, J = 8.3 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 6.88 (dd, J =
1.7 and 8.3 Hz, 1H), 6.90 (s, 1H), 6.93 (s, 1H), 7.03−7.15 (m, 5H).
13C NMR (100 MHz, CDCl3): δ 21.8, 22.1, 33.8, 45.7, 55.8, 55.9, 56.0,
Methyl 4-(3-Isopropoxy-4-methoxyphenyl)-5-(4-isopro-
poxy-3-methoxyphenyl)-3-(4-isopropoxy-5-methoxy-2-me-
thoxymethoxyphenyl)-1H-pyrrole-2-carboxylate (4). According
to the procedure described for the preparation of 14a, 12 (532 mg,
0.999 mmol), 79k (407 mg, 1.51 mmol), Pd(dba)2 (58.2 mg, 0.101
mmol), and dppf (55.1 mg, 99.4 μmol) were reacted. After purification
by flash chromatography over silica gel 60N (toluene−ethyl acetate =
5:1), 4 was obtained as a colorless solid (621 mg, 92%).
Recrystallization from Et2O−hexane gave a colorless powder. Mp
71.0, 71.2, 71.4, 103.4, 105.3, 110.2, 111.6, 114.1, 114.5, 114.5, 118.6,
118.7, 122.0, 123.3, 123.8, 125.9, 126.6, 127.8, 128.6, 128.8, 135.1,
143.0, 146.2, 146.5, 146.9, 147.3, 147.9, 149.6, 149.7, 155.5. Anal.
Calcd for C43H47NO8S: C, 69.99; H, 6.42; N, 1.90. Found: C, 69.87;
H, 6.62; N, 1.87.
7-Isopropoxy-1-(3-isopropoxy-4-methoxyphenyl)-2-(4-iso-
propoxy-3-methoxyphenyl)-8-methoxy-3-[2-(phenylsulfinyl)-
ethyl][1]benzopyrano[3,4-b]pyrrol-4(3H)-one (17). Under an
argon atmosphere, m-chloroperbenzoic acid (28.0 mg, 0.162 mmol)
was added portionwise to a solution of 16 (120 mg, 0.162 mmol) in
DCM (9 mL) at 0 °C. After 15 min of stirring at 0 °C, the mixture was
quenched with saturated aqueous NaHCO3, and the products were
extracted with DCM. The extract was washed with water and brine,
dried over Na2SO4, and evaporated. The residue was purified by
column chromatography over silica gel 60N (hexane−ethyl acetate =
1:1) to give 17 as a colorless solid (108 mg, 89%). Recrystallization
from DCM−hexane gave a colorless powder. Mp 182.5−183.5 °C. IR
(KBr): 1711, 1441, 1262, 1032 cm−1. 1H NMR (400 MHz, CDCl3): δ
1.14 (br s, 3H), 1.26 (br s, 3H), 1.40 (d, J = 6.1 Hz, 12H), 3.24−3.33
(m, 1H), 3.42−3.51 (m, 1H), 3.47 (s, 3H), 3.68 (s, 3H), 3.84 (s, 3H),
4.25−4.38 (m, 1H), 4.56 (sep, J = 6.1 Hz, 2H), 4.66 (br s, 1H), 4.87
(br s, 1H), 6.66 (d, J = 1.8 Hz, 1H), 6.73 (br s, 1H), 6.81 (dd, J = 1.8
and 8.3 Hz, 1H), 6.83−6.87 (m, 2H), 6.86 (d, J = 8.3 Hz, 1H), 6.90 (s,
1H), 6.91 (s, 1H), 7.44−7.51 (m, 3H), 7.53−7.58 (m, 2H). 13C NMR
(100 MHz, CDCl3): δ 21.5, 21.8, 22.1, 40.3, 55.7, 55.9, 56.0, 57.7,
71.1, 71.2, 71.5, 103.3, 105.3, 110.0, 111.6, 114.3, 114.5, 118.5, 118.9,
121.4, 123.3, 123.8, 124.0, 126.4, 128.4, 129.2, 131.0, 143.2, 143.3,
146.2, 146.6, 147.0, 147.5, 148.1, 149.6, 149.9, 155.5. Anal. Calcd for
C43H47NO9S: C, 68.51; H, 6.28; N, 1.86. Found: C, 68.19; H, 6.46; N,
1.78.
1
72−73 °C. IR (KBr): 3330, 1716, 1509, 1441, 1244, 1112 cm−1. H
NMR (400 MHz, CDCl3): δ 1.11 (d, J = 6.0 Hz, 3H), 1.11 (d, J = 6.0
Hz, 3H), 1.35 (d, J = 6.0 Hz, 3H), 1.37 (d, J = 6.0 Hz, 6H), 1.37 (d, J
= 6.0 Hz, 3H), 3.25 (s, 3H), 3.59 (s, 3H), 3.64 (s, 3H), 3.71 (s, 3H),
3.77 (s, 3H), 4.13 (sep, J = 6.0 Hz, 1H), 4.49 (sep, J = 6.0 Hz, 1H),
4.52 (sep, J = 6.0 Hz, 1H), 4.57 (d, J = 6.8 Hz, 1H), 4.80 (d, J = 6.8
Hz, 1H), 6.58 (dd, J = 1.9 and 8.1 Hz, 1H), 6.60 (d, J = 1.9 Hz, 1H),
6.62 (s, 1H), 6.66 (d, J = 8.1 Hz, 1H), 6.78 (d, J = 1.8 Hz, 1H), 6.80
(s, 1H), 6.83 (d, J = 8.3 Hz, 1H), 6.92 (dd, J = 1.8 and 8.3 Hz, 1H),
9.19 (br s, 1H). 13C NMR (100 MHz, CDCl3): δ 21.8, 22.1, 22.2, 51.3,
55.5, 55.7, 55.9, 56.4, 71.0, 71.3, 96.7, 105.5, 111.4, 111.9, 115.3, 116.0,
117.1, 117.9, 118.8, 119.8, 123.0, 123.8, 124.7, 127.4, 127.7, 132.5,
144.9, 146.6, 147.0, 147.2, 148.7, 149.9, 150.0, 161.8. Anal. Calcd for
C38H47NO10: C, 67.34; H, 6.99; N, 2.07. Found: C, 67.25; H, 7.28; N,
2.03.
7-Isopropoxy-1-(3-isopropoxy-4-methoxyphenyl)-2-(4-iso-
propoxy-3-methoxyphenyl)-8-methoxy[1]benzopyrano[3,4-
b]pyrrol-4(3H)-one (15). Under an argon atmosphere, a solution of
4 (143 mg, 0.211 mmol) and p-TsOH·H2O (10.5 mg, 55.2 μmol) in
MeOH (10 mL) was refluxed for 18.5 h. After cooling to room
temperature, the mixture was quenched with saturated aqueous
NaHCO3 and evaporated. The products were extracted with DCM,
and the extract was washed with water and brine, dried over Na2SO4,
and evaporated. The residue was purified by column chromatography
over silica gel 60N (hexane−ethyl acetate = 3:1) to give 15 as a pale-
yellow solid (121 mg, 95%). Recrystallization from DCM−hexane
gave a colorless powder. Mp 216−217 °C. IR (KBr): 3276, 1691,
3,11-Diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-
2,12-dimethoxy-9-(phenylsulfanyl)-8,9-dihydro-6H-[1]-
benzopyrano[4′,3′:4,5]pyrrolo[2,1-a]isoquinolin-6-one (18).
Under an argon atmosphere, TMSOTf (48 μL, 0.265 mmol) was
added to a solution of 17 (50.0 mg, 66.3 μmol) and i-Pr2NEt (46 μL,
0.264 mmol) in DCM (5.0 mL) at 0 °C. After 1 h of stirring at 0 °C,
the mixture was quenched with saturated aqueous NaHCO3, and the
products were extracted with DCM. The extract was washed with
water and brine, dried over Na2SO4, and evaporated. The residue was
purified by flash chromatography over silica gel 60N (hexane−ethyl
acetate = 3:1 containing 1% triethylamine) to give 18 as a colorless
solid (43.8 mg, 90%). Mp 94.5−95.5 °C. IR (KBr): 1709, 1418, 1239,
1
1442, 1267, 1143, 1111 cm−1. H NMR (400 MHz, CDCl3): δ 1.26
(br d, J = 6.1 Hz, 3H), 1.32 (br d, J = 6.1 Hz, 3H), 1.37 (d, J = 6.1 Hz,
6H), 1.41 (d, J = 6.1 Hz, 6H), 3.49 (s, 3H), 3.79 (s, 3H), 3.92 (s, 3H),
4.47 (sep, J = 6.1 Hz, 1H), 4.54 (sep, J = 6.1 Hz, 1H), 4.58 (sep, J =
6.1 Hz, 1H), 6.81 (d, J = 8.5 Hz, 1H), 6.81 (s, 1H), 6.93 (s, 1H), 6.97
(d, J = 1.8 Hz, 1H), 6.99 (dd, J = 2.1 and 8.5 Hz, 1H), 7.01 (d, J = 8.1
Hz, 1H), 7.04 (dd, J = 1.8 and 8.1 Hz, 1H), 7.16 (d, J = 2.1 Hz, 1H),
10.71 (br s, 1H). 13C NMR (100 MHz, CDCl3): δ 21.9, 22.0, 55.7,
55.8, 56.2, 71.2, 71.2, 71.5, 103.6, 105.1, 110.6, 111.3, 112.3, 114.7,
115.1, 117.2, 118.2, 120.2, 123.5, 123.8, 127.4, 129.1, 139.3, 146.2,
146.8, 147.3, 147.5, 147.6, 149.9, 150.0, 156.1. Anal. Calcd for
C35H39NO8: C, 69.87; H, 6.53; N, 2.33. Found: C, 69.63; H, 6.75; N,
2.18.
7-Isopropoxy-1-(3-isopropoxy-4-methoxyphenyl)-2-(4-iso-
propoxy-3-methoxyphenyl)-8-methoxy-3-[2-(phenylsulfanyl)-
ethyl][1]benzopyrano[3,4-b]pyrrol-4(3H)-one (16). Under an
argon atmosphere, a solution of 15 (190 mg, 0.316 mmol), 2-
bromoethyl phenyl sulfide (315 μL, 2.09 mmol), and Cs2CO3 (680
mg, 2.09 mmol) in DMF (15 mL) was stirred for 22 h at 80 °C. After
cooling to room temperature, the mixture was diluted with water, and
the products were extracted with ethyl acetate. The extract was washed
with water and brine, dried over Na2SO4, and evaporated. The residue
was purified by column chromatography over silica gel 60N (hexane−
ethyl acetate = 2:1) to give 16 as a colorless solid (222 mg, 95%).
Recrystallization from DCM−hexane gave a colorless powder. Mp
180−181 °C. IR (KBr): 1701, 1440, 1261, 1137, 1033 cm−1. 1H NMR
(400 MHz, CDCl3): δ 1.15 (br s, 3H), 1.27 (br s, 3H), 1.40 (d, J = 6.1
Hz, 6H), 1.40 (d, J = 6.1 Hz, 6H), 3.28 (t, J = 7.5 Hz, 2H), 3.47 (s,
3H), 3.64 (s, 3H), 3.84 (s, 3H), 4.33 (sep, J = 6.1 Hz, 1H), 4.53 (sep, J
= 6.1 Hz, 1H), 4.56 (sep, J = 6.1 Hz, 1H), 4.61−4.78 (m, 2H), 6.66 (d,
J = 1.7 Hz, 1H), 6.73 (d, J = 1.7 Hz, 1H), 6.75 (dd, J = 1.7 and 8.3 Hz,
1
1112, 1034 cm−1. H NMR (400 MHz, CDCl3, 20 °C): δ 1.31−1.41
(m, 18H), 3.34 (s, 1.5H), 3.34 (s, 1.5H), 3.43 (s, 1.5H), 3.45 (s,
1.5H), 3.93 (s, 3H), 4.31−4.37 (m, 1H), 4.46−4.59 (m, 4H), 5.55−
5.64 (m, 1H), 6.63 (s, 0.5H), 6.66 (s, 0.5H), 6.67 (s, 0.5H), 6.73 (s,
0.5H), 6.81 (s, 0.5H), 6.82 (s, 0.5H), 6.93 (s, 0.5H), 6.93 (s, 0.5H),
6.94 (d, J = 1.9 Hz, 0.5H), 6.98 (dd, J = 1.9 and 8.2 Hz, 0.5H), 7.05 (d,
J = 8.2 Hz, 0.5H), 7.11 (d, J = 8.2 Hz, 0.5H), 7.13 (d, J = 1.9 Hz,
0.5H), 7.16 (dd, J = 1.9 and 8.2 Hz, 0.5H), 7.25−7.34 (m, 3H), 7.41−
7.46 (m, 2H). 13C NMR (100 MHz, CDCl3, 20 °C): δ 21.8, 21.8, 21.9,
21.9, 22.0, 22.0, 22.1, 22.1, 22.1, 46.4, 46.4, 47.6, 55.1, 55.1, 55.5, 55.6,
56.3, 56.4, 71.3, 71.4, 71.4, 71.5, 103.6, 104.9, 105.1, 108.8, 108.8,
110.4, 112.6, 112.8, 114.2, 114.8, 114.9, 115.0, 115.1, 117.9, 118.1,
120.2, 120.2, 123.7, 123.9, 125.5, 125.6, 127.7, 127.9, 128.3, 128.5,
128.7, 129.1, 129.1, 132.5, 134.8, 134.9, 135.2, 135.3, 146.1, 146.1,
146.6, 146.6, 147.1, 147.1, 147.4, 147.4, 148.0, 148.1, 149.6, 149.7,
150.1, 150.2, 155.4, 155.5. 1H NMR (400 MHz, toluene-d8, 20 °C): δ
1.02 (d, J = 6.0 Hz, 1.5H), 1.04 (d, J = 6.0 Hz, 1.5H), 1.08 (d, J = 6.0
Hz, 1.5H), 1.10 (d, J = 6.0 Hz, 1.5H), 1.11 (d, J = 6.0 Hz, 3H), 1.13
(d, J = 6.0 Hz, 1.5H), 1.15 (d, J = 6.0 Hz, 1.5H), 1.17 (d, J = 6.0 Hz,
1.5H), 1.18 (d, J = 6.0 Hz, 1.5H), 1.20 (d, J = 6.0 Hz, 3H), 3.20 (s,
1.5H), 3.21 (s, 1.5H), 3.29 (s, 1.5H), 3.31 (s, 1.5H), 3.39 (s, 1.5H),
3.42 (s, 1.5H), 3.99−4.19 (m, 3.5H), 4.25 (sep, J = 6.0 Hz, 0.5H), 4.27
(sep, J = 6.0 Hz, 0.5H), 4.43 (sep, J = 6.0 Hz, 0.5H), 5.76−5.82 (m,
1H), 6.58 (d, J = 8.2 Hz, 0.5H), 6.76 (s, 0.5H), 6.76 (d, J = 8.2 Hz,
0.5H), 6.76 (s, 0.5H), 6.81 (s, 0.5H), 6.83−6.86 (m, 1.5H), 6.87 (s,
534
dx.doi.org/10.1021/jo402181w | J. Org. Chem. 2014, 79, 529−537