The Journal of Organic Chemistry
Article
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1
20.3; HRMS (ESI-Orbitrap) calcd for C24H26NO4 [M − H]−
2936, 1678 cm-1; d.r. >19:1; H NMR (400 MHz, chloroform-d): δ
7.88 (s, 1H), 7.80−7.85 (m, 3H), 7.65 (d, 1H, J = 8.2 Hz), 7.47−7.50
(m, 2H), 6.93 (s, 1H), 6.63 (s, 1H), 4.18−4.24 (m, 1H), 3.88 (s, 3H),
3.87 (s, 3H), 3.56−3.63 (m, 1H), 3.01−3.09 (m, 1H), 2.83−2.93 (m,
2H), 2.20−2.80 (br s, 1H), 1.98−2.07 (m, 2H), 1.78−1.90 (m, 2H),
1.23−1.39 (m, 2H), 1.15−1.19 (m, 1H), 0.18−0.27 (m, 1H); 13C{1H}
NMR (101 MHz, chloroform-d): δ 174.0, 147.9, 147.5, 137.9, 135.7,
133.0, 132.9, 128.5, 127.9, 127.7, 126.8, 126.4, 126.2, 125.4, 125.1,
112.1, 108.8, 81.9, 60.5, 56.3, 56.0, 49.7, 36.6, 36.4, 27.2, 24.7, 20.53,
392.1867; found: 392.1863.
1-(3,4-Dimethoxyphenethyl)-3-phenyl-5,6-dihydro-1H-indol-
2(4H)-one (4). Purified by column chromatography on silica gel
(hexane/AcOEt = 4:1): colorless oil (22.5 mg, 30%); IR(KBr) 2933,
1682, 1515 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 7.57 (d, 2H, J =
7.3 Hz), 7.41−7.44 (m, 2H), 7.33 (t, 1H, J = 7.3 Hz), 6.84 (d, 1H, J =
8.2 Hz), 6.79 (s, 1H), 6.73 (d, 1H, J = 7.3 Hz), 5.96 (t, 1H, J = 4.4 Hz),
3.74−3.78 (m, 2H), 3.70 (s, 3H), 3.70 (s, 3H), 2.73−2.79 (m, 4H),
2.32−2.37 (m, 2H), 1.71−1.77 (m, 2H); 13C{1H} NMR (101 MHz,
DMSO-d6): δ 167.8, 148.6, 147.4, 140.4, 137.8, 131.5, 131.1, 128.6,
128.2, 127.6, 124.3, 120.7, 112.6, 111.9, 111.3, 55.5, 55.3, 33.9, 23.9,
+
20.46; HRMS (ESI-Orbitrap) calcd for C28H30NO4 [M + H]+
444.2169; found: 444.2169.
(4aR,5R,13bS)-5-Hydroxy-11,12-dimethoxy-3,3-dimethyl-5-phe-
nyl-3,4,4a,5,8,9-hexahydro-1H-indolo[7a,1-a]isoquinolin-6(2H)-
one (3f). Purified by column chromatography on silica gel (hexane/
+
23.5, 23.2; HRMS (ESI-Orbitrap) calcd for C24H26NO3 [M + H]+
376.1907; found: 376.1903.
AcOEt = 4:1): white solid (26.1 mg, 31%); m.p. 230−231 °C; [α]D25
=
(4aR,5R,13bS)-5-(4-Fluorophenyl)-5-hydroxy-11,12-dimethoxy-
3,4,4a,5,8,9-hexahydro-1H-indolo[7a,1-a]isoquinolin-6(2H)-one
(3b). Purified by column chromatography on silica gel (hexane/AcOEt
= 4:1): white solid (53.5 mg, 65%); m.p. 238−240 °C; [α]2D5 = −84.8 (c
0.25, CHCl3); ee = 84% (DAICEL Chiralpak OD-H, hexane/2-
propanol = 75/25, λ = 220 nm, flow rate = 0.5 mL/min); IR(KBr) 3329,
2936, 1678, 1508 cm−1; d.r. >19:1; 1H NMR (400 MHz, chloroform-
d): δ 7.43−7.46 (m, 2H), 7.02−7.06 (m, 2H), 6.91 (s, 1H), 6.63 (s,
1H), 4.15−4.18 (m, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.49−3.55 (m,
1H), 3.01−3.09 (m, 1H), 2.86−2.89 (m, 1H), 2.81−2.83 (m, 1H), 2.50
(br s, 1H), 1.90−2.00 (m, 2H), 1.73−1.87 (m, 2H), 1.34−1.43 (m,
2H), 1.24−1.30 (m, 1H), 0.32−0.38 (m, 1H); 13C{1H} NMR (101
MHz, chloroform-d): δ 173.8, 162.6 (d, J = 248.5 Hz), 148.1, 147.6,
136.4, 135.7, 129.4 (d, J = 7.7 Hz), 125.1, 115.1 (d, J = 21.2 Hz), 112.2,
109.0, 81.4, 60.4, 56.4, 56.1, 49.5, 36.6, 36.4, 27.2, 24.8, 20.5; HRMS
−182.4 (c 0.25, CHCl3); ee = 91% (DAICEL Chiralpak OD-H,
hexane/2-propanol = 75/25, λ = 220 nm, flow rate = 0.5 mL/min);
IR(KBr) 3352, 2927, 1681, 1507 cm−1; d.r. >19:1; 1H NMR (400 MHz,
chloroform-d): δ 7.48 (d, 2H, J = 7.3 Hz), 7.32−7.35 (m, 2H), 7.28−
7.30 (m, 1H), 6.79 (s, 1H), 6.55 (s, 1H), 4.28−4.33 (m, 1H), 3.93 (s,
3H), 3.84 (s, 3H), 3.34 (td, 1H, J = 12.5, 5.2 Hz), 3.13−3.22 (m, 1H),
2.81−2.86 (m, 1H), 2.58 (dd, 1H, J = 16.3, 4.8 Hz), 2.34 (s, 1H), 2.01−
2.07 (m, 1H), 1.82−1.90 (m, 1H), 1.25−1.29 (m, 2H), 1.00 (s, 3H),
0.86−0.93 (m, 1H), 0.79 (s, 3H), 0.58 (dd, 1H, J = 14.0, 5.7 Hz);
13C{1H} NMR (101 MHz, chloroform-d): δ 175.9, 148.0, 147.6, 139.1,
136.2, 128.0, 125.2, 112.3, 108.3, 82.9, 61.6, 56.3, 56.0, 46.7, 39.8, 35.6,
34.1, 34.0, 32.3, 29.6, 26.1, 24.8; HRMS (ESI-Orbitrap) calcd for
C26H32NO4+ [M + H]+ 422.2326; found: 422.2325.
(4a′R,5′R,13b′S)-5′-Hydroxy-11′,12′-dimethoxy-5′-phenyl-
1′,2′,4a′,5′,8′,9′-hexahydrospiro[[1,3]dioxolane-2,3′-indolo[7a,1-
a]isoquinolin]-6′ (4′H)-one (3g). Purified by column chromatography
on silica gel (hexane/AcOEt = 4:1): white solid (22.6 mg, 25%); m.p.
229−231 °C; [α]2D5 = −139.2 (c 0.25, CHCl3); ee = 96% (DAICEL
Chiralpak OD-H, hexane/2-propanol = 75/25, λ = 220 nm, flow rate =
0.5 mL/min); IR(KBr) 2935, 1644, 1516 cm−1; d.r. >19:1; 1H NMR
(400 MHz, chloroform-d): δ 7.45 (d, 2H, J = 7.3 Hz), 7.33−7.36 (m,
2H), 7.29−7.31 (m, 1H), 6.96 (s, 1H), 6.56 (s, 1H), 4.33−4.38 (m,
1H), 3.93 (s, 3H), 3.86−3.91 (m, 2H), 3.85 (s, 3H), 3.73−3.82 (m,
2H), 3.38 (td, 1H, J = 12.5, 5.2 Hz), 3.16−3.25 (m, 1H), 3.04−3.09 (m,
1H), 2.64 (dd, 1H, J = 16.3, 4.8 Hz), 2.12 (t, 2H, J = 6.6 Hz), 1.69−1.93
(br s, 1H), 1.69−1.80 (m, 2H), 1.29−1.36 (m, 1H), 1.06 (dd, 1H, J =
13.7, 6.0 Hz); 13C{1H} NMR (101 MHz, chloroform-d): δ 175.2,
147.9, 147.5, 139.07, 134.9, 128.2, 128.1, 127.6, 124.7, 111.9, 108.8,
108.4, 82.8, 64.5, 64.3, 61.1, 56.2, 55.9, 48.4, 35.9, 35.3, 35.0, 30.9, 26.3;
+
(ESI-Orbitrap) calcd for C24H27FNO4 [M + H]+ 412.1919; found:
412.1920.
(4aR,5R,13bS)-5-(4-Bromophenyl)-5-hydroxy-11,12-dimethoxy-
3,4,4a,5,8,9-hexahydro-1H-indolo[7a,1-a]isoquinolin-6(2H)-one
(3c). Purified by column chromatography on silica gel (hexane/AcOEt
= 4:1): white solid (42.5 mg, 45%); m.p. 258−259 °C; [α]2D5 = −165.2
(c 0.25, CHCl3); ee = 86% (DAICEL Chiralpak OD-H, hexane/2-
propanol = 75/25, λ = 220 nm, flow rate = 0.5 mL/min); IR(KBr) 3329,
2931, 1677, 1511 cm−1; d.r. >19:1; 1H NMR (400 MHz, chloroform-
d): δ 7.49 (d, 2H, J = 8.7 Hz), 7.36 (d, 2H, J = 8.2 Hz), 6.90 (s, 1H), 6.63
(s, 1H), 4.09−4.20 (m, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.49−3.56 (m,
1H), 3.01−3.09 (m, 1H), 2.88 (t, 1H, J = 5.3 Hz), 2.82−2.84 (m, 1H),
1.97−2.01 (m, 1H), 1.88−1.94 (m, 1H), 1.71−1.84 (m, 2H), 1.37−
1.40 (m, 2H), 1.24−1.31 (m, 1H), 0.34−0.42 (m, 1H); 13C{1H} NMR
(101 MHz, chloroform-d): δ 173.5, 148.1, 147.5, 139.7, 135.5, 131.4,
129.4, 125.0, 122.3, 112.1, 108.8, 81.5, 60.4, 56.4, 56.0, 49.4, 36.7, 36.3,
+
HRMS (ESI-Orbitrap) calcd for C26H30NO6 [M + H]+ 452.2068;
+
27.2, 24.8, 20.6, 20.5; HRMS (ESI-Orbitrap) calcd for C24H27BrNO4
found: 452.2061.
[M + H]+ 472.1118; found: 472.1119.
(4aS,5R,13bS)-5-Hydroxy-11,12-dimethoxy-5-phenyl-
1,2,4a,5,8,9-hexahydropyrano[4′,3′:2,3]pyrrolo[2,1-a]isoquinolin-
6(4H)-one (3h). Purified by column chromatography on silica gel
(hexane/AcOEt = 4:1): white solid (34.8 mg, 44%); m.p. 226−229 °C;
[α]2D5 = −160.0 (c 0.25, CHCl3); ee = 95% (DAICEL Chiralpak OD-H,
hexane/2-propanol = 75/25, λ = 214 nm, flow rate = 0.5 mL/min);
IR(KBr) 3347, 2926, 1682, 1513 cm−1; d.r. >19:1; 1H NMR (400 MHz,
chloroform-d): δ 7.46 (d, 2H, J = 8.2 Hz), 7.30−7.39 (m, 3H), 6.94 (s,
1H), 6.61 (s, 1H), 4.28−4.33 (m, 1H), 3.90 (s, 3H), 3.86 (s, 3H),
3.57−3.71 (m, 3H), 3.39−3.50 (m, 2H), 3.09−3.17 (m, 1H), 2.94 (t,
1H, J = 6.4 Hz), 2.75 (d, 1H, J = 16.0 Hz), 2.50 (br s, 1H), 2.04−2.17
(m, 2H); 13C{1H} NMR (101 MHz, chloroform-d): δ 174.4, 148.3,
148.0, 139.2, 134.5, 128.44, 128.36, 127.2, 125.2, 112.2, 108.8, 81.0,
65.0, 62.8, 58.9, 56.3, 56.1, 49.8, 36.3, 35.7, 27.0; HRMS (ESI-
Orbitrap) calcd for C23H26NO5+ [M + H]+ 396.1805; found: 396.1804.
(4aR,5R,13bS)-5-Hydroxy-11,12-dimethoxy-5-phenyl-
1,2,4a,5,8,9-hexahydrothiopyrano[4′,3′:2,3]pyrrolo[2,1-a]-
isoquinolin-6(4H)-one (3i). Purified by column chromatography on
silica gel (hexane/AcOEt = 4:1): white solid (38.4 mg, 47%); m.p.
226−228 °C; [α]2D5 = −236.0 (c 0.25, CHCl3); ee = 86% (DAICEL
Chiralpak OD-H, hexane/2-propanol = 75/25, λ = 220 nm, flow rate =
(4aR,5R,13bS)-5-Hydroxy-11,12-dimethoxy-5-(p-tolyl)-
3,4,4a,5,8,9-hexahydro-1H-indolo[7a,1-a]isoquinolin-6(2H)-one
(3d). Purified by column chromatography on silica gel (hexane/AcOEt
= 4:1): purified by column chromatography on silica gel (hexane/
AcOEt = 4:1 to 2:1): white solid (25.3 mg, 31%); m.p. 244−246 °C;
[α]2D5 = −63.2 (c 0.25, CHCl3); ee = 90% (DAICEL Chiralpak OD-H,
hexane/2-propanol = 75/25, λ = 230 nm, flow rate = 0.5 mL/min);
IR(KBr) 3331, 2931, 1678, 1512 cm−1; d.r. >19:1; 1H NMR (400 MHz,
chloroform-d): δ 7.36 (d, 2H, J = 7.8 Hz), 7.16 (d, 2H, J = 7.8 Hz), 6.94
(s, 1H), 6.64 (s, 1H), 4.11−4.20 (m, 1H), 3.88 (s, 3H), 3.86 (s, 3H),
3.52−3.58 (m, 1H), 3.01−3.09 (m, 1H), 2.86−2.91 (m, 1H), 2.81−
2.84 (m, 1H), 2.31−2.51 (br s, 1H), 2.35 (s, 3H), 1.97−2.05 (m, 2H),
1.77−1.91 (m, 2H), 1.35−1.37 (m, 2H), 1.22−1.27 (m, 1H), 0.25−
0.34 (m, 1H); 13C{1H} NMR (101 MHz, chloroform-d): δ 174.1,
148.0, 147.5, 138.0, 137.5, 135.9, 129.0, 127.5, 125.1, 112.2, 109.1, 81.7,
60.4, 56.4, 56.1, 49.5, 36.5, 36.4, 27.3, 24.7, 21.3, 20.6, 20.4; HRMS
+
(ESI-Orbitrap) calcd for C25H30NO4 [M + H]+ 408.2169; found:
408.2172.
(4aR,5R,13bS)-5-Hydroxy-11,12-dimethoxy-5-(naphthalen-2-yl)-
3,4,4a,5,8,9-hexahydro-1H-indolo[7a,1-a]isoquinolin-6(2H)-one
(3e). Purified by column chromatography on silica gel (hexane/AcOEt
= 4:1): white solid (34.6 mg, 39%); m.p. 228−229 °C; [α]2D5 = −74.0 (c
0.25, CHCl3); ee = 91% (DAICEL Chiralpak OD-H, hexane/2-
propanol = 75/25, λ = 254 nm, flow rate = 0.5 mL/min); IR(KBr) 3343,
1
0.5 mL/min); IR(KBr) 3350, 2922, 1680, 1514 cm−1; d.r. >19:1; H
NMR (400 MHz, chloroform-d): δ 7.41 (d, 2H, J = 6.9 Hz), 7.29−7.37
(m, 3H), 7.34 (s, 1H), 6.60 (s, 1H), 4.38−4.44 (m, 1H), 3.91 (s, 3H),
3.86 (s, 3H), 3.38−3.45 (m, 1H), 3.19 (dd, 1H, J = 9.8, 5.7 Hz), 3.10−
G
J. Org. Chem. XXXX, XXX, XXX−XXX