7498 J . Org. Chem., Vol. 65, No. 22, 2000
Orito et al.
1-(2′-Br om o-4′,5m′-dim eth oxyben zyl)-2-eth oxycar bon yl-
6,7-d im eth oxy-1,2,3,4-tetr a h yd r oisoqu in olin e (1b): color-
less crystals (81%); mp 142-143 °C (MeOH) (lit.9 141-142 °C);
IR (Nujol) 1689, 1511 cm-1; 1H NMR (270 MHz, CDCl3) δ 1.05,
1.22 (1.8:1.2, each t, J ) 6.9 Hz, 3H), 2.59-3.76 (m, 5H), 3.79,
3.82, 3.85, 3.86 (each s, each 3H), 4.09 (q, J ) 6.9 Hz, 0.7H),
4.30 (ddd, J ) 10.3, 5.5, 2.3 Hz, 0.6H), 5.32 (q, J ) 4.6 Hz,
0.6H), 5.36 (t, J ) 5.6 Hz, 0.4H), 6.40, 6.50, 6.59, 6.62, 6.64,
6.65, 6.97, 7.04 (0.4:0.6:0.4:0.6:0.4:0.6:0.4:0.6, each s, 4H).
1-[4′-Br om o-3′,4′-(m et h ylen ed ioxy)b en zyl]-2-et h oxy-
ca r bon yl-6,7-d im et h oxy-1,2,3,4-t et r a h yd r oisoqu in olin e
(1c): colorless crystals (93%); mp 139-140 °C (MeOH); IR
(Nujol) 1700, 1613, 1513 cm-1; 1H NMR (270 MHz) δ 1.02, 1.21
(2:1, each t, J ) 7.1 Hz, 3H), 2.62-3.78 (m, 6.75H), 3.85, 3.87,
3.87, 3.88 (each s, each 3H), 4.11 (dd, J ) 6.9, 6.3 Hz, 0.5H),
4.34 (ddd, J ) 13.2, 7.9, 2.3 Hz, 0.75H), 6.62, 6.03 (2:1, each s,
2H), 6.66 (s, 1H), 6.55, 6.99 (AB type, J ) 7.8 Hz, 2H), 6.70 (s,
1H); FD-MS m/z (rel int) 479 (M+, 100), 477 (89.8), 264 (34.5).
Anal. Calcd for C22H24NO6Br: C, 55.24; H, 5.06; N, 2.93; Br,
16.70. Found: C, 54.96; H, 5.04; N, 2.96; Br, 16.90.
39.55, 39.64 (1:1, each t), 39.8 (t), 49.13, 49.18 (1:1, each d),
55.9 (q, 3 MeO), 56.66, 56.69 (1:1, each d), 61.6 (q), 109.3 (d),
111.6 (d), 113.1, 113.2 (1:1, each d), 126.3 (s), 127.08, 127.13
(1:1, each d), 129.0 (s), 130.78, 130.83 (1:1, each s), 130.78,
130.83 (s), 136.7 (s), 145.9 (s), 147.1, 147.4 (1:1, each d), 150.9
(s), 211.3 (s); FAB-MS m/z (rel int) 428 [(M + H)+, 29], 410
(38), 352 (100), 192 (52); FD-MS m/z (rel int) 427 (M+, 100),
192 (24). HR-MS calcd for
428.2426.
C25H34NO5, 428.2437; found,
5a : colorless crystals (9.3%); mp 187-189 °C (Et2O); Rf 0.8
(5% MeOH-CH2Cl2); IR (Nujol) 1639, 1515 cm-1; 1H NMR (270
MHz, CDCl3) δ 0.70 (t, J ) 3.5 Hz, 3H), 1.45 (d, J ) 5.9 Hz,
3H), 1.67-1.85 (m, 2H), 2.73-3.01 (m, 5H), 3.82, 3.89, 3.90
(each s, each 3H), 3.39-4.02 (m, 1H), 4.73 (dd, J ) 2.6 Hz,
1H), 4.99-5.04 (m, 1H), 6.68, 6.70 (each s, each 1H), 6.92, 7.03
(AB type, J ) 8.3 Hz, each 1H); EI-MS m/z (rel int) 395 (M+,
46), 204 (63), 192 (100), 175 (43). HR-MS calcd for C24H29NO4,
395.2096; found, 395.2119. Anal. Calcd for C24H29NO4: C,
72.89; H, 7.39; N, 3.54. Found: C, 72.64; H, 7.51; N, 3.57.
A similar treatment of 2a (18.5 mg, 0.05 mmol) with s-BuLi
(1.0 M solution in pentane, 0.1 mL, 0.1 mmol) gave a mixture
(20 mg) of 4a and 5a in a ratio of 5:1.
Gen er a l P r oced u r e. 9-ter t-Bu tyl-2,3,10-tr im eth oxy-8-
oxober bin e (6a ). To an ice-cooled and stirred solution of 1a
(99 mg, 0.2 mmol) in dry THF (20 mL) under an atmosphere
of nitrogen was added t-BuLi (1.7 M solution in pentane, 0.36
mL, 0.6 mmol). The mixture was kept at 0 °C for 30 min and
then at room temperature for 2.5 h. THF was removed in a
rotary evaporator, and the residue was treated with water and
CH2Cl2. The organic layer was washed with water, dried
(Na2SO4), and concentrated. The residue (116 mg) was purified
by preparative TLC on a Merck silica gel 60 PF254 developed
with CH2Cl2. A main band with Rf 0.6 gave 6a : colorless
crystals (65 mg, 82%); mp 197-199 °C (EtOH); IR (Nujol) 1700,
Rea ction of Ca r ba m a te 1c w ith t-Bu Li. 9-tert-Butyl-10-
hydroxy-2,3-dimethoxy-8-oxoberbine (7c) and 1-[2′-trimethyl-
acetyl-3′,4′-(methylenedioxy)benzyl]-6,7-dimethoxy-1,2,3,4-tet-
rahydroisoquinoline (8c) were obtained in a ratio of 5:4. 7c:
colorless crystals (43%); mp 183-185 °C (acetone), 212-215
°C (CHCl3); Rf 0.4 (5% MeOH-CH2Cl2); IR (Nujol) 3198, 1612,
1
1573, 1511 cm-1; H NMR (270 MHz, CD2Cl2) δ 1.52 (s, 9H),
2.65-2.90 (m, 4H), 3.11 (ddd, J ) 12.4, 8.9, 4.0 Hz, 1H), 3.79,
3.81 (each s, each 3H), 465 (dt, J ) 12.9, 4.0, 4.0 Hz, 1H), 4.76
(dd, J ) 3.0 Hz, 1H), 6.68 (AB type, partly hiding, J ) 8.3 Hz,
1H), 6.68, 6.69 (each s, each 1H), 6.87 (AB type, J ) 8.3 Hz,
1H); EI-MS m/z (rel int) 381 (M+, 10.5), 192 (100), 190 (18.6),
85 (15.0), 83 (21.5). Anal. Calcd for C23H27NO4: C, 72.42; H,
7.13; N, 3.67. Found: C, 72.60; H, 7.04; N, 3.62.
1
1613 cm-1; H NMR (270 MHz, CDCl3) δ 1.54 (s, 9H), 2.70-
2.93 (m, 4H), 3.16 (ddd, J ) 11.5, 8.6, 5.3 Hz, 1H), 3.83, 3.87,
3.90 (each s, each 3H), 4.77 (dt, J ) 12.9, 4.0, 4.0 Hz, 1H),
4.82 (dd, J ) 11.6, 3.0 Hz, 1H), 6.61, 6.69 (each s, each 1H),
6.89, 6.98 (AB type, J ) 8.3 Hz, 2H); EI-MS m/z (rel int) 395
(M+, 12.0), 204 (100), 192 (93.5), 161 (32.7). Anal. Calcd for
This phenol (6 mg) was treated with water (0.5 mL)
containing KOH (6 mg, 0.1 mmol) and two drops of Me2SO4
at 80 °C for 30 min. The mixture was extracted with CH2Cl2.
The organic layers were washed with water, dried (Na2SO4),
and evaporated to give a single product (6 mg), whose IR and
1H NMR spectral data were identical with those for 6a in all
respects.
C
24H29NO4: C, 72.89; H, 7.39; N, 3.54. Found: C, 72.76; H,
7.50; N, 3.48.
A similar treatment with t-BuLi (1.7 M solution in pentane,
0.06 mL, 0.1 mmol) of (()-8-oxotetrahydropalmatine 2a 5 (18.5
mg, 0.05 mmol) gave the crude 6a (19 mg). Crystallization from
EtOH afforded colorless crystals (16 mg) of 6a , mp 197-199
°C.
8c: a colorless oil (33%); Rf 0.2 (5% MeOH-CH2Cl2); IR
1
(neat) 3340, 1686, 1513 cm-1; H NMR (270 MHz, CDCl3) δ
8-Bu tylid en e-2,3,9,10-tetr a m eth oxyber bin e (3a ). Car-
bamate 1a (99 mg, 0.2 mmol) and BuLi (1.6 M solution in
hexane, 0.38 mL, 0.6 mmol) were used. The crude product (79
mg) was purified through a column of Celite (2.0 g) and
Mg2SO4 (2.0 g) with CH2Cl2 to give 3a as a colorless oil (75.5
1.28 (s, 9H), 2.65-2.75 (m, 3H), 2.87-3.00 (m, 2H), 3.13-3.20
(m, 1H), 3.85 (s, 6H), 4.04 (dd, J ) 3.3 Hz, 1H), 5.97, 5.99 (AB
type, J ) 1.3 Hz, each 1H), 6.57, 6.61 (each s, each 3H), 6.77,
6.81 (AB type, J ) 8.0 Hz, each 1H); 1H NMR (270 MHz,
CD2Cl2) δ 1.23 (s, 9H), 2.58-2.67 (m, 3H), 2.80-2.92 (m, 2H),
3.05-3.13 (m, 1H), 3.75, 3.76 (each s, each 3H), 3.96 (dd, J )
3.3 Hz, 1H), 5.94, 5.95 (AB type, J ) 1.3 Hz, each 1H), 6.54 (s,
2H), 6.75, 6.78 (AB type, J ) 8.3 Hz, each 1H); 13C NMR δ
27.2 (q), 29.4 (t), 39.6 (t), 40.0 (t), 44.9 (s), 55.8 (q), 56.8 (d),
101.1 (t), 108.6 (d), 109.6 (d), 111.6 (d), 123.6 (s), 123.9 (d),
127.1 (s), 129.8 (s), 130.7 (s), 143.1 (s), 145.9 (s), 147.1 (s), 147.4
(s), 213 (s); EI-MS m/z (rel int) 411 (M+, 0.8), 396 (1.1), 354
(8.3), 192 (100). HR-MS calcd for C24H29NO4, 411.2046; found,
411.2028.
mg, 92%): IR (neat) 1698, 1611, 1517 cm-1 1H NMR (270
;
MHz, CDCl3) δ 0.97 (t, J ) 6.6 Hz, 3H), 1.48 (q, J ) 6.9 H,
2H), 2.20-2.48 (m, 3H), 2.82-3.00 (m, 4H), 3.29-3.39 (m, 1H),
3.76, 3.83, 3.85, 3.88 (each s, each 3H), 4.07 (dd, J ) 10.0, 3.3
Hz, 1H), 6.26 (t, J ) 6.9 Hz, 1H), 6.63, 6.67 (each s, each 1H),
6.74, 6.83 (AB type, J ) 7.9 Hz, each 1H); EI-MS m/z (rel int.)
409 (M+, 5.2), 352 (100), 192 (45.5); FD-MS m/z (rel int) 410
[(M + H)+, 27.7), 409 (M+, 100), 192 (45.5). HR-MS calcd for
C
25H31NO4, 409.2253; found, 409.2235.
A similar treatment of 2a (18.5 mg, 0.05 mmol) with BuLi
(1.6 M solution in hexane, 0.063 mL, 0.1 mmol) gave 6a (18
mg).
8-Bu tylid en e-2,3,10,11-tetr a m eth oxyber bin e (3b). The
crude product (78 mg) was purified through a column of Celite
(2.0 g) and Mg2SO4 (2.0 g) with CH2Cl2 to give 3b as a colorless
1
Rea ction of Ca r ba m a te 1a w ith s-Bu Li. A mixture of
1-[2′-(2′′-methylbutyryl)-3′,4′-dimethoxybenzyl]-6,7-dimethoxy-
1,2,3,4-tetrahydroisoquinoline (4a ) and 9-(2-butyl)-2,3,10-tri-
methoxy-8-oxoberbine (5a ) was obtained in a ratio of 5:1. 4a :
a colorless oil (50%); Rf 0.1 (5% MeOH-CH2Cl2); IR (neat)
3346, 1693, 1611, 1572, 1516 cm-1; 1H NMR (270 MHz, CDCl3)
δ 0. 94, 0.95 (1:1, each dt, J ) 7.3 Hz, 3H), 1.13, 1.14 (1:1,
each d, J ) 7.0 Hz, 3H), 1.32-1.45 (m, 1H), 1.77-1.92 (m,
2H), 2.62-2.74 (m, 3H), 2.83-2.98 (m, 3H), 3.15-3.24 (m, 1H),
3.81, 3.84, 3.85, 3.88 (each s, each 3H), 4.13-4.19 (m, 1H),
6.57, 6.65 (each s, each 1H), 6.92, 7.12 (AB type, J ) 8.3 Hz,
each 1H); 13C NMR (270 MHz, CDCl3) δ 11.84, 11.88 (1:1, each
q), 15.1, 15.4 (1:1, each q), 25.18, 25.23 (1:1, each t), 29.4 (s),
oil (74 mg, 90%): IR (neat) 1696, 1612, 1573, 1517 cm-1; H
NMR (270 MHz, CDCl3) δ 0.99 (t, J ) 7.3 Hz, 3H), 1.49-1.56
(m, 2H), 2.10-2.50 (m, 2H), 2.51-3.30 (m, 6H), 3.87, 3.88, 3.89,
3.92 (each s, each 3H), 4.13 (dd, J ) 11.6, 3.3 Hz, 1H), 5.58
(dd, J ) 8.6, 5.6 Hz, 1H), 6.60, 6.64, 6.66, 7.16 (each s, each
1H); EI-MS m/z (rel int) 409 (M+, 12.0), 352 (100). HR-MS calcd
for C25H31NO4, 409.2248; found, 409.2248. Irradiation of an
aromatic proton signal at δ 7.16 caused an NOE enhancement
of an olefinic proton signal at δ 5.58 (17.5%). Irradiation in
the opposite way caused an NOE enhancement of the aromatic
proton signal (25%).
A similar treatment with BuLi (1.56 M, 0.07 mL, 0.11 mmol)
of (()-8-oxoxylopinine 2b (18.5 mg, 0.05 mmol) [mp 191-192