J. L. Vicario et al. / Tetrahedron: Asymmetry 10 (1999) 1947–1959
1957
3.6.3. (+)-(3S,4S)-N-Benzyl-3-(3,4-dimethoxyphenyl)-6,7-methylenedioxy-4-(2-propenyl)-1,2,3,4-
tetrahydroisoquinoline 7c
Yield: 89%. Mp: 119–121°C (MeOH). [α]D20=+39.9 (c=0.1, CH2Cl2). H-NMR (CDCl3): 2.40 (m,
1H); 2.69 (m, 1H); 2.98 (m, 1H); 3.36 (d, 1H, J=13.1 Hz); 3.42 (d, 1H, J=14.7 Hz); 3.54 (d, 1H, J=14.6
Hz); 3.61 (d, 1H, J=13.2 Hz); 3.75 (s, 3H); 3.79 (d, J=3.7 Hz); 3.86 (s, 3H); 5.03 (m, 2H); 5.73 (m, 1H);
5.90 (d, 2H, J=1.0 Hz); 6.49 (s, 1H); 6.67–6.81 (m, 4H); 7.23–7.42 (m, 5H). 13C-NMR (CDCl3): 40.6;
44.6; 51.9; 55.6; 55.7; 59.3; 64.1; 100.6; 105.9; 108.0; 110.4; 111.5; 116.8; 121.0; 126.9; 128.0; 128.2;
128.7; 130.8; 132.0; 136.8; 139.2; 145.6; 146.2; 148.0; 148.5. MS (EI) m/z (rel. int.): 443 (M+, 6), 370
(16), 281 (38), 265 (10), 219 (10), 209 (11), 207 (100), 193 (14), 142 (11), 134 (10), 119 (12), 105 (10),
91 (15), 83 (16), 77 (15), 64 (25) 51 (35). Anal. calcd for C28H29NO4: C, 75.82; H, 6.59; N, 3.16. Found:
C, 75.87; H, 6.61; N, 3.14.
1
3.6.4. (+)-(3S,4S)-N-Benzyl-3-(3,4-methylenedioxyphenyl)-6,7-dimethoxy-4-(2-propenyl)-1,2,3,4-
tetrahydroisoquinoline 7d
Yield: 84%. Mp: 126–128°C (MeOH). [α]D20=+25.7 (c=0.1, CH2Cl2). H-NMR (CDCl3): 2.43 (m,
1
1H); 2.74 (m, 1H); 2.98 (m, 1H); 3.34 (d, 1H, J=13.1 Hz); 3.45 (d, 1H, J=14.7 Hz); 3.52 (d, 1H, J=14.6
Hz); 3.63 (d, 1H, J=13.2 Hz); 3.73 (s, 3H); 3.75 (d, J=3.7 Hz); 3.84 (s, 3H); 5.00 (m, 2H); 5.77 (m, 1H);
5.94 (s, 2H); 6.45 (s, 1H); 6.59–6.77 (m, 4H); 7.24–7.39 (m, 5H). 13C-NMR (CDCl3): 40.9; 44.2; 51.1;
55.7; 55.9; 59.4; 64.1; 100.8; 107.7; 108.7; 109.9; 111.2; 116.7; 122.3; 123.5; 126.9; 128.2; 128.9; 129.5;
133.4; 137.0; 139.3; 145.4; 146.5; 147.1; 147.6. MS (EI) m/z (rel. int.): 443 (M+, 4), 401 (25), 280 (24),
204 (67), 189 (86), 176 (47), 173 (26), 161 (11), 158 (14), 129 (10), 117 (12), 91 (100), 77 (9), 65 (18).
Anal. calcd for C28H29NO4: C, 75.82; H, 6.59; N, 3.16. Found: C, 75.89; H, 6.44; N, 3.09.
3.7. General procedure for the acid catalyzed cyclization
3.7.1. Synthesis of (−)-(4bS,10bS,12S)-N-benzyl-2,3,8,9-tetramethoxy-12-methyl-4b,5,6,10b,11,12-
hexahydrobenzo[c]phenanthridine 8a
A mixture of the isoquinoline 7a (100 mg, 0.22 mmol) and PPA (2 mL) was heated at 60°C with
stirring for 12 h. The reaction was quenched with 4 M NaOH and extracted with CH2Cl2 (3×15 mL).
The combined organic fractions were collected, dried over Na2SO4, filtered and the solvent was removed
in vacuo yielding the pure heterocycle after flash column chromatography purification (hexanes:ethyl
acetate 1:1). The ee of the heterocycles 8 was >99% calculated by chiral HPLC analysis (Chiralcel
OD, UV detector, hexanes:isopropanol 90:10, flow rate 1.00 mL/min). An analytically pure sample
was obtained by crystallization in MeOH. Yield: 86%. Mp: 171–172°C (MeOH). [α]D20=−32.3 (c=0.1,
CH2Cl2). 1H-NMR (CDCl3): 1.33 (d, 3H, J=6.7 Hz); 1.37 (m, 1H); 2.73 (m, 1H); 2.97 (m, 1H); 3.12 (m,
1H); 3.30 (d, 1H, J=14.4 Hz); 3.59 (d, 1H, J=14.4 Hz); 3.66 (d, 1H, J=16.7); 3.74 (s, 6H); 3.80 (s, 3H);
3.82 (s, 3H); 4.05 (d, 1H, J=11.1 Hz); 4.17 (d, 1H, J=16.7 Hz); 6.43 (s, 1H); 6.75 (s, 1H); 6.89 (s, 1H);
7.10–7.40 (m, 5H); 7.43 (s, 1H). 13C-NMR (CDCl3): 22.6; 32.2; 33.5; 37.4; 49.2; 52.6; 55.6; 55.8; 55.9;
56.0; 64.1; 108.7; 108.9; 110.1; 110.2; 126.6; 128.0; 128.2; 129.7; 129.9; 134.1; 140.2; 140.3; 147.6;
147.9. MS (EI) m/z (rel. int.): 459 (M+, 3), (22), 337 (8), 177 (9), 146 (9), 91 (100), 77 (7), 65 (14). Anal.
calcd for C29H33NO4: C, 75.79; H, 7.24; N, 3.05. Found: C, 75.65; H, 7.29; N, 3.18.
3.7.2. (−)-(4bS,10bS,12S)-N-Benzyl-2,3,7,8,9-pentamethoxy-12-methyl-4b,5,6,10b,11,12-hexahydro-
benzo[c]phenanthridine 8b
1
Yield: 77%. Mp: 160–162°C (MeOH). [α]D20=−28.6 (c=0.1, CH2Cl2). H-NMR (CDCl3): 1.40 (d,
3H, J=6.7 Hz); 1.52 (m, 1H); 2.70 (m, 1H); 2.96 (m, 1H); 3.15 (m, 1H); 3.30 (d, 1H, J=14.7 Hz); 3.61