A. Alexakis, F. Amiot / Tetrahedron: Asymmetry 13 (2002) 2117–2122
2121
Table 6.
Entry
Solvent
T, °C (time, h)
Ligand (equiv.)
Yield (%) 12/13
ee (%) 12/13
1
2
3
4
5
6
7
Et2O
Toluene
Et2O
Toluene
Toluene
Et2O
−70 (2)
−70 (1)
−40 (1)
−40 (1)
−40 (1)
−40 (1)
−70 (1)
9 (0.2)
9 (0.2)
9 (0.2)
9 (0.2)
9 (1)
17/0
28/0
16/–
40/–
51/25
48/31
48/20
67/12
45/34
20/30
37/30
53/36
37/42
56/47
9 (1)
9 (1)
Toluene
Scheme 8.
Scheme 7.
153.4, 132.9, 132.1, 130, 127.6, 127.4, 127.3, 126.4, 126.3,
125.2, 124.4, 108.9, 108.7, 56, 55.53, 54.5, 53.8, 51.4, 34.9,
34.6, 27.3, 26.8, 22.5, 13.8; MS: 245, 188, 144, 129; MS:
303, 246, 202, 128.
4.3. 1-Methyl-1,2-dihydro-[N-methoxycarbonyl]-isoquino-
line, 4
1
The product was obtained as a yellow oil. H NMR
4.6. 1-Butyl-1,2-dihydro-[N-methylcarbonyl]-isoquino-
line, 12
(CDCl3): l 7.3–7 (m, 4H), 6.90 (d, 0.4H, J=7.54 Hz), 6.75
(d, 0.6H, J=7.9 Hz), 5.87 (d, 0.4H, J=7.6 Hz), 5.79 (d,
0.6H, J=7.7 Hz), 5.44 (q, 0.6H, J=6.4 Hz), 5.32 (q, 0.4H,
J=6.5 Hz), 3.90 (s, 1.2H), 3.85 (s, 1.8H), 1.25 (d, 3H,
J=6.9 Hz); 13C NMR (CDCl3): l 153.2, 134.2, 129.6,
127.4, 127.1, 126.9, 125.6, 125.5, 125.4, 124.7, 124.6,
123.9, 108.1, 107.9, 53.2, 52.1, 51.7, 21.8, 21.2. MS: 203,
188, 144, 129; [h]2D0=+18.5 (c 0.87, CHCl3) for ee=36%.
1
The product was obtained as a yellow oil. H NMR
(CDCl3): l 7.2–7.06 (m, 4H), 6.6 (dd, 1H, J1=1.2, J2=7.6
Hz), 5.9 (d, 1H, J=7.6 Hz), 5.65 (t, 1H, J=7 Hz), 2.2
(s, 3H), 1.6 (m, 2H), 1.2 (m, 4H), 0.82 (t, 3H, J=6.3 Hz);
13C NMR (CDCl3): l 168.4, 133.7, 129.8, 127.4, 127,
126.6, 124.9, 124.7, 110.5, 53.4, 34.5, 27.6, 22.6, 21.6, 13.9;
MS: 229, 172, 130; [h]2D0=+20.3 (c 1.02, CHCl3) for
ee=56%.
4.4. 1-Methyl-4-methoxycarbonyl-1,2-dihydro-[N-
methoxycarbonyl]-isoquinoline, 5
1
4.7. 1-Butyl-4-methylcarbonyl-1,2-dihydro-[N-methylcar-
The product was obtained as a yellow oil. H NMR
bonyl]-isoquinoline, 13
(CDCl3): l 8.21 (d, 1H, J=7.5 Hz), 8.02 (s, 1H), 7.24 (m,
2H), 7.05 (m, 1H), 5.3 (m, 1H), 3.89 (s, 3H), 3.84 (s, 3H),
1.29 (d, 3H, J=6.6 Hz); 13C NMR (CDCl3): l 212.4,
166.1, 135.2, 133.6, 127.7, 127.5, 127.1, 125.6, 124.9, 109,
53.9, 52.7, 51.5, 21.8; MS: 261, 246, 202, 187.
1H NMR (CDCl3): l 7.63 (s, 1H), 7.3–7 (m, 4H), 5.57,
(m, 1H), 2.50 (s, 3H), 2.37 (s, 3H), 1.55 (m, 2H), 1.20 (m,
4H), 0.82 (t, 3H, J=6.2 Hz); 13C NMR (CDCl3): l 193,
164.5, 136.1, 128.2, 127.8, 127.3, 126.8, 126.4, 122, 120.7,
54.8, 35.1, 28.0, 27.5, 22.9, 22.1, 14.4; MS: 271, 214, 172,
129; [h]2D0=+20 (c 1.18, CHCl3) for ee=47%;
4.5. 1-Butyl-1,2-dihydro-[N-methoxycarbonyl]-isoquino-
line, 10 and 1-butyl-4-methoxycarbonyl-1,2-dihydro-[N-
methoxycarbonyl]-isoquinoline, 11
4.8. (S)-1-Methyl-1,2,3,4-tetrahydro-[N-methoxycar-
bonyl]-isoquinoline, 16
1
These two products could not be separated. H NMR
(CDCl3): l 7.2–7.06 (m, 4H), 6.79 (d, 1H, J=0.8 Hz), 5.84
(m, 1H), 5.33 (m, 1H), 3.85 (m, 3H), 1.64 (m, 4H), 1.27
(m, 2H), 0.85 (m, 3H); 13C NMR (CDCl3): l 166, 154.1,
To a solution of 4 (150 mg, 0.74 mmol) in methanol (20
ml) was added a small amount of palladium on activated
Table 7.
Entry
Solvent
T, °C (time, h)
9 (equiv.)
Yield (%)
ee (%) 14
1
2
3
4
Toluene
Toluene
Toluene
Toluene
−40 (1)
−70 (1)
−40 (1)
−40 (1)
0.2
0.2
1
34
34
27
73
25
23
38
15a
0.2
a 4 equiv. of phenyllithium.