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Y.-B. Zhou et al. / Tetrahedron: Asymmetry 13 (2002) 469–473
3.2. General procedure for the synthesis of 8-quinoline-
carboxamides 3
Hz, 2H), 2.76 (t, J=6.3 Hz, 2H), 3.34 (t, J=5.7 Hz,
2H), 3.96 (d, J=4.8 Hz, 2H), 5.17 (q, J=6.6 Hz, 1H),
6.46 (t, J=7.5 Hz, 1H), 6.74 (d, J=6.3 Hz, 1H), 7.00
(d, J=7.2 Hz, 1H), 7.25 (d, J=7.5 Hz, 1H), 7.28–7.42
(m, 5H). IR: 3345, 2923, 2845, 1618, 1584, 1531, 1509,
1461, 1361, 1271, 1263, 1195, 1036 cm−1. MS (m/e,%):
296 (26, M+), 160 (100), 132 (7), 130 (17), 104 (33).
Anal. calcd for C18H20N2O2: C, 72.97; H, 6.76; N, 9.46.
Found: C, 73.30; H, 6.49; N, 9.63%.
In a double-necked round-bottomed flask, a mixture of
ethyl 8-quinolinecarboxylate (15.4 mmol), the (S)-
amino alcohol (18.5 mmol), KCN (5.2 mmol) and
toluene (50 mL) was heated under reflux temperature
under nitrogen for 3 days. After cooling to rt, the
reaction mixture was washed with water and brine and
dried over anhydrous MgSO4. The solvent was evapo-
rated under reduced pressure and the crude product
was purified by column chromatography on silica gel
with petroleum ether/EtOAc (1:1) to give product 3a in
97% yield, 3b in 92% yield and 3c in 93% yield,
respectively.17 The procedure for another route is
reported in the literature.8
3.4. Synthesis of tetrahydroquinolinyl-oxazoline ligands
2
3.4.1. General procedure for the synthesis of (4S)-4,5-
dihydro-4-benzyl-2-(1,2,3,4-tetrahydroquinolin-8-yl)-
oxazole 2a. Compound 4a (2.9 g, 9.45 mmol) was
dissolved in dry CH2Cl2 (150 mL) in a round-bottomed
flask fitted with a Sohxlet extraction apparatus into
which was placed CaH2 powder. Methanesulfonic acid
(5.4 mL) was then added to the flask. The resulting
mixture was heated under reflux for 2 days and diluted
with CH2Cl2 (150 mL), washed with aqueous NaHCO3,
water and brine. After drying over anhydrous K2CO3
and concentration, the crude product was purified by
flash column chromatography on silica gel with EtOAc
containing 0.5% Et3N to provide 2a (1.4 g, 51%).
Yellow oil. [h]D25=+43.5 (c 2.0, CHCl3). 1H NMR:
1.64–2.04 (m, 2H), 2.64–2.98 (m, 2H), 2.70–2.90 (m,
2H), 3.40–3.64 (m, 3H), 4.04–4.30 (m, 2H), 6.45 (t,
J=4.8 Hz, 1H), 7.05 (d, J=4.0 Hz, 1H), 7.18–7.36 (m,
5H), 7.69–7.84 (m, 2H). IR: 3372, 3061, 3026, 2931,
2887, 2844, 1676, 1602, 1589, 1513, 1465, 1414, 1363,
1250, 1181, 1145, 1030 cm−1. MS (m/e, %): 292 (8, M+),
201 (16), 177 (79), 160 (100), 158 (27), 132 (17), 130
(36), 104 (47), 91 (60). HRMS calcd for C19H20N2O:
292.1570. Found: 292.1568.
3.3. Synthesis of tetrahydroquinolinecarboxamides 4
3.3.1. General procedure for the synthesis of N-[(1S)-1-
benzyl-2-hydroxyethyl]-(1,2,3,4-tetrahydroquinolin-8-yl)-
carboxamide 4a. To a mixture of 3a (2.24 g, 8.1 mmol),
methanol (50 mL) and 1 M aqueous KOH (24 mL) was
added Ni–Al alloy (3.9 g) in portions over 30 min. The
mixture was stirred at room temperature for 8 h and
the methanol was removed under reduced pressure. The
residue was filtered through a pad of Celite and washed
with CHCl3. Layers were separated and the aqueous
layer was extracted twice with CHCl3. The organic
phase was dried over anhydrous Na2SO4. Evaporation
of solvent and purification by column chromatography
on silica gel with petroleum ether/EtOAc (1:1) afforded
4a as a white solid (3.11 g, 82%). Mp 118–119°C.
1
[h]2D5=+30.9 (c 1.0, CHCl3). H NMR: 1.82–1.97 (m,
2H), 2.75 (t, J=6.0 Hz, 2H), 2.88–3.06 (m, 2H), 3.36 (t,
J=5.4 Hz, 2H), 3.62–3.82 (m, 2H), 4.24–4.36 (m, 1H),
6.38 (d, J=6.6 Hz, 1H), 6.43 (t, J=7.8 Hz, 1H), 6.94
(d, J=7.2 Hz, 2H), 7.20–7.38 (m, 5H). IR: 3418, 3365,
3302, 2955, 2851, 1626, 1530, 1511, 1462, 1360, 1276,
1186, 1052, 1014 cm−1. MS (m/e,%): 310 (36, M+), 160
(100), 132 (11), 130 (24), 104 (38), 91 (32). Anal. calcd
for C19H22N2O2: C, 73.10; H, 6.73; N, 10.24. Found: C,
73.55; H, 7.09; N, 10.03%.
3.4.2. (4S)-4,5-Dihydro-4-isopropyl-2-(1,2,3,4-tetrahydro-
quinolin-8-yl)oxazole 2b. Pale yellow oil, 47% yield.
1
[h]2D5=+27.7 (c 2.35, CHCl3). H NMR: 0.88–1.04 (m,
6H), 1.67–1.84 (m, 1H), 1.85–1.96 (m, 2H), 2.77 (t,
J=5.4 Hz, 2H), 3.36–3.48 (m, 2H), 4.02–4.12 (m, 1H),
4.28–4.36 (m, 2H), 6.43 (t, J=7.5 Hz, 1H), 7.02 (d,
J=7.2 Hz, 1H), 7.70 (dd, J=1.5 Hz, 7.2 Hz, 1H), 7.78
(m, 1H). IR: 3371, 2872, 2843, 1677, 1602, 1589, 1513,
1465, 1414, 1364, 1251, 1181, 1144 cm−1. MS (m/e,%):
244 (9, M+), 177 (100), 160 (62), 158 (22), 132 (8), 130
(29), 104 (34). HRMS calcd for C15H20N2O: 244.1570.
Found: 244.1568.
3.3.2. N-[(1S)-1-Isopropyl-2-hydroxyethyl]-(1,2,3,4-tet-
rahydroquinolin-8-yl)-carboxamide 4b. White solid, 88%
1
yield. Mp 149–150.5°C. [h]2D5=−59.0 (c 1.0, CHCl3). H
NMR: 1.0 (d, J=4.5 Hz, 3H), 1.02 (d, J=4.5 Hz, 3H),
1.84–1.96 (m, 2H), 1.94–2.08 (m, 1H), 2.77 (t, J=6.0
Hz, 2H), 3.37 (t, J=5.7 Hz, 2H), 3.68–3.83 (m, 2H),
3.85–3.96 (m, 1H), 6.19 (d, J=9.0 Hz, 1H), 6.46 (t,
J=7.2 Hz, 1H), 7.00 (d, J=6.6 Hz, 1H), 7.17 (d, J=7.5
Hz, 1H). IR: 3388, 3306, 2982, 2923, 2888, 1616, 1584,
1532, 1513, 1472, 1406, 1354, 1275, 1185, 1068 cm−1.
MS (m/e,%): 262 (25, M+), 160 (100), 132 (6), 130 (15),
104 (23). Anal. calcd for C15H22N2O2: C, 68.70; H, 8.39;
N, 11.69. Found: C 68.68; H, 7.93; N, 11.58%.
3.4.3. (4S)-4,5-Dihydro-4-phenyl-2-(1,2,3,4-tetrahydro-
quinolin-8-yl)oxazole 2c. Pale yellow oil, 47% yield.
1
[h]2D5=+46.8 (c 1.73, CHCl3). H NMR: 1.80–2.02 (m,
2H), 2.77 (t, J=6.3 Hz, 2H), 3.41 (t, J=4.8 Hz, 2H),
4.17–4.28 (m, 1H), 4.35–4.43 (m, 2H), 6.44 (t, J=7.5
Hz, 1H), 7.04 (d, J=7.2 Hz, 1H), 7.26–7.50 (m, 5H),
7.64–7.80 (m, 2H). IR: 3373, 2945, 2885, 2843, 1677,
1602, 1588, 1513, 1465, 1248, 1181, 1143 cm−1. MS
(m/e,%): 278 (8, M+), 177 (58), 160 (40), 132 (29), 130
(25), 106 (100), 104 (47), 91 (11). HRMS calcd for
C18H18N2O: 278.1413. Found: 278.1415.
3.3.3. N-[(1S)-1-Phenyl-2-hydroxyethyl]-(1,2,3,4-tetra-
hydroquinolin-8-yl)-carboxamide 4c. Reaction tempera-
ture was 60°C. Yellow solid, 89% yield. Mp 119–120°C.
1
[h]2D5=+97.0 (c 1.04, CHCl3). H NMR: 1.88 (t, J=5.7