616
I. Szatma´ri et al. / Tetrahedron: Asymmetry 19 (2008) 612–617
129.5, 130.2, 132.3, 133.0, 142.0, 157.7. Anal. Calcd for
C29H25NO (403.5): C, 86.32; H, 6.24; N, 3.47. Found: C,
86.42; H, 6.27; N, 3.35.
C, 86.30; H, 6.52; N, 3.35. Found: C, 86.51; H, 6.48; N,
3.31.
4.4. 1-[(R)-Phenyl-(10R)-(2-naphthyl)ethylaminomethyl]-2-
naphthol 5
4.2. (1R)-1-Phenyl-2-[(10R)-10-(1-naphthylethyl)]-2,3-di-
hydro-1H-naphth[1,2-e][1,3]oxazine 3
A mixture of 2-naphthol (1.44 g, 10.0 mmol), R-(+)-1-
(2-naphthyl)ethylamine (Fluka, cat. no. 70940), (1.78 g,
10.4 mmol) and benzaldehyde (1.27 g, 12.0 mmol) was
stirred at 65 °C for 72 h. Then, 15 mL of MeOH was added
to the crude reaction mixture and the white crystals, which
separated out were filtered off and recrystallized from iPr2O
To a solution of 2 (1.21 g, 3.00 mmol) in toluene (30 mL),
paraformaldehyde (0.18 g, 6 mmol) was added. The reac-
tion mixture was stirred at room temperature for 10 h, after
which TLC revealed no more starting material. The solu-
tion was dried with Na2SO4. The solvent was evaporated
off under reduced pressure, and the residue was crystallized
(30 mL). Yield: 2.49 g (62%). White crystals, mp: 164–
20
from a mixture of n-hexane–EtOAc (4:1). Yield: 1.18 g
166 °C; ½aꢂD ¼ ꢀ236:0 (c 0.5, CHCl3); 1H NMR
20
(95%). White crystals, mp: 87–88 °C; ½aꢂD ¼ ꢀ218:3 (c
(400 MHz, CDCl3): d: 1.64 (d, 3H, J = 6.8 Hz), 2.43 (br
s, 1H), 4.12 (q, 1H, J = 6.7 Hz), 5.56 (s, 1H), 7.15–8.05
(m, 18H), 13.68 (br s, 1H); 13C NMR (100 MHz, CDCl3):
d: 23.6, 57.4, 61.0, 113.8, 120.8, 121.9, 123.1, 124.3, 126.8,
127.1, 127.2, 127.4, 128.4, 128.5, 128.5, 128.6, 129.3,
129.4, 129.7, 129.8, 130.5, 133.3, 133.8, 134.1, 140.8,
142.2, 158.0. Anal. Calcd for C29H25NO (403.5): C,
86.32; H, 6.24; N, 3.47. Found: C, 86.27; H, 6.21; N, 3.51.
0.5, CHCl3); 1H NMR (400 MHz, CDCl3): d: 1.71 (d,
3H, J = 6.8 Hz), 4.81 (q, 1H, J = 6.4 Hz), 5.07 (d, 1H,
J = 10.8 Hz), 5.23 (d, 1H, J = 12.2 Hz), 5.25 (s, 1H),
6.81–7.93 (m, 18H); 13C NMR (100 MHz, CDCl3): d:
21.4, 57.3, 58.5, 75.2, 113.0, 118.0, 119.2, 120.2, 123.4,
123.8, 124.4, 126.2, 126.3, 126.6, 127.1, 127.8, 128.7,
129.0, 129.5, 129.7, 130.0, 131.9, 132.2, 133.6, 134.9,
143.7, 152.9, 153.6. Anal. Calcd for C30H25NO (415.2):
C, 86.71; H, 6.06; N, 3.37. Found: C, 86.32; H, 6.10; N,
3.41.
4.5. (1R)-1-Phenyl-2-[(10R)-10-(2-naphthylethyl)]-2,3-di-
hydro-1H-naphth[1,2-e][1,3]oxazine 6
4.3. N-Methyl-1-[(R)-phenyl-(10R)-(1-naphthyl)ethylamino-
methyl]-2-naphthol 4
To a solution of 5 (1.21 g, 3.00 mmol) in toluene (30 mL),
paraformaldehyde (0.18 g, 6 mmol) was added. The
mixture was stirred at room temperature for 12 h, after
which TLC revealed no more starting material. The solu-
tion was dried with Na2SO4. The solvent was evaporated
off at reduced pressure, and the residue was crystallized
(A) To a stirred solution of 3 (1.04 g, 2.5 mmol) in THF
(50 mL), LiAlH4 (1.40 g) was added. The resulting suspen-
sion was stirred at rt for 4 h. Water (2.8 mL) in THF
(20 mL) was added dropwise to the stirred suspension
and the stirring was continued for an additional 30 min.
The mixture was filtered off and washed with EtOAc
(2 ꢃ 20 mL). The filtrate was dried over Na2SO4 and the
solvent was evaporated off. The crude product was crystal-
lized from Et2O (20 mL) and recrystallized from iPr2O
from a mixture of n-hexane–EtOAc (6:1). Yield: 1.14 g
20
(92%). White crystals, mp: 173–175 °C; ½aꢂD ¼ ꢀ143:0 (c
0.5, CHCl3); 1H NMR (400 MHz, CDCl3): d: 1.61 (d,
3H, J = 6.7 Hz), 4.16 (q, 1H, J = 6.7 Hz), 4.99 (d, 1H,
J = 10.7 Hz), 5.19 (d, 1H, J = 11.1 Hz), 5.26 (s, 1H),
6.94–7.97 (m, 18H); 13C NMR (100 MHz, CDCl3): d:
22.0, 57.7, 59.7, 74.7, 112.6, 118.9, 123.1, 123.5, 126.1,
126.5, 126.9, 127.1, 127.6, 128.2, 128.3, 128.5, 128.6,
128.7, 128.9, 129.3, 129.4, 129.6, 133.3, 133.6, 133.9,
143.3, 143.5, 153.2. Anal. Calcd for C30H25NO (415.2):
C, 86.71; H, 6.06; N, 3.37. Found: C, 86.81; H, 6.02; N,
3.35.
(25 mL), Yield: 1.02 g (98%). White crystals, mp: 202–
20
203 °C; ½aꢂD ¼ ꢀ399:4 (c 0.5, CHCl3).
(B) A mixture of 2-naphthol (0.36 g, 2.5 mmol), (R)-(+)-N-
methyl-1-(1-naphthyl)ethylamine (0.48 g, 2.6 mmol) and
benzaldehyde (0.32 g, 3.0 mmol) was stirred at 65 °C for
72 h. Then, 20 mL of MeOH was added to the crude reac-
tion mixture and the white crystals which separated out
4.6. N-Methyl-1-[(R)-Phenyl-(10R)-(2-naphthyl)ethylamino-
methyl]-2-naphthol 7
were filtered off and recrystallized from iPr2O (40 mL).
20
Yield: 0.82 (78%). White crystals, mp: 201–203 °C; ½aꢂD
¼
ꢀ397:4 (c 0.5, CHCl3).
To a stirred solution of 6 (1.04 g, 2.5 mmol) in THF
(50 mL), LiAlH4 (1.40 g) was added and the resulting sus-
pension was stirred at rt for 6 h. Water (2.8 mL) in THF
(20 mL) was then added dropwise to the stirred suspension
and the stirring was continued for an additional 30 min.
The mixture was next filtered off and washed with EtOAc
(2 ꢃ 20 mL). The filtrate was dried over Na2SO4 and the
solvent was evaporated off. The crude product was crystal-
lized from Et2O (20 mL) and recrystallized from iPr2O
In view of the very similar NMR spectroscopic and elemen-
tal analysis data on 4 obtained by methods A and B, ana-
lytical data are presented only for the compound prepared
by using method B.
1H NMR (400 MHz, CDCl3): d: 1.66 (d, 3H, J = 6.9 Hz),
2.19 (s, 3H), 4.84 (m, 1H), 5.49 (s, 1H), 7.02–8.04 (m,
18H), 13.32 (br s, 1H); 13C NMR (100 MHz, CDCl3): d:
30.2, 34.2, 52.3, 69.5, 117.2, 120.6, 121.8, 123.1, 124.3,
125.3, 126.2, 126.3, 126.4, 126.5, 126.9, 127.0, 128.1,
129.1, 129.2, 129.5, 129.8, 130.1, 130.2, 132.6, 132.8,
134.8, 140.2, 156.4. Anal. Calcd for C30H27NO (417.2):
(20 mL). Yield: 1.00 g (96%). White crystals, mp: 195–
20
196 °C; ½aꢂD ¼ ꢀ255:0 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): d: 1.64 (d, 3H, J = 6.0 Hz), 2.13 (s,
3H), 4.38 (m, 1H), 5.38 (s, 1H), 7.05–8.00 (m, 18H),
13.87 (br s, 1H); 13C NMR (100 MHz, CDCl3): d: 29.9,