S. Banerjee et al. / Tetrahedron: Asymmetry 21 (2010) 549–557
555
J = 7.9, 0.9 Hz, 2H). 13C NMR (125 MHz, CDCl3): 9.5, 38.1, 58.1, 63.6,
74.3, 124.1, 25.1, 125.6, 126.0, 126.3, 127.0, 127.3, 128.0, 128.0,
128.5, 132.3, 133.9, 134.8, 142.7. ESI- HRMS calcd for C21H24NO
(M+H)+: 306.1858. Found: 306.1847.
diastereomers were not characterized, CDCl3) d (ppm): 0.66 (d,
J = 6.67 Hz, 3H), 1.13–1.42 (m, 4H), 1.59–1.84 (m, 6H), 1.98–2.02
(m, 1H), 2.27 (s, 3H), 2.73–2.80 (m, 1H), 3.68 (d, J = 2.7 Hz, 1H),
4.94 (d, J = 8.0 Hz, 1H), 7.22–7.33 (m, 5H). 13C (125 MHz, minor
diastereomers were not characterized, CDCl3) d (ppm): 15.5, 26.0,
26.3, 26.6, 26.8, 29.7, 37.4, 40.2, 64.2, 80.9, 101.0, 127.4, 127.8,
127.9, and 139.8. IR (neat) cmꢀ1: 3332, 2927, 1215, 756. ESI-HRMS
calcd for C17H26NO (M+H)+: 260.2014. Found: 260.2013.
4.3.2. (1R,2S)-2-(Methyl(-2-naphthylmethyl)amino)-1-phenyl-
1-propanol 9b
The product was recrystallized using dichloromethane and hex-
anes and was obtained as a white solid (77%). Mp = 86–88 °C.
½
a 2D3:6
ꢁ
¼ ꢀ43:5 (c 1.0, CHCl3). IR (Nujol): 3421, 1620, 796 cmꢀ1
.
4.5. (1R,2S)-2-((Cyclohexylmethyl)(methyl)amino)-1-phenyl-1-
propanol 21
1H NMR (500 MHz, CDCl3) d (ppm): 1.04 (d, J = 6.8 Hz, 3H), 1.82
(s, 1H), 2.22 (s, 3H), 2.95–2.99 (m, 1H), 3.76 (dd, J = 19.8, 6.3 Hz,
2H), 4.90 (d, J = 5.1 Hz, 1H), 7.24–7.37 (m, 4H), 7.42–7.46 (m,
3H), 7.63–7.82(m, 5H). 13C NMR (125 MHz, CDCl3) d (ppm): 9.7,
38.5, 59.2, 63.5, 73.8, 125.4, 125.8, 126.2, 126.8, 126.9, 127.0,
127.6, 127.8, 127.9, 132.6, 133.2, 137.0, 142.6. ESI-HRMS calcd
for C21H24NO (M+H)+: 306.1858. Found: 306.1862.
In a 500 mL round-bottomed flask were added lithium alumi-
num hydride (2.00 g, 53.6 mmol) and THF (145 mL). The reaction
mixture was heated to 50 °C. To the reaction mixture was added
a solution of (4S,5R)-2-cyclohexyl-3,4-dimethyl-5-phenyloxazoli-
dine (7.00 g, 26.8 mmol) in THF (100 mL) dropwise over a 20-min
period. The reaction mixture was then heated at reflux and stirred
overnight. Then it was cooled to 0 °C. Water (100 mL) was added
drop wise to quench the lithium aluminum hydride. Next, THF
was evaporated completely via rotary evaporation. The reaction
was quenched with 1 M sodium hydroxide (250 mL) solution and
the residue was extracted with ethyl acetate (2 ꢂ 250 mL). The or-
ganic layer was washed with brine (250 mL) and dried over mag-
nesium sulfate. The solvent was evaporated via rotary
evaporation. The residue was purified by flash chromatography
using hexanes/ethyl acetate (75:25). The product was obtained as
4.3.3. (1R,2S)-2-((2-Biphenylmethyl)(methyl)amino)-1-phenyl-
1-propanol 9c
Yellow oil, 26%. ½a D22
ꢁ
¼ þ0:4 (c 1.0, CHCl3). IR: 3409, 3060, 1599,
1218, 1038, 753 cmꢀ1
.
1H NMR (400 MHz, CDCl3) d (ppm): 0.77–
0.79 (d, J = 6.8 Hz, 3H), 1.98 (s, 1H), 2.68–2.74 (dq, J = 6.8, 4.8 Hz,
1H), 3.06 (s, 1H), 3.49–3.56 (ABq, J = 13.6 Hz, 2H), 4.60–4.62 (d,
J = 4.8 Hz, 1H), 7.09–7.16 (m, 5H), 7.27–7.36 (m, 4H), 7.33–7.38
(m, 5H). 13C NMR (100 MHz, CDCl3): 9.6, 38.4, 56.7, 63.5, 73.3,
125.9, 126.4, 126.6, 126.8, 127.1, 127.2, 127.4, 127.6, 127.8,
128.1, 128.2, 128.3, 128.6, 128.7, 128.9, 129.4, 129.9, 129.9. ESI-
HRMS calcd for C23H25NO (M+H)+: 332.2001. Found: 332.2014.
a colorless liquid (32%). ½a D23
ꢁ
¼ ꢀ17:2 (c 1.0, CHCl3). 1H (500 MHz,
CDCl3) d (ppm): 0.85 (d, J = 6.9 Hz, 3H), 1.11–1.26 (m, 4H), 1.43
(s, 2H), 1.44–1.49 (m, 1H), 1.66–1.79 (m, 2H), 2.17 (s, 3H), 2.20–
2.24 (m, 2H), 2.27–2.33 (m, 2H), 2.71–2.76 (m, 1H), 3.77 (s, 1H),
4.79 (d, J = 4.6 Hz, 1H), 7.20–7.32 (m, 5H). 13C (125 MHz, CDCl3) d
(ppm): 10.1, 26.1, 30.3, 31.4, 31.7, 36.1, 38.8, 62.6, 64.3, 73.1,
126.1, 126.7, 127.9 and 142.4. IR (neat) cmꢀ1: 3411, 2848, 1449,
1040. ESI-HRMS calcd for C17H28NO (M+H)+: 262.2171. Found:
262.2182.
4.3.4. (1R,2S)-2-((4-Biphenylmethyl)(methyl)amino)-1-phenyl-
1-propanol 9d
The product was purified by recrystallization from hexanes and
dichloromethane. Solid flakes (73%). ½a D24
ꢁ
¼ ꢀ43:5 (c 1.0, CHCl3).
Mp = 65–68 °C. IR (CHCl3): 3422, 3028, 1039 cmꢀ1
.
1H NMR
(400 MHz, CDCl3) d (ppm): 1.01 (d, J = 5.4 Hz, 3H), 1.43 (s, 2H),
2.23 (s, 3H), 2.93–3.00 (m, 1H), 3.65 (d, J = 6.3 Hz, 1H), 4.90 (d,
J = 4.0, 1H), 7.24–7.26 (m, 1H), 7.28–7.32 (m, 2H), 7.32–7.36 (m,
4H), 7.41–7.46 (m, 3H), 7.51–7.55 (m, 2H), 7.58–7.61 (m, 2H). 13C
NMR (100 MHz, CDCl3): 10.0, 38.8, 58.9, 63.5, 73.8, 126.3, 127.0,
127.1, 127.2, 127.3, 128.1, 128.8, 129.1, 138.6, 140.0, 141.0,
142.6. ESI-HRMS calcd for C23H26NO (M+H)+: 332.2014. Found:
332.2016.
4.6. (1R,2S)-2-(Methylamino)-1,2-diphenylethanol 24
In a 250 mL round-bottomed flask were placed dichlorometh-
ane (117.0 mL) and (1R,2S)-2-amino-1,2-diphenyl-1-ethanol
(5.00 g, 23.4 mmol). The reaction mixture was cooled to 0 °C. To
the reaction mixture were added triethylamine (6.60 mL,
46.9 mmol) and methyl chloroformate (1.91, 24.6 mmol). The tem-
perature of the reaction mixture was raised to room temperature
and it was allowed to run overnight. The reaction was quenched
by the addition of 1 M HCl (100 mL) and the reaction mixture
was extracted with dichloromethane (100 mL). The organic layer
was washed with brine (50 mL) and dried (MgSO4). The solvents
were removed via rotary evaporation and the product was purified
by recrystallization (hexanes/EtOAc). The product was obtained as
a white solid (88%). The white solid was then dissolved in THF
(100 mL) and added dropwise to a preheated 500 mL round-bot-
tomed flask having THF (500 mL) and lithium aluminum hydride
(1.56 g, 41.3 mmol) in about 20 min. The reaction mixture was
then raised to reflux temperature and stirred overnight. The reac-
tion was quenched by the addition of water (100 mL) at 0 °C. The
solvent was evaporated completely via rotary evaporation. The
reaction was quenched with 1 M NaOH solution (300 mL) and
the residue was extracted with ethyl acetate (250 mL) and the or-
ganic layer was washed with brine (200 mL) and dried over mag-
nesium sulfate. The solvent was completely evaporated via rotary
evaporation. The residue was recrystallized with ethyl acetate
and hexane. The product was obtained as an off-white solid
4.3.5. (1R,2S)-2-((4-Fluorobenzyl)(methyl)amino)-1-phenyl-1-
propanol 9e
White solid (28%). Mp = 61–62 °C. ½a D23
ꢁ
¼ ꢀ22:6 (c 1.0, CHCl3).
1H
IR (Nujol): 3304, 2923, 2360, 1602, 1507, 1455, 1221 cmꢀ1
.
NMR (400 MHz, CDCl3) d (ppm): 0.99–1.01 (d, J = 6.8 Hz, 3H),
2.17 (s, 3H), 2.90–2.93 (dq, J = 5.1, 6.8 Hz, 1H), 3.20 (br s, 1H),
3.56–3.57 (AB q, J = 13.4 Hz, 2H), 4.85–4.86 (d, J = 5.1 Hz, 1H),
6.94–6.99 (m, 2H), 7.14–7.17 (m, 2H), 7.27–7.32 (m, 5H). 13C
NMR (100 MHz, CDCl3): 9.8, 38.4, 58.4, 63.5, 73.6, 114.9, 115.2,
126.2, 127.1, 128.1, 128.3, 130.0, 130.1, 135.2, 142.5, 142.6,
160.7, 163.1. ESI-HRMS calculated for C17H20NOF (M+H)+:
274.1597. Found: 274.1607.
4.4. (4S,5R)-2-Cyclohexyl-3,4-dimethyl-5-phenyloxazolidine 20
In
a 500 mL round-bottomed flask were added toluene
(152 mL), (1R,2S)-ephedrine (5.00 g, 30.3 mmol), cyclohexane–car-
boxaldehyde (3.64 mL, 30.3 mmol), and magnesium sulfate (2 g).
The reaction mixture was heated at reflux overnight. Then it was
cooled to ambient temperature and filtered. The filtrate was evap-
orated via rotary evaporation. The product was obtained as a yel-
(96%). ½a 2D3
ꢁ
¼ ꢀ37:3 (c 1.0, CHCl3). IR (Nujol): 3510, 1454, 1376,
low liquid (90%). ½a D23
ꢁ
¼ ꢀ41:3 (c 0.4, CHCl3). 1H (400 MHz, minor
1056, 698 cmꢀ1 1H (500 MHz, CDCl3) d (ppm): 2.28 (s, 3H), 3.77
.