Enantioselective Synthesis of Binaphthol Derivatives
73%) as a pale yellow oil. [R]28
J . Org. Chem., Vol. 64, No. 7, 1999 2269
:
+9.7 (c 1.1, EtOH). IR
74.01; H, 6.00; N, 7.28. 13. [R]24D: -1.3 (c 0.55, EtOH). IR
D
1
(neat): 3335, 1481 cm-1
.
1H NMR (CDCl3): δ 1.35-1.48 (m,
(neat): 3337, 862, 823, 744 cm-1. H NMR (CDCl3): δ 1.39-
1H), 1.66-1.96 (m, 3H), 2.80-3.07 (m, 2H), 3.05 (s, 3H), 3.38-
3.41 (m, 3H), 6.72 (d, J ) 8.9 Hz, 1H), 7.43 (d, J ) 8.9 Hz,
1H). 13C NMR (CDCl3): δ 24.9, 29.4, 39.2, 46.3, 57.1, 57.6,
110.9, 117.1 (q, J CF ) 33 Hz), 125.1 (q, J CF ) 270 Hz), 126.4,
151.4. MS m/z: 258 (M+), 239, 189, 145, 70 (bp). HRMS: calcd
for C13H17F3N2 258.1344, found 258.1333.
1.96 (m, 4H), 2.92 (ddd, J ) 6.5, 7.9, 10.2 Hz, 1H), 3.00 (ddd,
J ) 5.5, 7.5, 10.2 Hz, 1H), 3.09 (s, 3H), 3.43 (d, J ) 2.3 Hz,
1H), 7.03 (d, J ) 2.6 Hz, 1H), 7.18 (m, 2H), 7.35 (td, J ) 6.9,
1.4 Hz, 1H), 7.65 (t, J ) 9.1 Hz, 2H), 7.68 (d, J ) 9.1 Hz, 1H).
13C NMR (CDCl3): δ 24.8, 29.4, 39.3, 46.1, 57.3, 58.1, 105.8,
116.1, 121.8, 126.0, 126.0, 126.6, 127.3, 128.6, 135.0, 147.5.
MS m/z: 240 (M+), 171 (bp), 70. HRMS: calcd for C16H20N2
240.1626, found 240.1608. Anal. Calcd for C16H20N2‚HCl: C,
69.43; H, 7.65; N, 10.12. Found: C, 69.70; H, 7.51; N, 10.02.
(S)-N-Cycloh exyl-N-m et h yl-2-p yr r olid in em et h a n a m -
in e (14). To a solution of N-tert-butoxycarbonyl-L-proline (0.50
g, 2.3 mmol) and N-methylcyclohexylamine (0.35 g, 3.1 mmol)
in CH2Cl2 (3 mL) was added EDC (0.59 g, 3.1 mmol), and the
reaction mixture was stirred at room temperature for 12 h.
After addition of water, the mixture was extracted with EtOAc
and washed with 10% HCl, saturated NaHCO3, and brine.
Drying over Na2SO4 and concentration followed by silica gel
column chromatography (hexanes-EtOAc 1:1) afforded (S)-1-
tert-butoxycarbonyl-N-cyclohexyl-N-methyl-2-pyrrolidinecar-
boxamide (0.39 g, 54%) as a mixture of rotamers. [R]29D: -25.0
(c 1.0, CHCl3). IR (Nujol): 1699, 1685 cm-1. 1H NMR (CDCl3):
δ 1.00-1.89 (m, 16H), 1.39, 1.40, 1.45, and 1.45 (s × 4, 9H),
1.93-2.23 (m, 2H), 2.81-2.91 (m, 5H), 3.37-3.66 (m, 4H),
4.36-4.43 (m, 1H), 4.45-4.53 (m, 1H), 4.65 (td, 8.4, 2.9 Hz,
1H). 13C NMR (CDCl3): δ 23.1, 23.7, 24.9, 25.0, 25.2, 25.3, 25.4,
25.6, 27.0, 27.0, 28.1, 28.2, 28.8, 29.3, 29.4, 29.5, 29.8, 30.1,
30.3, 30.4, 30.6, 30.7, 30.7, 46.3, 46.5, 52.4, 52.5, 55.7, 55.8,
56.6, 56.9, 153.5, 153.7, 154.1, 171.6, 171.6, 172.0. MS m/z:
310 (M+), 237, 170, 70 (bp). HRMS: calcd for C17H30N2O3
310.2256, found 310.2256. Anal. Calcd for C17H30N2O3: C,
65.81; H, 9.75; N, 9.03. Found: C, 65.90; H, 9.62; N, 8.88.
To a solution of above amide (0.39 g, 0.87 mmol) in CH2Cl2
(1 mL) was added trifluoroacetic acid (1 mL) at 0 °C, and the
reaction mixture was stirred at the same temperature for 1 h.
The mixture was neutralized with saturated NaHCO3 and
extracted with CH2Cl2. Drying over Na2SO4 and concentration
gave crude amide, which was added to a solution of lithium
aluminum hydride (0.13 g, 3.3 mmol) in THF (20 mL) and the
mixture was heated at reflux for 1 h. After the addition of
water (0.13 mL), 15% NaOH (0.13 mL), and water (0.39 mL)
successively, the mixture was filtered through a Celite pad.
Concentration followed by silica gel column chromatography
(CH2Cl2-MeOH-aqueous NH3 100:10:1) afforded 14 (0.10 g,
36%) as a colorless oil. [R]26D: -3.5 (c 1.0, EtOH). IR (neat):
3319 cm-1. 1H NMR (CDCl3): δ 0.97-1.37 (m, 6H), 1.56-1.91
(m, 8H), 2.26 (s, 3H), 2.20-2.50 (m, 2H), 2.32 (d, J ) 6.8 Hz,
2H), 2.83 (dt, J ) 7.0, 9.9 Hz, 1H), 2.94 (dt, J ) 6.6, 10.0 Hz,
1H), 3.18 (dd, J ) 6.7, 6.7 Hz, 1H). 13C NMR (CDCl3): δ 25.1,
26.4, 26.7, 28.7, 29.1, 29.8, 38.7, 46.0, 56.7, 58.9, 63.7. MS
m/z: 196 (M+), 126, 84 (bp), 70. HRMS: calcd for C12H24N2
196.1940, found 196.1941.
(S)-N-Meth yl-N-(1-n a p h th yl)-2-p yr r olid in em eth a n a m -
in e (12). To a solution of (S)-1-benzyloxycarbonyl-N-(1-naph-
thyl)-2-pyrrolidinecarboxamide13 (1.5 g, 4.0 mmol) in DMF (10
mL) was added sodium hydride (60% in oil, 0.24 g, 5.0 mmol)
at 0 °C, and the mixture was stirred at the same temperature
for 15 min. Iodomethane (0.37 mL, 6.0 mmol) was added, and
the reaction mixture was stirred for 2 h at room temperature.
After addition of 10% HCl, the mixture was extracted with
EtOAc and washed with saturated NaHCO3 and brine. Drying
over Na2SO4 and concentration followed by silica gel chroma-
tography (hexanes-EtOAc 1:2) afforded (S)-1-benzyloxycar-
bonyl-N-methyl-N-(1-naphthyl)-2-pyrrolidinecarboxamide (1.3
g, 82%) as a mixture of rotamers. [R]28
:
+108.0 (c 0.56,
D
CHCl3). IR (neat): 1680, 1595, 1460, 1377 cm-1 1H NMR
.
(CDCl3): δ 1.90-2.07 (m, 4H), 3.25, 3.29, 3.38, and 3.40 (4 ×
s, 3H), 3.37-3.67 (m, 2H), 3.85-4.27 (m, 1H), 4.95-6.56 (m,
2H), 7.08-8.30 (m, 12H). 13C NMR (CDCl3): δ 23.5, 23.7, 24.4,
24.5, 29.2, 30.6, 31.1, 31.6, 32.3, 30.9, 37.3, 37.5, 37.5, 39.8,
46.8, 47.1, 47.3, 47.7, 48.1, 52.0, 53.4, 56.6, 57.1, 57.8, 58.3,
60.4, 66.7, 66.7, 66.8, 67.5, 122.3, 123.0, 123.9, 124.7, 125.3,
125.4, 125.8, 125.9, 126.0, 126.3, 126.3, 126.5, 126.6, 126.7,
126.8, 127.1, 127.2, 127.2, 127.6, 127.7, 127.8, 127.9, 128.1,
128.3, 128.3, 128.4, 128.6, 128.6, 128.7, 128.7, 129.0, 129.0,
130.0, 130.0, 130.1, 134.6, 134.7, 134.8, 136.7, 136.8, 137.3,
139.0, 139.1, 139.3, 139.4, 141.9, 154.1, 154.6, 154.8, 160.2,
172.6, 172.8, 173.4, 173.7, 206.9. MS m/z: 388 (M+), 312, 253,
204, 184, 91 (bp). HRMS: calcd for C24H24N2O3 388.1787, found
388.1816. Anal. Calcd for C24H24N2O3: C, 74.21; H, 6.23; N,
7.21. Found: C, 74.12; H, 5.98; N, 7.18.
To a solution of above amide (198 mg, 0.51 mmol) in THF
(2 mL) was added BH3‚THF complex (1 M in THF, 5.0 mL,
5.0 mmol), and the reaction mixture was heated at reflux for
1 h. After addition of 10% HCl, the mixture was neutralized
with NaOH and extracted with Et2O. Drying over Na2SO4 and
concentration gave crude amide, which was treated with 30%
HBr in acetic acid (1 mL) at 0 °C for 3 h. After addition of
water, the mixture was neutralized with NaOH and extracted
with Et2O. Drying over Na2SO4 and concentration followed by
silica gel column chromatography (CH2Cl2-MeOH-aqueous
NH3 100:10:1) afforded 12 (94 mg, 77%) as a pale yellow oil.
[R]24D: +11.0 (c 1.1, CHCl3). IR (neat): 3335, 802, 775 cm-1
.
1H NMR (CDCl3): δ 1.32-1.51 (m, 1H), 1.63-1.95 (m, 3H),
2.89 (s, 3H), 2.80-2.89 (m, 1H), 2.97 (td, J ) 6.8, 13.3 Hz,
1H), 3.13 (t, J ) 13.0 Hz, 1H), 3.15 (dd, J ) 13.9, 13.0 Hz,
1H), 3.42 (t, J ) 6.6 Hz, 1H), 3.53 (s, 1H), 7.16 (d, J ) 7.1 Hz,
1H), 7.37-7.57 (m, 4H), 7.81 (dd, J ) 6.7, 2.7 Hz, 1H), 8.36
(dd, J ) 7.5, 2.0 Hz, 1H). 13C NMR (CDCl3): δ 24.9, 29.7, 44.1,
46.0, 56.0, 61.6, 116.1, 123.4, 123.8, 125.2, 125.6, 125.7, 128.1,
129.7, 134.7, 150.3. MS m/z: 240 (M+), 171 (bp), 70. HRMS:
calcd for C16H20N2 240.1626, found 240.1638. Anal. Calcd for
(S)-N-Eth yl-N-p h en yl-2-p yr r olid in em eth a n a m in e (15).
Prepared by the same method as for 10 starting from N-
benzyloxycarbonyl-L-proline and N-ethylaniline. (S)-1-Benzyl-
oxycarbonyl-N-ethyl-N-phenyl-2-pyrrolidinecarboxamide. [R]22
:
D
+119.3 (c 1.2, CHCl3). IR (Nujol): 1730, 1668, 702 cm-1. H
NMR (CDCl3): δ 1.02-1.17 (m, 3H), 1.67-2.14 (m, 5H), 3.45-
3.87 (m, 4H), 4.06-4.26 (m, 1H), 5.09-5.19 (m, 2H), 6.72 (bs,
1H), 7.23-7.50 (m, 9H). 13C NMR (CDCl3): δ 12.8, 12.9, 23.6,
24.4, 30.3, 31.4, 44.3, 44.4, 47.0, 47.5, 57.0, 57.6, 66.8, 67.4,
127.6, 127.8, 127.9, 128.0, 128.3, 128.4, 128.5, 128.6, 128.9,
129.0, 129.5, 129.7, 136.6, 136.8, 141.4, 141.7, 154.1, 154.7,
171.8, 171.9. MS m/z: 352 (M+), 204, 148, 120, 91 (bp).
HRMS: calcd for C21H24N2O3 352.1787, found 352.1779. Anal.
Calcd for C21H24N2O3: C, 71.57; H, 6.86; N, 7.95. Found: C,
71.79; H, 6.97; N, 7.86. 15. [R]22D: +10.1 (c 1.0, EtOH). IR
1
C
16H20N2‚HCl: C, 69.43; H, 7.65; N, 10.12. Found: C, 69.28;
H, 7.70; N, 10.09.
(S)-N-Meth yl-N-(2-n a p h th yl)-2-p yr r olid in em eth a n a m -
in e (13). Prepared by the same method as for 12 starting from
(S)-1-benzyloxycarbonyl-N-(2-naphthyl)-2-pyrrolidinecarbox-
amide.13 (S)-1-benzyloxycarbonyl-N-methyl-N-(1-naphthyl)-2-
pyrrolidinecarboxamide. [R]27
: +184.6 (c 1.0, CHCl3). IR
D
(Nujol): 1712, 1680, 864, 821, 754 cm-1. H NMR (CDCl3): δ
1.66-2.11 (m, 4H), 3.23 and 3.38 (2 × s, 3H), 3.43-3.72 (m,
2H), 4.15-4.37 (m, 1H), 5.01-5.19 (m, 2H), 6.75-6.82 (m, 1H),
7.19-7.94 (m, 12H). 13C NMR (CDCl3): δ 14.1, 23.6, 24.4, 30.3,
31.4, 37.6, 37.8, 46.9, 47.4, 56.8, 57.4, 66.8, 67.4, 125.2, 125.7,
125.9, 126.1, 126.2, 126.7, 126.8, 127.6, 127.8, 128.0, 128.4,
128.6, 129.0, 129.8, 129.9, 132.3, 132.5, 133.4, 133.6, 136.7,
140.4, 140.8, 154.0, 172.6. MS m/z: 388 (M+), 204, 91 (bp).
HRMS: calcd for C24H24N2O3 388.1787, found 388.1801. Anal.
Calcd for C24H24N2O3: C, 74.21; H, 6.23; N, 7.21. Found: C,
1
(neat): 3329, 1599, 1248, 1196, 694 cm-1 1H NMR (CDCl3):
.
δ 1.14 (t, J ) 7.0 Hz, 3H), 1.38-1.51 (m, 1H), 1.68-1.98 (m,
3H), 2.83 (bs, 1H), 2.90 (ddd, J ) 6.6, 8.2, 10.3 Hz, 1H), 3.06
(ddd, J ) 5.7, 7.7, 10.3 Hz, 1H), 3.23-3.50 (m, 3H), 3.46 (q, J
) 7.0 Hz, 2H), 6.68-6.82 (m, 3H), 7.18-7.27 (m, 2H). 13C NMR
(CDCl3): δ 11.5, 24.6, 29.0, 45.5, 46.0, 55.4, 57.2, 112.2, 115.7,
129.0, 148.1. MS m/z: 204 (M+), 135, 120, 106, 70 (bp).