2.88 (1 H, dd, J 16.4, 8.8, 8-CH), 2.52 (1 H, dd, J 16.4, 11.4,
8-CH), 2.26 (1 H, td, J 11.2, 2.4, 2-CH), 1.70–1.79 (2 H, m,
3-CH2), 1.59–1.67 (1 H, m, 4-CH), 1.37–1.48 (1 H, m, 4-CH);
δC (CDCl ) 168.5 (C᎐O), 139.0 (phenyl C), 128.7 and 127.5
(o- and m-phenyl C), 128.1 (p-phenyl C), 67.4 (9-C), 55.4 (2-C),
42.0 (5-C), 39.9 (8-C), 23.9 (3-C), 22.7 (4-C); m/z 216 (100%,
Mϩ), 173 (7), 138 (13), 130 (8), 104 (20), 85 (28), 56 (20) (Calc.
for C13H16N2O: M, 216.1263 Found: Mϩ, 216.1273); [α]D Ϫ167
(c 1.30, CHCl3, 99% ee, after recrystallization from hexane);
optically active column [Daicel Chiralpak AD, retention time,
tR 18.1 min: 99.5% (S-form), tR = 20.4 min: 0.5% (R-form),
hexane–propan-2-ol 19 : 1; flow rate 1 mL minϪ1; detection, UV
254 nm].
(R)-(ϩ)-6: Rf (hexane–ethyl acetate 2 : 1) 0.10; mp 95.5–96.5
ЊC; νmax (KBr) 1665 (CO); δH (CDCl3) 7.28–7.41 (5 H, m,
phenyl), 4.17 (1 H, d, J 11.2, 5-CH), 3.85 (1 H, dd, J 11.2, 8.3,
9-CH), 3.06 (1 H, d, J 11.5, 2-CH), 2.98 (1 H, dd, J 12.7, 11.2,
5-CH), 2.88 (1 H, dd, J 16.6, 8.3, 8-CH), 2.52 (1 H, dd, J 16.6,
11.2, 8-CH), 2.26 (1 H, td, J 11.5, 2.0, 2-CH), 1.40–1.77 (4 H,
(o- and m-phenyl C), 127.6 (p-phenyl C), 61.5 (4-C), 51.5 (6-C),
46.3 (3-C), 40.4 (9-C), 29.3 (7-C), 25.8 (8-C); δC (signals of the
minor isomer) 176.48 (C᎐O), 146.19, 128.89, 127.41, 125.58,
᎐
60.01, 48.99, 45.39, 42.32, 29.88, 22.51; m/z 218 (4%, Mϩ), 159
(8), 146 (5), 132 (37), 118 (8), 105 (100), 91 (6), 77 (75), 51 (32)
(Calc. for C13H18N2O: M, 218.1420. Found: Mϩ, 218.1401); [α]D
Ϫ149 (c 1.20, CHCl3, 99% ee); optically active column [Daicel
Chiralpak AD, tR = 29.2 min: 99.5% (S-form), tR = 33.2 min:
0.5% (R-form), hexane–propan-2-ol 95 : 5 containing 0.1%
diethylamine, flow rate 1 mL minϪ1, detection UV 254 nm].
Isomer (R)-(ϩ)-7: showed Rf (ethyl acetate) 0.42; mp 70–71
ЊC; νmax (KBr) 1560, 1640 (CO), 3310 (NH); δH (CDCl3) (signals
of the major isomer) 7.24–7.36 (5 H, m, phenyl), 7.00 (1 H, d,
J 10.3, amide NH), 3.74 (1 H, d, J 10.3, 9-CH), 3.57 (1 H, dd,
J 11.7, 3.7, 4-CH), 2.80–2.95 (2 H, m, 6- and 9-CH), 2.74 (1 H,
td, J 11.9, 2.4, 6-CH), 2.49 (1 H, dd, J 11.7, 11.7, 3-CH), 2.35
(1 H, dd, J 11.7, 3.7, 3-CH), 1.87–2.00 (2 H, m, 7-CH and NH),
1.56–1.80 (1 H, m, 8-CH), 1.34–1.56 (2 H, m, 7- and 8-CH);
᎐
3
δC (CDCl ) (signals of the major isomer) 176.3 (C᎐O), 144.6
᎐
3
m, 3- and 4-CH2); δC (CDCl ) 168.5 (C᎐O), 139.1 (phenyl C),
(phenyl C), 129.0 and 125.8 (o- and m-phenyl C), 127.5
(p-phenyl C), 61.5 (4-C), 51.4 (6-C), 46.3 (3-C), 40.3 (9-C), 29.2
(7-C), 25.7 (8-C); m/z 218 (22%, Mϩ), 190 (6), 159 (39), 146 (61),
132 (51), 118 (81), 112 (26), 104 (100), 91 (80); [α]D ϩ142 (c 1.20,
CHCl3, 97% ee) (Calc. for C13H18N2O: M, 218.1420. Found:
Mϩ, 218.1401); optically active column [Daicel chiralpak AD,
tR = 30.0 min: 1.7% (S-form), tR = 31.4 min: 98.3% (R-form),
hexane–propan-2-ol 95 : 5 containing 0.1% diethylamine, flow
rate 1 mL minϪ1, detection UV 254 nm].
᎐
3
128.7 and 127.5 (o- and m-phenyl C), 128.1 (p-phenyl C), 67.5
(9-C), 55.4 (2-C), 42.1 (5-C), 39.9 (8-C), 23.9 (3-C), 22.8 (4-C);
m/z 216 (79%, Mϩ), 173 (12), 162 (41), 131 (100), 103 (81), 91
(13), 85 (54), 77 (49), 55 (56) (Calc. for C13H16N2O: M,
216.1263. Found: Mϩ, 216.1283); [α]D ϩ163 (c 1.60, CHCl3,
97% ee, after recrystallization from hexane); optically active
column [Daicel Chiralpak AD, retention time, tR = 18.9 min:
1.7% (S-form), tR = 21.1 min: 98.3% (R-form), hexane–propan-
2-ol 19 : 1; flow rate 1 mL minϪ1; detection, UV 254 nm].
(S)-4-Phenyl-1-(2Ј-cyanoethyl)-1,5-diazacyclononan-2-one 12
(S)- and (R)-4-Phenyl-1,5-diazacyclononan-2-one 7
To a solution of (S)-7 {127 mg, 0.58 mmol, [α]D Ϫ149 (c 1.20,
CHCl3, 99% ee} in dry ethanol (1 mL) was added sodium
ethoxide (44 mg, 0.65 mmol) and the mixture was irradiated
with ultrasonic apparatus (Yamato 2200) in a water-bath until
dissolution (for ca. 10 min) was observed. The solution was
evaporated to dryness under vacuum. The remaining salt was
dissolved in dry benzene (2 mL), and then acrylonitrile (2.3 mL,
35.0 mmol) was added to the solution under argon at 20 ЊC
in an ice-bath. The addition of acrylonitrile was stopped
when all the starting material had been consumed (by TLC) and
the mixture was stirred for 12 h at room temperature before
being poured into water and extracted with dichloromethane
(100 mL × 3). After chromatographic separation on silica gel,
nitrile (S)-12 (104 mg, 0.38 mmol) was obtained in 64% yield.
The 1H NMR spectrum revealed that product (S)-12 consisted
of only one isomer. (S)-(Ϫ)-12: Rf (CHCl3–MeOH 95 : 5)
0.50; νmax (liquid film) 3300–3600 (NH), 2248 (CN), 1628 (CO);
δH (CDCl3) 7.23–7.35 (5 H, m, phenyl), 4.92 (1 H, td, J 13.6, 3.9,
9-CH), 3.97 (1 H, m, 1Ј-CH), 3.75 (1 H, d, J 10.0, 4-CH), 3.39
(1 H, dd, J 13.2, 4.8, 9-CH), 3.19 (1 H, dd, J 12.2, 10.0, 3-CH),
3.13 (1 H, ddd, J 13.2, 8.4, 6.0, 1Ј-CH), 2.96 (1 H, dt, J 12.4, 3.2,
6-CH), 2.85 (1 H, ddd, J 16.8, 8.4, 6.8, 2Ј-CH), 2.78 (1 H, td,
J 12.4, 4.8, 6-CH), 2.57–2.64 (2 H, m, 3- and 2Ј-CH), 1.85–1.94
(1 H, m, 8-CH), 1.85 (1H, br s, NH), 1.55–1.64 (1 H, m, 8-CH),
In a 200-mL three-necked flask equipped with a Dewar con-
denser cooled with solid CO2 was placed ca. 50 mL of liquid
ammonia at Ϫ78 ЊC under nitrogen. A solution of (S)-(Ϫ)-6
{164 mg, 0.76 mmol, [α]D Ϫ167 (c 1.50, CHCl3), 99% ee} in dry
THF (5 mL) was added to the flask, and then sodium metal
(3 equiv.) was added until the color of the solution turned
to dark blue. After stirring of the mixture for 1 h, solid
ammonium chloride was added until the blue color of the
solution disappeared. Then the Dewar condenser and cooling
bath were removed, and liquid ammonia was distilled off.
The residue was dissolved in a mixture of dichloromethane
(50 mL) and water (50 mL), and the product was extracted with
dichloromethane (100 mL × 4). After the solution had been
concentrated, (S)-7 (156 mg, 0.72 mmol) was obtained in 94%
yield by column chromatography on silica gel (eluent hexane–
ethyl acetate 1 : 1). Similarly, (R)-7 (198 mg, 0.91 mmol) was
prepared in 87% yield by the reduction of the N–N bond of
(R)-6 {226 mg, 1.05 mmol, [α]D ϩ163 (c 1.20, CHCl3), 97% ee}.
The 1H NMR spectrum of (S)-7 at room temperature indicated
the product to be a mixture of major and minor isomers in the
ratio 1 : 0.1. The major and minor isomers were assigned to the
trans- and cis-conformer, respectively. These signals gradually
broadened with increasing temperature and coalesced at 100 ЊC.
The simplified 1H NMR chemical shifts at 125 ЊC and those of
the major isomer at room temperature are given here.
Compound (S)-(Ϫ)-7 showed mp 90.1–91.0 ЊC; δH (tetra-
chloroethane-d2; 125 ЊC) 7.31 (2H, m, phenyl), 7.29 (3 H, m,
phenyl), 3.63 (2 H, m, 4- and 9-CH), 2.79–2.85 (3H, m, 6-CH2
and 9-CH), 2.47 (1 H, m, 3-CH), 2.35 (1 H, d, J 11, 3-CH), 1.84
(1 H, m, 7-CH), 1.53 (5 H, m, NH, 7- and 8-CH2); δH (CDCl3;
24.5 ЊC) (signals of the major isomer) 7.24–7.37 (5 H, m,
phenyl), 6.98 (1 H, d, J 9.2, amide NH), 3.70–3.78 (1 H, m,
9-CH), 3.57 (1 H, dd, J 12.0, 2.8, 4-CH), 2.83–2.90 (2H,
m, 6- and 9-CH), 2.75 (1 H, td, J 12.0, 2.8, 6-CH), 2.51 (1 H, t,
J 12.0, 3-CH), 2.36 (1 H, dd, J 11.6, 2.8, 3-CH), 1.89–1.97 (1 H,
m, 7-CH), 1.86 (1 H, br s, NH), 1.59–1.68 (1 H, m, 8-CH), 1.36–
1.54 (2 H, m, 7- and 8-CH); δC (CDCl3; 24.5 ЊC) (signals of the
1.29–1.47 (2 H, m, 7-CH2); δC (CDCl ) 174.5 (C᎐O), 146.3
᎐
3
(phenyl C), 129.0 and 125.5 (o- and m-phenyl C), 127.3 (p-
phenyl C), 118.6 (CN), 61.1 (4-C), 49.5 (6-C), 49.0 (9-C), 46.5
(1Ј-C), 41.3 (3-C), 26.4 (8-C), 21.8 (7-C), 16.1 (2Ј-C); m/z 271
(49%, Mϩ), 228 (32), 159 (100), 146 (94), 132 (65), 123 (41), 119
(92), 104 (62), 91 (38) (Calc. for C16H21N3O: M, 271.1686.
Found: Mϩ, 271.1678); [α]D Ϫ85.4 (c 1.00, CHCl3).
(S)-(؊)-4-Phenyl-1-(3Ј-aminopropyl)-1,5-diazacyclononan-2-one
13
To a solution of nitrile (S)-12 (121 mg, 0.45 mmol) in dry
ethanol (10 mL) containing chloroform (0.2 mL) was added
platinum() oxide (30 mg). Then, gaseous H2 was introduced
with a balloon into the reaction flask, and the reaction mixture
was stirred for 14 h. The insoluble material was filtered off, and
major isomer) 176.4 (C᎐O), 144.7 (phenyl C), 129.1 and 125.9
᎐
2928
J. Chem. Soc., Perkin Trans. 1, 2001, 2924–2930