â-Amino Acids and 3-Amino-Substituted Carbohydrates
J . Org. Chem., Vol. 63, No. 21, 1998 7273
17.2, J 4.8, 1H), 2.59 (dd, J 17.2, 6.4, 1H), 3.26 (ddd, J 6.4,
6.0, 4.8), 3.77 (q, J 6.4, 1H), 4.50 (dq, J 6.0, 6.8, 1H), 7.20-
7.30 (m, 5H). 13C NMR: δ 15.06, 25.39, 36.09, 54.72, 56.29,
80.09, 127.07, 127.85, 129.15, 145.00, 176.29. GC-MS (a): tR
9.12 min. Anal. Calcd for C13H17NO2 (219.28): C, 71.20; H,
7.81; N, 6.39. Found: C, 70.79; H, 7.72; N, 6.90.
(4S,5S)-4-(Ben zyla m in o)-5-m et h ylt et r a h yd r ofu r a n -2-
on e (22d ) (fr om syn -19a ). Yield: 69 mg (67%). Rf ) 0.07
(1:2 EtOAc/petroleum ether). [R]2D0: +14.2 (c 0.52, CHCl3).
IR: ν 3333, 1776. 1H NMR (400 MHz): δ 1.40 (d, J 6.6, 3H),
1.50 (br s, 1H), 2.49 (dd, J 17.2, 5.5, 1H), 2.66 (dd, J 17.2, 7.0,
1H), 3.28 (ddd, J 7.8, 6.6, 5.8, 1H), 3.56 (dd, J 12.2, 4.2, 1H),
3.75 (dd, J 12.2, 3.5, 1H), 3.80 (q, J 6.6, 1H), 4.19 (ddd, 5.8,
4.2, 3.5), 7.20-7.35 (m, 5H). 13C NMR: δ 25.17, 36.99, 54.07,
56.96, 63.10, 86.02, 127.03, 128.09, 129.31, 144.54, 176.07. GC-
MS (a): tR 10.07 min. C13H17NO3 (235.28).
(3S,4R,5S)-3-Deu ter io-5-m eth yl-4-[(1′S)-(1′-p h en yleth y-
l)a m in o]tetr a h yd r ofu r a n -2-on e (23a ) (fr om 21a ). Yield:
88 mg (80%). Rf ) 0.16 (1:2 EtOAc/petroleum ether). [R]20
:
D
-132.6 (c 0.95, CHCl3). 1H NMR: δ 1.27 (d, J 6.4, 3H), 1.35
(d, J 6.6, 3H), 2.27 (br s, 1H), 2.71 (dt, J 7.2, J HD 2.4, 1H),
2.94 (dd, J 7.2, 6.0, 1H), 3.79 (q, J 6.6, 1H), 4.22 (dq, J 6.0,
6.4, 1H), 7.20-7.30 (m, 5H). 13C NMR: δ 19.35, 25.27, 36.35
(t, J CD 20), 56.91, 58.95, 82.53, 126.98, 127.98, 129.25, 144.76,
175.87. GC-MS (a): tR 8.94 min. Anal. Calcd for C13H16DNO2
(220.29): C, 70.88; H/D, 7.78; N, 6.36. Found: C, 71.00; H,
8.12; N, 5.90.
1H), 3.56 (ddd, J 7.0, 5.8, 5.5), 3.72 (dAB, J 13.2, 1H), 3.84 (dAB
,
J 13.2, 1H), 4.68 (dq, J 6.6, 5.8, 1H), 7.20-7.30 (m, 5H). 13C
NMR: δ 14.98, 36.03, 52.30, 56.60, 79.90, 127.90, 125.50,
129.09, 139.82, 175.93. GC-MS (a): tR 9.23 min. C12H15NO2
(205.26).
(4S,5S)-5-P h en yl-4-[(1′S)-(1′-ph en yleth yl)am in o]tetr ah y-
d r ofu r a n -2-on e (22e) (fr om syn -17b). Yield: 115 mg (82%).
Rf ) 0.10 (1:5 EtOAc/petroleum ether). [R]2D0: +12.5 (c 0.56,
CHCl3). IR: ν 3344, 1778. 1H NMR: δ 1.00 (d, J 6.6, 3H),
1.53 (br s, 1H), 2.31 (dd, J 17.3, 4.9, 1H), 2.62 (dd, J 17.3, 6.9,
1H), 3.27 (q, J 6.6, 1H), 3.67 (ddd, J 6.9, 5.5, 4.9, 1H), 5.56 (d,
J 5.5, 1H), 7.14-7.47 (m, 10 H). 13C NMR: δ 24.70, 37.44,
56.89, 56.89, 84.38, 126.77, 127.08, 127.78, 129.11, 129.25,
129.33, 135.32, 145.58, 176.42. GC-MS (a): tR 11.26 min.
(3R,4S,5S)-3-Deu ter io-5-m eth yl-4-[(1′R)-(1′-p h en yleth y-
l)a m in o]tetr a h yd r ofu r a n -2-on e (23b) (fr om 21b). Yield:
91 mg (83%). Rf ) 0.15 (1:2 EtOAc/petroleum ether). [R]20
:
D
+92.0 (c 1.0, CHCl3). IR: ν 3323, 1773. 1H NMR: δ 1.35 (d,
J 6.6, 3H), 1.36 (br s, 1H), 1.37 (d, J 6.6, 3H), 2.56 (dt, J 6.8,
J HD 2.4, 1H), 3.24 (dd, J 6.8, 5.8, 1H), 3.77 (q, J 6.6, 1H), 4.50
(dq, J 6.6, 5.8, 1H), 7.22-7.38 (m, 5H). 13C NMR: δ 14.96,
25.30, 35.74 (t, J CD 20), 54.59, 56.21, 80.08, 127.09, 127.89,
129.19, 145.00, 176.44. GC-MS (a): tR 9.00 min. Anal. Calcd
C
18H19NO2 (281.35).
for
C13H16DNO2 (220.29): C, 70.88; H/D, 7.78; N, 6.36.
(4S,5S)-5-P h en yl-4-[(1′R)-(1′-p h en ylet h yl)a m in o]t et -
Found: C, 70.51; H, 7.75; N, 6.41.
r a h yd r ofu r a n -2-on e (22f) (fr om syn -18b). Yield: 120 mg
(85%). Rf ) 0.07 (1:5 EtOAc/petroleum ether). [R]2D0: -42.1
(c 0.38, CHCl3). IR: ν 3328, 1778. 1H NMR: δ 1.16 (d, J 6.7,
Gen er a l P r oced u r e for th e DIBALH Red u ction of th e
La cton es 22 a n d 23. A 311 µL amount of diisobutylalumi-
num hydride (1.75 mmol) was added slowly to a solution of
the lactone 22 or 23 (0.5 mmol) in 20 mL of CH2Cl2 at -78 °C.
Stirring was continued at low temperature for a further 3 h.
After hydrolysis with 402 µL of trifluoroacetic acid (5.25 mmol),
the mixture was allowed to reach rt. A 1.5 mL volume of water
and 636 mg of NaHCO3 (6.0 mmol) were added, and the
organic layer was separated. A little water was added to the
aqueous residue, which was subsequently extracted twice with
25 mL of CH2Cl2. The organic layers were pooled, washed with
minute amounts of saturated NaHCO3 solution and brine,
dried over MgSO4, and evaporated. The crude products were
purified chromatographically.
(4R,5S)-2-Hyd r oxy-5-m et h yl-4-[(1′S)-(1′-p h en ylet h yl)-
a m in o]tetr a h yd r ofu r a n (24a ) (fr om 22a ). Yield: 95 mg
(86%). Anomer ratio R:â ≈ 2:1. Rf ) 0.17 (10:1 CHCl3/MeOH).
IR: ν 3400-3150. 1H NMR (400 MHz, DMSO-d6): major
anomer (R), δ 1.01 (d, J 6.2, 3H), 1.23 (d, J 6.6, 3H), 1.58 (ddd,
J 13.0, J 6.3, 3.1, 1H), 2.15 (ddd, J 13.0, J 7.7, 5.4, 1H), 2.36
(ddd, J 7.7, 6.3, 6.3, 1H), 3.75 (q, J 6.6, 1H), 3.79 (dq, J 6.3,
6.2, 1H), 5.20 (m, 1H), 6.00 (br d, J 4.0, 1H), 7.18-7.37 (m,
5H); minor anomer (â), δ 1.11 (d, J 6.2, 3H), 1.22 (d, J 6.5,
3H), 1.67 (dddd, J 12.2, J 9.0, 5.4, J 0.9, 1H), 1.92 (ddd, J 12.2,
J 6.8, 1.6, 1H), 2.67 (ddd, J 7.3, 6.8, 5.4, 1H), 3.54 (dq, J 7.3,
6.2, 1H), 3.73 (q, J 6.5, 1H), 5.22 (ddd, J 9.0, 5.0, 1.6, 1H),
5.90 (dd, J 5.0, J 0.9, 1H), 7.15-7.38 (m, 5H). 13C NMR
(DMSO-d6) major anomer (R), δ 19.21, 25.35, 40.20, 56.05,
61.67, 77.43, 97.03, 126.76, 126.85, 128.47, 146.19; minor
anomer (â), δ 21.00, 25.64, 40.96, 56.36, 60.59, 79.27, 97.16,
126.76, 126.85, 128.47, 146.48. GC-MS (a): tR 8.32 min.
3H), 1.40 (br s, 1H), 2.60 (ddABX, J 17.0, 3.9, 1H), 2.69 (ddABX
,
J 17.0, 5.0, 1H), 3.46 (ddd, J 5.2, 5.0, 3.9, 1H), 3.61 (q, J 6.7,
1H), 5.47 (d, J 5.2, 1H), 6.94-6.99 (m, 2H), 7.23-7.45 (m, 8H).
13C NMR: δ 24.84, 36.75, 55.02, 55.58, 84.04, 126.46, 126.76,
127.75, 129.11, 129.14, 129.20, 134.76, 144.82, 176.62. GC-
MS (a): tR 11.20 min. C18H19NO2 (281.35).
(4R,5S)-5-(H yd r oxym et h yl)-4-[(1′S)-(1′-p h en ylet h yl)-
a m in o]tetr a h yd r ofu r a n -2-on e (22g) (fr om syn -17c). Yield:
100 mg (85%). Rf ) 0.14 (25:1 CHCl3/MeOH). [R]2D0: -78.6 (c
1.85, CHCl3). IR (CHCl3): ν 3435, 1778. 1H NMR (400
MHz): δ 1.39 (d, J 6.5, 3H), 2.27 (br s, 1H), 2.57 (dd, J 17.3,
7.4, 1H), 2.69 (dd, J 17.3, 8.0, 1H), 3.51 (ddd, J 8.0, 7.4, 7.4,
1H), 3.80 (q, J 6.5, 1H), 3.93 (dd, J 12.5, 3.9, 1H), 4.00 (dd, J
12.5, 3.5, 1H), 4.37 (ddd, J 7.4, 3.9, 3.5, 1H), 7.20-7.35 (m,
5H). 13C NMR: δ 25.20, 36.25, 53.81, 57.17, 62.27, 81.61,
127.11, 128.19, 129.37, 144.33, 176.05. GC-MS (a): tR 9.98
min. Anal. Calcd for C13H17NO3 (235.28): C, 66.36; H, 7.28;
N, 5.95. Found: C, 66.46; H, 7.07; N, 5.84.
(4S,5S)-5-(H yd r oxym et h yl)-4-[(1′S)-(1′-p h en ylet h yl)-
a m in o]tetr a h yd r ofu r a n -2-on e (22h ) (fr om a n ti-17c). Rf
) 0.07 (25:1 CHCl3/MeOH). [R]20: -14.4 (c 1.25, CHCl3). IR
D
(CHCl3): ν 3430, 1778. 1H NMR (400 MHz): δ 1.38 (d, J 6.6,
3H), 1.94 (br s, 1H), 2.14 (dd, J 17.8, 6.0, 1H), 2.58 (dd, J 17.8,
8.0, 1H), 3.41 (ddd, J 8.0, 6.0, 4.9, 1H), 3.67 (dd, J 12.3, 4.1,
1H), 3.83 (q, J 6.6, 1H), 3.87 (dd, J 12.3, 3.5, 1H), 4.32 (ddd,
4.9, 4.1, 3.5), 7.20-7.35 (m, 5H). 13C NMR: δ 24.48, 37.60,
54.34, 57.16, 63.17, 85.94, 127.04, 128.07, 129.32, 145.16,
176.70. GC-MS (a): tR 10.01 min. C13H17NO3 (235.28).
(4R,5S)-5-(H yd r oxym et h yl)-4-[(1′R)-(1′-p h en ylet h yl)-
a m in o]tetr a h yd r ofu r a n -2-on e (22i) (fr om syn -18c). Yield:
64 mg (54%). Rf ) 0.20 (15:1 CHCl3/MeOH). [R]2D0: +13.3 (c
0.75, CHCl3). IR (CHCl3): ν 3430, 1778. 1H NMR (400
MHz): δ 1.40 (d, J 6.7, 3H), 2.33 (dd, J 17.5, 9.0, 1H), 2.42
(dd, J 17.5, 8.6, 1H), 2.89 (br s, 2H), 3.71 (ddd, J 9.0, 8.6, 7.3,
1H), 3.78 (q, J 6.7, 1H), 3.97 (dd, J 12.7, 3.9, 1H), 4.04 (dd, J
12.7, 3.1, 1H), 4.54 (ddd, J 7.3, 3.9, 3.1, 1H), 7.20-7.35 (m,
5H). 13C NMR: δ 24.39, 36.67, 54.57, 58.20, 62.34, 81.83,
126.87, 128.11, 129.32, 145.14, 176.26. GC-MS (a): tR 10.04
min. Anal. Calcd for C13H17NO3 (235.28): C, 66.36; H, 7.28;
N, 5.95. Found: C, 66.10; H, 7.37; N, 5.84.
C
13H19NO2 (221.30).
(4S,5S)-2-Hyd r oxy-5-m et h yl-4-[(1′R)-(1′-p h en ylet h yl)-
a m in o]tetr a h yd r ofu r a n (24b) (fr om 22c). Yield: 60 mg
(54%). Anomer ratio R:â ≈ 1:1. Rf ) 0.16 (20:1 CHCl3/MeOH).
1H NMR (DMSO-d6): anomeric mixture, R-anomer, δ 1.05 (d,
J 6.4, 3H), 1.21 (d, J 6.4, 3H), 1.65-1.97 (m, 3H), 2.90 (ddd, J
6.1, 6.0, 5.4, 1H), 3.77 (q, J 6.4, 1H), 3.95 (dq, J 6.1, 6.4, 1H),
5.29 (ddd, J 9.5, 5.0, 2.5, 1H), 5.82 (d, J 9.5, 1H), 7.14-7.35
(m, 5H); â-anomer, δ 1.16 (d, J 6.4, 3H), 1.21 (d, J 6.4, 3H),
1.65-1.97 (m, 3H), 2.68 (m, 1H), 3.71 (dq, J 5.4, 6.4, 1H), 3.76
(q, J 6.4, 1H), 5.17 (m, 1H), 6.10 (br d, J 7.3, 1H), 7.14-7.35
(m, 5H). 13C NMR (DMSO-d6) (anomeric mixture): δ ) 16.39,
17.57, 25.95, 26.04, 39.00, 40.50, 56.03, 56.26, 57.00, 57.23,
75.36, 77.53, 96.79, 97.87, 127.49, 127.56, 127.62, 129.18,
129.20, 146.97, 147.18. GC-MS (a): tR 8.36 min. C13H19NO2
(221.30).
(4S,5S)-5-(H yd r oxym et h yl)-4-[(1′R)-(1′-p h en ylet h yl)-
a m in o]tetr a h yd r ofu r a n -2-on e (22k ) (fr om a n ti-18c). Rf
) 0.10 (15:1 CHCl3/MeOH). 1H NMR: δ 1.36 (d, J 6.6, 3H),
2.12 (br s, 1H), 2.40 (dd, J 17.4, 6.6, 1H), 2.80 (dd, J 17.4, 7.8,