1538
L. Lei, X. He, and D. Bai
(S)-2-Phthalimido-3-phenylpropionaldehyde (3)
Chloride 2 (1.37 g, 4.36 mmol) was hydrogenated in toluene (40 mL) in the
presence of 1,2-butylene oxide (0.95 mL) and Pd/C (10%, 130 mg). The sus-
pension was stirred at 40–508C for 17 h until absorption of hydrogen was
stopped. The mixture was filtered and the filtrate was washed with saturated
sodium bicarbonate (2 mL ꢀ 3) and water (2 mL ꢀ 3). The organic layer
was concentrated in vacuum to provide the desired aldehyde 3 as a
yellowish solid, which was used without further purification. Recrystallization
from dichloromethane/petroleum ether afforded 3 as a white solid (662 mg,
55%). Mp 101–1048C, [a]D20 ¼ 22668C (c 0.5, benzene); lit.[13] Mp 110–
1138C, [a]2D0 ¼ 22078C (c 0.5, benzene). H NMR (CDCl3): d 9.8 (s, 1H),
1
7.10–7.20 (m, 5H), 7.70 (m, 2H), 7.80 (m, 2H), 5.0 (dd, J ¼ 5.5, 10.7 Hz,
1H), 3.60 (dd, J ¼ 5.5, 14.1 Hz, 2H), 3.30 (dd, J ¼ 10.7, 14.1 Hz, 2H); EI-
MS m/z (%): 279 (Mþ, 8), 251 (100), 91 (56).
2-Hydroxy-3-phthalimido-4-phenylbutyronitrile (4)
Aldehyde 3 (280 mg, 1.0 mmol) was dissolved in anhydrous toluene (30 mL)
and cooled to 2788C under argon. To the solution was added diethylalumi-
num cyanide (1.2 mL, 1 M in toluene, 1.2 mmol) dropwise over 10 min. The
mixture was stirred at this temperature for 20 h, and then saturated aqueous
ammonium chloride (10 mL) was added to quench the reaction. The organic
layer was separated and the aqueous phase was extracted with ethyl acetate
(10 mL ꢀ 3). The combined organic layers were washed with brine and
water and dried over anhydrous Na2SO4. The solid obtained after removal
of the solvent was recrystallized from dichloromethane/petroleum ether,
affording 4 as a white solid (245 mg, 80%). After separation with preparative
TLC, two diastereomeric isomers (2S,3S)-4 and (2R,3S)-4 were obtained,
respectively. The diastereoselection (2.6:1) of cyanohydrin 4 was measured
1
by H NMR.
(2S,3S)-2-Hydroxy-3-phthalimido-4-phenylbutyronitrile: Mp 133–1358C.
1H NMR (CDCl3): d 7.10–7.20 (m, 5H), 7.70 (m, 2H), 7.80 (m, 2H), 5.15 (dd,
J ¼ 5.2, 1.6 Hz, 1H), 4.80 (m, J ¼ 5.2, 1.6, 4.0 Hz, 1H), 4.10 (s, 1H), 3.40
(ABXsystem, J ¼ 4.0, 1.2Hz, 2H); EI-MS m/z(%): 306 (Mþ, 3), 279 (16),
251 (100), 250 (90), 232 (76), 91 (30); IR (KBr, cm21): 3494.4, 1774.2,
1390.4, 1365.4, 1107.0, 721.3.
(2R,3S) hyphen;2-Hydroxy-3-phthalimido -4-phenylbutyronitrile: Mp
1
155–1578C. H NMR (CDCl3): d 7.10–7.20 (m, 5H), 7.80 (m, 2H), 7.90
(m, 2H), 5.40 (d, J ¼ 11.2 Hz, 1H), 4.80 (m, J ¼ 4.8, 8.0 Hz, 1H), 4.75 (dd,
J ¼ 4.8 Hz, 1H), 3.30 (dd, J ¼ 8.0, 5.6 Hz, 1H), 3.10 (dd, J ¼ 8.0, 5.6 Hz,
1H); EI-MS m/z (%): 306 (Mþ, 3), 279 (16), 251 (100), 250 (90), 232 (76),
91 (30); IR(KBr, cm21): 3349.8, 1770.4, 1697.1, 1402.0, 1375.0, 1110.8, 721.3.