TABLE 1. Application of One-Step Aldehyde to Amide
Conversion to Carbohydrate and Amino Acid Derived Aldehydes
brine, dried over anhydrous magnesium sulfate, and filtered.
Evaporation afforded 408 mg (86%) of a white solid which was
used in the next step without further purification: mp 148 °C dec;
[R]D ) +8.1 (c 0.014 g/mL, acetone); IR (CHCl3) 3657 (NH), 3392
1
(OH), 1643 (CdO) cm-1; H NMR (acetone-d6) δ 7.51 (m, 2H,
aryl), 7.35 (m, 3H, aryl), 5.67 (s, 1H, acetal), 4.61 (1H, OH), 4.20
(dd, 1H, J ) 10.3, 5.1 Hz, C6HΒ,), 4.10 (d, 1H, J ) 9.16 Hz, C4H),
3.78 (m, 1H, C5H), 3.63 (app t, J ) 10.31 Hz, C6A); 13C NMR
(acetone-d6) δ 173.6 (CdO), 128.89 (aryl), 128.0 (aryl), 126.5-
(aryl), 101.0 (acetal), 78.8 (C4), 70.5 (C6), 64.4 (C5); HRMS (FAB)
calcd for C11H14NO4 (M + H) 224.0923, found 224.0912.
(2S,4S,5S)-5-Hydroxy-2-phenyl-1,3-dioxane-4-carboxam-
ide: [R]D ) -8.3 (c 0.02 g/mL, acetone); all other data were
identical to those for the 2R,4R,5R isomer.
(2R,4S,5R)-4-(Aminomethyl)-2-phenyl-1,3-dioxan-5-ol (3). The
amide (254 mg, 1.2 mmol) was dissolved in 4 mL of anhydrous
tetrahydrofuran and added to a suspension of lithium aluminum
hydride (0.22 g, 5.8mmol) in 12 mL of anhydrous tetrahydrofuran
under an argon atmosphere at 0 °C. The mixture was stirred at
room temperature for 1 h and then at reflux for 5 h. The mixture
was cooled to 0 °C, and 0.5 mL of water was added dropwise to
destroy excess lithium aluminum hydride. The resulting mixture
was filtered through Celite and washed with ether. The ether
solution was dried with anhydrous magnesium sulfate, filtered, and
evaporated. The crude product was purified by flash column
chromatography on silica gel, eluting with 85:8:7 acetonitrile/water/
NH4OH to afford 186 mg (77%) of the amine: [R]D ) -9.0 (c
a NaIO4 on silica gel. b I2, NH4OH followed by H2O2.
1
0.0032 g/mL, acetone); IR (CHCl3) 3379, 3300 cm-1; H NMR
amide 2 is a potential synthon in the synthesis of natural products
such as swainsonine and castanospermine.13
(CD3OD) δ 7.48 (m, 2H, aryl), 7.32 (m, 3H, aryl), 5.51 (s, 1H,
acetal H), 4.17 (dd, 1H, J ) 5.1, 10.3 Hz, C6H), 3.55 (m, 3H,
C6H, C5H, C4H), 3.08 (dd, 1H, J ) 2.3, 13.2 Hz, CHN), 2.79
(dd, 1H, J ) 6.9, 13.4 Hz, CHN); 13C NMR (CD3OD) δ 138.2
(aryl), 128.5 (aryl), 128.0 (aryl), 126.0 (aryl), 101.0 (acetal), 82.8
(C4), 70.6 (C6), 63.1 (C5), 47.4 (CH2N); HRMS (FAB) calcd for
C11H16NO3 (M + H) 210.1130, found 210.1146.
(2R,3S)-4-Aminobutane-1,2,3-triol (4). The benzylidene 3 (186
mg, 0.9mmol) was dissolved in 6.0 mL of anhydrous dichlo-
romethane and cooled to -78 °C under an argon atmosphere. A
solution of boron trichloride in dichloromethane was added (1.1
mmol of a 1 M solution). The resulting mixture was stirred at -78
°C for 1.5 h, poured into water, and extracted with dichloromethane.
The organic layer was washed once with water, and the aqueous
phase was lyophilized to afford a tan solid. The crude product was
purified by flash column chromatography on C18 reverse-phase
silica gel, eluting with water and then 86:9:5 acetonitrile/water/
NH4OH. Lyophilization afforded 105 mg (75%) of the aminotriol:
[R]D ) -5.9 (c 0.023 g/mL, H2O); 1H NMR (D2O) δ 3.61 (m, 4H,
C2H, C3H, C1H), 3.16 (m, 1H, C4H), 2.90 (m, 1H, C4H); 13C
NMR (D2O) δ 73.0 (C3), 67.6 (C2), 62.2 (C1), 41.8 (C4); HRMS
(FAB) calcd for C4H12NO3 (M + H) 122.0817, found 122.0816.
In conclusion, a very efficient synthesis of several novel chiral
aminoalcohols has been developed from inexpensive, readily
available starting materials. Both the (2S,3R) and (2R,3S)
enantiomers of 4-aminobutane-1,2,3-triol have been prepared,
as well as two novel dimeric amino alcohols. In addition, the
scope of a direct aldehyde to amide conversion has been
extended to carbohydrate-derived aldehydes.
Experimental Section
(2R,4R,5R)-5-Hydroxy-2-phenyl-1,3-dioxane-4-carbalde-
hyde (1). To a suspension of 4,6-O-benzylidene-D-glucopyranose
(600 mg, 2.2mmol) in 16 mL of dichloromethane was added freshly
prepared sodium periodate on silica gel: sodium periodate (700
mg, 1.3 mmol of NaIO4) was dissolved in 1.5 mL of hot H2O and
then mixed with 2.6 g of silica gel. The resulting suspension was
stirred at 25 °C for 2 h, filtered, and washed with ethyl acetate,
and the solvent was removed to afford 425 mg (91%) of aldehyde
1, which was used without further purification: 1H NMR (CDCl3)
δ 9.68 (d, J ) 1.7 Hz, 1H, aldehyde), 8.05-7.41 (m, 5H, aryl),
5.30 (s, 1H, acetal), 5.27 (m, 1H, C5H), 4.48 (dd, J ) 5.7 and 10.9
Hz), 1H, C-6âH), 4.27 (dd, J ) 1.7 and 9.7 Hz, 1H, C4H), 3.79
(apparent t, J ) 10.9 Hz, 1H, C-6RH), 1.66 (broad s, 1H, OH);
13C NMR (CDCl3) δ 196.6 (CdO), 159.4, 129.7, 128.5, 126.3
(aryl), 101.3 (acetal), 80.9 (C6), 67.6 (C5), 61.5 (C4).
(2R,4R,5R)-5-Hydroxy-2-phenyl-1,3-dioxane-4-carboxam-
ide (2). The aldehyde (441 mg, 12.1mmol) was dissolved in 1.0
mL of tetrahydrofuran. Aqueous ammonium hydroxide (13.0 mL
of 28% solution) was added, followed by iodine (591 mg, 2.3mmol).
The mixture was stirred at room temperature for 2 h, during which
time the brown mixture turned colorless. After 2 h, hydrogen
peroxide (1.3 mL of 35% solution) was added. Stirring was
continued for 2 h. The solution was extracted twice with dichlo-
romethane, and the combined organic layers were washed with
(2S,3R)-4-Aminobutane-1,2,3-triol (4): [R]D ) +6.6 (c 0.025
g/mL, H2O); all other data were identical to those for the 2R,3S
isomer.
(2R,2′R,4S,4′S,5R,5′R)-4,4′-Azanediylbis(methylene)bis(2-phen-
yl-1,3-dioxan-5-ol). The aldehyde (374 mg, 1.8 mmol) was
dissolved in 50 mL of methanol and cooled to 0 °C. Ammonia gas
was bubbled into the solution for 5 min and stirring continued at
25 °C for 1 h. Sodium cyanoborohydride (453 mg, 7.2mmol) was
added, and the resulting mixture was stirred at 25 °C for 18 h. The
methanol was evaporated, and the residue was diluted with 10 mL
of water and extracted twice with chloroform. The organic layer
was dried over anhydrous magnesium sulfate and filtered, and the
solvent evaporated to afford 220 mg (61%) of the amine: [R]D )
-18.0 (c 0.017 g/mL, CHCl3); IR (CHCl3) 3657 (NH), 3392 (OH),
1092 (C-O stretch) cm-1; 1H NMR (CDCl3) δ 7.55-7.25 (m, 5H,
aryl H), 5.49 (s, 1H, acetal), 4.27 (m, 2H, C6,6′H), 3.68 (m, 3H,
C4,4′H, C5,5′H, CHN), 3.07 (m, 1H, CHN); 13C NMR (CDCl3)
δ137.5, 129.2, 128.4, 126.2 (aryl), 101.2 (acetal), 79.2 (C5,5′), 71.1
(13) (a) Pyne, S. G. Curr. Org. Synth. 2005, 2(1), 39-57. (b) Pearson,
W. H.; HEbre, E. J. J. Org. Chem. 1996, 61, 7217-7221. (c) Pandit, U.
K.; Overkleeft, H. S.; Borer, B. C.; Bieraugel, H. Eur. J. Org. Chem. 1999,
959-968.
J. Org. Chem, Vol. 73, No. 7, 2008 2929