M. Brehm et al. / Tetrahedron: Asymmetry 19 (2008) 358–373
365
of 4 and the mixture was stirred at ambient temperature for
16 h, followed by pouring into water (200 mL) and extrac-
tion with chloroform (5 ꢃ 200 mL). Washing of the com-
bined extracts with water, drying over Na2SO4 and
evaporation in vacuo left a syrup that crystallized on tritur-
2 M HCl (2 ꢃ 40 mL) and water, dried over Na2SO4, and
taken to dryness. The resulting syrup, crystallized on tritur-
ation from EtOH: 1.70 g (91%) of oxime 11 as colorless
20
needles; mp 64–65 °C; ½aꢁD ¼ ꢀ29:0 (c 1.1, CHCl3); 1H
NMR (300 MHz, CDCl3): d 3.53 (ddd, 1H, 5-H), 3.60
(m, 2H, 6-H2), 3.79 (dd, 1H, 4-H), 4.15 (d, 1H, 3-H),
4.31 (d, 1H, 1-Ha), 4.33, 4.49, 4.55 and 4.76 (4d, 1H each,
2 BnCH2), 4.54 (s, 2H, BnCH2), 4.85 (d, 1H, 1-He), 7.1–7.4
(15H-m, 3C6H5), 9.24 (s, 1H, NOH); J1,1 = 16.4, J3,4 = 8.3,
J4,5 = 7.2, J5,6e = 3.9 Hz. 13C NMR (75.5 MHz, CDCl3,): d
62.8 (C-1), 70.1 (C-6), 71.4, 72.4 and 73.4 (3BnCH2), 76.4
(C-3), 78.0 (C-4), 78.6 (C-5), 154.6 (C-2), MS (FD): m/
z = 448 (M++H). Anal. Calcd for C27H29NO5 (447.52):
C, 72.48; H, 6.48; N, 3.13. Found: C, 72.54; H, 6.43; N,
3.19.
ation with ethanol: 7.9 g (86%) of 9; mp 89–90 °C;
21
½aꢁD ¼ ꢀ39:0 (c 0.4, CHCl3). The analytical sample was
purified by elution from a silica gel column (15 ꢃ 1 cm
for 1 g) with CH2Cl2/EtOAc (10:1) to give well-shaped nee-
20
1
dles; mp 90–91 °C; ½aꢁD ¼ ꢀ42:8 (c 0.5, CHCl3). H NMR
(300 MHz, DMSO-d6): d 1.99, 2.02 and 2.03 (3s, 3H each,
3AcCH3), 3.88 (ddd, 1H, 5-H), 4.05 and 4.12 (2dd, 1H
each, 6-H2), 4.04 and 4.88 (2d, 1H each, 1-H2), 4.94 (dd,
1H, 4-H), 5.54 (d, 1H, 3-H), 11.48 (s, 1H, N–OH);
J1,1 = 15.0, J3,4 = 8.0, J4,5 = 8.9, J5,6 = 3.0 and 5.5,
J6,6 = 12.0 Hz. 13C NMR (75.5 MHz, CDCl3): d 170.8,
169.9, 169.4 (3Ac-CO), 150.6 (C-2), 76.3 (C-5), 70.5 and
69.7 (C-3, C-4), 62.9 (C-1), 61.9 (C-6), 20.7–20.5 (Ac-
CH3). Anal. Calcd for C12H17NO8 (303.26): C, 47.52; H,
5.65; N, 4.62. Found: C, 47.58; H, 5.58; N, 4.58.
4.9. 1,5-Anhydro-D-fructose E-oxime 12
4.9.1. De-O-acetylation of 9. A stirred methanolic solu-
tion of sodium methoxide (prepared from 80 mg sodium
and 30 mL of methanol) was cooled to 0 °C and oxime 9
(800 mg, 2.6 mmol) was added. TLC showed complete con-
version of the educt within 15 min with the exclusive for-
mation of 12 (Rf = 0.4 in 200:50:15:1 benzene/EtOH/
water/25% aq NH3). Cation exchange resin was then added
to the mixture and after stirring for 10 min the suspension
was filtered and the resin was washed with methanol. Fil-
trate and washings were evaporated to a syrup which crys-
tallized from methanol: 260 mg (56%) of 10, mp 178–
4.7. 3,4,6-Tri-O-benzoyl-1,5-anhydro-D-fructose E-oxime 10
Hydroxylamine hydrochloride (8.3 g, 0.12 mol) was stirred
into a solution of 17.5 g (40 mmol) of 5 in dry pyridine
(25 mL) and kept at 70 °C (water bath) for 12 h (TLC on
silica gel with 10:1 dichloromethane/EtOAc for monitor-
ing). After cooling down, the mixture was diluted with
water (100 mL), and the precipitate was filtered off and
washed with water. The filtrate and washings were
extracted with chloroform (3 ꢃ 30 mL) and the combined
extracts were washed with water and then taken to dryness
to yield the second crop. Recrystallization from ethanol
21
1
180 °C; ½aꢁD ¼ ꢀ43:0 (c 0.3, water); H NMR (300 MHz,
D2O): d 3.44 (ddd, 1H, 5-H), 3.51 (dd, 1H, 4-H), 3.64
and 3.83 (2dd, 1H each, 6-H2), 3.89 and 5.03 (2d, 1H each,
1-H2), 4.25 (d, 1H, 3-H), 10.86 (s, 1H, NOH); J1,1 = 14.5,
gave 13.6 g (93%) of 10 as colorless needles, mp 176–
J3,4 = 9.0,
J4,5 = 8.0,
J6,6 = 12.6 Hz.
13C
NMR
22
177 °C, ½aꢁD ¼ ꢀ52:9 (c 0.5, CHCl3). 1H NMR
(75.5 MHz, D2O): d 61.5 (C-1), 61.8 (C-6), 72.6 and 73.3
(C-3/C-4), 80.9 (C-5), 156.1 (C-2). Anal. Calcd for
C6H11NO5 (177.16): C, 40.68; H, 6.26; N, 7.91. Found:
C, 40.63; H, 6.29; N, 7.85.
(500 MHz, CDCl3): d 4.08 (sept, 1H, H-5), 4.22 (dd, 1H,
J1,1 = 15.8 Hz, 1-Ha), 4.55 and 4.68 (2dd, 1H each,
J5,6 = 3.1 and 5.7, J6,6 = 12.1 Hz, 6-H2), 5.17 (d, 1H,
J1,1 = 15.8 Hz, 4-H), 5.72 (dd, 1H, J3,4 = 7.2,
J4,5 = 8.1 Hz, 4-H), 6.02 (d, J3,4 = 7.2 Hz, 1H, 3-H), 7.40,
7.55 and 8.03 (6H-, 3H- and 6H-m, 3C6H5), 8.55 (1H-s,
NOH). 13C NMR (125.76 MHz, CDCl3): 62.5 (C-1), 64.0
(C-6), 70.9 and 71.7 (C-3, C-4), 76.9 (C-5), 128.7–134.0
(3C6H5), 151.3 (C-2), 165.5, 165.8 and 166.7 (3BzCO).
Anal. Calcd for C27H23NO8 (489.46): C, 66.25; H, 4.74;
N, 2.86. Found: C, 66.19; H, 4.74; N, 2.82.
1
The H and 13C NMR data for 10 correlated well with
those reported for the oximation product of naturally
occurring 1,5-anhydrofructose,27 as did rotations of
23
½aꢁD ¼ ꢀ43 (c 2, water)4 and [a]D = ꢀ46.2 (c 1.2, water)2,27
and to a somewhat lesser degree, the melting points (155–
157 °C2 and 179–181 °C27).
4.9.2. De-O-benzoylation of 10. Exposure of 10 (2.95 g,
6 mmol) to 0.1 M methanolic sodium methoxide (90 mL)
for 1 h at 0–5 °C and processing of the mixture as described
under (a) gave 678 mg (64%) of 12.
Oxime 10 was similarly obtained by adding NH2OHꢂHCl
(5.0 g) to a pyridine solution of 5 (5.0 g in 25 mL) stirring
for 7 days at ambient temperature and processing as de-
scribed above. Recrystallization from MeOH/CH2Cl2 pro-
vided 4.9 g (87%).
4.10. 3,4,6-Tri-O-acetyl-1,5-anhydro-D-fructose
O-methyloxime 13
4.8. 3,4,6-Tri-O-benzyl-1,5-anhydro-D-fructose E-oxime 11
Oxime 9 (250 mg, 0.8 mmol) was added to a stirred suspen-
sion of methyl iodide (0.25 mL, 4 mmol) and Ag2O
(580 mg) in ether (8 mL) and stirring was continued for
15 h. Filtration, washing of the residue with acetone and
evaporation of the filtrate and washings to dryness in
vacuo left a syrup which was purified by elution from a
short silica gel column with 10:1 benzene/EtOAc: 146 mg
(56%) of 13 as a colorless syrup; Rf = 0.40 (10:1 benzene/
Hydroxylamine hydrochloride (1.4 g, 20 mmol) and
molecular sieves (4 A) were added to a solution of 2-O-
˚
acetyl-3,4,6-tri-O-benzyl-D-arabino-hex-1-enitol 617 (2.0 g,
4.2 mmol) in dry pyridine (13 mL) and the mixture was stir-
red at ambient temperature for 2 days, followed by stirring
into water (20 mL) and extraction with CH2Cl2
(3 ꢃ 40 mL). The combined extracts were washed with