F. W. Lichtenthaler, M. Lergenmüller, S. Schwidetzky
FULL PAPER
stirred for another hour, and quenched with water (5 mL). Evapor-
ation of the solvent in vacuo afforded a syrup, which was dissolved
in acetonitrile (40 mL) and extracted with pentane (3 ϫ 10 mL).
Reextraction of the pentane phase with acetonitrile (5 mL) and
concentration of the collected acetonitrile layers gave a residue,
which was subjected to chromatographic purification (silica gel, 3
ϫ 35 cm) with toluene/EtOAc (20:1) as the eluent. Evaporation of
the appropriate fraction to dryness left a syrup, which was crys-
tallized from diisopropyl ether to afford 12 (675 mg, 59%) as color-
less crystals of m.p. 103Ϫ104 °C; [α]2D0 ϭ ϩ39.9 (c ϭ 0.9, CHCl3).
1H NMR (300 MHz, CDCl3): δ ϭ 2.90 (dd, 3 H, 1Ј-H2, 2Ј-OH),
3.71 (s, 3 H, OCH3), 4.16 (dd, 1 H, 2-H), 4.37(ddd, 1 H, 5-H), 4.49
(m, 3 H, 1-H, 6-H2), 5.49 (dd, 1 H, 4-H), 5.60 (dd, 1 H, 3-H), 5.79
and 6.23 (2d, 2 H, 3Ј-H2) ppm; J1,2 ϭ 5.3, J2,3 ϭ 8.3, J3,4 ϭ 8.2,
J4,5 ϭ 8.1, J5,6a ϭ 5.9, J5,6b ϭ 3.7 Hz. 13C NMR (75.5 MHz,
CDCl3): δ ϭ 28.5 (C-1Ј), 52.1 (OCH3), 63.3 (C-6), 69.4 (C-4), 70.0
(C-5), 70.3 (C-2), 74.2 (C-1, C-3), 128.1 (C-3Ј), 128.4Ϫ136.5 (3 ϫ
C6H5, C-2Ј), 165.5, 166.3, 167.0, 167.5 (3 ϫ C6H5CO, 2Ј-COOMe)
ppm. MS (FD, 20 mA): m/z ϭ 574 [M؉]. C32H30O10 (574.58):
calcd. C 66.89, H 5.26; found C 66.91, H 5.10.
to the deposition of the copper on the zinc. The silt-like couple was
allowed to settle for about 1 min, followed by careful decantation
of as much of the acetic acid as possible without loss of the de-
posits. The dark red-gray couple was then washed with a 1 mL
portion of acetic acid and thrice with 1 mL of diethyl ether, fol-
lowed by drying in a stream of nitrogen and subsequent suspension
in dry THF (5 mL).
The Zn/Cu couple resulting from this procedure was used for reac-
tions with 1 mmol of 1. The procedure can readily be scaled up ten-
fold.
3,4,6-Tri-O-benzoyl-1,2-O-ethylene-β-D-arabino-hexopyranos-2-
uloside (2S)-Cyclohemiketal (14): Glycol (0.7 mL, 12 mmol) was ad-
ded to a suspension of Ag2CO3 (3.30 g, 12 mmol) and molecular
˚
sieves (4 A, 3 g) in CH2Cl2 (100 mL), followed, after stirring at am-
bient temperature for 15 min, by the addition of ulosyl bromide 1
(5.53 g, 10 mmol). Stirring was continued for 5 h with exclusion of
light, the mixture was filtered, and the solvent was removed in va-
cuo. The crystalline residue was recrystallized from EtOAc to give
14 (4.90 g, 92%). M.p. 181Ϫ182 °C; [α]2D0 ϭ Ϫ7.1 (c ϭ 1, CHCl3).
1H NMR (300 MHz, CDCl3): δ ϭ 3.57 and 4.33 (2m, 2 H each, 2
OCH2), 4.10 (ddd, 1 H, 5-H), 4.50 and 4.67 (2dd, 1 H each, 6-H2),
4.85 (s, 1 H, 1-H), 5.24 (d, 1 H, 3-H), 5.25 (s, 1 H, OH), 5.86 (dd,
1 H, 4-H) ppm; J3,4 ϭ J4,5 ϭ 10.0, J5,6 ϭ 2.9 and 5.0, J6,6
ϭ
12.1 Hz. 13C NMR (75.5 MHz, CDCl3): δ ϭ 59.1 and 59.4 (2 ϫ
OCH2), 63.2 (C-6), 67.9 (C-4), 71.8 (C-5), 79.1 (C-3), 90.9 (C-2),
95.3 (C-1) ppm. MS (FD, 14 mA): m/z ϭ 534 [Mϩ]. C29H26O10
(534.5): calcd. C 66.17, H 4.90; found C 64.89, H 4.91.
1Ј-C-(3,4,6-Tri-O-benzoyl-α-D-hexopyranosyl)propene (13): A mix-
ture of ulosyl bromide 1 (1.6 g, 2.9 mmol), allyltributylstannane[20b]
(4.5 mL, 15 mmol), and AIBN (40 mg, 0.2 mmol) in benzene
(30 mL) was heated at reflux under dry N2 for 4 h. Additional
AIBN (40 mg) was added and heating was continued for another
3 h. The mixture was concentrated to a syrup, dissolved in THF
(30 mL), cooled to Ϫ78 °C, and subjected to reduction with BH3/
pyridine (1.4 mL, 14 mmol) in THF (3 mL) for 30 min. The solu-
tion was then warmed to room temp., and was quenched with water
(5 mL), followed by removal of the solvents in vacuo. The remain-
ing syrup was dissolved in CH2Cl2 (50 mL), washed successively
with HCl (2 , 2 ϫ 15 mL) and satd. aq. NaHCO3 (10 mL), and
dried (Na2SO4). Evaporation of the solvent gave a syrup, which
was purified by chromatography on silica gel (4 ϫ 20 cm) with
cyclohexane/EtOAc (4:1) as eluent. Fractions with Rf ϭ 0.16 (TLC
in eluent), on evaporation to dryness, left a syrup, which was crys-
tallized from diisopropyl ether to afford 13 (390 mg, 26%). M.p.
Addition of 1 to Formaldehyde: C-(3,4,6-Tri-O-benzoyl-β-D-arabino-
hexopyranos-2-ulosyl)methanol (1Ј,2R)-O-Methylene Cyclohemiace-
tal (19): Zn-Cu pair, prepared from Cu(OAc)2 monohydrate
(224 mg, 1 mmol) and zinc dust (3.92 g, 60 mmol), was suspended
in dry THF (50 mL) and cooled to Ϫ35 °C. A solution of ulosyl
bromide 1 (5.50 g, 10 mmol) in dry THF (50 mL) was added drop-
wise, while gaseous formaldehyde, generated by pyrolysis of par-
aformaldehyde (10 g, 110 mmol), was bubbled through the stirred
mixture. Stirring was continued for 1 h at Ϫ35 °C, and the solution
was then warmed to room temp., filtered, and poured into water
(100 mL). After dilution with CH2Cl2 (500 mL), HCl (2 ⁾ was ad-
ded until clearness, and the organic layer was washed with satd.
aq. NaHCO3 (50 mL) and water (50 mL), followed by drying
(Na2SO4) and evaporation of the solvents in vacuo, which resulted
in a crystalline mass. Collection of the crystals and recrystallization
from diethyl ether at Ϫ30 °C afforded 19 (1.5 g, 29%). M.p.
1
164Ϫ165 °C; [α]2D0 ϭ ϩ13.3 (c ϭ 1, CHCl3). H NMR (300 MHz,
CDCl3): δ ϭ 2.64 (dd, 2 H, 1Ј-H2), 2.81 (d, 1 H, 2-OH), 4.12 (ddd,
1 H, 2-H), 4.26Ϫ4.32 (m, 2 H, 1-H, 5-H), 4.50 and 4.57 (2 dd, 1 H
each, 6-H2), 5.05 (ddd, 1 H, H-3Јa), 5.21 (ddd, 1 H, H-3Јb), 5.47
(dd, 1 H, 3-H), 5.56 (dd, 1 H, 4-H), 5.86 (ddt, 1 H, 2Ј-H) ppm;
J1,2 ϭ 5.2, J2,3 ϭ 8.0, J2,OH ϭ 6.3, J3,4 ϭ 8.0, J4,5 ϭ 8.0, J5,6 ϭ 3.6
and 6.6, J6,6 ϭ 11.9, J1Ј,1Ј ϭ 1.4, J1Ј,3Ј ϭ 3.0, J1Ј,1 ϭ 7.3, J1Ј,2Ј
ϭ
139Ϫ140 °C; [α]2D0
ϭ
Ϫ47.8 (c
ϭ
1.1, CHCl3);
7.1, J2Ј,3Јa ϭ 10.2, J2Ј,3Јb ϭ 17.1 Hz. 13C NMR (75.5 MHz, CDCl3):
δ ϭ 30.3 (C-1Ј), 62.9 (C-6), 69.1 (C-3), 69.7, 73.8 (C-1, C-5), 70.0
(C-2), 74.0 (C-4), 117.4 (C-3Ј), 128.1Ϫ133.6 (3 C6H5, C-2Ј)
ppm. C30H28O8 (516.55): calcd. C 69.76, H 5.46; found C 69.63,
H 5.43.
Rf ϭ 0.47 (CH2Cl2/EtOAc, 10:1). 1H NMR (300 MHz, CDCl3):
δ ϭ 3.51 (dd, 1 H, 1-H), 4.10 (m, 2 H, 1Ј-Ha, 5-H), 4.25 (dd, 1 H,
1Ј-Hb), 4.54 (dd, 1 H, 6-Ha), 4.64 (dd, 1 H, 6-Hb), 4.87, 5.26 (2d,
J ϭ 6 Hz, 1 H each, OCH2O), 5.11 (d, 1 H, 3-H), 5.78 (s, 1 H, 2-
OH), 5.90 (dd, 1 H, 4-H) ppm; JOCH O ϭ 6.0, J1Ј,1Ј ϭ 12.3, J1Јa,1 ϭ
2
0.5, J1Јb,1 ϭ 1.6, J3,4 ϭ 9.8, J4,5 ϭ 10.0, J5,6a ϭ 5.9, J5,6b
ϭ
Zn/Cu-Mediated Addition of Ulosyl Bromide 1 to Aldehydes
3.3 Hz. 13C NMR (75.5 MHz, CDCl3): δ ϭ 63.4 (C-1Ј), 64.6 (C-6),
69.0 (C-3), 72.3 (C-4), 74.3 (C-5), 76.1 (C-1), 85.6 (OCH2O), 92.3
(C-2) ppm. MS (FD, 12 mA): m/z ϭ 534 [M؉], 504 [M؉ Ϫ HCHO],
383 [M؉ Ϫ OBz]. C29H26O10 (534.52): calcd. C 65.16, H 4.91;
found C 65.12, H 4.83.
Preparation of Zinc-Copper Couple: (adapted from ref.[16]): Zinc
dust (392 mg, 6 mmol) was added to a hot (80 °C), well stirred
solution of Cu(OAc)2·H2O (22.4 mg, 0.1 mmol) in glacial acetic
acid (1 mL). After about 30 sec the solution became colorless due
3100
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 3094Ϫ3103