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M. Tollabi et al. / Tetrahedron: Asymmetry 14 (2003) 3329–3333
4. Experimental
in DMF (2 mL) was added, followed by the addition
of a solution of NaHCO3 (200 mg, 2.4 mmol) in H2O
(2 mL). After being stirred for 24 h at rt, the solvents
were evaporated under reduced pressure to give a
solid that was purified by flash-chromatography on
silica gel using CHCl3/EtOH 3:1 as the eluent to give
198 mg of phosphine 6b (yield 80%). Mp 60–63°C;
Rf=0.64 (CHCl3/C2H5OH 3:1); [h]2D0=+25.2 (c 1,
4.1. General
Solvents were purified by standard methods and dried
if necessary. All commercial available reagents were
used as received. All reactions were monitored by
TLC (TLC plates GF254 Merck); detection was
effected by UV absorbance. Air and moisture sensi-
tive reactions were performed under the usual inert
1
THF); H NMR (C5D5): l 5.46 (ddd, J=9.4, 5.7, 2.1
Hz, 0.13H, H-5b), 5.64 (dd, J=9.4, 8.7 Hz, 0.13H,
H-4b), 5.76 (dd, J=9.6, 8.9 Hz, 0.87H, H-4a), 5.81
(dd, J=11.7, 5.7 Hz, 0.87H, H-6a), 5.97 (dd, J=11.7,
2.3 Hz, 0.87H, H-6a), 6.20–6.32 (m, 1.74H, H-3a, H-
5a), 6.43 (ddd, J=10.7, 8.5, 3.4 Hz, 0.87H, H-2a),
6.79 (bs, 4H, OH), 6.99 (d, J=8.3 Hz, 0.13H, H-1b),
7.40 (d, J=3.4 Hz, 0.87H, H-1a), 8.70–8.79 (m, 10H,
atmosphere
techniques.
Reactions
involving
organometallic catalysis were carried out in a Schlenk
tube under an inert atmosphere. Column chromatog-
raphy was performed on silica gel 60 (230-240 mesh,
Merck). Optical rotations were recorded using a
Perkin–Elmer 241 polarimeter. NMR spectra were
recorded with a Bruker AMX 300 spectrometer and
referenced as following: 1H (300 MHz), internal
SiMe4 at l 0.00 ppm, 13C (75 MHz), internal CDCl3
at l 77.23 ppm, and 31P (121 MHz), external 85%
H3PO4 at l 0.00 ppm. Conversion was determined by
GC using a Quadrex OV1 column (30 m×0.25 mm),
and enantiomeric excess was determined by HPLC
with a ChiralpakAD column (25 cm×4.6 mm) using
different ratios of hexane-i-propanol as the eluent.
H
arom.), 8.84–8.95 (m, 3H, Harom.), 9.46–9.52 (m, 1H,
Harom.), 10.65 (d, J=8.5, 0.87H, NH), 11.13 (d, J=
8.3, 0.13H, NH); 31P NMR (C5D5N): l −7.1. Mass
[MH]+ C25H26O6NP calcd 468.1576, found 468.1574.
4.4. Saponification of compound 6a
To the acetylated phosphine 6a (300 mg, 0.47 mmol)
dissolved in THF (10 mL) under argon was slowly
added a solution of Na (20 mg, 0.87 mmol) in
CH3OH (5 mL). After being stirred for 1 h at rt, the
solvent was evaporated to give a yellow solid that
was purified by flash-chromatography on silica gel
using CH2Cl2/CH3CO2Et 90:10 as the eluent to give
187 mg of phosphine 6b (yield=85%).
4.2. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-{[2-(diphenylphos-
phino)benzoyl]amino}-b-D-glucopyranose, 6a
1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-b-D-glucopyra-
nose 4a (688 mg, 1.98 mmol), 2-diphenylphosphi-
nobenzoic acid (551 mg, 1.8 mmol), EDC (414 mg,
2.16 mmol), and HOBT (291 mg, 2.16 mmol) were
dissolved in a mixture of CH2Cl2 (10 mL) and THF
(20 mL) in a Schlenk tube under argon. After being
stirred for 5 h at rt, the solvents were evaporated.
The residue was washed with 5% NaOH (10 mL),
and 0.5 M HCl (5 mL), then dried under vacuum to
give 847 mg of phosphine 1a (yield 74%). Mp 148–
150°C; Rf=0.58 (petroleum ether/ethyl acetate 3:2);
4.5. Standard alkylation reaction
In a Schlenk tube, [Pd(C3H5)Cl]2 (8.8 mg, 24 mmol)
and the ligand (48 mmol) were dissolved in the sol-
vent (1 mL). After stirring the mixture for 1 h at the
desired temperature, a solution of the racemic acetate
14 (302 mg, 1.2 mmol) in solvent (1 mL) was added.
After 30 min, this solution was transferred to a
Schlenk tube containing the nucleophile (3.6 mmol),
N,O-bis-(trimethylsilyl)acetamid (732 mg, 3.6 mmol),
and LiOAc (2.5 mg, 24 mmol) in 2 mL of solvent.
The reaction mixture was stirred at the desired tem-
perature for 24 h. The conversion was determined by
GC analysis. The mixture was then diluted with
diethyl ether (15 mL), and water (5 mL). The organic
phase was washed with brine and dried over MgSO4.
Evaporation of the solvent gave a residue that was
purified by chromatography (petroleum ether/ethyl
acetate 10:1). The enantiomeric excess was determined
by HPLC analysis (column Chirapalk AD 0.46×25
cm).
1
[h]2D0=+36.3 (c 1, CHCl3); H NMR (CDCl3): l 2.03
(s, 3H, CH3), 2.07 (s, 3H, CH3), 2.09 (s, 3H, CH3),
2.18 (s, 3H, CH3), 3.77 (m, 1H, H-5), 4.13 (dd, J=
12.4, 2.1 Hz, 1H, H-6), 4.26 (dd, J=12.4, 4.2 Hz,
1H, H-6), 4.52 (ddd, J=9.8, 9.5, 8.8 Hz, 1H, H-2),
5.07 (dd, J=9.2, 8.8 Hz, 1H, H-4), 5.15 (dd, J=9.8,
8.8 Hz, 1H, H-3), 5.68 (d, J=8.8 Hz, 1H, H-1), 5.99
(d, J=9.5 Hz, 1H, NH), 6.95–7.55 (m, 14H, Harom.);
13C NMR (CDCl3): l 20.9, 21.0, 21.3, 21.4, 53.2,
61.7, 67.9, 72.4, 72.9, 92.6, 128.7, 128.8, 128.9, 129.2,
130.6, 131.8, 132.1, 132.5, 133.3, 133.4, 133.7, 133.8,
133.9, 135.1, 137.2, 137.4, 141.4, 141.7, 168.9, 169.3,
169.9, 170.8, 171.4; 31P NMR (CDCl3): l −10.3. Mass
[MH]+ C33H35O10NP calcd 636.1998, found 636.1986.
4.3. 2-Deoxy-2-{[2-(diphenylphosphino)benzoyl]amino]}-
D
-glucopyranose, 6b
A solution of 2-diphenylphosphinobenzoic acid (173.7
mg, 0.5 mmol), EDC (112 mg, 0.6 mmol), and HOBT
(81 mg, 0.6 mmol) in DMF (4 mL) was stirred in a
Schlenk tube under argon at 0°C for 1 h. A solution
Acknowledgements
This work was supported by a fellowship from
Region Rhoˆne-Alpes (M.T.).
of
D
-glucosamine hydrochloride (215 mg, 1.0 mmol)