PAPER
Stereocontrolled Formation of Protected Aminodeoxyalditols
2759
LCMS: m/z (%) = 720.8 (100) [M + Na]+.
Azido Anhydrosugars 7; General Procedure
To a magnetically stirred soln of anhydrosugar 2 (1 g, 2 mmol) in
anhyd DMF (15 mL) was added excess NaN3 (0.65 g, 10 mmol) and
Bu4NCl (0.5 g, 1.8 mmol), and the mixture was stirred at 120 °C.
When the reaction was complete, DMF was removed under reduced
pressure. The residue was washed with H2O and the aqueous phase
was extracted with EtOAc (3 × 15 mL). The combined organic
phases were dried (MgSO4) and evaporated. Purification by column
chromatography (silica gel, EtOAc–PE, 1:8) yielded azido anhydro-
sugars 7.
2,3,4,6-Tetra-O-benzyl-1,5-di-O-mesyl-D-mannitol (6b)
Yield: 6.63 g (95%).
1H NMR (300 MHz, CDCl3): d = 2.87 (s, 3 H, SO2CH3), 2.95 (s, 3
H, SO2CH3), 3.76–3.90 (m, 4 H, H2, H3, H6¢, H6), 4.03 (m, 1 H,
H4), 4.36–4.48 (m, 4 H, H1¢, OCH2Ph), 4.53–4.75 (m, 6 H, H1,
OCH2Ph), 4.98 (m, 1 H, H5), 7.23–7.35 (m, 20 H, C6H5). The data
is agreement with the literature.9d
LC-MS: m/z (%) = 720.9 (60) [M + Na]+.
1,4-Anhydro-5-azido-2,3,6-tri-O-benzyl-L-glucitol (7a)
Yield: 0.62 g (69%).
Anhydrosugars 2; General Procedure
To a soln of dimesylate 6 (2 g, 2.9 mmol) in an appropriate solvent
(see Table 1) was added NaOAc (0.24 g, 2.9 mmol). The mixture
was heated to reflux for 6 h and then cooled and EtOAc was added.
The soln was washed with H2O, dried (MgSO4), and evaporated to
give a light yellow syrup. Purification by column chromatography
(silica gel, EtOAc–PE, 1:6) yielded the anhydrosugars 2.
1H NMR (400 MHz, CDCl3): d = 3.30–3.42 (m, 2 H), 3.72–3.84 (m,
3 H), 4.01 (m, 2 H), 4.11 (dd, J = 4.8, 9.6 Hz, 1 H), 4.16 (d, J = 11.6
Hz, 1 H), 4.33 (d, J = 12.4 Hz, 1 H), 4.44 (m, 4 H), 7.12–7.28 (m,
15 H, C6H5).
13C NMR (75 MHz, CDCl3): d = 61.30 (C5), 69.74, 71.54 (C1, C6),
71.55, 71.79, 73.37 (3 OCH2Ph), 79.99, 81.64, 81.79 (C2, C3, C4),
127–138 (Carom).
1,4-Anhydro-2,3,6-tri-O-benzyl-5-O-mesyl-D-glucitol (2a)
Yield: 1.40 g (95%).
LCMS: m/z (%) = 482.1 (60) [M + Na]+, 432.2 (100) [M + H – N2]+.
1H NMR (400 MHz, CDCl3): d = 2.94 (s, 3 H, SO2CH3), 3.69–3.75
(m, 2 H, H1, H6), 3.85 (d, J = 11.2 Hz, 1 H, H6¢), 3.92 (d, J = 3.6
Hz, 1 H, H1¢), 4.02 (dd, J = 4.4, 9.6 Hz, 1 H, H2), 4.05 (d, J = 2.8
Hz, 1 H, H3), 4.11 (dd, J = 3.2, 8.0 Hz, 1 H, H4), 4.34–4.65 (m, 6
H, OCH2Ph), 5.17 (t, J = 7.6 Hz, 1 H, H5), 7.20 (m, 15 H, C6H5).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H30O4N3: 460.22308;
found: 460.22855.
2,5-Anhydro-1-azido-3,4,6-tri-O-benzyl-L-gulitol (7b)
Yield: 0.76 g (84%).
13C NMR (75 MHz, CDCl3): d = 38.98 (CH3), 70.31 (C6), 71.43
(C1), 72.32, 72.69, 73.32 (3 OCH2Ph), 78.54 (C5), 79.22, 81.19,
81.24 (C2, C3, C4), 127–138 (Carom).
1H NMR (400 MHz, CDCl3): d = 3.28 (m, 2 H, H1, H1¢), 3.65 (dd,
J = 6.4, 10.0 Hz, 1 H, H6¢), 3.71 (dd, J = 5.6, 10.0 Hz, 1 H, H6), 3.81
(dd, J = 0.8, 2.8 Hz, 1 H, H3), 3.93 (dd, J = 0.8, 4.0 Hz, 1 H, H4),
3.98 (dt, J = 2.8, 5.6, 8.4 Hz, 1 H, H2), 4.20 (dt, J = 4.0, 5.6, 9.6 Hz,
1 H, H5), 4.30–4.72 (m, 6 H, OCH2Ph), 7.18–7.25 (m, 15 H, C6H5).
LC-MS: m/z (%) = 534.8 (100) [M + Na]+.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H33O7S: 513.19415;
found: 513.20635.
13C NMR (75 MHz, CDCl3): d = 52.57 (C1), 68.35 (C6), 71.79,
71.87, 73.52 (3 OCH2Ph), 80.59, 82.45, 82.80, 83.98 (C5, C4, C3,
C2), 127–138 (Carom).
2,5-Anhydro-3,4,6-tri-O-benzyl-1-O-mesyl-L-gulitol (2b)
Yield: 1.30 g (89%).
LC-MS: m/z (%) = 482.0 (100) [M + Na]+, 432.2 (70) [M + H –
N2]+.
1H NMR (400 MHz, CDCl3): d = 2.85 (s, 3 H, SO2CH3), 3.61 (dd,
J = 6.4, 10.0 Hz, 1 H, H6¢), 3.66 (dd, J = 5.6, 10.0 Hz, 1 H, H6), 3.87
(dd, J = 1.2, 2.8 Hz, 1 H, H3), 3.91 (dd, J = 1.2, 4.0 Hz, 1 H, H4),
4.07 (dt, J = 2.8, 5.6, 8.4 Hz, 1 H, H2), 4.19–4.24 (m, 3 H, H1¢, H1,
H5), 4.33–4.54 (m, 6 H, OCH2Ph), 7.16–7.30 (m, 15 H, C6H5).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H30O4N3: 460.22308;
found: 460.22440.
1,4-Anhydro-5-azido-2,3,6-tri-O-benzyl-L-galactitol (7c)
Yield: 0.65 g (72%).
13C NMR (75 MHz, CDCl3): d = 37.58 (CH3), 68.16, 68.71 (C1,
C6), 72.01, 72.10, 73.43 (3 OCH2Ph), 80.72, 81.43, 82.07, 82.83
(C5, C4, C3, C2), 127–138 (Carom).
1H NMR (400 MHz, CDCl3): d = 3.53 (m, 1 H), 3.64 (t, J = 7.6 Hz,
1 H), 3.72 (d, J = 10.0 Hz, 1 H), 3.79 (d, J = 8.0 Hz, 1 H), 3.84 (dd,
J = 3.2, 10.0 Hz, 1 H), 3.92–3.96 (m, 2 H), 4.04 (s, 1 H), 4.30–4.74
(m, 6 H), 7.18–7.44 (m, 15 H, C6H5).
LCMS: m/z (%) = 535.0 (100) [M + Na]+.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H33O7S: 513.19415;
found: 513.19962.
13C NMR (75 MHz, CDCl3): d = 62.07 (C5), 70.31, 71.31 (C1, C6),
71.74, 71.98, 73.45 (3 OCH2Ph), 82.69, 82.75, 84.23 (C2, C3, C4),
127–137 (Carom).
1,4-Anhydro-2,3,6-tri-O-benzyl-5-O-mesyl-D-galactitol (2c)
Yield: 1.42 g (97%).
LC-MS: m/z (%) = 482.1 (100) [M + Na]+, 432.2 (55) [M + H –
N2]+.
1H NMR (400 MHz, CDCl3): d = 2.97 (s, 3 H, SO2CH3), 3.60–3.68
(m, 2 H, H1¢, H6), 3.84 (dd, J = 3.6, 10.0 Hz, 1 H, H6¢), 3.94–4.01
(m, 3 H, H1, H2, H3), 4.05 (d, J = 3.6 Hz, 1 H, H4), 4.45–4.50 (m,
6 H, OCH2Ph), 4.88 (dt, J = 4.0, 5.6, 10.0 Hz, 1 H, H5), 7.12–7.26
(m, 15 H, C6H5).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H30O4N3: 460.22308;
found: 460.22155.
Aminodeoxyalditols 1
13C NMR (75 MHz, CDCl3): d = 38.61 (CH3), 69.70, 71.30 (C1,
C6), 71.79, 72.06, 73.49 (3 OCH2Ph), 80.70 (C5), 82.55, 82.91,
83.49 (C2, C3, C4), 127–138 (Carom).
To a soln of 7 (0.5 g, 1 mmol) and H2O (0.2 mL) in THF (5 mL) was
added Ph3P at 50 °C and the mixture was stirred for 6 h. The reac-
tion was quenched by the addition of 3% aq HCl (10 mL) and ex-
tracted with CH2Cl2 (3 × 20 mL). The combined organic extracts
were washed with 3% aq NaOH (20 mL) and concentrated in vacuo
to give the corresponding amine, which was used without further
purification. To a soln of the crude amine and pyridine in CH2Cl2
was added Ac2O; the mixture was stirred for 3 h. The reaction was
quenched by the addition of H2O and extracted with EtOAc (3 × 20
LC-MS: m/z (%) = 535.1 (100) [M + Na]+.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H33O7S: 513.19415;
found: 513.19483.
Synthesis 2009, No. 16, 2756–2760 © Thieme Stuttgart · New York