S. Stecko et al. / Carbohydrate Research 344 (2009) 167–176
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4.2. (R)-2-(tert-Butyldiphenylsilyloxy)-1-((2S,3S,3aS,4S,5S)-
4,5-di-tert-butoxy-3-(tert-butyldiphenylsilyloxymethyl)-
hexahydropyrrolo[1,2-b]-isoxazol-2-yl)ethanol (14)
1.7 Hz, H6), 3.81–3.72 (2H, m, for H7; dd, J 10.3, 5.0 Hz, for C1CHHO-
Si), 3.59 (1H, dd, J 10.3, 6.4 Hz, C1CHHOSi), 3.38 (1H, ddd, J 8.8, 7.9,
5.7 Hz, H3), 3.14–3.06 (2H, dd, J 5.3, 1.7 Hz, for H7a; dd, J 11.8,
0
4.9 Hz, for H5), 2.98 (1H, dd, J 11.8, 2.9 Hz, H5 ), 2.36 (1H, dddd, J
The soln of diol 13 (1.79 g, 2.97 mmol) and imidazole (0.40 g,
5.95 mmol) in 50 mL of CH2Cl2 was cooled to ꢀ15 °C, and t-
BuPh2SiCl was added (0.57 g, 3.23 mmol). The progress of the
reaction was monitored by TLC (4:1 hexane–EtOAc). Subse-
quently, the reaction mixture was diluted with CH2Cl2 (50 mL),
washed with water (50 mL), brine (30 mL) and dried over anhyd
Na2SO4. After solvent removal, the residue was purified by col-
umn chromatography on a silica gel column (4:1 hexane–EtOAc)
6.4, 5.3, 5.0, 3.8 Hz, H1), 1.13 (9H, s, t-Bu), 1.11 (9H, s, t-Bu), 1.07
(9H, s, t-Bu), 1.05 (9H, s, t-Bu); IR (film) m
: 3401, 1111 cmꢀ1; HRES-
I-TOFMS: calcd for [M+H+] C49H70NO5Si2: 808.4787. Found: m/z
808.4856; Anal. Calcd for C49H69NO5Si2: C, 72.81; H, 6.80; N,
1.73. Found: C, 72.83; H, 6.81; N, 1.74.
4.5. (1S,2S,3S,6S,7S,7aS)-2-Acetoxy-1,3-bis(acetoxymethyl)-6,7-
di-tert-butoxy-pyrrolizidine (17)
affording 2.25 g (92%) of compound 14 as a colourless oil; [a]
D
+17.5 (c 0.34, CH2Cl2); 1H NMR (500 MHz, C6D6): d 8.00–7.00
(20H, 4 ꢁ Ph), 4.52 (1H, dd, J 9.1, 5.2 Hz, H2), 4.30–4.20 (3H,
A soln of TBAF (0.10 g, 0.31 mmol) in 5 mL of THF was added to
a soln of compound 16 (0.30 g, 0.37 mmol) in 20 mL of THF. After
1 h, the solvent was removed and the residue was dissolved in
Et3N (10 mL). After cooling to ꢀ5 °C, Ac2O was added (2 mL) and
the reaction mixture was stirred for 2 h. After removal of solvents,
the residue was purified chromatographically (4:1, then 1:1 hex-
ane–EtOAc) affording 122 mg (72%) of triacetate 17 as a colourless
0
0
H1 ,H5, CHHOSi), 4.07 (1H, dd, J 10.3, 6.0 Hz, H2 a), 3.89–3.73
0
0
(3H, H4, CHHOSi, H2 b), 3.57–3.50 (2H, H6,H6 ), 3.46 (1H, dd, J
4.8, 2.1 Hz, H3a), 3.04 (1H, m, H3), 1.22 (9H, s, t-Bu), 1.20 (9H, s,
t-Bu), 1.09 (9H, s, t-Bu), 1.00 (9H, s, t-Bu); 13C NMR (125 MHz,
C6D6, without Ph groups): d 81.5, 76.3, 75.4, 73.9, 73.7, 72.6,
69.6, 66.3, 63.3, 60.2, 51.8, 29.0, 28.5, 26.9, 26.8, 19.4, 19.1; IR
oil; [a]
D +2.6 (c 0.79, CH2Cl2); 1H NMR (500 MHz, C6D6): d 5.39 (1H,
(film)
m
:
3480, 1112 cmꢀ1
C49H70NO6Si2: 824.4736. Found: m/z 824.4771. Anal. Calcd for
C49H69O6Si2: C, 71.40; H, 8.44; N, 1.70. Found: C, 71.51; H, 8.44;
N, 1.71.
;
HRESI-TOFMS: calcd for [M+H+]
dd, J 4.8, 2.4 Hz, H2), 4.50 (1H, dd, J 11.3, 6.8 Hz, C3CHHOSi), 4.42
(1H, dd, J 11.3, 7.0 Hz, C3CHHOSi), 4.30 (1H, dd, J 11.4, 4.8 Hz,
C1CHHOSi), 4.15 (1H, ddd, J 8.3, 6.6, 5.3 Hz, H6), 4.02 (1H, dd, J
11.4, 7.5 Hz, C1CHHOSi), 3.94 (1H, dd, J 5.3, 3.9 Hz, H7), 3.42 (1H,
ddd, J 7.0, 6.2, 4.8 Hz, H3), 3.20 (1H, dd, J 8.3, 6.6 Hz, H5), 3.10
0
4.3. (R)-2-(tert-Butyldiphenylsilyloxy)-1-((2S,3S,3aS,4S,5S)-
4,5-di-tert-butoxy-3-(tert-butyldiphenylsilyloxymethyl)-
hexahydropyrrolo[1,2-b]-isoxazol-2-yl)ethyl mesylate (15)
(1H, dd, J 6.9, 3.9 Hz, H7a), 3.01 (1H, t, J 8.3 Hz, H5 ), 2.58 (1H, dddd,
J 7.5, 6.9, 4.8, 2.4 Hz, H1), 1.74 (3H, s, Ac), 1.72 (3H, s, Ac), 1.58 (3H,
s, Ac), 1.20 (9H, s, t-Bu), 1.09 (9H, s, t-Bu); 13C NMR (125 MHz,
CDCl3): d 170.08, 170.00, 169.5, 82.4, 79.8, 79.6, 73.7, 73.4, 71.5,
A soln of alcohol 14 (1.40 g, 1.70 mmol) and Et3N (0.34 g,
3.40 mmol) in 50 mL of CH2Cl2 was cooled to ꢀ15 °C, and MsCl
was added (0.29 g, 2.55 mmol). After disappearance of the starting
material, the reaction mixture was diluted with CH2Cl2 (20 mL),
washed with water and brine and dried over anhyd Na2SO4. After
removal of the solvent, the residue was chromatographed on a sil-
ica gel column (4:1 hexane–EtOAc) to afford 1.22 g (84%) of mesy-
late 15 as colourless crystals; mp 53–55 °C (1:1 benzene–hexane);
64.1, 62.8, 60.4, 53.6, 51.1, 29.2, 28.6, 20.4, 20.3; IR (film) m:
1745, 1231 cmꢀ1; HRESI-TOFMS: calcd for [M+H+] C23H40NO8:
458.2748. Found: m/z 458.2736.
4.6. (1S,2S,3S,6S,7S,7aS)-2,6,7-Triacetoxy-1,3-
bis(acetoxymethyl)-pyrrolizidine (18)
The triacetate 17 (65 mg, 0.14 mmol) dissolved in trifluoroace-
tic acid (5 mL) was stirred overnight. After solvent removal, the
residue was acetylated following standard conditions. Chromato-
graphic purification on silica gel (1:4 hexane–EtOAc) afforded
47 mg (78%) of peracetylated pyrrolizidine 18 as a colourless oil;
[
a]
D
+36.6 (c 0.21, CH2Cl2); 1H NMR (500 MHz, C6D6): d 8.00–7.20
0
(20H, 4 ꢁ Ph), 5.28 (1H, ddd, J 5.8, 5.6, 3.1 Hz, H1 ), 4.72 (1H, dd, J
6.0, 5.8 Hz, H2), 4.27 (1H, dd, J 10.5, 5.7 Hz, CHHOSi), 4.20–4.00
0
0
(3H, dd, J 11.9, 3.1 Hz, for H2 a, dd, J 11.9, 5.6 Hz, for H2 b, dd, J
10.5, 8.2 Hz, for CHHOSi), 3.89 (1H, m, H3a), 3.85–3.75 (2H,
[
a
]
ꢀ1.5 (c 3.05, CH2Cl2); 1H NMR (500 MHz, C6D6): d 5.54 (1H,
D
0
H4,H5), 3.57 (1H, dd, J 12.2, 5.0 Hz, H6), 3.13–3.03 (2H, H3,H6 ),
m, H6), 5.30–5.22 (2H, H7, H2), 4.36–4.24 (2H, C3CHHOSi, C1CHHO-
2.48 (3H, s, Ms), 1.26 (9H, s, t-Bu), 1.18 (9H, s, t-Bu), 1.11 (9H, s,
t-Bu), 1.01 (9H, s, t-Bu); 13C NMR (125 MHz, C6D6, without Ph
groups): d 82.5, 80.4, 77.1, 75.8, 73.9, 73.8, 73.5, 64.4, 62.1, 51.8,
38.5, 29.0, 28.4, 27.3, 27.1, 19.6, 19.5; HRESI-TOFMS: calcd for
[M+H+] C50H72NO8Si2S: 902.4511. Found: m/z 902.4555; Anal.
Calcd for C50H71O8SSi2: C, 66.55; H, 7.93; N, 1.55; S, 3.55. Found:
C, 66.67; H, 7.96; N, 1.56; S, 3.56.
Si), 4.19–4.11 (2H, C3CHHOSi, C1CHHOSi), 3.27 (1H, dd, J 9.3, 7.0 Hz,
0
H5), 3.1 (1H, m, H3), 2.99–2.91 (2H, H5 , H7a), 2.54 (1H, m, H1), 1.68
(3H, s, Ac), 1.66 (3H, s, Ac), 1.62 (3H, s, Ac), 1.61 (3H, s, Ac), 1.54
(3H, s, Ac); 13C NMR (125 MHz, C6D6): d 170.2, 170.0, 169.9,
169.6, 169.2, 81.0, 78.8, 78.7, 71.4, 63.5, 62.5, 60.3, 51.2, 50.6,
30.1, 20.30, 20.27, 20.23, 20.22; IR (film)
m ;
: 1740, 1234 cmꢀ1
HRESI-TOFMS: calcd for [M+H+] C19H28NO10: 430.1707. Found:
m/z 430.1724.
4.4. (1S,2S,3S,6S,7S,7aS)-6,7-Di-tert-butoxy-1,3-bis(tert-
butyldiphenylsilyloxymethyl)-2-hydroxypyrrolizidine (16)
4.7. (1S,2S,3S,6S,7S,7aS)-2,6,7-Hydroxy-1,3-bis(hydroxymethyl)-
pyrrolizidine (9)
Mesylate 15 (0.15 g, 0.17 mmol) was dissolved in 10 mL of 4:1
EtOAc–MeOH, 10% Pd/C was added (20 mg) and the reaction mix-
ture was saturated with hydrogen at atmospheric pressure. The
disappearance of substrate was monitored by TLC (4:1 hexane–
EtOAc). Subsequently, the reaction mixture was filtered through
Celite and concentrated. The crude residue was chromatographed
on a short silica gel pad (2:1 hexane–EtOAc) to afford 0.11 g
Compound 18 (40 mg, 0.09 mmol) was dissolved in 5 mL of a
1% soln of ammonia in MeOH. After disappearance of the sub-
strate, the reaction mixture was filtered through a Florisil pad
and concentrated to afford 18 mg (89%) of the pyrrolizidine 9 as
a colourless oil; [
a]
ꢀ5.2 (c 2.8, CH2Cl2); 1H NMR (500 MHz,
D
CD3OD): d 3.94 (1H, dd, J 11.5, 6.0 Hz, C3CHHOH), 3.88 (1H, dd,
J 11.5, 6.9 Hz, C3CHHOH), 3.57–3.50 (2H, C1CH2OH); 3.22 (1H,
(80%) of pyrrolizidine 16 as a colourless oil; [
a
]
D
+13.1 (c 2.0,
CH2Cl2); 1H NMR (500 MHz, CDCl3): d 7.82–7.30 (20H, 4 ꢁ Ph),
4.29 (1H, dd, J 8.8, 3.8 Hz, H2), 4.10 (1H, dd, J 9.8, 7.9 Hz, C3CHHO-
Si), 4.00 (1H, dd, J 9.8, 5.7 Hz, C3CHHOSi), 3.84 (1H, ddd, J 4.9, 2.9,
dd, J 9.7, 7.8 Hz, H5), 3.14–3.08 (2H, H5 ,H3), 4.17 (1H, dd, J 4.2,
0
2.2 Hz, H2), 4.06 (1H, ddd, J 7.6, 6.2, 5.9 Hz, H6), 4.00 (1H, dd, J
5.9, 5.1 Hz, H7), 3.00 (1H, t, J 5.1 Hz, H7a), 2.34 (1H, dddd, J 7.1,