Sletten and Liotta
2.5% OsO4 in tert-butyl alcohol, 0.0055 mmol). The reaction was
kept at 0 °C and monitored by TLC (1:2:3:1 CH2Cl2/CH3CN/
MeOH/hexane) for the disappearance of 33 (Rf 0.54). Upon
completion of the reaction (approximately 1 h), Na2SO3 (0.215 g,
2.09 mmol) was added and the solution was stirred at 0 °C. After
1.5 h, H2O (3 mL) was added, and the aqueous layer was extracted
with CH2Cl2 (3 × 5 mL). The organic layers were combined, dried
with MgSO4, decanted, evaporated to dryness, and chromatographed
through silica gel with CH2Cl2/CH3CN/MeOH/hexane starting with
a 6:6:3:8 ratio and gradually decreasing to 6:6:3:0, while carefully
monitoring by TLC in 6:6:3:1 CH2Cl2/CH3CN/MeOH/hexane. This
procedure resulted in the isolation of three diols, all as clear oils,
that darkened upon exposure to air at room temperature: 34 (Rf
0.08, 0.0127 g, 0.0357 mmol, 26%), 35 (Rf 0.25, 0.0071 g, 0.0200
mmol, 15%), and 36 (Rf 0.83, 0.0066 g, 0.0187 mmol, 13%).
34: [R]27D +24.4 (c 0.515, CH2Cl2) 1H NMR δ 7.36-7.23 (m, 10
× Ar-H), 4.64 (d, J ) 12.0 Hz, 1 × OBn-H), 4.57-4.50 (m, 3 ×
OBn-H), 4.14 (m, C6-H), 4.10-4.04 (m, C5-H, C3-H, C2-H),
3.43 (dd, J ) 7.1, 2.1 Hz, C4-H), 3.25 (m, C7-H, C1-H), 2.99
(dd, J ) 11.2, 3.8 Hz, C7-H′), 2.81 (dd, J ) 12.3, 2.9 Hz, C1-
H′). 13C NMR δ 57.4 (CH2), 60.5 (CH2), 71.4 (CH2), 71.6 (CH2),
73.2 (CH), 73.8 (CH), 76.3 (CH), 84.7 (CH), 85.0 (CH), 127.5
(CH), 127.70 (CH), 127.73 (CH), 127.8 (CH), 128.4 (CH), 128.5
(CH), 137.4 (C), 137.6 (C). IR 3331 (br), 3031, 2922, 1605, 1453,
19.8 (CH3), 19.9 (CH3), 56.9 (CH2), 57.0 (CH2), 70.1 (CH), 70.50
(CH2), 70.54 (CH2), 72.5 (CH), 73.9 (CH), 83.3 (CH), 83.6 (CH),
126.5 (CH), 126.6 (CH), 126.7 (CH), 126.8 (CH), 127.4 (CH), 127.5
(CH), 136.8 (C), 136.9 (C), 169.3 (C), 169.4 (C). IR 3031, 2922,
1744, 1453, 1370, 1247 cm-1. HRMS calculated for C25H30NO6
(M+ + H) 440.2073, found 440.2050.
(1S,2R,6S,7S,7aR)-6,7-Bis(benzyloxy)hexahydro-1H-pyrroliz-
ine-1,2-diyl Diacetate (38). The same procedure was used as for
the synthesis of 37 above but starting with pyrrolizidine diol 35
(3.4 mg, 0.0096 mmol). This procedure resulted in the isolation of
pure 38 as a clear oil that darkened upon exposure to air at room
temperature (Rf 0.30, 3.5 mg, 0.0080 mmol, 83%). [R]26 14.1 (c
D
0.20, CH2Cl2). 1H NMR δ 7.36-7.16 (m, 10 × Ar-H), 5.39 (t, J
) 4.1 Hz, C5-H), 5.27 (ddd, J ) 10.5, 6.9, 3.8 Hz, C6-H), 4.72-
4.51 (m, 4 × OBn-H), 4.30 (dt, J ) 9.2, 6.5 Hz, C2-H), 4.13 (t,
J ) 6.6 Hz, C3-H), 3.56 (dd, J ) 6.3, 4.4 Hz, C4-H), 3.40 (dd,
J ) 8.7, 6.3 Hz, C1-H), 3.29 (dd, J ) 9.2, 6.9 Hz, C7-H), 2.63
(t, J ) 9.3 Hz, C1-H′), 2.61 (t, J ) 9.0 Hz, C7-H′), 2.00 (s, 3 ×
Ac-H), 1.98 (s, 3 × Ac-H). 13C NMR δ 20.6 (CH3), 20.7 (CH3),
54.7 (CH2), 58.2 (CH2), 68.0 (CH), 71.7 (CH), 72.1 (CH2), 72.7
(CH2), 73.6 (CH), 80.6 (CH), 84.6 (CH), 127.6 (CH), 127.8 (CH),
127.8 (CH), 128.4 (CH), 129.1 (CH), 136.6 (C), 138.1 (C), 169.6
(C), 169.9 (C). IR 3063, 2923, 1754, 1744, 1453, 1370, 1246 cm-1
.
HRMS calculated for C25H30NO6 (M+ + H) 440.2073, found
440.2109.
1094 cm-1. HRMS calculated for C21H26NO4 (M+ + H) 356.1862,
1
found 356.1843. 35: [R]27 +10.1 (c 0.14, CH2Cl2). H NMR δ
(1R,2S,6R,7S,7aR)-6,7-Bis(benzyloxy)-5-oxohexahydro-1H-
pyrrolizine-1,2-diyl Diacetate (39). The same procedure was used
as for the synthesis of 37 above but starting with lactam pyrrolizi-
done diol 36 (5.7 mg, 0.016 mmol). After chromatography through
silica gel with CH2Cl2/CH3CN first in a 5:1 ratio followed by a
3:1 ratio, this procedure resulted in the isolation of pure 39 as a
clear oil that darkened upon exposure to air at room temperature
(Rf 0.45, 4.7 mg, 0.011 mmol, 66%). [R]26D 27.4 (c 0.20, CH2Cl2).
1H NMR δ 7.45-7.24 (m, 10 × Ar-H), 5.44-5.38 (m, C5-H,
C6-H), 5.12 (d, J ) 11.6 Hz, OBn-H), 4.82 (d, J ) 11.6 Hz, OBn-
H), 4.56 (s, 2 × OBn-H), 4.47 (d, J ) 7.9 Hz, C2-H), 4.21 (t, J
) 6.6 Hz, C3-H), 3.83 (dd, J ) 3.5, 6.4 Hz, C4-H), 3.48 (d, J )
7.3 Hz, 2 × C7-H), 2.01 (s, 3 × Ac-H), 1.95 (s, 3 × Ac-H).
13C NMR δ 20.5 (2 × CH3), 43.5 (CH2), 62.4 (CH), 69.4 (CH),
72.2 (CH2), 72.3 (CH), 72.8 (CH2), 78.7 (CH), 82.5 (CH), 127.7
(CH), 128.0 (CH), 128.0 (CH), 128.3 (CH), 128.4 (CH), 128.5 (CH),
137.2 (C), 137.5 (C), 169.5 (C), 169.8 (C), 171.2.8 (C). IR 3031,
2925, 1754, 1745, 1722, 1710, 1370, 1239 cm-1. HRMS calculated
for C25H28NO6 (M+ + H) 454.1866, found 454.1824. Anal. Calcd
for C25H27NO7: C, 66.21; H, 6.00; N, 3.09. Found: C, 59.73; H,
5.10; N, 2.19.
D
7.40-7.23 (m, 10 × Ar-H), 4.57 (s, 2 × OBn-H), 4.56 (s, 2 ×
OBn-H), 4.32 (m, C3-H), 4.18 (ddd, J ) 10.5, 6.3, 4.2 Hz, C6-
H), 4.09 (dt, J ) 3.9, 2.6 Hz, C2-H), 4.00 (t, J ) 4.6 Hz, C5-H),
3.64 (dd, J ) 4.9, 2.8 Hz, C4-H), 3.37 (dd, J ) 9.2, 6.5 Hz, C7-
H), 3.22 (dd, J ) 12.4, 4.1 Hz, C1-H), 2.94 (dd, J ) 12.2, 2.4
Hz, C1-H′), 2.59 (t, J ) 9.1 Hz, C7-H′). 13C NMR δ 56.0 (CH2),
57.5 (CH2), 71.0 (CH2), 71.0 (CH2), 71.4 (CH), 76.5 (CH), 80.6
(CH), 83.2 (CH), 127.0 (CH), 127.3 (CH), 127.3 (CH), 127.6 (CH),
127.8 (CH), 128.0 (CH), 136.0 (C), 137.0 (C). IR 3406 (br), 3063,
3031, 2922, 2867, 1954, 1692, 1606, 1454, 1368, 1109 cm-1
.
HRMS calculated for C21H26NO4 (M+ + H) 356.1862, found
1
356.1883. 36: [R]25.5 +15.7 (c 0.42, CH2Cl2). H NMR δ 7.40-
D
7.23 (m, 10 × Ar-H), 5.07 (d, J ) 11.7 Hz, OBn-H), 4.79 (d, J
) 11.7 Hz, OBn-H), 4.64 (d, J ) 11.6 Hz, OBn-H), 4.60 (dd, J )
8.0, 6.4 Hz, C3-H), 4.53 (d, J ) 11.8 Hz, OBn-H), 4.44 (d, J )
8.1 Hz, C2-H), 4.37 (td, J ) 8.1, 3.8 Hz, C6-H), 3.78 (t, J ) 3.5
Hz, C5-H), 3.57 (dd, J ) 3.3, 6.3 Hz, C4-H), 3.40 (m, 2 × C7-
H). 13C NMR δ 45.7 (CH2), 64.8 (CH), 69.6 (CH), 72.7 (CH2),
73.1 (CH2), 73.9 (CH), 79.4 (CH), 82.7 (CH), 127.8 (CH), 128.0
(CH), 128.3 (CH), 128.4 (CH), 137.3 (C), 137.8 (C), 171.7 (C). IR
3388 (br), 3031, 2924, 1709, 1453, 1364, 1109 cm-1. HRMS
calculated for C21H24NO5 (M+ + H) 370.1654, found 370.1649.
(1R,2S,6S,7S,7aS)-Hexahydro-1H-pyrrolizine-1,2,6,7-tetrol (40).
Ten percent Pd/C (ca. 5 mg) was added to a solution of diol 34
(11.1 mg, 0.031 mmol) in ethanol (2 mL). Once the metal catalyst
was added, a drop of 6 M HCl was added to the solution and the
reaction was placed under a hydrogen atmosphere delivered by a
balloon. The reaction was monitored by TLC (1:1:3 CH2Cl2/CH3-
CN/CH3OH) for the disappearance of 34 (Rf 0.264). Once 34 was
no longer present, the mixture was filtered through Celite and
evaporated to dryness. The residue was dissolved in H2O, washed
with CH2Cl2, and lyophilized to a very hydroscopic solid (6.5 mg,
(1R,2S,6S,7S,7aR)-6,7-Bis(benzyloxy)hexahydro-1H-pyrroliz-
ine-1,2-diyl diacetate (37). Diol 34 (5.9 mg, 0.017 mmol) was
dissolved in pyridine (0.3 mL) and cooled to 0 °C. Acetic anhydride
(100 µL, 1.05 mmol) was added dropwise. The reaction was placed
in a sonicating bath for 3 h and then evaporated to dryness. The
residue was dissolved in CH2Cl2 (3 mL) and washed with saturated
NaHCO3 (1 × 3 mL). The aqueous layer was extracted with CH2-
Cl2 (2 × 3 mL). The organic layers were combined, dried with
MgSO4 decanted, evaporated to dryness, and chromatographed
through silica gel with CH2Cl2/CH3CN first in a 3:1 ratio followed
by 2:1 and 1:1 ratios. Fractions were analyzed by TLC in 3:1 CH2-
Cl2/CH3CN. This procedure resulted in the isolation of pure 37 as
a clear oil that darkened upon exposure to air at room temperature
0.031 mmol, 99%). Mp ∼210 °C dec. [R]26 23.1 (c 0.23, H2O).
D
1H NMR δ 4.28 (dd, J ) 8.9, 3.6 Hz, C5-H), 4.15 (m, C2-H,
C3-H), 4.08 (m, C6-H), 3.57 (d, J ) 8.9 Hz, C4-H), 3.51 (d, J
) 12.6 Hz, C7-H), 3.41 (dd, J ) 13.2, 3.2 Hz, C1-H), 3.20 (dd,
J ) 12.6, 2.6 Hz, C1-H′), 3.12 (d, J ) 13.1 Hz, C7-H′). 13C
NMR δ 57.9 (CH2), 60.9 (CH2), 71.4 (CH), 73.7 (CH), 75.5 (CH),
(Rf 0.25, 7.3 mg, 0.0066 mmol, 100%). [R]26 19.6 (c 0.33, CH2-
D
76.1 (CH), 77.0 (CH). IR 3378, 3301, 2943, 2726, 1136 cm-1
.
1
Cl2). H NMR δ 7.34-7.19 (m, 10 × Ar-H), 5.38 (m, C6-H),
HRMS calculated for C7H15NO4Cl (M+ + H) 176.0923, found
176.0931.
5.26 (dd, J ) 4.5, 7.5 Hz, C5-H), 4.59 (d, J ) 12.0 Hz, 1 × OBn-
H), 4.56 (d, J ) 11.7 Hz, 1 × OBn-H), 4.50 (d, J ) 11.8 Hz, 1 ×
OBn-H), 4.48 (d, J ) 11.8 Hz, 1 × OBn-H), 4.07 (m, C3-H, C2-
H), 3.60 (dd, J ) 7.5, 1.8 Hz, C4-H), 3.31-3.25 (m, C1-H, C7-
H), 3.17 (dd, J ) 11.5, 4.2 Hz, C7-H′), 2.88 (dd, J ) 2.2, 12.5
Hz, C1-H′), 2.10 (s, 3 × Ac H), 2.07 (s, 3 × Ac H). 13C NMR δ
(1S,2R,6S,7S,7aS)-Hexahydro-1H-pyrrolizine-1,2,6,7-tetrol (41).
The same procedure used as for the synthesis of 40 above but
starting with pyrrolizidone diol 35 (11.7 mg, 0.033 mmol) yielded
41 (7.3 mg, 0.034 mmol, 103%) as a very hydroscopic solid, mp
1342 J. Org. Chem., Vol. 71, No. 4, 2006