G. De Coster et al. / Tetrahedron: Asymmetry 13 (2002) 1673–1679
1677
4
.5. (3R,3aR,6R,6aR)-3,6-Diazidohexahydrofuro[3,2-b]-
furan, 10 and (3R,3aR,6aR)-2,3,3a,6a-tetrahydrofuro-
3,2-b]furan-3-yl azide, 11
filtered off and rinsed with dichloromethane. After
evaporation of the combined solvents, the imines 4
where crystallized or used as such. When the imine
[
was
a
solid, the residue was dissolved in
The exo-dimesylate 9 (7.93 g, 26 mmol) was dissolved
in dimethylsulfoxide (160 ml), and sodium azide (20.3
g, 312 mmol) was added. The suspension was stirred
for 15 h at 125° C and then diluted with brine (800
ml). The reaction mixture was extracted with diethyl
ether (4×700 ml) and the combined organic phases
dichloromethane (1 ml), and n-hexane (10 ml) was
added. Slow evaporation under reduced pressure
yielded crystals, which were separated by filtration.
The crystals were washed with n-hexane (2×3 ml).
4.7.1. N-[(E)-Phenylmethylidene]-N-(3R,3aR,6R,6aR)-
6-{[(E)-phenylmethylidene]amino}hexahydrofuro[3,2-b]-
were dried (MgSO ) and concentrated in vacuo. The
4
2
0
crude product was purified by column chromatogra-
phy with gradient elution (n-hexane/diethyl ether
furan-3-yl)amine, 4a. Mp 112°C; [h] =+320.3 (c 0.75,
−1
D
CHCl ); IR (KBr) w
1102, 1042, 805; H NMR (500 MHz, DMSO-d ): l
cm : 2875, 1644, 1453, 1263,
max
3
1
8
5
+
7.5:12.5, 7:3) to afford 10 as a colorless oil (2.85 g,
6
20
6%); R =0.34 (n-hexane/ethyl acetate 1:1); [h] =
8.46 (s, 2H), 7.77 (m, 4H), 7.46 (m, 6H), 4.72 (m, 2H),
f
D
−
1
307.4 (c 1.32, CHCl ); IR (KBr) w
107, 1260, 1104; H NMR (500 MHz, CDCl ): l 4.70
cm : 2359,
4.12 (m, 2H), 3.91 (dd [app. t], J=8.2 Hz, 8.2 Hz,
3
max
1
13
2
2H), 3.86 (dd, J=6.8 Hz, 8.2 Hz, 2H); C NMR
3
(
2
m, 2H), 4.08 (dd, J=8.9 Hz, 6.9 Hz, 2H), 3.90 (m,
(125.7 MHz, DMSO-d ): 163.3 (CH), 136.4 (C), 131.2
6
13
H), 3.80 (dd [app. t], J=8.7 Hz, 8.9 Hz, 2H);
C
(CH), 129.0 (CH), 128.3 (CH), 84.7(CH), 72.2(CH2),
71.9 (CH); MS (m/z): 219 (10), 217 (42), 187 (37), 156
(40), 130 (40), 117 (28), 106 (74), 69 (100), 41 (32).
Anal. calcd for C H N O : C, 74.98; H, 6.29; N,
NMR (125.7 MHz, CDCl ): 83.2 (CH), 70.5 (CH ),
3
2
6
2.2 (CH); MS (m/z): 164 (8), 142 (19), 85 (27), 69
(
100). Anal. calcd for C H N O : C, 36.74; H, 4.11.
6
8
6
2
20 20
2
2
Found: C, 36.85; H, 4.09%.
8.74. Found: C, 74.81; H, 6.27; N, 8.72%.
The elimination product 11 was isolated as a side
4.7.2.
N-[(E)-(4-Methoxyphenyl)methylidene]-N-
product (colorless oil; 636 mg, 16%); R =0.40 (n-hex-
(3R,3aR,6R,6aR) - 6 - {[(E) - (4 - methoxyphenyl)methyli-
f
2
0
ane/ethyl acetate 1:1); [h] =+149.0 (c 0.52, CHCl );
H NMR (500 MHz, CDCl ): l 6.67 (d, J=2.6 Hz,
dene]amino}hexahydrofuro[3,2-b]furan-3-yl)amine,
4b.
D
3
1
20
Mp 152°C; [h] =+253.0 (c 0.91, CHCl ); IR (KBr)
D 3
−1 1
3
1H), 5.43 (dd, J=2.6 Hz, 6.0 Hz, 1H), 5.08 (dd [app.
wmax cm : 2875, 1634, 1604, 1513, 1248, 1017, 825; H
t], J=2.6 Hz, 2.6 Hz, 1H); 4.92 (dd [app. t], J=6.0
Hz, 6.0 Hz, 1H); 4.01 (dd, J=6.5 Hz, 8.8 Hz, 1H),
NMR (500 MHz, DMSO-d ): l 8.38 (s, 2H), 7.71 (m
6
[app. d], J=8.8 Hz, 4H), 7.01 (m [app. d], J=8.8 Hz,
4H), 4.68 (m, 2H), 4.06 (m, 2H), 3.90 (dd [app. t],
J=8.4 Hz, 7.1 Hz, 2H), 3.82 (dd [app. t], J=8.4 Hz,
3.78 (ddd [app. dt], J=6.0 Hz, 6.5 Hz, 10.2 Hz, 1H),
.43 (dd, J=8.8 Hz, 10.2 Hz, 1H).
3
13
8
.4 Hz, 2H), 3.80 (s, 6H); C NMR (125.7 MHz,
4
.6. (3R,3aR,6R,6aR)-6-Aminohexahydrofuro[3,2-b]-
DMSO-d ): 162.2 (CH), 161.4 (C), 129.7 (CH), 129.1
6
furan-3-ylamine, 5
(C), 114.1 (CH), 84.4 (CH), 72.0 (CH ), 71.7 (CH),
2
5
5.4 (CH ); MS (m/z): 305 (11), 217 (69), 214 (82),
3
The endo-diazide 10 (2.85 g, 14.5 mmol) was hydro-
179 (26), 121 (70), 91 (54), 69 (100). Anal. calcd for
C H N O : C, 69.46; H, 6.36; N, 7.36. Found: C,
genated at 4 bar pressure H in methanol (190 ml)
2
22 24
2
4
with palladium on carbon 10% (200 mg) for 6 h at
ambient temperature. The reaction mixture was filtered
through Celite and the filtrate was concentrated in
vacuo to afford 14 as a white solid (2.02 g, 96%); mp
69.58; H, 6.38; N, 7.33%.
4.7.3. N-[(E)-(2,6-Dichlorophenyl)methylidene]-N-(3R,
3aR,6R,6aR)-6-{[(E)-(2,6-dichlorophenyl)methylidene]-
amino}hexahydrofuro[3,2-b]furan-3-yl)amine, 4c. Mp
3
5°C; R =0.15 (dichloromethane/methanol 87.5:12.5);
f
20 −1
20
[
2
h] =+61.2 (c 0.97, H O); IR (KBr) w
cm : 3385,
125°C; [h] =+156.5 (c 1.10, CHCl ); IR (KBr) w
D
2
max
D
3
max
1
−1
615, 2513, 1636, 1508, 1405, 1139, 1113, 1041;
H
cm : 2875, 1654, 1579, 1553, 1428, 1104, 1039, 776;
1
NMR (500 MHz, D O): l 4.42 (m, 2H), 4.03 (dd [app.
H NMR (500 MHz, DMSO-d ): l 8.59 (s, 2H), 7.53
2
6
t], J=8.0 Hz, 8.7 Hz, 2H), 3.51 (m, 2H), 3.29 (dd,
(m [app d], J$8.1 Hz, 4H), 7.44 (dd, J=8.7 Hz, 7.4
Hz, 2H), 4.77 (m, 2H), 4.22 (m, 2H), 3.94 (dd, J=7.2
Hz, 8.3 Hz, 2H), 3.86 (dd [app. t], J=8.3 Hz, 8.3 Hz,
13
J=8.7 Hz, 10.2 Hz, 2H); C NMR (125.7 MHz,
D O): 82.9 (CH), 72.3 (CH ), 54.7 (CH); MS (m/z):
2
2
13
121 (22), 109 (23), 84 (100), 69 (81), 55 (42). Anal.
2H); C NMR (125.7 MHz, DMSO-d ): 159.0 (CH),
6
calcd for C H N O : C, 49.99; H, 8.39. Found: C,
133.6 (C), 132.8 (C), 131.5 (CH), 129.0 (CH), 84.5
6
12
2
2
49.78; H, 8.37%.
(CH), 72.1 (CH), 71.9 (CH ); MS (m/z): 285 (18), 219
2
(
10), 217 (18), 174 (60), 123 (38), 82 (25), 69 (100).
4.7. Formation of the imines 4a–g: general procedure
Anal. calcd for C H Cl N O : C, 52.43; H, 3.52; N,
6
20
16
4
2
2
.11. Found: C, 52.56; H, 3.51; N, 6.13%.
The diamine 14 (50 mg, 0.35 mmol) was dissolved in
dry dichloromethane (2 ml). Anhydrous magnesium
sulfate (84 mg, 0.7 mmol) and the aldehyde (0.7
mmol) were added and the resulting mixture was
stirred for 16 h at ambient temperature. As the prod-
ucts tend to decompose on silica gel, the reaction was
not monitored by TLC. Magnesium sulfate was
4.7.4. N-[(E)-(2,3,4,5,6-Pentafluorophenyl)methylidene]-
N - (3R,3aR,6R,6aR) - 6 - {[(E) - (2,3,4,5,6 - pentafluoro-
phenyl)methylidene]amino}hexahydrofuro[3,2-b]furan-3-
yl)amine, 4d. Oil, used without further purification; IR
−
1
(KBr) w
cm : 2923, 1654, 1526, 1500, 1098, 1010;
max
1
H NMR (500 MHz, DMSO-d ): l 8.56 (s, 2H), 4.77
6