1768
P. Pia˛tek et al. / Tetrahedron: Asymmetry 12 (2001) 1763–1769
Method B (under high pressure): An equimolar solution
of the dimethyl a,v-dicarboxylate (0.5 mmol) and the
appropriate a,v-diamine (0.5 mmol) in methanol (5
mL) was filled into a Teflon ampoule, placed in a
high-pressure vessel filled with ligroine as a trans-
mission medium and compressed (12 kbar) at room
temperature for 48 h. After decompression, the reaction
mixture was transferred quantitatively to a round-bot-
tomed flask and the solvent was evaporated. The
residue was chromatographed on a silica gel column
using 0.5–3% mixtures of methanol in chloroform.
was added. The solution was stirred overnight at 40°C
and NaHCO3 (2 g) was added, and the mixture stirred
for 1 h. The mixture was filtered and the filtrate evapo-
rated. The oil residue was purified by column chro-
matography using hexane/ethyl acetate (2:3) as eluent
giving diol 12 as a colorless oil (0.13 g, 39%).
From 10: The compound was prepared according to
literature procedure.
From 11: To a solution of diester 11 (2.45 g, 5 mmol)
in dry dioxane (40 mL) LiAlH4 (0.4 g, 10.5 mmol) was
added. The mixture was stirred under reflux under
argon for 12 h. After cooling, water (5 mL), aqueous
NaOH (20%, 10 mL) and water (50 mL) were sequen-
tially added. The mixture was extracted with
dichloromethane (3×50 mL), and the combined extracts
were dried over MgSO4. After filtration, the solvent was
evaporated to yield diol 12 as a colorless oil or semi-
solid. Crude product was purified by column chro-
matography using gradient eluation with toluene/
chloroform–chloroform/methanol to yield diol 12 (1.42
g, 81%). White crystals, mp 76–77°C, [h]2D0=+15.3 (c=
3.8.1. (7R,8R)-7,8-Bis((4R)-2,2-dimethyl-1,3-dioxalan-
4-yl)-6,9-dioxa-3,12,18-triazabicyclo[12.3.1]octadeka-
1(17),14(18),15-triene-2,13-dione 17. Method A. Reac-
tion time 6 days. Yield 18.8%. Method B. Yield 39.0%.
White solid, [h]2D4=−2.1 (c=1.2, CHCl3); 1H NMR (500
MHz, CDCl3), l 8.93 (2H, bt, -NHCO-); 8.27 (2H, d,
J=7.5); 8.06 (1H, t, J=7.5); 4.20 (2H, m); 4.12 (2H,
dd, J=6, J=8.5); 3.92 (2H, dd, J=6, J=8.5); 3.89–
3.83 (4H, m); 3.76–3.65 (4H, m); 3.65–3.58 (2H, m);
1.40 (6H, s, -CH3); 1.32 (6H, s, -CH3); 13C NMR (125
MHz, CDCl3), l 162.59; 148.34; 139.64; 123.93; 108.76;
78.91; 75.46; 68.13; 67.13; 38.62; 26.68; 25.30; HR EI
m/z, calcd for C23H33O8N3 [M]+: 479.2268; found
479.2243.
1
1.1, CHCl3); H NMR (200 MHz, CDCl3), l 4.3–3.65
(16H, m); 3.53 (2H, bs, -OH); 1.44 (6H, s, -CH3); 1.35
(6H, s, -CH3); 13C NMR (50 MHz, CDCl3), l 109.5;
108.6; 78.2; 76.6; 75.2; 74.1; 72.7; 67.5; 65.7; 62.7; 26.8;
26.4; 25.7; HR LSIMS m/z, calcd for C16H30O8Na
[M+Na]+: 373.1838; found 373.1841.
3.8.2. (9R,10R)-9,10-Bis((4R)-2,2-dimethyl-1,3-dioxalan-
4-yl)-6,9,12,15-tetraoxa-3,18,24-triazabicyclo[18.3.1]-
tetracoza-1(23),20(24),21-triene-2,19-dione 18. Method
A. Reaction time 5 days. Yield 48.8%. Method B. Yield
59.7%. White solid, [h]2D4=+7.6 (c=2.5, CHCl3); 1H
NMR (200 MHz, CDCl3), l 9.23 (2H, bt, -NHCO-);
8.33 (2H, d, J=7.6 Hz); 8.00 (1H, t, J=7.6); 4.3–3.5
(24H, m); 1.39 (6H, s, -CH3); 1.32 (6H, s, -CH3); 13C
NMR (50 MHz, CDCl3), l 164.0; 148.7; 138.4; 124.6;
108.8; 80.0; 74.4; 71.6; 71.4; 70.2; 67.1; 39.7; 26.8; 25.3;
HR EI m/z, calcd for C27H41O10N3 [M]+: 567.2792;
found 567.2799.
3.7. 3,4-Bis-O-(2-phthalimidoethyl)-1,2;5,6-di-O-iso-
propylidene-D-mannitol 13
To a solution of diol 12 (1 g, 2.86 mmol), phthalimide
(1 g, 6.86 mmol) and triphenylphosphine (1.8 g, 6.86
mmol) in dry THF (50 mL) was added dropwise di-iso-
propyl azadicarboxylate (DIAD) (1.35 mL, 6.86 mmol).
The mixture was stirred at rt under argon for 3 days
and the solvent was evaporated. The crude oil was
purified by column chromatography using hexane/ethyl
acetate (3:2) as an eluent to afford the diphthalimide as
white crystals (1.27 g, 73%), mp 131–135°C. [h]2D4=
3.8.3. (9S,10S)-9,10-Bis(benzyloxymethyl)-6,9,12,15-tet-
raoxa-3,18,24-triazabicyclo[18.3.1]tetracoza-1(23),
20(24),21-triene-2,19-dione 19. Method A. Reaction time
2 days. Yield 40.2%. Method B. Yield 41.9%. White
solid, [h]2D0=+42.3 (c=1.97, CHCl3); 1H NMR (500
MHz, CDCl3), l 8.95 (2H, bt, -NHCO-); 8.32 (2H, d,
J=7.5); 7.97 (1H, t, J=7.5); 7.34–7.25 (10H, m); 4.49
(2H, dAB, J=12); 4.44 (2H, dAB, J=12); 3.85–3.79 (2H,
m); 3.77–3.52 (20H, m); 13C NMR (125 MHz, CDCl3),
l 164.0; 148.9; 138.5; 138.0; 128.4; 127.7; 124.8; 78.5;
73.4; 70.8; 70.7; 70.6; 69.1; 39.8; HR LSIMS m/z, calcd
for C33H41O8N3Na [M+Na]+: 630.2791; found
630.2795.
1
+12.8 (c=1.0, CHCl3); H NMR (200 MHz, CDCl3), l
7.90–7.65 (8H, AB, -NPht); 4.20–3.50 (16H, m); 1.32
(6H, s, -CH3); 1.23 (6H, s, -CH3); 13C NMR (50 MHz,
CDCl3), l 168.0; 133.9; 132.0; 123.2; 108.6; 80.7; 76.2;
75.2; 69.2; 66.4; 37.9; 26.5; 25.0; HR LSIMS m/z, calcd
for C32H36O10N2Na [M+Na]+: 631.2267; found
631.2279.
3.8. General procedures for synthesis of bisamides 17–22
Method A (in the presence of MeO−): The solution of
ester (0.35 mmol) in dry methanol (5 mL) was cooled to
5°C and sodium (8 mg, 0.35 mmol) was added. A
solution of diamine (0.35 mmol) in dry methanol (5
mL) was added. The mixture was left at rt for a period
of 2–26 days (monitored by TLC). The solvent was
evaporated and the residue was purified by column
chromatography using gradient eluation with toluene/
chloroform, chloroform and chloroform/methanol mix-
tures as eluent.
3.8.4. (9R,10R)-9,10-Bis((4R)-2,2-dimethyl-1,3-dioxalan-
4-yl)-6,9,12,15-tetraoxa-3,18-diazabicyclo[18.3.1]tetra-
coza-1(23),20(24),21-triene-2,19-dione 21. Method A.
Reaction time 26 days. Yield 24.0%. Method B. Yield
25.1%. Colorless crystals, mp 109–116°C, [h]2D0=−28.5
1
(c=2.2, CHCl3); H NMR (500 MHz, CDCl3), l 8.38
(1H, s); 8.21 (2H, dd, J=7.5, J=1.5); 7.62 (2H, bt,
J=5, -NHCO-); 7.56 (1H, t, J=7.5); 4.25–4.20 (2H, m);
4.14 (2H, dd, J=5.5, J=8.5); 3.97–3.89 (6H, m); 3.80–
3.74 (2H, m); 3.71–3.50 (14H, m); 1.41 (6H, s, -CH3);