9984
S. Monge et al. / Tetrahedron 57 02001) 9979±9987
system, q, 2H-4 and 2H-6, Jgem8.8 Hz); 5.55 /2H, s, H-2,
H-8); 7.25±7.45 /10H, m, Ph); 13C NMR /CDCl3) d: 66.0,
74.5, 75.5 /C-4, C-5, C-6, C-9); 98.0 /C-2, C-8); 127.0,
128.9, 129.1 and 140.0 /aromatic carbons). trans Isomer:
1H NMR /CDCl3) d: 2.40 /1H, t, OH, J5.8 Hz); 3.70
and 3.75 /2H, AB system, q, H-9, Jgem11.1 Hz); 3.88
and 3.92 /2H, AB system, q, 2H-4, Jgem8.8 Hz); 4.15
and 4.19 /2H, AB system, q, 2H-6, Jgem9.7 Hz); 5.30
and 5.50 /2H, 2s, H-2, H-8); 7.20±7.45 /10H, m, Ph); 13C
NMR /CDCl3) d: 65.0, 72.0, 74.5, 75.0 /C-4, C-5, C-6, C-9);
93.5, 95.0 /C-2, C-8); 127.3, 127.7, 128.3, 129.0, 134.5 and
140.5 /aromatic carbons); FAB1 MS /NOBA) m/z: 298
[M1H]1; 320; 266; Anal. Calcd for C18H19NO3: C, 72.73;
H, 6.40; N, 4.71; Found: C, 72.84; H, 6.41; N, 4.63.
4.2.4.
cis-2,8-Diphenyl-5-.20-oxa-50-tosyloxypentyl)-1-
aza-3,7-dioxabicyclo[3.3.0]octane .5). To the solution of
compound 4 /0.4 g, 1.1 mmol) in CH2Cl2 /5 mL) at 208C
were successively added triethylamine /0.2 mL, 1.35
mmol), tosyl chloride /0.26 g, 1.35 mmol) and DMAP
/20 mg, 0.13 mmol). The reaction mixture wasallowed to
react at rt for about 4 h then ®ltered over celite. After dilu-
tion with CH2Cl2 /10 mL), the organic phase was washed
with a saturated sodium chloride solution, dried over
sodium sulfate and evaporated to dryness. The residue
waspuri®ed on a islica gel column /80:20 petroleum
ether±AcOEt, v/v). Compound 5 wasioslated asan oil
1
/0.5 g, 87%). H NMR /CDCl3) d: 1.80 /2H, t, 2H-40);
2.45 /3H, s, CH3±Ts); 3.30 /2H, s, 2H-10); 3.35 /2H, t,
2H-30); 3.82 and 3.95 /4H, AB system, q, 2H-4, 2H-6);
4.05 /2H, t, 2H-50); 5.55 /2H, s, H-2, H-8); 7.30±7.80
/14H, m, Ph); 13C NMR /CDCl3) d: 22 /CH3); 29.0 /C-
40); 67.0 /C-50); 67.5, 73.5 /C-10, C-30); 74.1 /C-4, C-6);
76.0 /C-5); 98.0 /C-2, C-8); 127.5, 128.5, 128.5, 129.5;
130.0, 133.4, 140.0 and 145.0 /aromatic carbons); FAB1
MS /NOBA) m/z: 510 [M1H]1; 266; 91; Anal. Calcd for
C28H31NO6S: C, 66.01; H, 6.09; N, 2.75; Found: C, 65.50;
H, 6.29; N, 2.68.
4.2.2. cis-2,8-Diphenyl-5-.40-ethoxycarbonyl-20-oxabutyl)-
1-aza-3,7-dioxabicyclo[3.3.0]octane .3). To the mixture of
powdered sodium hydroxide /0.34 g, 8.4 mmol) and tetra-
butylammonium hydrogenosulfate /TAH) /0.03 g, 0.08
mmol) wasadded the oslution of compound
2 /0.5 g,
1.7 mmol) in hot toluene /5 mL). Ethyl 3-bromopropanoate
/0.43 mL, 3.4 mmol) wasadded dropwise and the reaction
mixture subjected to ultrasound for 1 h. After addition of
water /5 mL) and magnetic stirring for about 10 min, the
organic layer was isolated by decantation and washed
with a saturated solution of NaCl /3£5 mL), dried over
sodium sulfate and evaporated. Recrystallization from
ethyl acetate±petroleum ether gave a white solid material
4.2.5. 2-Amino-2-.20-oxa-50-tosyloxypentyl)propan-1,3-
diol hydrochloride .6). A suspension of compound 5
/0.48 g, 0.9 mmol) in a 1N HCl methanolic solution
/10 mL) washeated until homogeneousand heating was
prolonged for further 15 min. After cooling, the reaction
mixture wasconcentrated. The aqueousphaes wasthen
extracted with CH2Cl2 /3£5 mL) and subjected to freeze
drying. The title compound wasobtained asan oily material
1
/0.47 g, 70%, mp 688C). H NMR /CDCl3) d: 1.20 /3H, t,
3H-80, J7.2 Hz); 2.40 /2H, t, 2H-40, J6.3 Hz); 3.35 /2H,
s, 2H-10); 3.55 /2H, t, 2H-30, J6.3 Hz); 3.8 and 3.95 /4H,
AB system, q, 2H-4 and 2H-6, Jgem9.0 Hz); 4.05 /2H, q,
2H-70, J7.2 Hz); 5.50 /2H, s, H-2, H-8); 7.30±7.50 /10H,
m, Ph); 13C NMR /CDCl3) d: 15.0 /C-80); 35.0 /C-40); 61.0
/C-70); 68. 7 /C-10, C-30); 74.0 /C-4, C-6); 75.5 /C-5); 98.0
/C-2, C-8); 127.6, 128.7, 129.0 and 140.0 /aromatic
carbons); 172.0 /C-50); FAB1 MS /NOBA) m/z: 398
|M1H]1; 266; Anal. Calcd for C23H27NO5: C, 69.08; H,
6.91; N, 3.36; Found: C, 69.52; H, 6.80; N, 3.53.
1
/0.34 g, 98%). H NMR /D2O) d: 1.80 /2H, t, 2H-40); 2.35
/3H, s, CH3±Ts); 3.45 /6H, m, 2H-1, 2H-3, 2H-10); 4.05
/2H, t, 2H-30); 7.35 and 7.50 /4H, AB system, 4H±Ts);
13C NMR /D2O) d: 31.0 /CH3); 28.5 /C-40); 60.0 /C-50);
61.0 /C-2); 67.5 and 69.5 /C-10, C-30); 68.0 /C-1, C-3);
128.5, 130.5, 131.0 and 147.0 /aromatic carbons); FAB1
MS /NOBA) m/z: 334 [M1H]1; 302; 155.
4.2.3. cis-2,8-Diphenyl-5-.50-hydroxy-20-oxapentyl)-1-aza-
3,7-dioxabicyclo[3.3.0]octane .4). A solution of compound
3 /0.2 g, 0.5 mmol) in anhydrousTHF /3 mL) wasadded
dropwise to a suspension of LiAlH4 /0.04 g, 1 mmol) in
anhydrousTHF /5 mL) under cooling /0 8C). Stirring was
maintained for 1 h. A solution of 10% aqueous sodium
hydroxide /2 mL) and ether /10 mL) were successively
added. The phases were separated. The organic phase was
washed with a saturated aqueous solution of NaCl. The
aqueousphaes wasextracted with diethylether /3 £5 mL).
The organic layer obtained was dried over sodium sulfate,
the solvent was removed under vacuum to leave a white
4.2.6. 2-Acrylamido-2-.20-oxa-50-tosyloxypentyl)propan-
1,3-diol .8). To a solution of 6 /0.34 g, 0.9 mmol) in
anhydrousCH 2Cl2 /10 mL) at 08C were added successively
acryloyl chloride /0.45 mL, 5.5 mmol), catalytic amount of
sodium nitrite and triethylamine /1 mL, 7.4 mmol). After
stirring 4 h at rt the reaction mixture was washed succes-
sively with water /8 mL), 1N HCl /8 mL) and water /8 mL).
After drying and evaporation to dryness the oily residue was
puri®ed by silica gel column chromatography /20:80
petroleum ether±AcOEt, v/v) to leave 1,3-di-O-acryloyl-
2-acrylamido-2-/20-oxa-50-tosyloxypentyl)propan-1,3-diol
/7) asan oil /0.3 g, 65%). Compound 7 /0.39 g, 0.8 mmol)
dissolved in anhydrous methanol /8 mL) was treated by a
catalytic amount of sodium methoxide for 1 h at rt. The
reaction mixture was then stirred in the presence of H1
resin Amberlite IRC 50 until pH 6. Subsequent ®ltration
and evaporation afforded the title compound asan oil
/0.3 g, 98%). 1H NMR /acetone-d6) d: 1.90 /2H, m,
2H-40); 2.50 /3H, s, CH3±Ts); 2.90 /2H, s, 2OH); 3.50
/2H, t, 2H-30), 3.55 /2H, s, 2H-10); 3.60 and 3.70 /4H, AB
system, 2H-1, 2H-3); 4.20 /2H, t, 2H-50); 5.60 and 5.65 /1H,
dd, Jcis9.8 Hz, Jgem2.4 Hz, Hb); 6.18 and 6.25 /1H, dd,
Jtr16.9 Hz, Hc); 6.40 and 6.45 /1H, dd, Ha); 7.05 /s, 1H,
1
solid /0.17 g, 95%, mp 66±688C). H NMR /CDCl3) d:
1.70 /2H, m, 2H-40); 1.90 /1H, s, OH); 3.40 /2H, s,
2H-10); 3.50 /2H, t, 2H-30, J5.8 Hz); 3.70 /2H, t, 2H-50,
J5.8 Hz); 3.90 and 4.05 /4H, AB system, q, 2H-4, 2H-6,
Jgem8.9 Hz); 5.55 /2H, s, H-2, H-8); 7.30±7.55 /10H, m,
Ph); 13C NMR /CDCl3) d: 32.5 /C-40); 62.1 and 71.0 /C-10,
C-30); 74.2 /C-4, C-6); 76.0 /C-5); 97.5 /C-2, C-8); 127.5,
128.5, 129.0 and 140.0 /aromatic carbons); FAB1 MS
/NOBA) m/z: 356 [M1H]1; 266; Anal. Calcd for
C21H25NO4: C, 70.98; H, 7.04; N, 3.94; Found: C, 70.27;
H, 7.04; N, 3.78.