Y. Vera-Ayoso et al. / Tetrahedron: Asymmetry 12 (2001) 2031–2041
2039
HRCIMS: m/z 470.2186 (calcd for C23H32FNO8+H:
470.2190). Anal. calcd for C23H32FNO8·H2O: C, 56.66;
H, 7.03; N, 2.87. Found: C, 57.03; H, 6.72; N, 2.80.
and 5% aqueous sodium hydrogencarbonate (20 mL),
dried (MgSO4), and concentrated. The residue was
purified by TLC (several plates, 3:1 hexane:ethyl acet-
ate, half plus one runs) to afford unreacted starting
substrate (0.070 g, indicating 41% of conversion) and
compound 12 (0.015 g, 12%, corresponding to 29%
yield from converted substrate): syrup; Rf=0.55 (3:1,
hexane:ethyl acetate); [h]2D7 −22.5 (c 0.50, acetone); IR
(film) wmax 2244 (CꢁN), 1752 (CꢂO), 1259 and 1100
4.10. 3-C-Cyano-2,3-dideoxy-3-ethoxycarbonyl-2-
phenylthio-a- -mannopyranosyl fluoride 14, 3-C-cyano-
D
2,3,6-trideoxy-3-ethoxycarbonyl-6-fluoro-2-phenylthio-a-
D
-mannopyranosyl fluoride 15, and phenyl 3-C-cyano-
3,6-dideoxy-3-ethoxycarbonyl-6-fluoro-1-thio-a-D-
glucopyranoside 16
1
cm−1 (ester CꢀOꢀC); H NMR (500 MHz, acetone-d6) l
7.45–7.36 (m, 5H, Ph), 5.69 (s, 1H, CH-Ph), 4.98 (d,
1H, J1,2=8.5, H-1), 4.35 (dd, 1H, J5,6=4.8, J6,6%=9.9,
H-6), 4.35 (q, 2H, J=7.0, O-CH2-Me), 4.09 (d, 1H,
,
Freshly activated molecular sieves (4 A) were added,
under argon, to a solution of a 0.6:1 9:10 mixture
(0.165 g, 0.467 mmol) in dry dichloromethane (3 mL).
After 45 min, the mixture was cooled to −40°C, DAST
(370 mL, 2.80 mmol) was added, and the temperature
was allowed to rise to 20°C and the mixture stirred for
5 h. After cooling to 0°C, the reaction was quenched
via addition of methanol (2 mL). Evaporation of the
solvents left a crude residue, which was purified by
TLC (3:1 ether:hexane) to afford unreacted substrate
(0.065 g of a 1:0.8 mixture of 9:10, indicating 42%
conversion for 9 and 72% conversion for 10), rear-
ranged monofluoro compound 14 (0.015 g, 15%, corre-
sponding to 20% yield from converted 10), rearranged
difluoro compound 15 (0.008 g, 8%, corresponding to
11% yield from converted 10), and compound 16 (0.011
g, 11%, corresponding to 26% yield from converted 9).
J
4,5=9.2, H-4), 3.88 (dd, 1H, J5,6%=9.8, H-6%), 3.83
(ddd, 1H, H-5), 3.55 (s, 3H, MeO), 3.13 (d, 1H, H-2),
2.95 [dq, 2H, JCH ,Me=7.1, Jgem=14.0, N(CHa-Me)2],
a
2.71 [dq, 2H, JCH ,Me=6.8, N(CHb-Me)2], 1.29 (t, 3H,
b
Me-CH2-O), and 0.97 [dt, 6H, J=7.1, (Me-CH2)2N];
13C NMR (125.7 MHz, acetone-d6) l 166.8 (C-COO),
138.2–127.1 (Ph), 116.7 (CN), 103.2 (C-1), 102.1 (CH-
Ph), 80.1 (C-4), 69.1 (C-6), 67.2 (C-2), 67.1 (C-5), 63.5
(Me-CH2-O), 57.4 (C-3), 56.8 (MeO), 46.8 [(Me-
CH2)2N], 14.7 [(Me-CH2)2N], and 14.4 (Me-CH2-O);
HREIMS: m/z 418.2106 (calcd for C22H30N2O6:
418.2104).
4.9. 4,6-O-Benzylidene-3-C-[(tert-butoxycarbonyl-
amino)methyl]-3-deoxy-3-ethoxycarbonyl-2-O-methyl-a-
Compound 14: syrup; Rf=0.21 (3:1 ether:hexane); [h]D26
+39.5 (c 1.14, acetone); IR (film) wmax 3370 (OH), 2258
(CꢁN), 1743 (CꢂO), 1261 and 1179 (ester CꢀOꢀC), 1097
D
-mannopyranosyl fluoride 13
,
Molecular sieves (4 A) were added to a solution of
compound (0.114 g, 0.245 mmol) in dry
1
CF), and 614 cm−1 (CꢀS); H NMR (500 MHz, acet-
6
one-d6) l 7.57–7.38 (m, 5H, Ph), 5.98 (dd, 1H, J1,2
=
dichloromethane (5 mL). After 45 min, the mixture was
cooled in an ice bath, DAST (160 mL, 1.23 mmol) was
added, and the whole was heated under reflux until the
starting substrate was consumed (5 h, TLC monitoring,
1:1 hexane:ethyl acetate). The mixture was cooled at
0°C and methanol (2 mL) was added to quench the
reaction. After evaporation of the solvents, the crude
residue was subjected to TLC (1:1 hexane:ethyl acetate)
to give unreacted 6 (0.075 g, indicating 34% of conver-
sion) and the sugar fluoride 13 monohydrate (0.020 g,
17%, corresponding to 51% yield from converted sub-
strate): syrup; Rf=0.47 (2:1, hexane:ethyl acetate); [h]D26
−42 (c 0.50, acetone); IR (film) wmax 3445 (NH), 1744
and 1721 (CꢂO), 1179 and 1109 (ester CꢀOꢀC), and
1097 cm−1 (CF); 1H NMR (500 MHz, acetone-d6) l
7.50–7.38 (m, 5H, Ph), 5.76 (s, 1H, CH-Ph), 5.73 (dd,
1H, J1,2=1.1, 2J1,F=49.7, H-1), 5.45 (br d, 1H,
2
1.3, J1,F=51.8, H-1), 5.36 (d, 1H, J4,HO=5.8, HO-4),
4.50 (dd, 1H, J4,5=10.0, H-4), 4.20 (q, 2H, J=7.1,
CH2-Me), 4.06 (dd, 1H, 3J2,F=4.7, H-2), 3.98 (ddd, 1H,
J
5,6=J5,6%=3.1, H-5), 3.88 (dd, 1H, J6,6%=10.5, H-6),
3.87 (dd, 1H, H-6%), and 1.12 (t, 3H, Me-CH2); 13C
NMR (125.7 MHz, acetone-d6) l 165.1 (COO), 134.0–
127.0 (Ph), 116.5 (CN), 108.3 (d, 1J1,F=230.0, C-1),
74.0 (C-5), 63.8 (C-4), 63.7 (Me-CH2), 61.3 (C-6), 53.7
2
(d, J2,F=28.0, C-2), 52.6 (C-3), and 13.9 (Me-CH2);
HRCIMS: m/z 356.0963 (calcd for C16H18FNO5S+H:
356.0968), 355.0892 (calcd for C16H18FNO5S:
355.0890).
Compound 15: syrup; Rf=0.32 (1:1 ether:hexane); [h]D24
+28 (c 0.54, acetone); IR (film) wmax 3486 (OH), 2269
(CꢁN), 1746 (CꢂO), 1247 and 1167 (ester CꢀOꢀC), 1106
1
CF), and 620 cm−1 (CꢀS); H NMR (500 MHz, ace-
tone-d6) l 7.58–7.41 (m, 5H, Ph), 6.04 (dd, 1H, J1,2
=
J
CH ,NH=8.9, NH), 4.49 (d, 1H, J4,5=10.1, H-4), 4.32
2
2
1.5, J1,F=51.2, H-1), 5.69 (d, 1H, J4,HO=6.0, HO-4),
(dd, 1H, J5,6=4.9, J6,6%=10.2, H-6), 4.17 (q, 2H, J=7.1,
CH2-Me), 4.14 (ddd, 1H, J5,6%=10.1, H-5), 3.90 (dd,
1H, Jgem=13.9, CHa-NH), 3.89 (dd, 1H, H-6%), 3.66 (d,
1H, CHb-NH), 3.66 (overlapped dd, 1H, J2,F=13.9,
H-2), 3.44 (s, 3H, MeO), 1.34 (s, 9H, Me3C), and 1.27
(t, 3H, Me-CH2); 13C NMR (125.7 MHz, acetone-d6) l
169.9 (C-COO), 155.6 (N-COO), 138.8–126.9 (Ph),
2
4.82 (ddd, 1H, J5,6=3.3, J6,6%=10.7, J6,F=47.0, H-6),
2
4.72 (ddd, 1H, J5,6%=1.7, J6%,F=48.2, H-6%), 4.49 (dd,
1H, J4,5=10.3, H-4), 4.21 (q, 2H, J=7.1, CH2-Me),
3
3
4.15 (dddd, 1H, J5,F=27.2, H-5), 4.13 (dd, 1H, J2,F
=
4.2, H-2), and 1.11 (t, 3H, Me-CH2); 13C NMR (125.7
MHz, acetone-d6) l 167.9 (COO), 135.0–129.0 (Ph),
116.1 (CN), 108.0 (d, J1,F=232.5, C-1), 82.1 (d, J6,F
172.6, C-6), 72.3 (d, J5,F=18.2, C-5), 63.9 (Me-CH2),
62.7 (d, J4,F=7.9, C-4), 53.5 (d, J2,F=27.3, C-2), 52.3
(C-3), and 13.8 (Me-CH2); HRCIMS: m/z 358.0925
(calcd for C16H17F2NO4S+H: 358.0925).
1
1
=
1
2
105.4 (d, J1,F=222.5, C-1), 102.7 (CH-Ph), 81.9 (C-4),
2
3
2
80.2 (d, J2,F=36.5, C-2), 78.8 (CMe3), 69.3 (C-6), 62.5
(Me-CH2), 61.3 (C-5), 59.8 (MeO), 53.1 (C-3), 41.1
(CH2-NH), 28.4 (Me3C), and 14.5 (Me-CH2);