Boto et al.
ylene-â-D-galactopyranoside (40) (32.8 mg, 70%) and methyl 2,3-
di-O-methyl-4-O-(methyl acetate)-â-D-galactopyranoside (41) (6
mg, 11%). Compound 40: crystalline solid; mp 118-120 °C (from
219.0869; found, 219.0891; calcd for C7H7, 91.0548; found,
91.0546. Anal. Calcd for C16H22O6: C, 61.92; H, 7.15. Found: C,
62.17; H, 6.82.
1
EtOAc/n-pentane); [R]D +3 (c 0.29, CHCl3); IR 1173 cm-1; H
IHA Reaction of Substrate 11. Compound 11 was treated under
the standard IHA conditions and after column chromatography
(hexanes/EtOAc, 9:1) afforded benzyl 2,3-di-O-methyl-4,6-O-
methylene-R-D-glucopyranoside (45) (66%) as a crystalline solid:
mp 121-123 °C (from n-pentane); [R]D +151 (c 0.14, CHCl3); IR
NMR (500 MHz) δH 3.20 (1H, dd, J ) 3.7, 9.6 Hz), 3.34 (1H, d,
J ) 1.2 Hz), 3.42 (1H, dd, J ) 7.8, 9.6 Hz), 3.51 (3H, s), 3.55
(3H, s), 3.59 (3H, s), 3.82 (1H, dd, J ) 1.5, 12.3 Hz), 4.03 (1H, d,
J ) 3.6 Hz), 4.18 (1H, d, J ) 12.2 Hz), 4.19 (1H, d, J ) 7.7 Hz),
4.73 (1H, d, J ) 6.3 Hz), 5.19 (1H, d, J ) 6.3 Hz); 13C NMR
(100.6 MHz) δC 56.8 (CH3), 58.1 (CH3), 60.8 (CH3), 67.0 (CH),
68.6 (CH2), 72.5 (CH), 79.6 (CH), 81.3 (CH), 93.5 (CH2), 104.3
(CH); MS m/z (rel intensity) 234 (M+, 1), 75 (MeOCHdCHOH +
H, 100); HRMS calcd for C10H18O6, 234.1103; found, 234.1118;
calcd for C3H7O2, 75.0446; found, 75.0447. Anal. Calcd for
C10H18O6: C, 51.27; H, 7.75. Found: C, 51.43; H, 7.74. Compound
1
(CHCl3) 3090, 3067 cm-1; H NMR (500 MHz) δH 3.22 (1H, dd,
J ) 9.4, 9.7 Hz), 3.25 (1H, dd, J ) 3.8, 9.4 Hz), 3.39 (1H, dd, J
) 10.5, 10.5 Hz), 3.41 (3H, s), 3.63 (3H, s), 3.65 (1H, dd, J ) 9.3,
9.4 Hz), 3.73 (1H, ddd, J ) 4.9, 10.0, 10.0 Hz), 4.01 (1H, dd, J )
4.9, 10.2 Hz), 4.60 (1H, d, J ) 6.3 Hz), 4.62 (1H, d, J ) 12.2 Hz),
4.73 (1H, d, J ) 12.2 Hz), 4.98 (1H, d, J ) 3.8 Hz), 5.06 (1H, d,
J ) 6.3 Hz), 7.31 (1H, dd, J ) 7.1, 7.1 Hz), 7.37 (2H, dd, J ) 7.1,
7.6 Hz), 7.39 (2H, d, J ) 7.0 Hz); 13C NMR (125.7 MHz) δC 58.6
(CH3), 61.0 (CH3), 62.7 (CH), 68.7 (CH2), 69.5 (CH2), 79.5 (CH),
81.6 (CH), 81.7 (CH), 93.7 (CH2), 95.8 (CH), 128.0 (CH), 128.3
(2 × CH), 128.4 (2 × CH), 136.9 (C); MS m/z (rel intensity) 219
(M+ - PhCH2, 2), 91 (PhCH2, 100); HRMS calcd for C9H15O6,
219.0869; found, 219.0938; calcd for C7H7, 91.0548; found, 91.0545
Anal. Calcd for C16H22O6: C, 61.92; H, 7.15. Found: C, 61.87; H,
7.11.
41: syrup; [R]D +10 (c 0.30, CHCl3); IR (film) 3518, 1735 cm-1
;
1H NMR (500 MHz) δH 2.10 (3H, s), 3.16 (1H, dd, J ) 3.0, 9.7
Hz), 3.30 (1H, dd, J ) 7.7, 9.6 Hz), 3.46 (1H, dd, J ) 6.3, 6.5
Hz), 3.53 (3H, s), 3.54 (3H, s), 3.58 (3H, s), 3.68 (1H, dd, J ) 6.6,
11.4 Hz), 3.78 (1H, dd, J ) 6.5, 11.4 Hz), 4.17 (1H, d, J ) 4.1
Hz), 4.18 (1H, d, J ) 7.4 Hz), 5.35 (1H, d, J ) 6.1 Hz), 5.38 (1H,
d, J ) 6.1 Hz); 13C NMR (100.6 MHz) δC 19.6 (CH3), 56.9 (CH3),
59.0 (CH3), 60.4 (CH3), 60.8 (CH2), 73.6 (2 × CH), 80.7 (CH),
83.4 (CH), 89.9 (CH2), 104.7 (CH), 169.9 (C); MS m/z (rel intensity)
234 (M+ - MeCO2H, 2), 75 (MeOCHdCHOH + H, 100); HRMS
calcd for C10H18O6, 234.1103; found, 234.1091; calcd for C3H7O2,
75.0446; found, 75.0449. Anal. Calcd for C12H22O8: C, 48.97; H,
7.53. Found: C, 49.14; H, 7.33.
IHA Reaction of Substrate 12. The general procedure afforded
methyl 2,6-di-O-methyl-3-O-(methyl acetate)-â-D-glucopyranoside
(46) (54%) as a syrup: [R]D -22 (c 0.13, CHCl3); IR (film) 3518,
1
1742 cm-1; H NMR (500 MHz) δH 2.10 (3H, s), 3.01 (1H, dd, J
) 8.2, 8.3 Hz), 3.41 (1H, m), 3.42 (3H, s), 3.53 (3H, s), 3.54 (3H,
s), 3.55 (1H, m), 3.64 (1H, dd, J ) 5.1, 10.3 Hz), 3.68 (1H, dd, J
) 3.8, 10.4 Hz), 4.19 (1H, d, J ) 7.8 Hz), 5.38 (1H, d, J ) 6.0
Hz), 5.46 (1H, d, J ) 6.0 Hz); 13C NMR (125.7 MHz) δC 21.1
(CH3), 57.0 (CH3), 59.6 (CH3), 60.6 (CH3), 70.5 (CH), 72.6 (CH2),
73.8 (CH), 82.5 (CH), 84.3 (CH), 89.9 (CH2), 104.4 (CH), 170.7
(C); MS m/z (rel intensity) 234 (M+ - MeCO2H, <1), 74 (MeCHd
CHOH, 100); HRMS calcd for C10H18O6, 234.1103; found,
234.1053; calcd for C3H6O2, 74.0368; found, 74.0360. Anal. Calcd
for C12H22O8: C, 48.97; H, 7.53. Found: C, 49.29; H, 7.84.
IHA Reaction of Substrate 9. When the standard IHA reaction
was carried out with compound 9, followed by column chroma-
tography (hexanes/EtOAc, 9:1), two products were isolated: methyl
2,3-di-O-methyl-4,6-O-methylene-R-D-galactopyranoside (42) (68%)
and methyl 2,3-di-O-methyl-4-O-(methyl acetate)-R-D-galactopy-
ranoside (43) (14%) (overall yield 82%). Compound 42: non-
crystalline solid; [R]D +108 (c 0.13, CHCl3); IR (film) 1173, 1110,
1
1091 cm-1; H NMR (500 MHz, C6D6) δH 3.05 (1H, br s), 3.13
(3H, s), 3.23 (1H, dd, J ) 1.8, 12.1 Hz), 3.29 (3H, s), 3.30 (3H, s),
3.54 (1H, d, J ) 3.6 Hz), 3.59 (1H, dd, J ) 3.5, 10.0 Hz), 3.89
(1H, dd, J ) 3.5, 10.0 Hz), 3.90 (1H, d, J ) 12.2 Hz), 4.31 (1H,
d, J ) 6.2 Hz), 4.79 (1H, d, J ) 3.5 Hz), 5.07 (1H, d, J ) 6.2 Hz);
13C NMR (100.6 MHz, C6D6) δC 55.2 (CH3), 56.9 (CH3), 58.8
(CH3), 63.7 (CH), 68.9 (CH2), 73.2 (CH), 77.8 (CH), 77.9 (CH),
93.3 (CH2), 99.4 (CH); MS m/z (rel intensity) 234 (M+, 2), 75
(MeCHdCHOH + H, 100); HRMS calcd for C10H18O6, 234.1103;
found, 234.1084; calcd for C3H7O2, 75.0446; found, 75.0438. Anal.
Calcd for C10H18O6: C, 51.27; H, 7.75. Found: C, 51.34; H, 7.81.
Compound 43 could not be totally purified from its mixture with
the major product 42. 1H NMR (500 MHz, C6D6) δH 1.65 (3H, s),
3.13 (3H, s), 3.21 (3H, s), 3.26 (3H, s), 3.51 (1H, m), 3.71 (2H,
m), 3.80 (2H, m), 4.03 (1H, d, J ) 2.9 Hz), 4.73 (1H, d, J ) 3.5
Hz), 5.34 (1H, d, J ) 6.1 Hz), 5.36 (1H, d, J ) 6.1 Hz); 13C NMR
(100.6 MHz, C6D6) δC 16.4 (CH3), 55.0 (CH3), 55.2 (CH3), 58.2
(CH3), 61.1 (CH), 70.3 (CH2), 75.6 (CH), 78.8 (CH), 80.0 (CH),
88.9 (CH2), 98.5 (CH), 167.4 (C).
IHA Reaction of Substrate 13. Compound 13 was treated under
the usual IHA conditions. Standard workup followed by column
chromatography (hexanes/EtOAc, 9:1) afforded benzyl 2,6-di-O-
methyl-3-O-(methyl acetate)-â-D-glucopyranoside (48) (52%) and
benzyl 2,6-di-O-methyl-3,4-O-methylene-â-D-glucopyranoside (49)
(17%). Compound 48: syrup; [R]D -12 (c 0.10, CHCl3); IR (film)
3592, 1739 cm-1; 1H NMR (500 MHz) δH 2.10 (3H, s), 3.11 (1H,
dd, J ) 8.0, 8.8 Hz), 3.40 (1H, m), 3.42 (3H, s), 3.50 (1H, dd, J )
8.8, 9.2 Hz), 3.54 (1H, dd, J ) 7.5, 9.0 Hz), 3.56 (3H, s), 3.65
(1H, dd, J ) 5.1, 10.5 Hz), 3.70 (1H, dd, J ) 3.7, 10.4 Hz), 4.40
(1H, d, J ) 7.8 Hz), 4.63 (1H, d, J ) 11.9 Hz), 4.93 (1H, d, J )
11.9 Hz), 5.38 (1H, d, J ) 6.1 Hz), 5.45 (1H, d, J ) 6.0 Hz),
7.35-7.42 (5H, m); 13C NMR (100.6 MHz) δC 30.0 (CH3), 60.0
(CH3), 61.1 (CH3), 70.8 (CH), 71.4 (CH2), 73.8 (CH2), 74.3 (CH),
83.0 (CH), 84.7 (CH), 90.3 (CH2), 102.8 (CH), 128.1 (2 × CH),
128.2 (CH), 128.8 (2 × CH), 137.7 (C), 164.8 (C); MS m/z (rel
intensity) 295 (M+ - [MeOCHdCHOH + H], <1), 91 (PhCH2,
100); HRMS calcd for C15H19O6, 295.1182; found, 219.1191; calcd
for C7H7, 91.0548; found, 91.0546. Anal. Calcd for C18H26O8: C,
58.37; H, 7.08. Found: C, 58.07; H, 7.43. Compound 49: syrup;
IHA Reaction of Substrate 10. Compound 10 was treated under
the usual IHA conditions. Standard workup followed by column
chromatography (hexanes/EtOAc, 9:1) afforded benzyl 2,3-di-O-
methyl-4,6-O-methylene-â-D-glucopyranoside (44) (51%) as a
crystalline solid: mp 117-119 °C (from n-pentane); [R]D -55 (c
1
[R]D -33 (c 0.11, CHCl3); IR (film) 3095, 3067 cm-1; H NMR
1
0.18, CHCl3); IR 3090, 3063 cm-1; H NMR (500 MHz) δH 3.12
(500 MHz) δH 3.49 (1H, m), 3.43 (3H, s), 3.51 (1H, m), 3.53 (1H,
m), 3.61 (3H, s), 3.65 (1H, dd, J ) 3.8, 8.4 Hz), 4.13 (1H, m),
4.35 (1H, dd, J ) 4.5, 4.5 Hz), 4.67 (1H, d, J ) 11.9 Hz), 4.81
(1H, d, J ) 7.6 Hz), 4.94 (1H, d, J ) 11.9 Hz), 4.97 (1H, s), 5.23
(1H, s), 7.27-7.38 (5H, m); 13C NMR (125.7 MHz) δC 59.4 (CH3),
59.6 (CH3), 70.7 (CH2), 71.7 (CH), 71.9 (CH2), 73.1 (CH), 75.8
(CH), 77.7 (CH), 95.7 (CH2), 99.8 (CH), 127.6 (CH), 127.7 (2 ×
CH), 128.3 (2 × CH), 137.3 (C); MS m/z (rel intensity) 267 (M+
- [CH2dCO + H], 3), 91 (PhCH2, 100); HRMS calcd for
C14H19O5, 267.1232; found, 267.1227; calcd for C7H7, 91.0548;
(1H, dd, J ) 7.8, 8.1 Hz), 3.23-3.30 (3H, m), 3.48 (1H, dd, J )
9.8, 10.2 Hz), 3.60 (3H, s), 3.61 (3H, s), 4.20 (1H, dd, J ) 4.3,
10.6 Hz), 4.48 (1H, d, J ) 7.6 Hz), 4.60 (1H, d, J ) 6.3 Hz), 4.64
(1H, d, J ) 12.0 Hz), 4.89 (1H, d, J ) 11.8 Hz), 5.05 (1H, d, J )
6.3 Hz), 7.28-7.36 (5H, m); 13C NMR (125.7 MHz) δC 60.8 (CH3),
60.9 (CH3), 66.2 (CH), 68.5 (CH2), 71.3 (CH2), 80.7 (CH), 82.5
(CH), 84.2 (CH), 93.6 (CH2), 102.9 (CH), 127.8 (2 × CH), 127.9
(CH), 128.4 (2 × CH), 137.1 (C); MS m/z (rel intensity) 219 (M+
- PhCH2, <1), 91 (PhCH2, 100); HRMS calcd for C9H15O6,
1946 J. Org. Chem., Vol. 71, No. 5, 2006