Coupling of Thioethyl Glycosyl Donors with Glycal Acceptors
J. Am. Chem. Soc., Vol. 119, No. 42, 1997 10071
100.2, 83.1, 78.8, 75.8, 74.8, 74.1, 73.5, 68.5, 68.3, 61.9, 55.1, 38.7,
27.0, 17.9, 14.0, 11.8; MS (ES+): 869.6 (M+ + Na+), (ES-): 881.6
(M- + Cl-).
(310 mg, 0.536 mmol) and acceptor 57 (46 mg, 0.172 mmol) was
azeotroped with benzene (3 × 50 mL) and dried under vacuum for 1
h. Freshly dried 4 Å molecular sieves (300 mg) were added. Into the
mixture was added CH2Cl2 and di-tert-butylpyridine (0.48 mL, 12.4
mmol). The mixture was stirred at room temperature for 30 min and
cooled to 0 °C, and MeOTf (0.24 mL, 12.4 mmol) was added slowly.
After being stirred at 0 °C for 24 h, the reaction mixture was diluted
with EtOAc (500 mL) and washed with saturated aqueous NaHCO3
(100 mL) and saturated aqueous NaCl (100 mL), dried (MgSO4), and
purified by flash column chromatography.
3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triisopropylsilyl-â-D-galactopy-
ranoside-â-(1f3)-4,6-O-(4-methoxy)benzylidene-D-glucal 45: (77%)
[R]24D: -34.9° (c 2.75, CH2Cl2); IR (thin film) 2941, 2865, 1740, 1645,
1615, 1518, 1463, 1366, 1278, 1251, 1235, 1172, 1128, 1097, 1071,
1
1029, 1009, 883, 825, 734, 696 cm-1; H-NMR (CDCl3) δ 7.41 (d, J
) 8.7 Hz, 2H), 7.35-7.16 (m, 10H), 6.87 (d, J ) 8.7 Hz, 2H), 6.31
(dd, J ) 6.1, 1.2 Hz, 1H), 5.55 (s, 1H), 5.41 (dd, J ) 10.1, 8.0 Hz,
1H), 4.97 (d, J ) 11.2 Hz, 1H), 4.70 (dd, J ) 6.2, 2.0 Hz, 1H), 4.66-
4.54 (m, 4H), 4.43 (m, 1H), 4.30 (m, 1H), 3.99 (m, 2H), 3.86 (t, J )
10.0 Hz, 1H), 3.83-3.75 (m, 5H), 3.64 (m, 1H), 3.57 (dd, J ) 10.2,
2.7 Hz, 1H), 3.39 (m, 1H), 1.20 (s, 9H), 0.98 and 0.97 (2 s, 21H);
13C-NMR (CDCl3) δ 176.8, 159.9, 144.7, 138.8, 137.9, 129.8, 128.3,
128.0, 127.8, 127.6, 127.4, 127.2, 113.5, 101.6, 100.8, 100.7, 80.7,
78.7, 75.1, 74.4, 74.1, 72.6, 72.1, 71.8, 68.7, 68.1, 61.3, 55.2, 38.8,
27.2, 18.0, 11.8; MS (ES+): 869.5 (M+ + Na+), (ES-): 881.5 (M-
+ Cl-).
59: (63%) [R]24D: +0.3° (c 2.72, CHCl3); IR (film) 3030, 2970,
1
2870, 1732, 1649, 1514, 1454, 1279, 835 cm-1; H-NMR (CDCl3) δ
7.38-7.12 (m, 32 H), 6.81 (d, J ) 8.6 Hz, 1H), 6.21 (d, J ) 6.1 Hz,
1H), 5.45 (m, 1H), 5.36 (m, 1H), 5.10 (s, 1H), 4.92-4.82 (m, 4H),
4.84 (d, J ) 10.8 Hz, 2H), 4.79 (d, J ) 2.0 Hz, 1H), 4.78 (d, J ) 11.7
Hz, 1H), 4.76-4.62 (m, 5H), 4.57-4.46 (m, 7H), 4.49-4.34 (m, 1H),
4.05-3.66 (m, 18H), 1.22 and 1.21 (2 s, 17H);
13C-NMR (CDCl3) δ
177.5, 159.3, 144.5, 138.4, 138.3, 138.1, 129.8, 129.7, 129.5, 128.3,
128.2, 128.2, 128.1, 128.1, 128.0, 127.6, 127.5, 127.4, 127.3, 127.3,
127.2, 114.0, 101.5, 99.1, 98.3, 78.2, 79.9, 79.1, 75.0, 75.0, 74.8, 74.6,
74.0, 73.1, 73.0, 72.6, 72.3, 72.1, 68.5, 67.9, 65.8, 55.2, 38.9, 27.1,
25.4; MS (ES+): 1321.8 (M+ + Na+), (ES-): 1333.6 (M- + Cl-).
Synthesis of Thioethyl 3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triiso-
propylsilyl-â-D-galactopyranoside-(1f4)-3,6-di-O-benzyl-â-D-glu-
copyranoside 63. Disaccharide 38 was converted into 63 using general
procedure A: (78%) [R]24D: -9.4° (c 1.05, CH2Cl2); IR (thin film)
3470, 2940, 2865, 1741, 1454, 1276, 1087, 1028, 801 cm-1; 1H-NMR
(CDCl3) δ 7.36-7.18 (m, 20H), 5.40 (dd, J ) 9.0, 8.0 Hz, 1H), 5.08
(d, J ) 10.8 Hz, 1H), 4.98 (d, J ) 11.1 Hz, 1H), 4.68 (d, J ) 12.0 Hz,
1H), 4.65 (d, J ) 12.1 Hz, 1H), 4.61 (d, J ) 10.8 Hz, 1H), 4.56 (d, J
) 6.4 Hz, 1H), 4.53 (d, J ) 5.6 Hz, 1H), 4.45 (d, J ) 2.5 Hz, 1H),
4.43 (s, 1H), 4.32 (d, J ) 9.1 Hz, 1H), 4.14-4.08 (m, 2H), 3.83-3.71
(m, 3H), 3.71 (m, 1H), 3.46 (m, 2H), 3.40-3.32 (m, 2H), 3.27 (m,
1H), 2.71 (m, 2H), 2.49 (s, 1H), 1.30 (t, J ) 7.4 Hz, 3H), 1.17 (s, 9H),
1.02 (m, 21H); 13C-NMR (CDCl3) δ 176.8, 138.9, 138.6, 138.1, 137.8,
128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 127.7, 127.6, 127.5, 127.3,
127.2, 127.1, 99.8, 85.4, 84.0, 80.8, 79.4, 75.2, 74.8, 74.5, 74.4, 73.6,
72.5, 72.0, 71.8, 68.2, 38.8, 27.3, 24.0, 18.0, 18.0, 15.2, 11.8; MS
(ES+): 1009.5 (M+ + Na+), (ES-): 1021.6 (M- + Cl-).
3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triisopropylsilyl-r-D-mannopy-
ranoside-(1f6)-3,4-di-O-benzyl-D-glucal 48: (78%) [R]24D: +22.4°
(c 2.01, CH2Cl2); IR (thin film) 3030, 2940, 2865, 1733, 1648, 1454,
1
1102, 697 cm-1; H-NMR (CDCl3) δ 7.34-7.11 (m, 20H), 6.31 (d, J
) 6.0 Hz, 1H), 5.43 (br s, 1H), 4.83-4.78 (m, 3H), 4.71 (s, 1H), 4.62-
4.41 (m, 6H), 4.17 (m, 1H), 3.96-3.65 (m, 8H), 3.55 (m, 1H), 1.15 (s,
9H), 0.98 (m, 21H); 13C-NMR (CDCl3) δ 177.5, 144.5, 138.6, 138.0,
128.3, 128.2, 128.0, 127.8, 127.6, 127.5, 127.3, 127.2, 99.6, 98.0, 78.2,
75.9, 75.7, 75.0, 74.0, 73.8, 73.4, 72.5, 71.2, 70.3, 67.9, 65.6, 62.4,
38.7, 27.0, 17.9, 11.8; MS (ES+): 931.6 (M+ + Na+), (ES-): 943.6
(M- + Cl-).
3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triisopropylsilyl-r-D-mannopy-
ranoside-(1f4)-3,6-di-O-benzyl-D-glucal 51: (91%) [R]24D: +16.1°
(c 2.71, CH2Cl2); IR (thin film) 3064, 3030, 2940, 2865, 1732, 1648,
1140, 1073, 883 cm-1; 1H-NMR (CDCl3) δ 7.31-7.15 (m, 20H), 6.38
(d, J ) 6.1 Hz, 1H), 5.32 (m, 1H), 5.20 (d, J ) 7.3 Hz, 1H), 4.80 (m,
2H), 4.65-4.39 (m, 7H), 4.08 (s, 3H), 3.90-3.79 (m, 3H), 3.71-3.54
(m, 4H), 1.11 (s, 9H), 0.99 (m, 21H); 13C-NMR (CDCl3) δ 177.4, 144.8,
138.6, 138.3, 137.8, 128.2, 128.1, 128.1, 128.0, 127.9, 127.6, 127.5,
127.4, 127.3, 99.2, 97.2, 78.3, 75.0, 74.0, 73.6, 73.1, 73.0, 71.3, 69.8,
69.2, 68.3, 62.1, 38.7, 26.9, 17.8, 11.7; MS (ES+): 931.6 (M+ + Na+),
(ES-): 839.4 (M- + Cl-).
Synthesis of Thioethyl 3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triiso-
propylsilyl-â-D-galactopyranoside-(1f4)-3,6-di-O-benzyl-2-O-piv-
aloyl-â-D-glucopyranoside 64. Thioethyl disaccharide 63 was pro-
tected using general procedure C to afford 64 (98%): [R]24D: -8.8°
(c 2.73, CH2Cl2); IR (thin film) 3030, 2940, 2865, 1739, 1454, 1277,
3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triisopropylsilyl-R-D-mannopy-
ranoside-(1f3)-4,6-O-(4-methoxy)benzylidene-D-glucal 54: (76%)
[R]24D: -30.1° (c 3.05, CH2Cl2); IR (thin film), 3030, 2940, 2865,
1
1143 cm-1; H-NMR (CDCl3) δ 7.32-7.10 (m, 15H), 7.08-6.94 (m,
1
1732, 1641, 1517, 1021 cm-1; H-NMR (CDCl3) δ 7.38 (d, J ) 12.0
5H), 5.33 (t, J ) 8.0 Hz, 1H), 4.92 (m, 2H), 4.88 (d, J ) 11.0 Hz,
1H), 4.68 (d, J ) 9.2 Hz, 1H), 4.42 (t, J ) 11.5 Hz, 1H), 4.39 (m,
1H), 4.30 (m, 4H), 4.00 (t, J ) 10.8 Hz, 1H), 3.90 (m 1H), 3.78-3.61
(m, 3H), 3.50 (m, 2H), 3.38 (m, 2H), 3.29 (m, 2H), 3.19 (m, 1H), 2.60
(m, 2H), 1.20 (t, J ) 7.5 Hz, 3H), 1.12 (m, 18H), 0.90 (m, 21H); 13C-
NMR (CDCl3) δ 176.7, 176.6, 138.8, 138.6, 138.4, 138.0, 128.3, 128.1,
128.0, 127.9, 127.6, 127.5, 127.3, 127.1, 127.0, 126.6, 99.7, 83.4, 81.9,
80.6, 79.4, 74.6, 73.4, 72.3, 72.1, 71.8, 70.5, 67.9, 60.5, 38.7, 38.5,
27.2, 26.9, 23.3, 17.9, 14.8, 11.6; MS (ES+): 1093.7 (M+ + Na+),
(ES-): 1105.6 (M- + Cl-).
Hz, 2H), 7.27-7.18 (m, 11H), 6.81 (d, J ) 8.5 Hz, 2H), 5.53 (s, 1H),
5.39 (m, 1H), 5.15 (s, 1H), 4.81 (d, J ) 10.6 Hz, 1H), 4.69 (m, 1H),
4.62 (d, J ) 11.0 Hz, 1H), 4.53 (d, J ) 10.7 Hz, 1H), 4.45 (d, J )
11.1 Hz, 1H), 4.29 (m, 1H), 3.96-3.78 (m, 8H), 3.74 (s, 3H), 1.12 (s,
9H), 1.03 (m, 21H); 13C-NMR (CDCl3) δ 177.5, 159.8, 144.7, 138.4,
138.2, 129.4, 128.2, 128.0, 127.6, 127.5, 127.2, 127.1, 113.3, 102.2,
100.8, 97.7, 79.3, 78.3, 75.1, 74.0, 72.8, 71.2, 71.1, 68.5, 68.1, 62.7,
55.1, 38.7, 26.9, 17.9, 11.8; MS (ES+): 869.6 (M+ + Na+), (ES-):
881.5 (M- + Cl-).
Synthesis of 3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triisopropylsilyl-
â-D-galactopyranoside-(1f2)-3,4,6-tri-O-benzyl-â-D-glucopyrano-
side-(1f6)-3,4-di-O-benzyl-glucal 56: (68%) [R]24D: -1.1° (c 1.19,
CH2Cl2); IR (thin film) 2939, 2865, 1740, 1648, 1454, 1363, 1100,
Synthesis of 3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triisopropylsilyl-
â-D-galactopyranoside-(1f4)-3,6-di-O-benzyl-2-O-pivaloyl-â-D-glu-
copyranoside-(1f4)-3,6-di-O-benzyl-D-glucal 65. Coupling of donor
64 and acceptor 30 was accomplished using general procedure D to
yield 69% of 65: [R]24D: -14.4° (c 2.4, CH2Cl2); IR (thin film) 3029,
1
1069 cm-1; H-NMR (CDCl3) δ 7.38-7.13 (m, 32H), 7.08 (m, 2H),
6.36 (d, J ) 5.9 Hz, 1H), 5.49 (dd, J ) 9.9, 8.2 Hz, 1H), 5.03-4.83
(m, 5H), 4.76-4.65 (m, 3H), 4.62-4.44 (m, 9H), 4.21-4.12 (m, 3H),
4.03-3.93 (m, 2H), 3.87-3.71 (m, 4H), 3.68-3.55 (m, 4H), 3.49-
3.35 (m, 3H), 1.12 (s, 9H), 1.04 (br. s, 21H); 13C-NMR (CDCl3) δ
176.5, 144.3, 139.0, 138.8, 138.5, 138.4, 138.2, 138.1, 137.9, 128.3,
128.3, 128.1, 127.9, 127.9, 127.8, 127.7, 127.7, 127.6, 127.5, 127.5,
127.2, 127.1, 102.6, 100.0, 84.9, 81.5, 80.2, 77.5, 76.8, 75.4, 74.9, 74.8,
74.7, 74.6, 74.3, 73.4, 72.2, 72.0, 70.3, 69.0, 68.9, 61.2, 38.7, 27.2,
18.1, 18.0, 14.2, 11.9; MS (ES+): 1363.9 (M+ + Na+), (ES-): 1375.8
(M- + Cl-).
1
2949, 2865, 1740, 1454, 1096 cm-1; H-NMR (CDCl3) δ 7.38-7.10
(m, 25H), 7.07-6.92 (m, 5H), 6.32 (d, J ) 6.2 Hz, 1H), 5.34 (t, J )
8.0 Hz, 1H), 4.98 (d, J ) 11.2 Hz, 1H), 4.89-4.85 (m, 2H), 4.76 (m,
1H), 4.65-4.38 (m, 10H), 4.32-4.26 (m, 3H), 4.11-3.96 (m, 4H),
3.86 (m, 1H), 3.78-3.59 (m, 4H), 3.48-3.29 (m, 3H), 3.25 (m, 1H),
3.18-3.12 (m, 2H), 1.11 (s, 9H), 1.09 (s, 9H), 0.91 (m, 21H); 13C-
NMR (CDCl3) δ 176.6, 176.3, 144.2, 138.8, 138.7, 137.9, 137.6, 128.4,
128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.6, 127.5, 127.3, 127.1,
127.0, 126.6, 100.0, 99.7, 99.4, 80.6, 75.7, 75.0, 74.8, 74.4, 74.3, 73.4,
72.7, 72.3, 71.8, 71.7, 70.5, 67.8, 60.4, 38.6, 27.2, 27.0, 17.9, 17.8,
11.6; MS (ES+): 1358.9 (M+ + Na+), (ES-): 1370.8 (M- + Cl-).
Synthesis of Thioethyl 3,4-Di-O-benzyl-2-O-pivaloyl-6-O-triiso-
Synthesis of 3,4,6-Tri-O-benzyl-2-O-pivaloyl-r-D-mannopyrano-
side-(1f6)[3,4,6-tri-O-benzyl-2-O-pivaloyl-r-D-mannopyranoside-
(1f3)]-4-O-(4-methoxy)benzyl-D-glucal 59. A mixture of donor 20