ˆ
V. Michelet, K. Adiey, S. Tanier, G. Dujardin, J.-P. Genet
FULL PAPER
5.72 mmol) afforded the diastereomers (R,R)-13 (80 mg, colorless The hydroxy alkylation of aldehyde 7 (318 mg, 1.04 mmol) in the
oil) and (S,R)-13 (343 mg, colorless oil), together with unchanged
aldehyde 4 (150 mg, 28%). dr 88:12, Yield 52%.
presence of (R)-3-(tert-butyldimethylsilyloxy)but-1-yne (10b)
(843 mg, 4.57 mmol) afforded the diastereomers (R,R)-15 (188 mg,
colorless oil) and (S,R)-15 (49 mg, colorless oil), together with un-
changed aldehyde 7 (37 mg). dr 80:20, Yield 50%.
(1R,4R)-1-[2,3-Di-O-benzyl-4,6-dideoxy-6-(methoxycarbonyl)-D-
gluco-β-C-pyranosyl]-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-
1
diol [(R,R)-13]: [α]2D0 ϭ ϩ5 (c ϭ 1.1, CHCl3). H NMR (250 MHz,
(1R,4R)-1-[6-O-Benzyl-3-O-tert-butyl-2,4-dideoxy-D-gluco-β-C-py-
CDCl3): δ ϭ 7.39Ϫ7.28 (m, 10 H), 5.03, 4.62:4.70, 4.65 (2 AB sys-
tem, J ϭ 10.7, 11.6 Hz, 4 H), 4.56Ϫ4.53 (m, 2 H), 3.90Ϫ3.70 (m,
2 H), 3.68 (s, 3 H), 3.56 (app. t, J ϭ 9.3 Hz, 1 H), 3.20 (dd, J ϭ
2.8, 9.3 Hz, 1 H), 2.66, 2.46 (2dd, J ϭ 15.8, 7.3 Hz and 15.8, 5.8 Hz,
2 H), 2.26 (dd, J ϭ 12.7, 5.1 Hz, 1 H), 1.75 (broad s, 1 H),
1.45Ϫ1.39 (m, 1 H), 1.40 (d, J ϭ 6.5 Hz, 3 H), 0.90 (s, 9 H), 0.15,
0.14 (2s, 6 H) ppm. 13C NMR (63 MHz, CDCl3): δ ϭ 171.9, 138.2,
138.1, 128.3, 128.1, 127.9, 127.5, 88.8, 82.0, 80.5, 80.0, 78.4, 72.1,
75.2, 71.3, 61.8, 58.9, 51.7, 40.2, 36.3, 25.7, 25.3, 18.1, Ϫ4.6, Ϫ5.0
ppm. MS (CI, NH3): m/z ϭ 583 [M ϩ 1], 600 [M ϩ 18]. HRMS-
DCI/NH3: [M ϩ NH4]ϩ calculated for C33H50NO7Si: 600.3357;
found 600.3361.
ranosyl]-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-diol [(R,R)-15]:
[α]2D0 ϭ ϩ31 (c ϭ 1, CHCl3). 1H NMR (250 MHz, CDCl3): δ ϭ
7.34Ϫ7.27 (m, 5 H), 4.56 (AB system, J ϭ 12.1 Hz, 2 H), 4.53Ϫ4.47
(m, 2 H), 3.67Ϫ3.46 (m, 4 H), 3.42 (dd, J ϭ 10, 4.3 Hz, 1 H), 2.37
(d, J ϭ 5.9 Hz, 1 H), 1.90Ϫ1.76 (m, 2 H), 1.60Ϫ1.25 (m, 2 H), 1.39
(d, J ϭ 6.5 Hz, 3 H), 1.23 (s, 9 H), 0.89 (s, 9 H), 0.11, 0.10 (2s, 6
H) ppm. 13C NMR (63 MHz, CDCl3): δ ϭ 138.2, 128.5, 127.8,
127.7, 88.7, 80.6, 78.1, 75.7, 73.8, 73.5, 73.3, 67.3, 64.9, 59.0, 37.6,
34.8, 28.6, 25.9, 25.4, 18.3, Ϫ4.39, Ϫ4.83 ppm. IR (neat): ν˜ ϭ 3450,
2100 cmϪ1. MS (CI, NH3): m/z ϭ 508 [M ϩ 18]. HRMS-DCI/
NH3: [M ϩ NH4]ϩ calculated for C28H50NO5Si: 508.3458; found
508.3447.
(1S,4R)-1-[2,3-Di-O-benzyl-4,6-dideoxy-6-(methoxycarbonyl)-D-
(1S,4R)-1-[6-O-Benzyl-3-O-tert-butyl-2,4-dideoxy-D-gluco-β-C-py-
gluco-β-C-pyranosyl]-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-
ranosyl]-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-diol [(S,R)-15]:
[α]2D0 ϭ ϩ12 (c ϭ 1, CHCl3). 1H NMR (250 MHz, CDCl3): δ ϭ
7.35Ϫ7.26 (m, 5 H), 4.55 (s, 2 H), 4.54 (dq, J ϭ 6.5, 1.4 Hz, 1 H),
4.28 (dd, J ϭ 7.7 Hz, 1.4 Hz, 1 H), 3.71Ϫ3.40 (m, 4 H), 3.37 (ddd,
J ϭ 11.6, 7.7, 1.8 Hz), 2.8 (broad s, 1 H), 2.01 (m, 1 H), 1.81 (m,
1 H), 1.40 (d, J ϭ 6.5 Hz, 3 H), 1.33Ϫ1.15 (m, 2 H), 1.20 (s, 9 H),
0.89 (s, 9 H), 0.11, 0.10 (2s, 6 H) ppm. 13C NMR (63 MHz, CDCl3):
δ ϭ 138.2, 128.5, 127.7, 88.9, 80.3, 78.9, 75.5, 73.9, 73.5, 73.1, 65.9,
59.0, 37.5, 36.7, 28.6, 25.9, 25.3, 18.3, Ϫ4.43, Ϫ4.86 ppm. IR (neat):
ν˜ ϭ 3470, 2110 cmϪ1. MS (CI, NH3): m/z ϭ 508 [M ϩ 18]. HRMS-
DCI/NH3: [M ϩ NH4]ϩ calculated for C28H50NO5Si: 508.3458;
found 508.3448.
1
diol [(S,R)-13]: [α]2D0 ϭ Ϫ20 (c ϭ 1, CHCl3). H NMR (400 MHz,
CDCl3): δ ϭ 7.38Ϫ7.26 (m, 10 H), 4.88, 4.59/4.71, 4.62 (2 AB sys-
tem, J ϭ 10.8, 11.5 Hz, 4 H), 4.60Ϫ4.53 (m, 2 H), 3.90Ϫ3.80 (m,
2 H), 3.68 (s, 3 H), 3.51 (app. t, J ϭ 9.5 Hz, 1 H), 3.41 (dd, J. ϭ
9.5, 3.2 Hz, 1 H), 2.63, 2.41 (2dd, J ϭ 15.8, 7.0 Hz and 15.8, 5.9 Hz,
2 H), 2.28 (dd, J ϭ 11.8, 4.8 Hz, 1 H), 1.65Ϫ1.63 (m, 1 H), 1.44
(d, J ϭ 6.4 Hz, 3 H), 0.92 (s, 9 H), 0.14, 0.13 (2s, 6 H) ppm. 13C
NMR (63 MHz, CDCl3): δ ϭ 170.9, 138.2, 138.1, 128.3, 128.1,
127.9, 127.5, 88.9, 88.8, 80.4, 80.2, 79.8, 75.1, 72.1, 71.4, 62.6, 58.9,
51.7, 40.0, 36.3, 25.7, 25.3, 18.1, Ϫ4.5; Ϫ4.9 ppm. MS (CI, NH3):
m/z ϭ 600 [M ϩ 18].
The hydroxy alkylation of aldehyde 6 (259 mg, 0.56 mmol) in the
presence of (R)-3-(tert-butyldimethylsilyloxy)but-1-yne (10b)
(469 mg, 2.46 mmol) afforded the diastereomers (R,R)-14 (171 mg,
colorless oil) and (S,R)-14 (96 mg, colorless oil). dr 65:35, Yield
73%.
(1R,4R)-1-O-Allyloxycarbonyl-1-(2,3,4,6-tetra-O-benzyl-D-
gluco-β؊C-pyranosyl)-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-
diol: Allyloxycarbonyl chloride (52 µL, 0.49 mmol) was slowly ad-
ded at 0 °C to a CH2Cl2 (4.5 mL) solution of alcohol 11b (300 mg,
0.41 mmol) and pyridine (66 µL, 0.81 mmol). The solution was
stirred at 0 °C for 1 h and for 1 h at room temp. After completion,
the reaction mixture was washed with 5% aqueous HCl and brine
to pH ϭ 7. The organic phase was dried with MgSO4, filtered,
and concentrated under reduced pressure. Column chromatography
(SiO2, cyclohexane/EtOAc, 9:1) afforded the diprotected derivative
as a colorless oil (318 mg, 95%).[α]2D0 ϭ ϩ3 (c ϭ 1, CHCl3). 1H
NMR (250 MHz, CDCl3): δ ϭ 7.33Ϫ7.19 (m, 20 H), 5.92 (ddt, J ϭ
16.2, 10.5, 5.7 Hz, 1 H), 5.68 (t, J ϭ 1.8 Hz, 1 H), 5.38 (dq, J ϭ
16.2, 1.3 Hz, 1 H), 5.27 (dq, J ϭ 10.5, 1.3 Hz, 1 H), 4.93Ϫ4.54 (m,
10 H), 4.51 (qd, J ϭ 6.5, 1.6 Hz, 1 H), 3.77Ϫ3.45 (m, 7 H), 1.36
(d, J ϭ 6.5 Hz, 3 H), 0.86 (s, 9 H), 0.08Ϫ0.07 (2s, 6 H) ppm. 13C
NMR (63 MHz, CDCl3): δ ϭ 153.9, 138.2, 138.1, 137.8, 137.4,
131.1, 128.2, 128.0, 127.7, 127.6, 127.5, 127.3, 127.2, 127.1, 118.8,
89.2, 77.4, 86.8, 79.6, 78.8, 77.9, 77.2, 75.2, 74.9, 74.7, 73.2, 68.5,
68.4, 66.1, 58.7, 25.5, 24.8, 17.9, Ϫ4.82, Ϫ5.27 ppm. IR (neat): ν˜ ϭ
2225, 1750 cmϪ1. MS (CI, NH3): m/z ϭ 838 [M ϩ 18]. HRMS-
DCI/NH3: [M ϩ NH4]ϩ calculated for C49H64NO9Si: 838.4350;
found 838.4338.
(1R,4R)-1-[2,3-Di-O-benzyl-6-(benzyloxymethyl)-4,6-dideoxy-D-
gluco-β-C-pyranosyl]-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-
diol [(R,R)-14]: [α]2D0 ϭ ϩ25 (c ϭ 1, CHCl3). H NMR (250 MHz,
1
CDCl3): δ ϭ 7.34Ϫ7.36 (m, 15 H), 5.03Ϫ4.49 (m, 8 H), 3.72Ϫ3.27
(m, 6 H), 2.60 (d, J ϭ 10.7 Hz, 1 H), 2.2Ϫ2.1 (m, 1 H), 1.95Ϫ1.75
(m, 2 H), 1.38 (d, J ϭ 6.5 Hz, 3 H), 1.25Ϫ1.35 (m, 1 H), 0.88 (s, 9
H), 0.11, 0.10 (2s, 6 H) ppm. 13C NMR (63 MHz, CDCl3): δ ϭ
138.2, 138.1, 137.9, 128.2, 128.1, 127.6, 127.5, 127.3, 87.1, 82.1,
80.6, 79.7, 78.6, 72.5, 75.0, 72.8, 71.0, 66.4, 61.8, 58.7, 36.5, 35.4,
25.5, 17.9, Ϫ4.7, Ϫ5.2 ppm. IR (neat): ν˜ ϭ 3450, 2100 cmϪ1. MS
(CI, NH3): m/z ϭ 645 [M ϩ 1], 662 [M ϩ 18]. HRMS-DCI/NH3:
[M ϩ H]ϩ calculated for C39H53O6Si: 645.3611; found 645.3609,
[M
ϩ
NH4]ϩ calculated for C39H56O6NSi: 662.3877; found
662.3871.
(1S,4R)-1-[2,3-Di-O-benzyl-6-(benzyloxymethyl)-4,6-dideoxy-D-
gluco-β-C-pyranosyl]-4-O-(tert-butyldimethylsilyl)pent-2-yne-1,4-
1
diol [(S,R)-14]: [α]2D0 ϭ ϩ10 (c ϭ 1, CHCl3). H NMR (200 MHz,
CDCl3): δ ϭ 7.33Ϫ7.27 (m, 15 H), 4.98Ϫ4.50 (m, 8 H), 3.58Ϫ3.43
(m, 6 H), 2.60 (d, J ϭ 10.8 Hz, 1 H), 2.2Ϫ2.1 (m, 1 H), 1.95Ϫ1.8
(1R,4R)-1-O-Allyloxycarbonyl-1-(2,3,4,6-tetra-O-benzyl-D-gluco-β-
(m, 2 H), 1.40 (d, J ϭ 6.5 Hz, 3 H), 1.20Ϫ1.30 (m, 1 H), 0.9 (s, 9 C-pyranosyl)pent-2-yne-1,4-diol: Tetrabutylammonium fluoride
H), 0.13, 0.12 (2s, 6 H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ (215 µL, 1 mol·LϪ1 in THF) was slowly added at 0 °C to a solution
138.1, 137.9, 128.5, 128.1, 127.5, 127.3, 87.3, 82.0, 80.6, 79.5, 78.9,
75.0, 72.8, 72.7, 71.3, 66.7, 61.4, 58.7, 36.5, 35.4, 25.3, 25.3, 17.8,
of the O-silyl compound (192 mg, 0.19 mmol) in THF (2 mL). The
solution was stirred at 0 °C for 1 h and at room temp. for 1 h, and
Ϫ4.6, Ϫ5.2 ppm. IR (neat): ν˜ ϭ 3445, 2100 cmϪ1. MS (CI, NH3): was then treated with water after completion. The aqueous phase
m/z ϭ 645 [M ϩ 1], 662 [M ϩ 18].
was extracted with diethyl ether. The organic phase was washed
2954
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 2947Ϫ2958