Carrel and Seeberger
Cleavage from Solid Support: The resin was swollen in CH2Cl2
(1.5 mL), and Grubbs’ first-generation catalyst (20% mol) was
added. The solution was purged five times with ethylene, and the
pink solution was stirred under atmospheric pressure of ethylene
overnight. The black solution was filtered, and the resin was washed
three times with CH2Cl2 (2 mL). The combined filtrates were
evaporated to afford a black oil.
Gradient FSPE: The residue was dissolved in the minimum
amount of DMF/H2O (9:1) and loaded on top of selfed-packed 3 g
Tridecafluoro SiliaBond (Silicycle, Quebec, Canada) column. The
column was eluted under pressure with gradient MeOH/H2O solvent
extraction systems: 80/20 (20 mL), 85/5 (20 mL), 90/10 (20 mL),
95/5 (20 mL), and 100/0 (20 mL). The solvents were evaporated,
and each residue was analyzed by TLC and/or LC-MS.
Pent-4-enyl 3,4-Di-O-benzyl-2-O-pivaloyl-â-D-glucopyranosyl-
(1f6)-2-O-acetyl-3,4-di-O-benzyl-r-D-mannopyranosyl-(1f6)-
3,4-di-O-benzyl-2-O-pivaloyl-â-D-glucopyranoside (1). Method
A, Fmoc Deprotection: A solution of 13 (114 mg, 74 µmol) in
piperidine/DMF (0.6 mL/2.4 mL) was stirred at room temperature
for 30 min. The solvents were evaporated, and residual piperidine
was coevaporated with toluene (2 × 10 mL). The residue was
purified by silica gel flash column chromatography (gradient eluent
EtOAc/cyclohexane (1:8) to (1:2)) to afford 1 (92 mg, 94%) as a
colorless oil.
and was dried over MgSO4. The solvents were evaporated, and the
residue was purified by silica gel flash column chromatography
(product absorbed on silica gel, eluent hexane, Rf (hexane) ) 0.76,
KMnO4 stain) to afford 5 (15.38 g, 89%) as a white solid. The
NMR data and the melting point are in agreement with literature17
and are the same as the commercial product from Fluorous
Technologies Inc. (Pittsburgh, U.S.A., http://fluorous.com/).
Diisopropyl-(1H,1H,2H,2H-perfluorodecyl)silane (6).12 To a
stirred solution of t-BuLi (1.7 M in pentane, 19.1 mL, 32.5 mmol)
in Et2O (55 mL) at -78 °C was added a solution of 5 (9.326 g,
16.24 mmol) in Et2O (75 mL) over 15 min. The turbid yellow
solution was stirred at -78 °C for 1 h. Chlorodiisopropylsilane
(2.45 mL, 13.54 mmol) was added, and the solution was allowed
to warm to room temperature. After 2 h, the gray solution was
slowly treated with a saturated aqueous solution of NH4Cl (50 mL)
and water (until clear aqueous phase). The aqueous phase was
extracted with CH2Cl2 (3 × 150 mL). The combined organic layers
were washed with brine (50 mL, the chlorinated phase was above
the aqueous phase), dried over MgSO4, and the solvents were
evaporated. The residue was distilled under reduced pressure to
give 6 (7.314 g, 96%, Rf (hexane) ) 0.89, KMnO4 stain) as a
colorless liquid. The NMR data were the same as the commercial
product from Fluorous Technologies Inc. (Pittsburgh, USA, http://
fluorous.com/).
Pent-4-enyl 3,4-Di-O-benzyl-6-O-(fluorenylmethoxycarbonyl)-
2-O-pivaloyl-â-D-glucopyranoside (7). General procedure for
glycosylation in solution using pent-4-en-1-ol (96 mg, 1.11 mmol),
2 (379 mg, 0.44 mmol), and TMSOTf (96 µL, 0.53 mmol) in
CH2Cl2 (4.4 mL) between -30 °C and -20 °C for 30 min. The
reaction was quenched with pyridine (100 µL). Silica gel flash
column chromatography (gradient eluent EtOAc/cyclohexane (1:
9) to (1:4)) afforded 7 (260 mg, 80%) as a colorless oil. Rf (EtOAc:
cyclohexane (1:4)) ) 0.41. 1H NMR (300 MHz, CDCl3): 7.77 (d,
J ) 7.5 Hz, 2H), 7.65-7.60 (m, 2H), 7.44-7.24 (m, 14H), 5.78
(dddd, J ) 17.1, 10.3, 6.5, 6.5 Hz, 1H), 5.10 (dd, J ) 9.1, 8.2 Hz,
1H), 5.04-4.92 (m, 2H), 4.84 (d, J ) 11.0 Hz, 1H), 4.59 (d, J )
11.0 Hz, 1H), 4.78 (d, J ) 11.2 Hz, 1H), 4.73 (d, J ) 11.2 Hz,
1H), 4.47 (dd, J ) 11.5, 1.9 Hz, 1H), 4.45-4.23 (m, 5H), 3.86
(ddd, J ) 9.3, 6.3, 6.3 Hz, 1H), 3.75 (dd, J ) 9.1, 8.5 Hz, 1H),
3.68 (dd, J ) 9.3, 8.5 Hz, 1H), 3.61 (ddd, J ) 9.3, 4.9, 1.9 Hz,
1H), 3.46 (ddd, J ) 9.3, 6.3, 6.3 Hz, 1H), 2.12-2.02 (m, 2H),
1.70-1.60 (m, 2H), 1.21 (s, 9H). 13C NMR (75 MHz, CDCl3):
176.6, 154.9, 143.3, 143.2, 141.2, 141.2, 137.9, 137.8, 137.5, 128.4,
128.3, 128.0, 127.9, 127.6, 127.4, 127.1, 125.2, 125.1, 119.9, 114.7,
101.0, 83.2, 77.3, 75.0, 75.0, 72.9, 69.9, 69.0, 66.4, 46.6, 38.7, 29.9,
28.7, 27.1. [R]D (CHCl3, c ) 1): -4.7°. IR (CHCl3): 3068, 3032,
2960, 2872, 1740, 1640, 1602, 1497, 1478, 1452, 1397, 1363, 1263,
1137, 1036, 1011, 972, 916. HRMS (MALDI) calcd for C45H50O9Na,
757.3347; found, 757.3335.
Pent-4-enyl 3,4-Di-O-benzyl-6-O-{(1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-
heptadecafluorodecyl)diisopropylsilyl}-2-O-pivaloyl-â-D-gluco-
pyranosyl-(1f6)-2-O-acetyl-3,4-di-O-benzyl-r-D-mannopyranosyl-
(1f6)-3,4-di-O-benzyl-2-O-pivaloyl-â-D-glucopyranoside (14).
Method A, Solid Phase Oligosaccharide Synthesis Using 4 equiv
of Donor 2 (69 mg, 80 µmol) or 3 (65 mg, 80 µmol) and
TMSOTf (15 µL, 80 µmol): Octenediol-functionalized resin
(DMT loading: 0.267 mmol/g, 20 µmol, 75 mg) was loaded in a
solid phase vessel. A first glycosylation using donor 2 was
performed, followed by acetyl-capping and Fmoc deprotection. The
second glycosylation was performed using donor 3, followed by
acetyl-capping and Fmoc deprotection. The third glycosylation using
2, followed by acetyl-capping and Fmoc deprotection, afforded the
trisaccharide-functionalized resin (100 mg). Part of the resin (80%,
80 mg, 16 µmol) was F-tagged. The resulting resin was cleaved
for 17 h using Grubbs’ first-generation catalyst (2.6 mg, 3.2 µmol),
and the LC-MS was recorded. Conventional F-SPE14 afforded 14
(22 mg, 73%) as a colorless oil.
Method B, Cleavage of F-Tag: To a solution of 14 (47 mg, 25
µmol) in THF (1 mL) was added TBAF (1 M in THF, 50 µL, 50
µmol) at room temperature. After 15 min at room temperature, the
solution was diluted with CH2Cl2 (10 mL) and treated with a
saturated aqueous solution of NaHCO3 (3 mL). The aqueous phase
was extracted with CH2Cl2 (3 × 5 mL). The combined organic
layers were dried over MgSO4, and the solvents were evaporated.
The residue was purified by silica gel flash column chromatography
(gradient eluent EtOAc/cyclohexane (1:5) to (1:2)) to afford 1 (32
mg, 97%) as a colorless oil. Ret. time (40-100) ) 12.5 min; Rf
(EtOAc:hexane (1:2)) ) 0.39. 1H NMR (300 MHz, CDCl3): 7.36-
7.17 (m, 30H), 5.76 (dddd, J ) 17.1, 10.3, 6.5, 6.5 Hz, 1H), 5.40
(dd, J ) 3.4, 1.9 Hz, 1H), 5.10 (dd, J ) 8.7, 7.5 Hz, 1H), 5.06 (dd,
J ) 9.3, 8.1 Hz, 1H), 5.02-4.90 (m, 2H), 4.89 (d, J ) 11.5 Hz,
1H), 4.85 (d, J ) 1.6 Hz, 1H), 4.82-4.68 (m, 7H), 4.62 (d, J )
10.9 Hz, 1H), 4.54 (d, J ) 10.9 Hz, 1H), 4.52 (d, J ) 11.5 Hz,
2H), 4.42 (d, J ) 7.5 Hz, 1H), 4.38 (d, J ) 8.1 Hz, 1H), 3.94-
3.36 (m, 17H), 2.34 (dd, J ) 7.2, 6.5 Hz, 1H), 2.14 (s, 3H), 2.08-
1.98 (m, 2H,), 1.66-1.54 (m, 2H), 1.21 (s, 9H), 1.17 (s, 9H). 13C
NMR (75 MHz, CDCl3): 176.6, 176.4, 170.1, 138.5, 138.1, 138.0,
137.8, 128.4, 128.3, 128.2, 128.0, 127.9, 127.6, 127.6, 127.5, 127.4,
127.2, 114.7, 101.5, 101.0, 97.8, 83.5, 82.9, 77.7, 75.5, 74.9, 74.6,
74.2, 73.2, 73.1, 71.4, 70.9, 69.1, 68.9, 68.2, 66.1, 62.0, 38.9, 38.8,
30.2, 28.9, 27.3, 27.3, 21.2. [R]D (CHCl3, c ) 1): 2.9°. IR
(CHCl3): 3466, 3066, 3008, 2876, 1737, 1604, 1497, 1479, 1454,
1397, 1365, 1277, 1088, 912. HRMS (MALDI) calcd for
C77H94O19Na, 1345.6282; found, 1345.6300.
Diisopropyl-(1H,1H,2H,2H-perfluorodecyl)silyl Triflate (4).
To a solution of 6 (200 mg, 352 µmol) in CH2Cl2 (2 mL) was
added triflic acid (28 µL, 320 µmol) at room temperature. The
solution was stirred for 60 min, and the volume of the solution
was readjusted to 2 mL. (NB: Due to the low stability of 4 upon
storage, this stock solution was freshly prepared prior to use.)
1-Iodo-1H,1H,2H,2H-perfluorodecane (5). To a solution of
perfluorooctylethanol (13.92 g, 30 mmol) in Et2O (75 mL) and
acetonitrile (25 mL) was added successively imidazole (6.127 g,
90 mmol) and triphenylphosphine (11.8 g, 45 mmol). The solution
was cooled to 0 °C, and iodine (11.42 g, 45 mmol) was added
portion wise over 15 min. The solution was kept for a further 15
min at 0 °C and was then allowed to warm to room temperature
overnight. After 19 h, Et2O (200 mL) was added to the red solution
and filtered over a pad of Celite (height ) 3 cm). The Celite was
washed with Et2O (4 × 50 mL). The combined organic layer was
washed with a saturated aqueous solution of Na2S2O3 (until
destruction of residual iodine, ∼50 mL) and with brine (50 mL)
(17) Feiring, A. E. J. Org. Chem. 1985, 50, 3269-3274.
2064 J. Org. Chem., Vol. 73, No. 6, 2008