ꢀ- and R-Directing Effects in Mannopyranosylations
A R T I C L E S
with CH2Cl2. The combined organic phase was washed with brine,
dried over MgSO4, and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography (hexane/EtOAc,
6:1) to afford compound 68 (84.6 mg, 85%): colorless oil, Rf )
0.35 (hexane/EtOAc, 5:1, v/v); 1H NMR (400 MHz, CDCl3) δ 3.38
(dd, J ) 9.6, 8.3 Hz, 1H, H-6), 3.45 (dd, J ) 9.7, 4.8 Hz, 1H,
H-6′), 3.96 (t, J ) 2.8 Hz, 1H, H-4), 3.98-4.04 (m, 1H, H-5),
4.08 (t, J ) 2.4 Hz, 1H, H-2), 4.44 and 4.50 (ABq, J ) 12.0 Hz,
2H), 4.55 and 4.62 (ABq, J ) 12.0 Hz, 2H), 4.59 and 4.61 (ABq,
J ) 12.0 Hz, 2H), 4.85 (dd, J ) 2.8, 2.4 Hz, 1H, H-3), 5.35 (t, J
) 2.4 Hz, 1H, H-1), 7.21-7.35 (m, 15H); 13C NMR (100 MHz,
CDCl3) δ 65.7, 70.7, 70.8, 71.7, 72.0, 73.47, 73.52, 75.6, 76.5,
127.8, 127.85, 127.88, 128.1, 128.2, 128.3, 128.5, 128.65, 128.69,
137.0, 137.2, 138.0, 155.8. HRMS calcd for C29H28Cl3NO5Na [M
+ Na]+, 598.0931; found, 598.0934.
at -78 °C for 2 h, quenched with triethylamine, and concentrated
in vacuo. The residue was purified by silica gel flash column
chromatography (hexane/EtOAc/CH2Cl2, 3:1:1) to afford compound
82r (20 mg, 12%): colorless oil, Rf ) 0.38 (hexane/EtOAc/CH2Cl2,
1
3:1:1, v/v/v); [R]20 ) 20.7 (c 1.1, CHCl3); H NMR (400 MHz,
D
CDCl3) δ 3.36 (s, 3H), 3.38-3.44 (m, 2H), 3.51 (dd, J ) 11.2, 3.6
Hz, 1H), 3.55 (dd, J ) 11.2, 3.6 Hz, 1H), 3.65-3.71 (m, 2H),
3.78-3.91 (m, 2H), 3.93 (d, J ) 9.2 Hz, 1H), 4.01 (d, J ) 14.0
Hz, 1H), 4.13 (d, J ) 14.4 Hz, 1H), 4.22 (d, J ) 14.4 Hz, 1H),
4.24 (d, J ) 10.4 Hz, 1H), 4.33-4.39 (m, 2H), 4.46-4.58 (m,
6H), 4.65 (d, J ) 12.0 Hz, 1H), 4.86 (d, J ) 11.6 Hz, 1H), 5.01
(d, J ) 11.6 Hz, 1H), 5.02-5.08 (m, 2H), 5.41 (d, J ) 1.2 Hz, 1H,
H-1′), 7.12-7.41 (m, 35H); 13C NMR (100 MHz, CDCl3) δ 55.4,
57.6, 57.7, 68.4, 69.0, 69.5, 72.4, 72.8, 73.3, 73.4, 73.7, 74.9, 76.7,
77.12, 77.13, 80.4, 81.1, 97.9, 98.9 (C-1′, JC1′-H1′ ) 174 Hz), 127.4,
127.5, 127.6, 127.9, 128.0, 128.1, 128.3, 128.4, 128.52, 128.53,
128.6, 128.90, 128.92, 129.1, 129.3, 130.7, 131.0, 131.1, 137.6,
138.0, 138.3, 139.0. HRMS calcd for C62H66O15S2Na [M + Na]+,
1137.3741; found, 1137.3740.
Procedure for the Detection and Thermal Decomposition of
r-Mannosyl Triflates 69-74 in CD2Cl2 by Low-Temperature
NMR Analysis. A 5 mm NMR tube containing a solution of a
mannosyl trichloroacetimidate 2, 4, 9, 11, 13, 15, or 17 (0.05-0.10
mmol) in CD2Cl2 (500 µL) was placed in the NMR probe at room
Further elution provided compound 82ꢀ (118 mg, 70%): colorless
1
temperature, cooled to -60 °C, and then the reference H NMR
oil, Rf ) 0.35 (hexane/EtOAc/CH2Cl2, 3:1:1, v/v/v); [R]20 ) 8.9
D
spectrum was obtained. The NMR tube was removed from the NMR
probe, and TMSOTf (1.2 equiv) was added to the tube at -78 °C
in an acetone/dry ice bath. After being briefly agitated, the NMR
tube was placed in the precooled NMR probe at -60 °C, and the
1H NMR spectrum was recorded again. The conversion of the
mannosyl trichloroacetimidate into the R-mannosyl triflate was
almost instantaneous, and the 1H NMR spectrum showed the
anomeric proton signal of the R-mannosyl triflate. Also, then the
1H-13C HSQC spectrum was recorded to assign 13C chemical shifts
and to confirm the anomeric proton signal. The NMR probe
1
(c 5.7, CHCl3); H NMR (400 MHz, CDCl3) δ 3.42 (s, 3H), 3.56
(dd, J ) 9.6, 3.6 Hz, 1H), 3.63 (d, J ) 5.6 Hz, 1H), 3.68 (d, J )
5.6 Hz, 1H), 3.72-3.76 (m, 3H), 3.84-3.88 (m, 2H, H-3′, H-5′),
3.90 (dd, J ) 9.6, 2.8 Hz, 1H), 4.10 (dd, J ) 11.4, 4.4 Hz, 1H),
4.11 (d, J ) 11.6 Hz, 1H), 4.17 (d, J ) 9.2 Hz, 1H), 4.18 (d, J )
14.4 Hz, 1H), 4.20-4.28 (m, 2H), 4.29 (d, J ) 14.4 Hz, 1H), 4.34
(d, J ) 14.0 Hz, 1H), 4.41 and 4.44 (ABq, J ) 11.2 Hz, 2H), 4.48
(d, J ) 12.2 Hz, 1H), 4.53-4.65 (m, 4H), 4.68 (d, J ) 12.0 Hz,
1H), 4.95 (t, J ) 9.7 Hz, 1H, H-4′), 5.16 (d, J ) 12.0 Hz, 1H),
5.32 (d, J ) 1.8 Hz, 1H, H-1′), 7.02-7.38 (m, 35H); 13C NMR
(100 MHz, CDCl3) δ 55.5, 68.8, 69.2, 69.8, 70.0, 71.6, 72.5, 73.3,
73.5, 75.0, 75.1, 76.1, 76.7, 77.4, 80.1, 81.5, 97.8, 99.5 (C-1′, JC1′-
H1′ ) 171 Hz), 126.6, 127.4, 127.66, 127.73, 127.80, 127.84, 128.0,
128.2, 128.3, 128.4, 128.56, 128.60, 128.64, 128.7, 128.89, 128.93,
129.0, 130.7, 130.9, 137.3, 137.8, 137.9, 138.2, 138.8. HRMS calcd
for C62H66O15S2Na [M + Na]+, 1137.3741; found, 1137.3743.
1
temperature was increased by 10 °C increments, and H NMR
spectra were acquired at each temperature until the thermal
decomposition of the R-mannosyl triflate was completed.
General Procedure for Mannosylations of 20 with Mannosyl
Bromides 75 and 76 Employing AgClO4 or AgOTf as the
Promoter. A solution of a mannosyl bromide (70 mg, 0.105 mmol)
and a promoter (AgClO4 or AgOTf, 0.157 mmol) in CH2Cl2 (3
mL) in the presence of 4A molecular sieves was stirred for 10 min
at -50 °C. After addition of acceptor 20 (63.7 mg, 0.126 mmol)
to the above solution, the reaction mixture was stirred at -50 °C
for 2 h, quenched with saturated aqueous NaHCO3, and extracted
with CH2Cl2. The combined organic phase was washed with brine,
dried over MgSO4, and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography.
Acknowledgment. This Article is dedicated with respect and
affection to the late Professor Chi Sun Hahn, an inspiring teacher
and mentor, for his contributions to the field of organic chemistry
in Korea. This work was supported by a grant from the Korea
Science and Engineering Foundation through the Center for
Bioactive Molecular Hybrids (CBMH). J.Y.B., B.-Y.L., and M.G.J.
thank the fellowship of the BK 21 program from the Ministry of
Education and Human Resources Development. We thank Dr. Hye-
Seo Park for her help with NMR studies.
Methyl (2,3-Di-O-benzyl-4,6-di-O-benzylsulfonyl-r-D-mannopy-
ranosyl)-(1f4)-2,3,6-tri-O-benzyl-r-D-mannopyranoside (82r) and
Methyl (2,3-Di-O-benzyl-O-4,6-di-O-benzylsulfonyl-ꢀ-D-mannopy-
ranosyl)-(1f4)-2,3,6-tri-O-benzyl-r-D-mannopyranoside (82ꢀ). A
solution of 2,3-di-O-benzyl-4,6-di-O-benzylsulfonyl-R-D-mannopy-
ranosyl trichloroacetimidate (81, 183 mg, 0.226 mmol) and acceptor
77 (70 mg, 0.151 mmol) in CH2Cl2 (5 mL) was stirred for 5 min
at room temperature and cooled to -78 °C. After the addition of
TMSOTf (4.1 µL, 0.0226 mmol), the reaction mixture was stirred
Supporting Information Available: Experimental procedure,
characterization data, and NMR spectra. This material is
JA907252U
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J. AM. CHEM. SOC. VOL. 131, NO. 48, 2009 17713