Sulfenates in the Sulfoxide Glycosylation Reaction
J. Am. Chem. Soc., Vol. 120, No. 24, 1998 5967
mg, 60%). Disaccharide 3: Rf ) 0.3 (30% EtOAc/petroleum ether);
1H NMR (CDCl3, 270 MHz) δ 8.03 (d, J ) 6.9 Hz, 2H), 7.15-7.65
(m, 18 H), 5.03 (d, J ) 3.6 Hz, 1H), 4.95 (d, J ) 11.5 Hz, 1H), 4.6-
4.9 (m, 11H), 4.52 (dd, J ) 4.3,12.2 Hz, 1H), 4.25 (q, J ) 6.3 Hz,
1H), 4.07 (dd, J ) 3.6, 10.2 Hz, 1H), 3.8-4.0 (m, 3H), 3.74 (dd, J )
9.3, 9.3 Hz, 1H), 3.68 (br s, 1H), 3.53 (dd, J ) 3.6, 9.3 Hz, 1H), 3.39
(s, 3H), 3.38 (s, 3H), 3.36 (s, 3H), 1.11 (d, J ) 6.3 Hz, 3H); 13C NMR
(CD3COCD3, 67.5 MHz) δ 166.6, 140.4, 140.2, 139.8, 130.3, 129.5,
129.2, 129.1, 129.05, 129.0, 128.7, 128.4, 128.3, 128.2, 128.16, 100.0,
99.9, 99.3, 98.4, 80.5, 80.2, 79.3, 79.0, 77.2, 77.1, 75.7, 74.5, 73.0,
69.9, 68.1, 64.7, 56.6, 55.5, 55.3, 17.1; HRFABMS calcd for C45H53O13
(M - H-) 801.3486, found 801.3499. Sulfenate 4: Rf ) 0.4 (10%
EtOAc/petroleum ether); 1H NMR (CDCl3, 270 MHz) δ 7.15-7.5 (m,
20 H), 5.01 (d, J ) 3.6 Hz, 1H), 4.96 (d, J ) 11.6 Hz, 1H), 4.87 (d,
J ) 11.6 Hz, 1H), 4.77 (t, J ) 11.3 Hz, 2H), 4.62 (d, J ) 11.6 Hz,
2H), 4.07 (dd, J ) 3.6, 10.2 Hz, 1H), 3.97 (dd, J ) 2.6, 10.2 Hz, 1H),
quenched by slow addition of H2O (10 mL) and then diluted with EtOAc
(100 mL), extracted with H2O (50 mL) and brine (50 mL), dried over
Na2SO4, and concentrated in Vacuo. The product was purified by flash
chromatography (50% methylene chloride/petroleum ether) to afford
2,6-dimethylphenyl 2,3,4-tri-O-benzyl-1-thio-â-L-fucopyranoside (3.0
1
g, 74%): Rf ) 0.3 (5% EtOAc/petroleum ether); H NMR (CDCl3,
270 MHz) δ 7.0-7.5 (m, 18H), 5.06 (d, J ) 10.5 Hz, 1H), 4.98 (d, J
) 11.9 Hz, 1H), 4.88 (d, J ) 10.5 Hz, 1H), 4.72 (m, 3H), 4.27 (d, J
) 9.6 Hz, 1H), 3.87 (dd, J ) 9.6, 9.6 Hz, 1H), 3.57 (d, J ) 2.6 Hz,
1H), 3.50 (dd, J ) 2.6, 9.6 Hz, 1H), 3.26 (q, J ) 6.3 Hz, 1H), 2.56 (s,
6H), 1.07 (d, J ) 6.3 Hz, 3H); 13C NMR (CD3COCD3, 67.5 MHz) δ
145.0, 140.3, 140.0, 139.9, 133.3, 129.7, 129.2, 129.0, 128.95, 128.9,
128.8, 128.5, 128.3, 128.25, 128.2, 90.9, 85.5, 79.5, 78.0, 76.2, 75.7,
74.7, 73.2, 22.9, 17.5; HRFABMS calcd for C35H37O4S (M - H-)
553.2413, found 553.2438.
To the above sulfide (500 mg, 0.903 mmol) in methylene chloride
(10 mL) at -42 °C was added 3-chloroperoxybenzoic acid (272 mg of
65% dispersion, 1.02 mmol). The reaction was allowed to warm to
-5 °C and then cooled to -30 °C, and dimethyl sulfide (100 µL) was
added. The reaction was diluted with methylene chloride (50 mL) and
extracted with saturated aqueous NaHCO3 (50 mL). The organic layer
was dried over Na2SO4 and concentrated in Vacuo. The products were
purified by flash chromatography (5:4:1 methylene chloride/petroleum
ether/EtOAc) to afford a mixture of 2,3,4-tri-O-benzyl-1-(2,6-dimeth-
ylphenylsulfinyl)-â-L-fucopyranosides 5 (430 mg, 84%). More polar
diastereomer: Rf ) 0.3 (5:4:1 methylene chloride/petroleum ether/
3.79 (q, J ) 6.6 Hz, 1H), 3.65 (m, 1H), 1.03 (d, J ) 6.6 Hz, 3H); 13
C
NMR (CD3COCD3, 67.5 MHz) δ 142.2, 140.7, 140.6, 140.3, 130.3,
129.7, 129.6, 129.5, 129.3, 129.2, 128.8, 128.7, 125.4, 106.9, 80.2,
79.4, 79.2, 76.3, 74.7, 73.7, 69.3, 29.6; HRDCIMS calcd for C33H38-
NO5S (M + NH4+) 560.2471, found 560.2471.
General Procedure for the Catalytic Conversion of Sulfoxides.
The combined sulfoxide (0.20 mmol) and 2,6-di-tert-butyl-4-meth-
ylpyridine (0.40 mmol) were azeotroped three times with toluene (10
mL). The residue was taken up in methylene chloride (7 mL), and 4
Å molecular sieves (500 mg) was added. The resulting suspension
was stirred at room temperature for 1 h and then cooled to -78 °C.
Forty microliters of a triflic anhydride stock solution (10 µL triflic
anhydride in 400 µL of methylene chloride; 40 µL of stock is
approximately 0.006 mmol) was added over 1 min via syringe. The
reaction was monitored by TLC and warmed if necessary until all of
the sulfoxide completely disappeared. The reaction was filtered into
saturated aqueous NaHCO3 (30 mL) and extracted with methylene
chloride (3 × 20 mL). The organic layers were combined, dried over
Na2SO4, and concentrated in Vacuo. The products were purified by
flash chromatography.
1
EtOAc); H NMR (CDCl3, 270 MHz) δ 7.1-7.5 (m, 16H), 7.01 (d, J
) 7.6 Hz, 2H), 5.09 (d, J ) 9.9 Hz, 1H), 4.99 (d, J ) 11.9 Hz, 1H),
4.87 (d, J ) 9.9 Hz, 1H), 4.70 (m, 3H), 4.35 (dd, J ) 9.1, 9.1 Hz, 1H),
3.69 (dd, J ) 2.4, 9.1 Hz, 1H), 3.59 (d, J ) 2.4 Hz, 1H), 3.44 (q, J )
6.3 Hz, 1H), 2.57 (s, 6H), 1.01 (d, J ) 6.3 Hz, 3H); 13C NMR (CD3-
COCD3, 67.5 MHz) δ 140.9, 140.7, 140.5, 140.2, 132.1, 130.8, 129.7,
129.6, 129.5, 129.3, 129.1, 129.0, 128.9, 128.7, 128.6, 94.4, 85.8, 78.3,
77.7, 76.0, 75.9, 75.7, 73.4, 20.6, 17.7; HRDCIMS calcd for C35H42-
NO5S (M + NH4+) 588.2784, found 588.2804. Less polar diastere-
omer: Rf ) 0.35 (5:4:1 methylene chloride/petroleum ether/ EtOAc);
1H NMR (CDCl3, 270 MHz) δ 7.1-7.5 (m, 18H), 6.98 (d, J ) 7.6 Hz,
2H), 5.0 (m, 3H), 4.75 (m, 3H), 4.53 (dd, J ) 9.6, 9.6 Hz, 1H), 4.06
(d, J ) 9.6 Hz, 1H), 3.68 (dd, J ) 2.6, 9.6 Hz, 1H), 3.62 (m, 1H), 3.42
(q, J ) 6.3 Hz, 1H), 2.55 (s, 6H), 1.10 (d, J ) 6.3 Hz, 3H); 13C NMR
(CD3COCD3, 67.5 MHz) δ 140.8, 140.3, 140.2, 137.2, 131.6, 131.1,
129.8, 129.6, 129.5, 129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 94.4,
85.8, 78.2, 76.9, 76.5, 76.2, 75.1, 73.4, 20.4, 17.8; HRDCIMS calcd
for C35H39O5S (M + H+) 571.2518, found 571.2528.
Catalytic Conversion of 2,3,4-Tri-O-benzyl-1-(phenylsulfinyl)-
r-L-fucopyranose (1). Catalytic conversion of sulfoxide 1 afforded
25% of 2,3,4-tri-O-benzyl-1-(phenylsulfenyl)-R-L-fucopyranose (4) and
65% of an anomeric mixture of lactols.
Synthesis and Catalytic Conversion of 2,3,4-Tri-O-benzyl-1-(2,6-
dimethylphenylsulfinyl)-â-L-fucopyranoside (5a,b). To a solution
of 1,2,3,4-tetra-O-acetyl-L-fucopyranoside (7.8 g, 23.5 mmol) in
methylene chloride (60 mL) was added 2,6-dimethylthiophenol (4.7
mL, 35.3 mmol). The reaction was cooled to at -72 °C, and boron
trifluoride etherate (5.8 mL, 47.2 mmol) was added dropwise via
syringe. The reaction was warmed slowly to 0 °C and stirred at 0 °C
overnight. Saturated aqueous NaHCO3 (50 mL) was added, and the
reaction was stirred vigorously for 15 min. The organic layer was then
separated, dried over Na2SO4, and concentrated in Vacuo. The product
was purified by flash chromatography (10% acetone/petroleum ether)
to afford 2,6-dimethylphenyl 2,3,4-tri-O-acetyl-1-thio-â-L-fucopyrano-
side (7.7 g, 80%): Rf ) 0.25 (15% acetone/petroleum ether); 1H NMR
(CDCl3, 270 MHz) δ 7.13 (m, 3H), 5.31 (dd, J ) 10.2, 10.2 Hz, 1H),
5.22 (d, J ) 3.6 Hz, 1H), 4.99 (dd, J ) 3.6, 10.2 Hz, 1H), 4.38 (d, J
) 10.2 Hz, 1H), 3.62 (q, J ) 6.6 Hz, 1H), 2.55 (s, 6H), 2.20 (s, 3H),
2.13 (s, 3H), 1.99 (s, 3H), 1.14 (d, J ) 6.6 Hz, 3H); 13C NMR (CD3-
COCD3, 67.5 MHz) δ 171.6, 170.7, 170.5, 145.4, 132.9, 130.7, 129.7,
89.7, 73.8, 73.5, 71.9, 69.4, 23.2, 21.4, 21.2, 17.1; HRFABMS calcd
for C20H26O7SNa (M + Na+) 433.1297, found 433.1313.
Catalytic conversion of sulfoxide 5 afforded 66% of 2,3,4-tri-O-
benzyl-1-(2,6-dimethylphenylsulfenyl)-R-L-fucopyranose (6a), 5% of
2,3,4-tri-O-benzyl-1-(2,6-dimethylphenylsulfenyl)-â-L-fucopyranose (6b),
and 21% of an anomeric mixture of lactols. Sulfenate 6a: Rf ) 0.5
1
(10% EtOAc/petroleum ether); H NMR (CDCl3, 270 MHz) δ 7.0-
7.5 (m, 18H), 4.95 (d, J ) 3.6 Hz, 1H), 4.89 (d, J ) 11.5 Hz, 1H),
4.83 (d, J ) 11.7 Hz, 1H), 4.69 (d, J ) 11.7 Hz, 1H), 4.66 (d, J )
12.2 Hz, 1H), 4.57 (d, J ) 11.5 Hz, 1H), 4.52 (d, J ) 12.2 Hz, 1H),
3.96 (dd, J ) 3.6, 10.2 Hz, 1H), 3.80 (dd, J ) 2.4, 10.2 Hz, 1H), 3.50
(d, J ) 2.4 Hz, 1H), 3.26 (q, J ) 6.6 Hz, 1H), 2.57 (s, 6H), 0.62 (d,
J ) 6.6 Hz, 3H); 13C NMR (CD2Cl2, 67.5 MHz) δ 143.4, 139.5, 139.4,
139.2, 136.9, 131.4, 128.9, 128.8, 128.7, 128.65, 128.6, 128.3, 128.0,
104.7, 79.2, 78.8, 77.5, 75.5, 73.5, 73.4, 68.0, 22.0, 16.3; HRDCIMS
calcd for C35H42NO5S (M + NH4+) 588.2784, found 588.2795.
Sulfenate 6b: Rf ) 0.4 (10% EtOAc/petroleum ether); 1H NMR
(CDCl3, 270 MHz) δ 7.0-7.5 (m, 18H), 4.95 (d, J ) 11.5 Hz, 1H),
4.65 (m, 5H), 4.39 (d, J ) 7.6 Hz, 1H), 3.76 (dd, J ) 7.6, 9.5 Hz, 1H),
3.47 (m, 3H), 2.59 (s, 6H), 1.19 (d, J ) 6.3 Hz, 3H); 13C NMR (CD3-
COCD3, 67.5 MHz) δ 144.5, 140.8, 140.5, 137.5, 132.7, 129.6, 129.5,
129.4, 129.3, 129.1, 129.0, 128.7, 128.6, 109.2, 84.0, 81.0, 78.4, 76.2,
75,9, 73.9, 72.3, 22.6, 17.6; HRDCIMS calcd for C35H42NO5S (M +
NH4+) 588.2784, found 588.2783.
To the above sulfide (3.0 g, 7.32 mmol) in methanol (25 mL) was
added sodium methoxide (100 mg). The resulting solution was stirred
at room temperature overnight and then neutralized with Amberlite IR-
120 (plus) acidic resin. The resin was filtered and rinsed several times
with methanol (3 × 30 mL). The combined filtrate was concentrated
in Vacuo and used without further purification.
To the crude tetraol (∼7.32 mmol) in THF (20 mL) was added benzyl
bromide (5.2 mL, 43.9 mmol). The reaction was cooled to 0 °C, and
NaH (925 mg of 95% dispersion, 36.6 mmol) was added. Tetrabuty-
lammonium iodide (1.0 g) and DMF (10 mL) were added, and the
reaction was allowed to warm to room temperature. The reaction was
Catalytic Conversion of 2,3,4-Tri-O-pivaloyl-1-(phenylsulfinyl)-
r-L-fucopyranose (7). Catalytic conversion of sulfoxide 729 afforded
81% of 1,3,4-tri-O-pivaloyl-R-L-fucopyranose (8): Rf ) 0.33 (20%
1
EtOAc/petroleum ether); H NMR (CDCl3, 270 MHz) δ 6.24 (d, J )
3.6 Hz, 1H), 5.30 (d, J ) 3.3 Hz, 1H), 5.24 (dd, J ) 3.3, 10.6 Hz,