Chen et al.
897
20:1) showed that the thioglycosylation was complete. After
filtration with suction, the solid residue was washed with
DCM. The combined filtrates were evaporated in vacuo to
afford a crude product, which was purified and partially sep-
arated by flash chromatography on silica gel (PE–EE, 20:1).
Yield: 2.131 g (9.0 mmol, 78%).
(±)-5: Rf = 0.26 (silica gel, PE–EE, 6:1). 1H NMR
(300 MHz, CDCl3) ꢄ: 7.45–7.25 (m, 5H, Ph), 4.25 (dd, 1H,
J = 11.4, 2.2 Hz, 2-H), 3.52–3.42 (m, 2H, 6-H and
SO2CHH), 3.32 (m, 1H, SO2CHH), 3.18 (m, 2H, CH2Ph),
2.10–1.28 (m, 6H, 2 × 3-H, 2 × 4-H, and 2 × 5-H), 1.26 (d,
J = 6.3 Hz, 3H, Me). 13C NMR (75 MHz, CDCl3) ꢄ: 140.8
(s, Ph-C1), 128.7, 128.5 (2d, Ph-C2,6 and Ph-C3,5), 126.9
(d, Ph-C4), 90.3 (d, OCHSO2CH2CH2Ph), 76.1 (d,
CHOCHSO2CH2CH2Ph), 50.0 (SO2CH2CH2Ph), 27.8
(SO2CH2CH2Ph), 32.2, 22.3, 21.9 (3t, 3 × CH2), 21.8 (q,
CH3). ES-MS m/z (%): 286.2 (100) [M + NH4]+; 554.2 (9)
[2M + NH4]+; 559.2 (23) [2M + Na]+; 291.1 (100) [M +
Na]+; 559.2 (26) [2M + Na]+.
1
trans-Isomer: Rf = 0.46 (silica gel, PE–EE, 20:1). H NMR
(300 MHz, CDCl3) ꢄ: 7.35–7.15 (m, 5H, Ph), 5.37 (d, J =
5.1 Hz, 1H, 2-H), 4.19 (dqd, J = 11.0, 6.2, 2.2 Hz, 1H, 6-
H), 2.98–2.75 (m, 4H, CH2CH2Ph), 2.00–1.22 (m, 6H, 2 ×
3-H, 2 × 4-H, and 2 × 5-H), 1.17 (d, J = 6.2 Hz, 3H, Me).
13C NMR (75 MHz, CDCl3) ꢄ: 140.7 (s, Ph-C1), 128.4,
128.2 (2d, Ph-C2,6 and Ph-C3,5), 126.1 (d, Ph-C4), 81.9 (d,
OCHOCH2CH2Ph), 64.8 (d, CHOCHOCH2CH2Ph), 36.7,
33.3, 32.0, 30.3, 19.6 (5t, 5 × CH2), 21.7 (q, CH3).
Preparation of phenylsulfone (±)-6 and (±)-7 (15)
Lactol acetate 11 (50 mg, 0.32 mmol) was dissolved in
dry DCM (15 mL) and to it was added sodium
benzenesulfinate (109 mg, 0.66 mmol, 2 equiv). After addi-
tion of trifluoroacetic acid (0.1 mL, 4 equiv) the mixture was
allowed to stir for 4 h at RT, whereupon TLC (PE–EE, 4:1)
indicated the completion of the reaction. The mixture was
diluted with DCM (15 mL) and then decanted into a satu-
rated solution of NaHCO3 (30 mL). The organic phase was
washed once with water (20 mL) and dried over Na2SO4.
Evaporation of the solvent in vacuo gave a crude product,
which was subsequently purified by flash chromatography
(PE–EE, 4:1) to afford each pure title phenylsulfone (±)-6
and (±)-7 Yield: 59 mg (0.246 mmol, 78%, trans-(±)-6–cis-
(±)-7 = 2:1, separable).
(±)-6: Rf = 0.30 (silica gel, PE–EE, 6:1); amorphous solid.
1H NMR (300 MHz, CDCl3) ꢄ: 7.90–7.40 (m, 5H, Ph), 4.38
(dd, J = 6.6, 1.5 Hz, 1H, 2-H), 3.45 (dqd, J = 10.6, 6.2,
2.3 Hz, 1H, 6-H), 2.10–1.29 (m, 6H, 2 × 3-H, 2 × 4-H, and
2 × 5-H), 1.19 (d, J = 6.2 Hz, 3H, Me). 13C NMR (75 MHz,
CDCl3) ꢄ: 133.6 (s, Ph-C1), 129.0, 128.6 (2d, Ph-C2,6 and
Ph-C3,5), 128.8 (d, Ph-C4), 92.1 (d, OCHSO2Ph), 69.6 (d,
CHOCHSO2Ph), 32.2, 23.6, 18.6 (3t, 3 × CH2), 21.6 (q,
CH3).
(±)-7: amorphous solid; Rf = 0.22 (silica gel, PE–EE, 6:1).
1H NMR (300 MHz, CDCl3) ꢄ: 7.90–7.40 (m, 5H, Ph), 4.73
(dd, J = 11.0, 2.2 Hz, 1H, 2-H), 4.60 (dqd, J = 11.0, 6.2,
2.2 Hz, 1H, 6-H), 2.20–1.29 (m, 6H, 2 × 3-H, 2 × 4-H, and
2 × 5-H), 1.13 (d, J = 6.2 Hz, 3H, Me). 13C NMR (75 MHz,
CDCl3) ꢄ: 133.5 (s, Ph-C1), 129.6, 128.7 (2d, Ph-C2,6 and
Ph-C3,5), 128.8 (d, Ph-C4), 90.6 (d, OCHSO2Ph), 74.5 (d,
CHOCHSO2Ph), 31.8, 22.5, 21.9 (3t, 3 × CH2), 21.6 (q,
CH3). ES-MS m/z (%): 258.2 (100) [M + NH4]+; 498.2 (25)
[2M + NH4]+; 263.1 (70) [M + Na]+; 503.2 (18) [2M + Na]+.
1
cis-Isomer: Rf = 0.40 (silica gel, PE–EE, 20:1). H NMR
(300 MHz, CDCl3) ꢄ: 7.30–7.14 (m, 5H, Ph), 4.47 (dd, J =
11.0, 2.2 Hz, 1H, 2-H), 3.46 (dqd, J = 11.0, 6.2, 1.8 Hz, 1H,
6-H), 3.02–2.84 (m, 4H, CH2CH2Ph), 1.92–1.10 (m, 6H, 2 ×
3-H, 2 × 4-H, and 2 × 5-H), 1.22 (d, J = 6.2 Hz, 3H, Me).
13C NMR (75 MHz, CDCl3) ꢄ: 140.8 (s, Ph-C1), 128.4,
128.3 (2d, Ph-C2,6 and Ph-C3,5), 126.1 (d, Ph-C4), 82.6 (d,
OCHOCH2CH2Ph), 75.0 (d, CHOCHOCH2CH2Ph), 36.8,
32.6, 31.8, 31.5, 24.4 (5t, 5 × CH2), 22.1 (q, CH3). ES-MS
m/z (%): 254.2 (100) [M + NH4]+; 498.2 (25) [2M + NH4]+;
263.1 (70) [M + Na]+; 503.2 (18) [2M + Na]+.
Oxidation of thioglycoside for syntheses of anomeric
sulfones (±)-4 and (±)-5 (14)
The isomeric mixture of thioglycosides (±)-12 (1.076 g,
4.0 mmol) was dissolved in a mixed solvent (54 mL, THF–
H2O–EtOH, 4:4:1) and to it at 0°C was added MMPP (7.9 g,
2.5 equiv). The mixture was allowed to stir at 0°C for 1 h, at
which time TLC (PE–EE, 6:1) indicated the completion of
the oxidation. The mixture was neutralized with a saturated
solution of NaHCO3 (30 mL). The aqueous phase was ex-
tracted with DCM (3 × 20 mL). The combined organic
phases were dried over Na2SO4. Evaporation of the solvent
in vacuo afforded a crude product, which was subsequently
purified by flash chromatography (PE–EE, 8:1 to 5:1) to af-
ford the pure title phenylethylsulfone of both (±)-4 (trans)
and (±)-5 (cis) in a ratio of 2:3. Yield: 1.16 g (4.32 mmol,
95%). Pure trans-sulfide (60 mg, 0.254 mmol) was oxidized
according to the same procedure. After work-up and flash
chromatography pure trans-anomeric sulfone (±)-4 was ob-
tained (yield: 64 mg, 0.239 mmol, 94%) without observing
any isomerization at the anomeric position under the oxida-
tion conditions.
(±)-4: Rf = 0.40 (silica gel, PE–EE, 6:1). 1H NMR
(300 MHz, CDCl3) ꢄ: 7.42–7.22 (m, 5H, Ph), 4.73 (dd, J =
6.2, 2.2 Hz, 1H, 2-H), 4.48 (dqd, J = 10.4, 6.2, 2.2 Hz, 1H,
6-H), 3.40–3.12 (2m, 4H, CH2CH2Ph), 2.15–1.21 (m, 6H,
2 × 3-H, 2 × 4-H, and 2 × 5-H), 1.23 (d, J = 6.2 Hz, 3H,
Me). 13C NMR (75 MHz, CDCl3) ꢄ: 140.7 (s, Ph-C1), 128.0,
127.6 (2d, Ph-C2,6 and Ph-C3,5), 126.1 (d, Ph-C4), 86.3 (d,
OCHSO2CH2CH2Ph), 68.9 (d, CHOCHSO2CH2CH2Ph),
50.7 (t, SO2CH2CH2Ph), 30.9, 27.2, 20.1, 17.8 (4t, 4 × CH2),
20.9 (q, CH3). ES-MS m/z (%): 286.2 (100) [M + NH4]+;
554.2 (9) [2M + NH4]+; 291.1 (38) [M + Na]+; 559.2 (8)
[2M + Na]+.
Isomerization
Initially, isomerization was carried out under basic condi-
tions. Molecules trans-(±)-6 and cis-(±)-7 were separately
dissolved in dry benzene (2 mL). After addition of t-BuOK
(10 mg) the solution was isomerized by heating at reflux for
5 days, whereupon the equilibrium was achieved according
to the NMR analysis. isomerizations with compounds (±)-4
and (±)-5 were done under the similar conditions (t-BuOK);
however, no isomerization was detected after heating at re-
flux for 5 days by NMR analysis. (Table 1).
Interestingly, after trans-isomer (±)-4 was stored in CDCl3
in the refrigerator for 3 weeks isomerization was observed,
© 2002 NRC Canada